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PURPOSE: A rise in affective and anxiety disorders and in antidepressant (AD) treatment during the COVID-19 pandemic has been extensively described, but few studies were provided at the individual level, further considering COVID-19 severity and vaccination status. METHODS: Case-control study evaluating the association between the new use of ADs and a previous COVID-19 infection, in Friuli Venezia Giulia Region, Italy, from March 1, 2020, to July 19, 2022. Multiple conditional logistic regressions assess the association between a new AD use and a COVID-19 infection previous to the index date, stratified by gender, age and anti-COVID-19 vaccination status. Odds Ratios (OR) and 95% confidence intervals were reported. RESULTS: COVID-19 was associated with AD treatment after the infection. The disease severity was positively associated with a growing risk of being dispensed an AD, with the highest risk in unvaccinated subjects previously hospitalised in ICU (OR = 28.77). The risk of using ADs after COVID-19 infection was higher in unvaccinated subjects aged 65 years and older, both females and males. The association between COVID-19 infection and AD dispensation in vaccinated subjects was not significant, with the exception of females aged 65 years and over. CONCLUSIONS: Anti-COVID-19 vaccination, especially among the elderly, might prevent post-COVID AD treatment. Clinicians should be aware that COVID-19 patients requiring hospitalisation are more likely to experience these symptoms, given their higher risk of being dispensed ADs. Future studies may benefit by analysing the incidence of both mental disorders and psychotropic treatment in post-COVID patients, considering socioeconomic factors and vaccination status.
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Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (É2, É3, É4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.
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BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.
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COVID-19 , Hospitalização , Aceitação pelo Paciente de Cuidados de Saúde , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Hospitalização/estatística & dados numéricos , Itália/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Síndrome de COVID-19 Pós-Aguda , Estudos de Coortes , Recursos em Saúde/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricosRESUMO
The impacts of single-nucleotide polymorphisms (SNPs) in ALAD and VDR genes on Pb health effects and/or kinetics are inconclusive at low exposure levels, while studies including APOE SNPs are rare. In this study, we examined the associations of ALAD, VDR and APOE SNPs with exposure biomarkers of Pb and other trace elements (TEs) in Italian pregnant women (N = 873, aged 18-44 years) and their newborns (N = 619) with low-level mixed-element exposure through diet, the environment or endogenously. DNA from maternal peripheral venous blood (mB), sampled during the second and third trimesters, was genotyped for ALAD (rs1800435, rs1805313, rs1139488, rs818708), VDR (rs2228570, rs1544410, rs7975232, rs731236) and APOE (rs429358, rs7421) using TaqMan SNP assays. Personal and lifestyle data and TE levels (mB, maternal plasma, hair and mixed umbilical cord blood [CB]) from the PHIME project were used. Multiple linear regression models, controlling for confounding variables, were performed to test the associations between SNPs and TEs. The geometric means of mB-Pb, mB-Hg, mB-As and mB-Cd (11.0 ng/g, 2.16 ng/g, 1.38 ng/g and 0.31 ng/g, respectively) indicated low exposure levels, whereas maternal plasma Zn and Se (0.72 µg/mL and 78.6 ng/g, respectively) indicated adequate micronutritional status. Variant alleles of ALAD rs1800435 and rs1805313 were negatively associated with mB-Pb levels, whereas a positive association was observed for rs1139488. None of the VDR SNPs or their haplotypes had any association with Pb levels. Regarding APOE, the ϵ4 allele was associated with lower mB-Hg and CB-Hg, while a positive association was found with the ϵ2 allele and CB-Pb when the model included only newborn girls. The observed associations indicate possible modification effects of ALAD and APOE SNPs on Pb or Hg kinetics in women and their newborns with low exposure to non-essential TEs, as well as an adequate nutritional status of Zn and Se.
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Mercúrio , Selênio , Oligoelementos , Feminino , Humanos , Recém-Nascido , Gravidez , Apolipoproteínas E/genética , Chumbo , Estado Nutricional , Polimorfismo de Nucleotídeo Único , Gestantes , ZincoRESUMO
BACKGROUND: Vaccine effectiveness (VE) studies consolidate knowledge of real-world effectiveness in different contexts. However, methodological issues may undermine their conclusions: to assess the VE against COVID-19 within the Italian population, a specific threat to validity is related to the consequences of divergent compliance to the Green Pass policy. METHODS: To address this challenge we conducted a test negative case-control (TNCC) study and multiple sensitivity analysis among residents aged ≥ 12 in Friuli Venezia Giulia Region (FVG), North-east Italy, from February 1, 2021 to March 31, 2022. Information regarding 211,437 cases of COVID-19 infection and 845,748 matched controls was obtained from the regional computerized health database. The investigation considered: COVID-19 infection, hospitalization, and death. Multiple conditional logistic regressions adjusted for covariates were performed and VE was estimated as (1-OR COVID-19vaccinated vs. unvaccinated)x100. Mediation analyses were carried out to offset potential collider variables, particularly, the number of swabs performed after the introduction of pandemic restrictions. RESULTS: Full-cycle VE against infection decreased from 96% (95% CI: 96, 97) in the Alpha period to 43% (95% CI: 42, 45) in the Omicron period. Booster dose raised the protection in Omicron period to 67% (95% CI: 66, 67). Against the evasive Omicron variant, the protection of the booster dose was 87% (95% CI: 83, 90) for hospitalization and 90% (95% CI: 82, 95) for death. The number of swabs performed was included as a covariate in the adjustments, and the mediation analysis confirmed that it was a strong mediator between vaccination and COVID-19-related outcomes. CONCLUSIONS: The study suggests that, under similar TNCC settings, mediation analysis and adjustment for number of diagnostic tests should be included, as an effective approach to the challenge of differential testing behavior that may determine substantial selection bias. This correction allowed us to align with results from other studies that show how full-cycle VE against infection was initially high but decreased over time by variant circulation, counterbalanced by booster dose that raised protection across variants and outcome severity.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Estudos de Casos e Controles , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , PolíticasRESUMO
BACKGROUND: The extent to which prenatal low-level mercury (Hg) exposure through maternal fish intake and heavy metals exposure affect children's neurodevelopment is controversial and may appear in the long term. In 2007, a prospective cohort, the Northern Adriatic Cohort II (NAC-II), was established to investigate the association between prenatal Hg exposure from maternal fish consumption and child neurodevelopment. The study enrolled 900 pregnant women, and 632 and 470 children underwent neurodevelopmental evaluation at 18 and 40 months of age, respectively. The NAC-II cohort is a part of the Mediterranean cohort in the "Public health impact of long-term, low-level, mixed element exposure in susceptible population strata" project. METHODS: This protocol describes the follow-up assessment of the effects of prenatal low level Hg and other heavy metals exposure on the developing nervous system of the children born within the NAC-II who reached the age of 7 years. Child diet components are estimated through a Diet Diary. Child hair and urine are collected for determination of Hg level. In addition, levels of other potentially neurotoxic metals, namely Manganese, Cadmium, Lead, Arsenic, and Selenium, are also measured in the same matrices. DISCUSSION: This protocol extends to the first years of schooling age the evaluation of the neurotoxicant effect of Mercury and of the other heavy metals on children's neurodevelopment, adjusting for the potential confounders, such as the lifestyles and social economic status of children's families. Longitudinal analysis of neurodevelopment, assessed in different ages (18 months, 40 months, and 7 years), are performed.
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Fenômenos Fisiológicos da Nutrição Materna , Metais Pesados/toxicidade , Compostos de Metilmercúrio/toxicidade , Transtornos do Neurodesenvolvimento/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Adulto , Animais , Criança , Pré-Escolar , Inquéritos sobre Dietas , Feminino , Peixes , Seguimentos , Contaminação de Alimentos , Cabelo/química , Humanos , Lactente , Itália/epidemiologia , Masculino , Metais Pesados/análise , Metais Pesados/urina , Compostos de Metilmercúrio/análise , Compostos de Metilmercúrio/urina , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVES: to investigate the role of gender, age, province of residence, and nursing home residency on the risk of death for residents in the Friuli Venezia Giulia (FVG) Region (Northern Italy) tested positive for Covid-19, considering recovery as a competing event. The secondary objective is to describe the impact of the Covid-19 epidemic in FVG and in the Regions of Northern and Central Italy in terms of incidence and mortality compared to the national data. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: resident population in FVG in the period between 29 February and 25 June 2020. MAIN OUTCOME MEASURES: in order to describe the impact of the Covid-19 outbreak in FVG, in terms of incidence and mortality compared to the national data, the standardized incidence (SIR) and mortality (SMR) ratios and their respective 95% confidence intervals (95%CI) were calculated compared to the Italian population for the northern and central Regions of Italy and the autonomous Provinces (PA) of Trento and Bolzano. A retrospective cohort study was conducted on subjects residing in FVG to whom at least one naso-oropharyngeal swab (hereafter, named swab) resulted positive for Covid-19. For each subject included in the cohort, the observation period started with the first positive swab and ended with the first of the following events: death, recovery or censored, which means that at the end of the observation period the subject was still alive and positive. The cause of death was assigned to Covid-19 if a subject had not yet recovered at the time when the event occurred. Cohort members were considered recovered after two negative consecutive swabs. The sub-hazard ratio (SHR) was estimated by applying the regression model of competing risks by Fine and Gray, in which the event of interest was the death caused by Covid-19 and the competing event was recovery. The explanatory variables included in the multiple models are: gender, age at the beginning of the observation period, the Province of residence, and nursing home residency. The cause-specific hazard was estimated using Cox proportional hazard regression. RESULTS: during the observation period, 3,305 cases and 345 deaths were recorded in FVG; SIR and SMR resulted, respectively, equal to 0.64 (95%CI 0.61-0.68) and 0.43 (95%CI 0.37-0.50). The FVG was the Northern Region one with the lowest incidence and mortality. The cohort consisted of 3,121 residents in FVG with at least one swab with a positive Covid-19 result during the study period. The SHR of dying for Covid-19 is equal to 16.13 (95%CI 9.73-26.74) for people with age 70-79 years and 35.58 (95%CI 21.77-58.15) with age >=80 years respect those with age <70 years. It is higher in males (SHR 1.71; 95%CI 1.34-2.17). There is no evidence that being resident in a nursing home affects the SHR (SHR 0.91 and 95%CI 0.69-1.20). As regards the province as an explanatory variable, the sub-hazard of death in the province of Trieste appears to overlap to the sub-hazard of Pordenone used as a reference; for the provinces of Udine and Gorizia the sub-hazards seem lower than the reference. CONCLUSIONS: while other Northern Regions and autonomous Provinces show higher standardized incidence and mortality compared with Italy, FVG and Veneto do not. In FVG, male gender and age are important determinants of death while there is no evidence that the condition of guest in a nursing home increases the sub-hazard of death.
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COVID-19/mortalidade , Pandemias , SARS-CoV-2 , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Geografia Médica , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Casas de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Características de Residência , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
Urinary metabolites of organophosphate (OP) and pyrethroid (PYR) pesticides from seven years old children of a birth cohort study (n=199; PHIME cohort of Trieste, Italy) have been measured. Six OP and two PYR metabolites have been investigated, 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY, pirimiphos metabolite) was the one found at higher concentrations, median 3.4â¯ng/mL specific gravity adjusted (SG adjusted), followed by 4-nitrophenol (PNP, median 1.4â¯ng/mL SG adjusted) and 3,5,6-trichloro-2-pyridinol (TCPY, median 0.36â¯ng/mL SG adjusted), parathion and chlorpyriphos metabolites, respectively. TCPY concentrations were low in comparison to other distributions of OP metabolites in children from other studies. Accordingly, the PHIME cohort showed a distinct OP metabolite distribution with high concentrations of pirimiphos and parathion. Another specific characteristic of this cohort was the high concentration of 3-phenoxybenzoic acid (3-BPA, median 0.36â¯ng/mL SG adjusted), a general metabolite of PYR pesticides. Evaluation of anthropometric and socio-demographic characteristics of children and families only showed a positive association between family educational level and urinary concentrations of DEAMPY metabolite (p<0.05), which could reflect distinct dietary habits depending on the educational level. Estimated daily intakes were evaluated, all studied metabolites were found within safe levels.
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Poluentes Ambientais , Praguicidas , Piretrinas , Criança , Estudos de Coortes , Dieta , Exposição Ambiental , Poluentes Ambientais/metabolismo , Poluentes Ambientais/urina , Feminino , Humanos , Itália , Masculino , Organofosfatos , Praguicidas/metabolismo , Praguicidas/urina , Piretrinas/metabolismo , Piretrinas/urinaRESUMO
OBJECTIVES: To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study. METHODS: Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up. RESULTS: Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR = 1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR = 2.94 95% CI 1.01-8.57). CONCLUSIONS: This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.
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Amianto/toxicidade , Neoplasias Pulmonares/epidemiologia , Mesotelioma/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Humanos , Incidência , Itália/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Mesotelioma/etiologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/etiologia , Doenças Profissionais/etiologia , Vigilância da PopulaçãoRESUMO
BACKGROUND: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health surveillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality. OBJECTIVES: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy. METHODS: Standardized Mortality Ratios (SMR), with 95% Confidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994). RESULTS: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60). CONCLUSIONS: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.
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Amianto/efeitos adversos , Asbestose/mortalidade , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Doenças Profissionais/mortalidade , Exposição Ocupacional/efeitos adversos , Neoplasias Pleurais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbestose/complicações , Carcinógenos , Criança , Pré-Escolar , Estudos de Coortes , Materiais de Construção/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Mesotelioma/etiologia , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Neoplasias Pleurais/etiologia , Vigilância da PopulaçãoRESUMO
INTRODUCTION: The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006. OBJECTIVES: To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort. METHODS: We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate. RESULTS: During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively. CONCLUSIONS: Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.
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Amianto/efeitos adversos , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Estudos de Coortes , Humanos , Incidência , Itália/epidemiologia , MasculinoRESUMO
Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.
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Ablação por Cateter , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Estudos Retrospectivos , Itália , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodosRESUMO
BACKGROUND: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. OBJECTIVE: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. METHOD: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6-12 years, 2014-2021) and 2499 adolescents (10 studies, 12-18 years, 2014-2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. RESULTS: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (ß = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (ß = -0.13, 95 % CI: -0.19, -0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (ß = -0.08, 95 % CI: -0.14, -0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (ß = -0.11, 95 % CI: -0.25, 0.03, per joint exposure quantile). CONCLUSION: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.
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PURPOSE: To validate the International Classification of Diseases, 9th Revision, Clinical Modification discharge codes used to identify cases of upper gastrointestinal complications (UGICs) in hospitals of Friuli Venezia Giulia, Italy. METHODS: Cohort study on the risk of UGIC in users of nonsteroidal anti-inflammatory drugs conducted in Friuli Venezia Giulia between 2001 and 2008. Cases were identified through primary and secondary International Classification of Diseases, 9th Revision Clinical specific codes 531 (gastric ulcer), 532 (duodenal ulcer), 533 (peptic ulcer), 534 (gastrojejunal ulcer), and nonspecific code 578 (gastrointestinal hemorrhage). Potential cases were confirmed through hospital chart review. RESULTS: The chart retrieval percentage was 98.4%.The positive predictive value (PPV) was 94.3% for primary codes 531 and 532, 79.5% for code 533, 83.1% for code 534, 40.2% for code 578. The PPV for secondary codes was 34.7% but increased to 88.9% and 79.2% when the primary code was for peritonitis or acute post-hemorrhagic anemia, respectively. Validation of secondary codes increased case ascertainment by 4.9%. Endoscopy confirmed 79.4% of cases but only 67.2% of those above age 84 years. CONCLUSIONS: The PPV was high for specific primary codes and moderate to low for nonspecific primary and secondary codes. The inclusion of confirmed cases identified by nonspecific and secondary codes can be of value in studies that need a complete ascertainment of cases occurring in the study population. In this cohort, not including these cases would underestimate the incidence of UGICs. A potential for case misclassification exists in particular in eldest ages.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Classificação Internacional de Doenças , Farmacoepidemiologia/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/diagnóstico , Úlcera Péptica/epidemiologia , Valor Preditivo dos Testes , RiscoRESUMO
PURPOSE: Information on the risk of upper gastrointestinal complications (UGIC) in users of nimesulide, the most used nonsteroidal anti-inflammatory drug (NSAID) in Italy, is scarce. In the context of the European regulatory review on nimesulide, we estimated and compared the risk associated with nimesulide and other individual NSAIDs with the risk in nonusers. METHODS: We used 2001-2008 data from regional health databases in Friuli Venezia Giulia (FVG), Italy, to conduct a cohort and nested case-control study of users of NSAIDs. Cases were identified by specific and nonspecific hospital discharge diagnoses in primary and secondary position and validated through hospital records. Ten controls per case were selected using density-based sampling from the cohort. Conditional logistic regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: The cohort included 588,827 NSAIDs users and 3031 UGIC cases. Nonspecific codes contributed to 23% of cases and secondary codes to 5%. Among current users, IR per 1000 person-years decreased from 4.45 cases in 2001 to 2.21 cases in 2008. The RR (95%CI) for current use of NSAIDs was 3.28 (2.86, 3.76). RR was <2 for rofecoxib, celecoxib, and nimesulide; 2 to <5 for naproxen, ibuprofen, diclofenac, etoricoxib, and meloxicam; and ≥ 5 for ketoprofen, piroxicam, and ketorolac. CONCLUSIONS: IRs of UGIC in FVG decreased about 50% between 2001 and 2008. Nimesulide was in the low-medium range of RR. A complete ascertainment of UGIC cases in databases may require validation of nonspecific codes, secondary codes, and additional codes such as peritonitis and acute posthemorrhagic anemia.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Sulfonamidas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , RiscoRESUMO
OBJECTIVE: to assess the agreement between two trained psychologists who administered the Bayley Scale of Infant Development III (BSID III) to detect neurodevelopment deficits in a cohort of children within the Northern Adriatic Cohort II (NAC II) longitudinal study, which aims to assess the impact of mercury exposure through food consumption of mothers in pregnancy on their children's neurodevelopment. DESIGN: a reliability study was carried out. Two trained psychologists administered the test, each one scoring the test independently, and serving as the primary examiner for half of the sample and as the observer for the other half. SETTING AND PARTICIPANTS: a sample of 53 children of 18 months of age was enrolled consecutively within the Italian NAC II, and tested using the Bayley Scale of Infant Development III (BSID III) to detect neurodevelopment deficits. MAIN OUTCOME MEASURES: the cognitive, language, and motor scales of the BSID III were evaluated and the respective Intraclass Correlation Coefficients (ICC) were calculated. RESULTS: overall, the ICCs for the cognitive and language scales were very high (≥0.98), while the ICCs for the motor scales were slightly lower, ranging from 0.86 (gross motor, scaled) to 0.97 (fine motor, scaled), but still higher than 0.80, reported as the general acceptable benchmark for psychological testing. CONCLUSION: the interrater reliability of all BSID III scales for this sample of 18-month-old children is very high and assures comparable results between the two psychologists involved in the Italian NAC II study. The reasons are a common training, the joint evaluation of many children during the preliminary phase of the study, the discussion of inconsistent results, but also the "go no-go" nature of the items in BSID III.
Assuntos
Desenvolvimento Infantil , Deficiências do Desenvolvimento/diagnóstico , Pré-Escolar , Estudos de Coortes , Técnicas de Diagnóstico Neurológico/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Sistema Nervoso/crescimento & desenvolvimento , Testes Neuropsicológicos/estatística & dados numéricos , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
The knowledge of the effects of organophosphate flame retardants on children's neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children's neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children's urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (ß = -1.30; 95%CI = -2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (ß = -0.98; 95%CI = -2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (ß = -1.42; 95% CI = -2.70; -0.06; p-value = 0.04) and no clear association with DPHP (ß = -1.09; 95% CI = -2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was -0.49 (95%CI = -1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was -0.35 (95%CI = -1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.
RESUMO
Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (ß coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:ß = - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: ß = - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:ß = - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:ß = - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:ß = - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:ß = - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.
Assuntos
Acrilamida , Monitoramento Biológico , Adolescente , Humanos , Adulto , Criança , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Acrilamida/toxicidade , Creatinina , Biomarcadores , Inquéritos e QuestionáriosRESUMO
Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined.
Assuntos
Ácidos Ftálicos , Masculino , Criança , Feminino , Adolescente , Humanos , Políticas , Monitoramento Biológico , Ácidos CarboxílicosRESUMO
Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes â¼5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for ∑DEHP metabolites (33.6 µg/L), MiBP (26.6 µg/L), and MEP (24.4 µg/L) and lowest for∑DiDP metabolites (1.91 µg/L) and ∑DINCH metabolites (3.57 µg/L). In adolescents highest GMs were found for MEP (43.3 µg/L), ∑DEHP metabolites (28.8 µg/L), and MiBP (25.6 µg/L) and lowest for ∑DiDP metabolites (= 2.02 µg/L) and ∑DINCH metabolites (2.51 µg/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions.