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Background: Excess weight is a public health challenge affecting millions worldwide, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at susceptible time windows. Objective: Our study aimed to describe the association between multiple lifestyle and nutritional exposures and body mass index (BMI) in adolescents using the exposome framework. Methods: We conducted an exposome-wide association study using the U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004 survey for discovery of associations between the study population characteristics and BMI, and the 2013-2014 survey to replicate analysis. We included non-diabetic and non-pregnant adolescents aged 12-18 years. We analyzed variables available in both survey rounds, with Results: A total of 1899 and 1224 participants were eligible from the 2003-2004 and 2013-2014 survey waves. The weighted proportions of overweight were 18.4% and 18.5% whereas those for obese were 18.1% and 20.6% in 2003-2004 and 2013-2014, respectively. Retained exposure agents included 63 dietary, 57 clinical and 1 physical activity variables. After FDR correction, univariable regression identified 35 and 18 predictors in the discovery and replication datasets, respectively, while multivariable regression identified 20 and 9 predictors in the discovery and replication datasets, respectively. Seven were significant in both datasets: alanine aminotransferase, gamma glutamyl transferase, mean cell volume, segmented neutrophils number, triglycerides; uric acid and white blood cell count. Discussion: This is the first ExWAS study in NHANES describing associations between zBMI, nutritional and clinical factors in adolescents. Future studies are warranted to investigate the role of the identified predictors as early-stage biomarkers of increased BMI and associated pathologies among adolescents and to replicate findings to other populations.

To assess the impact of the COVID-19 pandemic on all-cause mortality in Italy during the first wave of the epidemic, taking into consideration the geographical heterogeneity of the spread of COVID-19.This study is a retrospective, population-based cohort study using national statistics throughout Italy. Survival analysis was applied to data aggregated by day of death, age groups, sex, and Italian administrative units (107 provinces). We applied Cox models to estimate the relative hazards (RH) of excess mortality, comparing all-cause deaths in 2020 with the expected deaths from all causes in the same time period. The RH of excess deaths was estimated in areas with a high, moderate, and low spread of COVID-19. We reported the estimate also restricting the analysis to the period of March-April 2020 (first peak of the epidemic).The study population consisted of 57,204,501 individuals living in Italy as of January 1, 2020. The number of excess deaths was 36,445, which accounts for 13.4% of excess mortalities from all causes during January-May 2020 (i.e., RH = 1.134; 95% confidence interval (CI): 1.129-1.140). In the macro-area with a relatively higher spread of COVID-19 (i.e., incidence rate, IR): 450-1,610 cases per 100,000 residents), the RH of excess deaths was 1.375 (95% CI: 1.364-1.386). In the area with a relatively moderate spread of COVID-19 (i.e., IR: 150-449 cases) it was 1.049 (95% CI: 1.038-1.060). In the area with a relatively lower spread of COVID-19 (i.e., IR: 30-149 cases), it was 0.967 (95% CI: 0.959-0.976). Between March and April (peak months of the first wave of the epidemic in Italy), we estimated an excess mortality from all causes of 43.5%. The RH of all-cause mortality for increments of 500 cases per 100,000 residents was 1.352 (95% CI: 1.346-1.359), corresponding to an increase of about 35%.Our analysis, making use of a population-based cohort model, estimated all-cause excess mortality in Italy taking account of both time period and of COVID-19 geographical spread. The study highlights the importance of a temporal/geographic framework in analyzing the risk of COVID-19-epidemy related mortality.

To counter the second COVID-19 wave in autumn 2020, the Italian government introduced a system of physical distancing measures organized in progressively restrictive tiers (coded as yellow, orange, and red) imposed on a regional basis according to real-time epidemiological risk assessments. We leverage the data from the Italian COVID-19 integrated surveillance system and publicly available mobility data to evaluate the impact of the three-tiered regional restriction system on human activities, SARS-CoV-2 transmissibility and hospitalization burden in Italy. The individuals’ attendance to locations outside the residential settings was progressively reduced with tiers, but less than during the national lockdown against the first COVID-19 wave in the spring. The reproduction number R(t) decreased below the epidemic threshold in 85 out of 107 provinces after the introduction of the tier system, reaching average values of about 0.95-1.02 in the yellow tier, 0.80-0.93 in the orange tier and 0.74-0.83 in the red tier. We estimate that the reduced transmissibility resulted in averting about 36% of the hospitalizations between November 6 and November 25, 2020. These results are instrumental to inform public health efforts aimed at preventing future resurgence of cases., Italy introduced a system of tiered SARS-CoV-2 control measures in November 2020. Here, the authors quantify the effect of these measures on SARS-CoV-2 transmissibility and hospitalisation, and find reductions across all tiers with the greatest impacts associated with the most restrictive level.

BACKGROUND AND AIM: Excess weight is a global public health challenge affecting millions of people, including younger age groups. The human exposome concept presents a novel opportunity to comprehe...

COVID-19 dramatically influenced mortality worldwide, in Italy as well, the first European country to experience the Sars-Cov2 epidemic. Many countries reported a two-wave pattern of COVID-19 deaths; however, studies comparing the two waves are limited. The objective of the study was to compare all-cause excess mortality between the two waves that occurred during the year 2020 using nationwide data. All-cause excess mortalities were estimated using negative binomial models with time modeled by quadratic splines. The models were also applied to estimate all-cause excess deaths “not directly attributable to COVD-19”, i.e., without a previous COVID-19 diagnosis. During the first wave (25th February−31st May), we estimated 52,437 excess deaths (95% CI: 49,213–55,863) and 50,979 (95% CI: 50,333–51,425) during the second phase (10th October−31st December), corresponding to percentage 34.8% (95% CI: 33.8%–35.8%) in the second wave and 31.0% (95%CI: 27.2%–35.4%) in the first. During both waves, all-cause excess deaths percentages were higher in northern regions (59.1% during the first and 42.2% in the second wave), with a significant increase in the rest of Italy (from 6.7% to 27.1%) during the second wave. Males and those aged 80 or over were the most hit groups with an increase in both during the second wave. Excess deaths not directly attributable to COVID-19 decreased during the second phase with respect to the first phase, from 10.8% (95% CI: 9.5%–12.4%) to 7.7% (95% CI: 7.5%–7.9%), respectively. The percentage increase in excess deaths from all causes suggests in Italy a different impact of the SARS-CoV-2 virus during the second wave in 2020. The decrease in excess deaths not directly attributable to COVID-19 may indicate an improvement in the preparedness of the Italian health care services during this second wave, in the detection of COVID-19 diagnoses and/or clinical practice toward the other severe diseases.

After Italy's first national restriction measures in 2020, a robust approach was needed to monitor the emerging epidemic of coronavirus disease 2019 (COVID-19) at subnational level and provide data to inform the strengthening or easing of epidemic control measures.We adapted the European Centre for Disease Prevention and Control rapid risk assessment tool by including quantitative and qualitative indicators from existing national surveillance systems. We defined COVID-19 risk as a combination of the probability of uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 and of an unsustainable impact of COVID-19 cases on hospital services, adjusted in relation to the health system's resilience. The monitoring system was implemented with no additional cost in May 2020.The infectious diseases surveillance system in Italy uses consistent data collection methods across the country's decentralized regions and autonomous provinces.Weekly risk assessments using this approach were sustainable in monitoring the epidemic at regional level from 4 May 2020 to 24 September 2021. The tool provided reliable assessments of when and where a rapid increase in demand for health-care services would occur if control or mitigation measures were not increased in the following 3 weeks.Although the system worked well, framing the risk assessment tool in a legal decree hampered its flexibility, as indicators could not be changed without changing the law. The relative complexity of the tool, the impossibility of real-time validation and its use for the definition of restrictions posed communication challenges.Après avoir pris ses premières mesures de restriction nationales en 2020, l'Italie avait besoin d'une approche solide pour surveiller l'épidémie naissante de maladie à coronavirus 2019 (COVID-19) au niveau régional, et fournir les données permettant de renforcer ou d'alléger les mesures destinées à l'endiguer.Nous avons adapté l'outil d'évaluation rapide des risques du Centre européen de prévention et de contrôle des maladies en y intégrant des indicateurs quantitatifs et qualitatifs issus des systèmes de surveillance nationaux existants. Pour définir le risque lié à la COVID-19, nous avons associé la probabilité d'une transmission incontrôlée du coronavirus 2 du syndrome respiratoire aigu sévère, à l'impact immédiat des cas de COVID-19 sur les services hospitaliers, en procédant à des ajustements selon la résilience du système de soins de santé. Le dispositif de surveillance a été mis en œuvre en mai 2020 sans entraîner de coûts supplémentaires.En Italie, le système de surveillance des maladies infectieuses repose sur des méthodes uniformes de collecte de données dans les provinces autonomes et régions décentralisées à travers le pays.Les évaluations des risques réalisées toutes les semaines avec cette approche ont permis de surveiller l'épidémie à l'échelle régionale du 4 mai 2020 au 24 septembre 2021. L'outil a identifié les dates et lieux susceptibles de connaître une augmentation rapide de la demande en services de soins de santé si aucune mesure supplémentaire de contrôle et de lutte n'était prise dans les trois semaines.Bien que le système ait fonctionné, inscrire l'outil d'évaluation des risques dans un décret législatif a réduit sa flexibilité, car les indicateurs ne pouvaient être modifiés sans réformer la loi. La relative complexité de l'outil, l'impossibilité de procéder à une validation en temps réel et son usage pour imposer des restrictions ont posé des problèmes de communication.Tras las primeras medidas nacionales de restricción en Italia en 2020, se necesitaba un enfoque sólido para supervisar la epidemia emergente de la coronavirosis de 2019 (COVID-19) a nivel subnacional y proporcionar datos que informaran sobre el refuerzo o la flexibilización de las medidas de contención de la epidemia.Se adaptó la herramienta de valoración rápida de riesgos del Centro Europeo para la Prevención y el Control de las Enfermedades, al incluir indicadores cuantitativos y cualitativos de los sistemas nacionales de vigilancia existentes. Se definió el riesgo de la COVID-19 como una combinación de la probabilidad de transmisión descontrolada del coronavirus del síndrome respiratorio agudo grave de tipo 2 y de un efecto no sostenible de los casos de la COVID-19 en los servicios hospitalarios, y se ajustó en relación con la capacidad de recuperación del sistema sanitario. El sistema de supervisión se aplicó sin costes adicionales en mayo de 2020.El sistema de vigilancia de las enfermedades infecciosas en Italia aplica métodos de recopilación de datos coherentes en todas las regiones y provincias autónomas descentralizadas del país.Las valoraciones semanales de los riesgos mediante este enfoque fueron sostenibles en la supervisión de la epidemia a nivel regional entre el 4 de mayo de 2020 y el 24 de septiembre de 2021. La herramienta proporcionó valoraciones fiables de cuándo y dónde se produciría un rápido aumento de la demanda de servicios sanitarios si no se incrementaban las medidas de contención o mitigación en las tres semanas siguientes.Aunque el sistema funcionó bien, el hecho de enmarcar la herramienta de valoración de los riesgos en un decreto legal dificultó su flexibilidad, ya que los indicadores no se podían modificar sin cambiar la ley. La relativa complejidad de la herramienta, la imposibilidad de validación en tiempo real y su uso para la definición de las restricciones plantearon problemas de comunicación.المشكلة بعد إجراءات التقييد الوطنية الأولى بإيطاليا في عام 2020، كانت هناك حاجة إلى أسلوب فعّال لرصد الوباء المستجد لمرض فيروس كورونا 2019 (كوفيد 19) على المستوى دون الوطني، وتوفير البيانات لدراسة إمكانية تعزيز أو تخفيف تدابير مكافحة الوباء. الأسلوب قمنا بتكييف أداة لتقييم المخاطر السريعة تابعة للمركز الأوروبي للوقاية من الأمراض ومكافحتها، وذلك من خلال تضمين مؤشرات كمية ونوعية من أنظمة المراقبة الوطنية الحالية. كذلك قمنا بتعريف مخاطر كوفيد 19 على أنها مزيج من احتمالية الانتقال غير المُقيد لمتلازمة الجهاز التنفسي الحادة الشديدة لفيروس كورونا 2، والتأثير غير المستدام لحالات كوفيد 19 على خدمات المستشفيات، مع تعديلها فيما يتعلق بمرونة النظام الصحي. تم تنفيذ نظام المراقبة دون تكلفة إضافية في مايو/أيار 2020. المواقع المحلية يستخدم نظام مراقبة الأمراض المعدية في إيطاليا طرقًا متسقة لجمع البيانات عبر المناطق اللامركزية في البلد والمقاطعات المستقلة. التغيّرات ذات الصلة كانت تقييمات المخاطر الأسبوعية باستخدام هذا الأسلوب مستدامة في رصد الوباء على المستوى الإقليمي، طوال الفترة من 4 مايو/أيار 2020 إلى 24 سبتمبر/أيلول 2021. قدمت الأداة تقييمات موثوقة حول توقيت ومكان حدوث زيادة سريعة في الطلب على خدمات الرعاية الصحية في حالة السيطرة، أو إذا لم يتم زيادة تدابير التخفيف في الأسابيع الثلاثة التالية. الدروس المستفادة على الرغم من أن النظام قد عمل بشكل جيد، إلا أن صياغة أداة تقييم المخاطر في مرسوم قانوني أعاقت مرونته، حيث لا يمكن تغيير المؤشرات دون تغيير القانون. أدى التعقيد النسبي للأداة، واستحالة التحقق من فعاليتها في الوقت الفعلي، واستخدامها لتعريف القيود، إلى ظهور تحديات في التواصل.问题 2020 年意大利首次实施全国性限制措施后，需要采取可靠方法以监测新型冠状病毒肺炎（新冠肺炎）疫情在地方层面的蔓延情况，并提供数据以表明是否需要加强或放松疫情控制措施。方法 通过纳入现有国家监测系统的定量和定性指标，我们调整了欧洲疾病预防和控制中心的快速风险评估工具。我们将新型冠状病毒肺炎风险综合定义为严重急性呼吸系统综合症冠状病毒 2 不受控制传播的可能性以及新型冠状病毒肺炎病例对医院服务的非持续性影响，并根据卫生系统的顺应力进行了调整。2020 年 5 月，在没有产生额外成本的前提下实施了监测系统。当地状况 意大利传染病监测系统在全国各个分散的地区和自治省统一使用相同的数据收集方法。相关变化 在 2020 年 5 月 4 日至 2021 年 9 月 24 日期间，使用这种方法开展的每周风险评估在监测区域层面疫情情况方面具有可持续性。该工具能够可靠地评估，如果在接下来的 3 周内没有加强控制或缓解措施，何时何地医疗保健服务需求会迅速增加。经验教训 尽管该系统运作良好，但将风险评估工具纳入法令范畴限制了其灵活性，因为若不更改法律，则无法变更指标。该工具的相对复杂性、实时验证的不可能性及其在法规限定方面的用途导致产生了沟通挑战。.После первых национальных ограничительных мер в Италии в 2020 году потребовался активный подход для мониторинга зарождающейся эпидемии коронавирусной инфекции 2019 года (COVID-19) на субнациональном уровне и для предоставления данных для обоснования усиления или ослабления мер по борьбе с эпидемией.Авторы адаптировали инструмент для оперативных оценок рисков Европейского центра по контролю и профилактике заболеваний, включив в него количественные и качественные показатели из существующих национальных систем эпиднадзора. Авторы определили риск COVID-19 как комбинацию вероятности неконтролируемой передачи тяжелого острого респираторного синдрома, вызванного коронавирусом-2, и разрушительного воздействия случаев COVID-19 на больничное обслуживание, которая скорректирована с учетом устойчивости системы здравоохранения. Система мониторинга была внедрена без каких-либо дополнительных затрат в мае 2020 года.В системе эпиднадзора за инфекционными заболеваниями в Италии используются последовательные методы сбора данных по децентрализованным регионам и автономным провинциям страны.Еженедельные оценки рисков с использованием данного подхода регулярно применялись при мониторинге эпидемии на региональном уровне с 4 мая 2020 года по 24 сентября 2021 года. Инструмент обеспечил надежную оценку того, когда и где может произойти быстрое увеличение спроса на медицинские услуги, если меры по борьбе или смягчению последствий не будут усилены в течение следующих 3 недель.Несмотря на то что система работала эффективно, включение инструмента для оценок рисков в юридические постановления ограничивало его гибкость, поскольку показатели не могли быть изменены без изменения закона. Относительная сложность инструмента, невозможность проверки в реальном времени и его использование для определения ограничений создают проблемы коммуникации.

In Italy, the COVID-19 vaccination campaign started in December 2020 with the vaccination of healthcare workers (HCW). To analyse the real-life impact that vaccination is having on this population group, we measured the association between week of diagnosis and HCW status using log-binomial regression. By the week 22-28 March, we observed a 74% reduction (PPR 0.26; 95% CI 0.22-0.29) in the proportion of cases reported as HCW and 81% reduction in the proportion of symptomatic cases reported as HCW, compared with the week with the lowest proportion of cases among HCWs prior to the vaccination campaign (31 August-7 September). The reduction, both in relative and absolute terms, of COVID-19 cases in HCWs that started around 30 days after the start of the vaccination campaign suggest that COVID-19 vaccines are being effective in preventing infection in this group.

SARS-CoV-2 variants of concern (B.1.1.7, P.1 and B.1.351) have emerged in different continents of the world. To date, little information is available on their ecological interactions. Based on two genomic surveillance surveys conducted on February 18 and March 18, 2021 across the whole Italian territory and covering over 3,000 clinical samples, we found significant co-circulation of B.1.1.7 and P.1. We showed that B.1.1.7 was already dominant on February 18 in a majority of regions/autonomous provinces (national prevalence 54%) and almost completely replaced historical lineages by March 18 (dominant in all regions/autonomous provinces, national prevalence 86%). At the same time, we found a substantial proportion of cases of the P.1 lineage on February 18, almost exclusively in Central Italy (with an overall prevalence in the macro-area of 18%), which remained at similar values on March 18, suggesting the inability by this lineage to outcompete B.1.1.7. Only 9 cases from variant B.1.351 were identified in the two surveys. At the national level, we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). The relative transmissibility of P.1 estimated at the national level varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. These observations may have important consequences on the assessment of future pandemic scenarios.

Introduction. In May–June 2018, an outbreak of campylobacteriosis involved students and school staff from kindergartens and primary schools in Pescara, southern Italy. Aim. We present details of the epidemiological and microbiological investigation, and the findings of the analytical study, as well as the implemented control measures. Methodology. To identify possible risk factors associated with the observed outbreak, a case control study was conducted using a questionnaire to collect information on the date of symptoms onset, type and duration of symptoms, type of healthcare contact, school attendance, and food items consumed at school lunches during the presumed days of exposure. Attack rates were calculated for each date and school. Logistic regression models were used to estimate the odds ratios of being a case and the odds of illness by food items consumed, respectively. Moreover, we carried out a comparative genomic analysis using whole genome multilocus sequence typing (wgMLST) of Campylobacter jejuni strains isolated during the outbreak investigation to identify the source of the outbreak. Results. Overall, 222 probable cases from 21 schools were identified, and C. jejuni was successfully isolated from 60 patients. The meals in the schools involved were provided by two cooking centres managed by a joint venture between two food companies. Environmental and food sampling, epidemiological and microbiological analyses, as well as a case control study with 176 cases and 62 controls from the same schools were performed to identify the source of the outbreak. The highest attack rate was recorded among those having lunch at school on 29 May (7.8 %), and the most likely exposure was ‘caciotta’ cheese (odds ratio 2.40, 95 % confidence interval 1.10–5.26, P=0.028). C. jejuni was isolated from the cheese, and wgMLST showed that the human and cheese isolates belonged to the same genomic cluster, confirming that the cheese was the vehicle of the infection. Conclusion. It is plausible that a failure of the pasteurization process contributed to the contamination of the cheese batches. Timely suspension of the catering service and summer closure of the schools prevented further spread.

Objective: To investigate the association between deprivation and COVID-19 outcomes in Italy during pre-lockdown, lockdown and post-lockdown periods.Design: Retrospective cohort study.Setting: All municipalities in Italy with less than 50,000 population.Participants: 38,534,169 citizens and 222,875 COVID-19 cases reported to the Italian epidemiological surveillance were assigned to quintiles based on the deprivation index of their municipality of residence.Interventions: The COVID-19 pandemic during pre-lockdown, lockdown and post-lockdown from the 20th of February to the 15th of October of 2020.Main outcome measures: Multilevel negative binomial regression models, adjusting for age, sex, population-density and region of residence were conducted to evaluate the association between deprivation and COVID-19 incidence, case-hospitalisation rate and case-fatality. The association measure was the rate ratio.Results: During pre-lockdown, lockdown and post-lockdown, the incidence rate ratios (IRR) with 95% confidence interval (CI) in the most deprived quintile with respect to the least deprived quintile were 1.17 (95% CI 0.98 to 1.41), 1.14 (1.03 to 1.27) and 1.47 (1.32 to 1.63), respectively. In those three periods, the case-hospitalization IRR were 0.68 (0.51 to 0.92), 0.89 (0.72 to 1.11) and 0.99 (0.81 to 1.22) and the case-fatality IRR were 0.92 (0.75 to 1.13), 0.95 (0.85 to 1.07) and 1.02 (0.73 to 1.41), respectively.Conclusions: During lockdown and post-lockdown, but not during pre-lockdown, a higher incidence of cases was observed in the most deprived municipalities compared with the least deprived ones. No differences in case-hospitalisation and case-fatality according to deprivation were observed in any period under study.

Background International literature suggests that disadvantaged groups are at higher risk of morbidity and mortality from SARS-CoV-2 infection due to poorer living/working conditions and barriers to healthcare access. Yet, to date, there is no evidence of this disproportionate impact on non-national individuals, including economic migrants, short-term travellers and refugees. Methods We analyzed data from the Italian surveillance system of all COVID-19 laboratory-confirmed cases tested positive from the beginning of the outbreak (20th of February) to the 19th of July 2020. We used multilevel negative-binomial regression models to compare the case fatality and the rate of admission to hospital and intensive care unit (ICU) between Italian and non-Italian nationals. The analysis was adjusted for differences in demographic characteristics, pre-existing comorbidities, and period of diagnosis. Results We analyzed 213 180 COVID-19 cases, including 15 974 (7.5%) non-Italian nationals. We found that, compared to Italian cases, non-Italian cases were diagnosed at a later date and were more likely to be hospitalized {[adjusted rate ratio (ARR)=1.39, 95% confidence interval (CI): 1.33–1.44]} and admitted to ICU (ARR=1.19, 95% CI: 1.07–1.32), with differences being more pronounced in those coming from countries with lower human development index (HDI). We also observed an increased risk of death in non-Italian cases from low-HDI countries (ARR=1.32, 95% CI: 1.01–1.75). Conclusions A delayed diagnosis in non-Italian cases could explain their worse outcomes compared to Italian cases. Ensuring early access to diagnosis and treatment to non-Italians could facilitate the control of SARS-CoV-2 transmission and improve health outcomes in all people living in Italy, regardless of nationality.

to describe the integrated surveillance system of COVID-19 in Italy, to illustrate the outputs used to return epidemiological information on the spread of the epidemic to the competent public health bodies and to the Italian population, and to describe how the surveillance data contributes to the ongoing weekly regional monitoring and risk assessment system.the COVID-19 integrated surveillance system is the result of a close and continuous collaboration between the Italian National Institute of Health (ISS), the Italian Ministry of Health, and the regional and local health authorities. Through a web platform, it collects individual data of laboratory confirmed cases of SARS-CoV-2 infection and gathers information on their residence, laboratory diagnosis, hospitalisation, clinical status, risk factors, and outcome. Results, for different levels of aggregation and risk categories, are published daily and weekly on the ISS website, and made available to national and regional public health authorities; these results contribute one of the information sources of the regional monitoring and risk assessment system.the COVID-19 integrated surveillance system monitors the space-time distribution of cases and their characteristics. Indicators used in the weekly regional monitoring and risk assessment system include process indicators on completeness and results indicators on weekly trends of newly diagnosed cases per Region.the outputs of the integrated surveillance system for COVID-19 provide timely information to health authorities and to the general population on the evolution of the epidemic in Italy. They also contribute to the continuous re-assessment of risk related to transmission and impact of the epidemic thus contributing to the management of COVID-19 in Italy.

to assess the temporal variation in excess total mortality and the portion of excess explained by COVID-19 deaths by geographical area, gender, and age during the COVID-19 epidemic.descriptive analysis of temporal variations of total excess deaths and COVID-19 deaths in the phase 1 and phase 2 of the epidemic in Italy.12 Northern cities and 20 Central-Southern cities from December 2019 to June 2020: daily mortality from the National Surveillance System of Daily Mortality (SiSMG) and COVID-19 deaths from the integrated COVID-19 surveillance system.total mortality excess and COVID-19 deaths, defined as deaths in microbiologically confirmed cases of SARS-CoV-2, by gender and age groups.the largest excess mortality was observed in the North and during the first phase of the epidemic. The portion of excess mortality explained by COVID-19 decreases with age, decreasing to 51% among the very old (=85 years). In phase 2 (until June 2020), the impact was more contained and totally attributable to COVID-19 deaths and this suggests an effectiveness of social distancing measures.mortality surveillance is a sensible information basis for the monitoring of health impact of the different phases of the epidemic and supporting decision making at the local and national level on containment measures to put in place in coming months.

Highlights • Exposome approaches can aid the development of comprehensive public health measures. • Exposomic tools can be integrated in infectious diseases surveillance/monitoring in urban areas. • The exposome could aid in risk assessment, preparedness and response to events of public health impact., The COVID-19 pandemic placed public health measures against infectious diseases at the core of global health challenges, especially in cities where more than half of the global population lives. SARS-CoV-2 is an exposure agent recently added to the network of exposures that comprise the human exposome, i.e. the totality of all environmental exposures throughout one’s lifetime. At the same time, the application of measures to tackle SARS-CoV-2 transmission leads to changes in the exposome components and in characteristics of urban environments that define the urban exposome, a complementary concept to the human exposome, which focuses on monitoring urban health. This work highlights the use of a comprehensive systems-based approach of the exposome for better capturing the population-wide and individual-level variability in SARS-CoV-2 spread and its associated urban and individual exposures towards improved guidance and response. Population characteristics, the built environment and spatiotemporal features of city infrastructure, as well as individual characteristics/parameters, socioeconomic status, occupation and biological susceptibility need to be simultaneously considered when deploying non-pharmacological public health measures. Integrating individual and population characteristics, as well as urban-specific parameters is the prerequisite in urban exposome studies. Applications of the exposome approach in cities/towns could facilitate assessment of health disparities and better identification of vulnerable populations, as framed by multiple environmental, urban design and planning co-exposures. Exposome-based applications in epidemics control and response include the implementation of exposomic tools that have been quite mature in non-communicable disease research, ranging from biomonitoring and surveillance to sensors and modeling. Therefore, the exposome can be a novel tool in risk assessment and management during epidemics and other major public health events. This is a unique opportunity for the research community to exploit the exposome concept and its tools in upgrading and further developing site-specific public health measures in cities.

Enhanced laboratory-based surveillance of invasive meningococcal disease (IMD) in Italy was only assessed indirectly by numerically comparing surveillance data cases with hospital discharge records (HDR). In this study, we evaluated the completeness, timeliness and sensitivity of the IMD surveillance in Italy from 2015 to 2018. Completeness and timeliness were described at the national and subnational level. A capture-recapture analysis was conducted to evaluate the sensitivity and positive predictive value (PPV) using HDR as the external source with a combination of deterministic and probabilistic approaches. The characteristics of the unmatched vs. matched cases were compared using multivariable Poisson modeling. Overall, the completeness of data improved, except for specific variables. Timeliness of notifications also improved to a median of 4 days from onset to reporting. For the years 2015–2017, the sensitivity of the surveillance was estimated at 71.4% and the PPV at 77.5%, changing to 80.6% and 66.9% respectively after removing cases with a secondary meningitis diagnosis. We noted substantial sub-national differences. In 2018 sensitivity was 66.5% (135/203) and the PPV was 79.4% (135/170). The adjusted relative risk of being unmatched in 2015–2017 was higher in cases that were ≥60 years, had missing information or symptom onset in December. The IMD surveillance system overall performs well with completeness and timeliness improving in time. Specific challenges identified for individual variables should guide further improvement. Notwithstanding limitations posed by the comparison database, sensitivity and PPV are promising. The study highlights that promoting etiological ascertainment in people ≥60 years and addressing sub-national challenges are the main current challenges to address.

SummaryBackgroundSchool closures were part of a series of non-pharmacological intervention (NPI) measures addressing the COVID-19 pandemic in Cyprus. We aimed to study changes in the environment, diet, behavior, personal hygiene, contacts, lifestyle choices and the degree of compliance to NPI measures by primary school children in Cyprus at school and at home for two periods, i.e., before lockdown and during the school re-opening using the methodological context of the human exposome.MethodsDuring June 2020, an online survey questionnaire was forwarded to parents of primary school children through schools’ administrations, with questions about the children’s lifestyle/behaviours for two periods; school re-opening, following the population-wide lockdown (May 21-June 26, 2020), and the school period before lockdown (before March 2020). Descriptive statistics and exposome wide association analysis were implemented to agnostically assess associations of demographic, lifestyle and behavioral parameters with the degree of compliance to NPI measures.FindingsA total of 1509 children from more than 180 primary schools (out of 330 schools) in Cyprus were included. Median number of contacts per day at home, school and other places during weekdays was lower (pInterpretationIn this national survey, children showed a high degree of compliance to most NPI measures for the community and primary school settings in Cyprus. The initial NPI measures may have affected the children’s exposome profile in the following months, by altering their diet, physical activity, sedentary lifestyle and hand hygiene habits.FundingThe study was partially funded by the EXPOSOGAS project, H2020 under grant agreement #810995Panel: Research in contextEvidence before this studyWe searched PubMed for studies published until September 30, 2020 using the search terms: COVID-19, children and lifestyle. Only six peer-reviewed, English-language studies were retrieved on the effect of COVID-19 measures on children’s lifestyle. The impact of non-pharmacological intervention (NPI) measures on children’s health during the pandemic period has been sporadically studied by focusing on a few risk factors at a time without using the exposome’s methodological framework, which is defined as the comprehensive characterization of all environmental exposures during one’s lifetime.Added value of this studyA survey targeted all primary schools of Cyprus to comprehensively study the impact of the initial population-wide NPI measures (lockdown) (March 13-May 4) on the children’s exposome during the school re-opening period (May 21 – June 26). To the best of our knowledge, this is the first study looking at the post-confinement (lockdown) exposome profile changes of children during schools’ re-opening, after the initial population-wide NPI measures of COVID-19 response. The comprehensive and agnostic description of the children’s exposome profile may help to comprehensively account for both known and possibly unknown effects of NPI measures on children’s health and for delineating the children’s degree of compliance to infection prevention and control protocols at school and at home.Implications of all the available evidenceThis dataset could inform COVID-19 risk-based public health response strategies targeted for school settings. Future response strategies to epidemic waves shall consider elements of promoting a healthy lifestyle for children at school and at home. Public health policy could ultimately benefit from the inclusion of the human exposome methodological framework and its tools towards the improved identification of susceptible sub-population groups and to facilitate the deployment of site-tailored public health measures; this may be particularly relevant for children and their potential to spread the disease to vulnerable groups.

Background: In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death.Methods: Death certificates of persons who died and tested positive for SARS-CoV-2, provided by the National Surveillance system, were coded according to ICD rev10. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death.Results: The percentage of COVID-19 deaths varied over time. It decreased in the downward phase of the epidemic curve (76.6 vs. 88.7%). In February–April 2020, hypertensive heart disease was mentioned as a comorbidity in 18.5% of death certificates, followed by diabetes (15.9% of cases), ischemic heart disease (13.1%), and neoplasms (12.1%). In May–September, the most frequent comorbidity was neoplasms (17.3% of cases), followed by hypertensive heart disease (14.9%), diabetes (14.8%), and dementia/Alzheimer's disease (11.9%). The most mentioned complications in both periods were pneumonia and respiratory failure with a frequency far higher than any other condition (78.4% in February–April 2020 and 63.7% in May–September 2020).Discussion: The age of patients dying from COVID-19 and their disease burden increased in the May–September 2020 period. A more serious disease burden was observed in this period, with a significantly higher frequency of chronic pathologies. Our study suggests better control of the virus' lethality in the second phase of the epidemic, when the health system was less burdened. Moreover, COVID-19 care protocols had been created in hospitals, and knowledge about the diagnosis and treatment of COVID-19 had improved, potentially leading to more accurate diagnosis and better treatment. All these factors may have improved survival in patients with COVID-19 and led to a shift in mortality to older, more vulnerable, and complex patients.

Background On 20 February 2020, a locally acquired coronavirus disease (COVID-19) case was detected in Lombardy, Italy. This was the first signal of ongoing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the country. The number of cases in Italy increased rapidly and the country became the first in Europe to experience a SARS-CoV-2 outbreak. Aim Our aim was to describe the epidemiology and transmission dynamics of the first COVID-19 cases in Italy amid ongoing control measures. Methods We analysed all RT-PCR-confirmed COVID-19 cases reported to the national integrated surveillance system until 31 March 2020. We provide a descriptive epidemiological summary and estimate the basic and net reproductive numbers by region. Results Of the 98,716 cases of COVID-19 analysed, 9,512 were healthcare workers. Of the 10,943 reported COVID-19-associated deaths (crude case fatality ratio: 11.1%) 49.5% occurred in cases older than 80 years. Male sex and age were independent risk factors for COVID-19 death. Estimates of R0 varied between 2.50 (95% confidence interval (CI): 2.18–2.83) in Tuscany and 3.00 (95% CI: 2.68–3.33) in Lazio. The net reproduction number Rt in northern regions started decreasing immediately after the first detection. Conclusion The COVID-19 outbreak in Italy showed a clustering onset similar to the one in Wuhan, China. R0 at 2.96 in Lombardy combined with delayed detection explains the high case load and rapid geographical spread. Overall, Rt in Italian regions showed early signs of decrease, with large diversity in incidence, supporting the importance of combined non-pharmacological control measures.

Background After Action Reviews (AAR) with a One Health perspective were performed in Slovenia, Italy, Serbia and Greece following a severe West Nile virus (WNV) transmission season in 2018. A protocol combining traditional techniques and organizational process analysis was developed and then implemented in each country. Results In 2018, response to the unusually intense transmission season of WNV in Slovenia, Italy, Serbia and Greece took place through routine response mechanisms. None of the four countries declared a national or subnational emergency. We found a very strong consensus on the strengths identified in responding to this event. All countries indicated the availability of One Health Plans for surveillance and response; very high laboratory diagnostic capacity in the human, veterinary and entomology sectors and strong inter-sectoral collaboration with strong commitment of engaged institutions as critical in the management of the event. Finally, countries implementing One Health surveillance for WNV (in terms of early warning and early activation of prevention measures) consistently reported a positive impact on their activities, in particular when combining mosquito and bird surveillance with surveillance of cases in humans and equids. Recurring priority areas for improvement included: increasing knowledge on vector-control measures, ensuring the sustainability of vector monitoring and surveillance, and improving capacity to manage media pressure. Conclusions The AARs presented here demonstrate the benefit of cross-sectoral and cross-disciplinary approaches to preparedness for West Nile virus outbreaks in Europe. In the coming years, priorities include fostering and strengthening arrangements that: enable coordinated One Health surveillance and response during WNV transmission seasons; ensure adequate laboratory capacities; strengthen risk communication; and fund longer-term research to address the knowledge gaps identified in this study.

SUMMARYBackgroundIn February 2020, a locally-acquired COVID-19 case was detected in Lombardia, Italy. This was the first signal of ongoing transmission of SARS-CoV-2 in the country. The outbreak rapidly escalated to a national level epidemic, amid the WHO declaration of a pandemic.MethodsWe analysed data from the national case-based integrated surveillance system of all RT-PCR confirmed COVID-19 infections as of March 24th 2020, collected from all Italian regions and autonomous provinces. Here we provide a descriptive epidemiological summary on the first 62,843 COVID-19 cases in Italy as well as estimates of the basic and net reproductive numbers by region.FindingsOf the 62,843 cases of COVID-19 analysed, 71.6% were reported from three Regions (Lombardia, Veneto and Emilia-Romagna). All cases reported after February 20th were locally acquired. Estimates of R0 varied between 2.5 (95%CI: 2.18-2.83) in Toscana and 3 (95%CI: 2.68-3.33) in Lazio, with epidemic doubling time of 3.2 days (95%CI: 2.3-5.2) and 2.9 days (95%CI: 2.2-4.3), respectively. The net reproduction number showed a decreasing trend starting around February 20-25, 2020 in Northern regions. Notably, 5,760 cases were reported among health care workers. Of the 5,541 reported COVID-19 associated deaths, 49% occurred in people aged 80 years or above with an overall crude CFR of 8.8%. Male sex and age were independent risk factors for COVID-19 death.InterpretationThe COVID-19 infection in Italy emerged with a clustering onset similar to the one described in Wuhan, China and likewise showed worse outcomes in older males with comorbidities. Initial R0 at 2.96 in Lombardia, explains the high case-load and rapid geographical spread observed. Overall Rt in Italian regions is currently decreasing albeit with large diversities across the country, supporting the importance of combined non-pharmacological control measures.Fundingroutine institutional funding was used to perform this work.

OBJECTIVES: To describe the epidemiological and clinical characteristics of coronavirus disease (COVID-19) pediatric patients aged METHODS: Data from the national case-based surveillance system of confirmed COVID-19 infections until May 8, 2020, were analyzed. Demographic and clinical characteristics of subjects were summarized by age groups (0–1, 2–6, 7–12, 13–18 years), and risk factors for disease severity were evaluated by using a multilevel (clustered by region) multivariable logistic regression model. Furthermore, a comparison among children, adults, and elderly was performed. RESULTS: Pediatric patients (3836) accounted for 1.8% of total infections (216 305); the median age was 11 years, 51.4% were male, 13.3% were hospitalized, and 5.4% presented underlying medical conditions. The disease was mild in 32.4% of cases and severe in 4.3%, particularly in children ≤6 years old (10.8%); among 511 hospitalized patients, 3.5% were admitted in ICU, and 4 deaths occurred. Lower risk of disease severity was associated with increasing age and calendar time, whereas a higher risk was associated with preexisting underlying medical conditions (odds ratio = 2.80, 95% confidence interval = 1.74–4.48). Hospitalization rate, admission in ICU, disease severity, and days from symptoms onset to recovery significantly increased with age among children, adults and elderly. CONCLUSIONS: Data suggest that pediatric cases of COVID-19 are less severe than adults; however, age ≤1 year and the presence of underlying conditions represent severity risk factors. A better understanding of the infection in children may give important insights into disease pathogenesis, health care practices, and public health policies.

The objective was to investigate the association between deprivation and COVID-19 outcomes in Italy during pre-lockdown, lockdown and post-lockdown periods using a retrospective cohort study with 38,534,169 citizens and 222,875 COVID-19 cases. Multilevel negative binomial regression models, adjusting for age, sex, population-density and region of residence were conducted to evaluate the association between area-level deprivation and COVID-19 incidence, case-hospitalisation rate and case-fatality. During lockdown and post-lockdown, but not during pre-lockdown, higher incidence of cases was observed in the most deprived municipalities compared with the least deprived ones. No differences in case-hospitalisation and case-fatality according to deprivation were observed in any period under study.

Italy is a low-incidence country for tuberculosis (TB). We describe a TB outbreak in a primary school in north-eastern Italy, involving 10 cases of active pulmonary disease and 42 cases of latent infection. The index case was detected in March 2019, while the primary case, an Italian-born schoolteacher, was likely infectious since January 2018. Administration of a pre-employment health questionnaire to school staff with sustained contact with children should be considered in low-incidence countries.

Objectives A cross-sectional study was designed in two hospitals of Cyprus to: (i) examine the possible association between exposure to disinfectants/trihalomethanes (THM) with point of care glycosylated hemoglobin (HbA1c) levels among active nurses, and (ii) identify the main determinants of pre-diabetes metabolic risk among active nurses in Cyprus. Methods In total, 179 nurses from two public hospitals in Cyprus were recruited excluding pregnant or nurses working

Embraced as a breaking through methodological framework, the exposome is accompanied by novel exposure assessment methods and data processing tools or models. However, systematic mapping of the landscape of exposome studies, including their characteristics, components, tools and language has not been done so far. We conducted a scoping review to answer the question: “Which main domains of the human exposome have been included in the literature and which metrics of exposure(s)/outcome(s) have been used?” We performed a comprehensive search of human studies containing the word “exposom*” and published up to March 8, 2019. We screened 1133 records and 82 studies were included in the analysis. Most studies took place in Europe. Data analysis showed the non-systematic use of the exposome term. Most studies had a longitudinal design (n = 30, 37%), were conducted on adults (n = 40, 51%), and had a clearly defined health outcome in methodology (n = 48, 61%). Omics tools, such as metabolomics were used in 38 studies (49%), while environment-wide association analysis was used in 9 studies (11%). Thirty-seven (48%) studies included all three exposome domains (general external, specific external and internal) while 33 (42%) studies included two. Despite the large number of environmental components that comprise each of the exposome domains, only a subset has been currently studied. An optimized consideration of the components from all exposome domains, as well as the standardization of the exposure and outcome assessment methods is warranted to advance the utility of the human exposome concept.

In 2017, a chikungunya outbreak in central Italy later evolved into a secondary cluster in southern Italy, providing evidence of disease emergence in new areas. Officials have taken action to raise awareness among clinicians and the general population, increase timely case detection, reduce mosquito breeding sites, and promote mosquito bite prevention.

Cities face rapid changes leading to increasing inequalities and emerging public health issues that require cost-effective interventions. The urban exposome framework constitutes a novel approach in tackling city-wide challenges, such as those of drinking water quality and quality of life. In this proof-of-concept study, we presented part of the urban exposome of Limassol (Cyprus) focusing on chemical and microbial drinking water quality parameters and their association with urban neighborhood indicators. A perceptions study and an urban population study was conducted. We mapped the water quality parameters and participants’ opinions on city life (i.e. neighborhood life, health care and green space access) using quarters (small administrative areas) as the reference unit of the city. In an exploratory environment-wide association study analysis, we used all variables (questionnaire responses and water quality metrics) to describe correlations between them accounting, also, for self-reported health status. Overall, urban drinking-water quality using conventional indicators of chemical (disinfection byproducts-trihalomethanes) and microbial (coliforms, E. coli, and Enterococci) quality did not raise particular concerns. The general health and chronic health status of the urban participants were significantly (all >FDR corrected p value of 0.1) associated with different health conditions such as hypertension and asthma, or having financial issues in access to dental care. Additionally, correlations between trihalomethanes and participant characteristics (e.g. household cleaning, drinking water habits) were documented. This proof-of-concept study showed the potential of using integrative approaches to develop urban exposomic profiles and identifying within-city differentiated environmental and health indicators. The characterization of the urban exposome of Limassol will be expanded via the inclusion of biomonitoring tools and untargeted metabolomics platforms.

Evidence of bisphenols’ obesogenic effects on humans is mixed and inconsistent. We aimed to explore the presence of bisphenol A (BPA), bisphenol F (BPF) and chlorinated BPA (ClBPA), collectively called the bisphenols, in different brain regions and their association with obesity using post-mortem hypothalamic and white matter brain material from twelve pairs of obese (body mass index (BMI) >30 kg/m2) and normal-weight individuals (BMI 2). Mean ratios of hypothalamus:white matter for BPA, BPF and ClBPA were 1.5, 0.92, 0.95, respectively, suggesting no preferential accumulation of the bisphenols in the grey matter (hypothalamic) or white matter-enriched brain areas. We observed differences in hypothalamic concentrations among the bisphenols, with highest median level detected for ClBPA (median: 2.4 ng/g), followed by BPF (2.2 ng/g) and BPA (1.2 ng/g); similar ranking was observed for the white matter samples (median for: ClBPA-2.5 ng/g, BPF-2.3 ng/g, and BPA-1.0 ng/g). Furthermore, all bisphenol concentrations, except for white-matter BPF were associated with obesity (p

Horizontal challenges, such as climate change or the growing populations, and their manifestations require the development of multidisciplinary research synergies in urban health that could benefit from concepts, such as the human exposome. Cities are composed of interconnected systems which are influenced, by global trends, national policies and local complexities. In this context, the exposome concept could be expanded having the city setting in its core, providing the conceptual framework for the new generation of urban studies. The objectives of this work were to define the urban exposome and outline its utility. The urban exposome can be defined as the continuous spatiotemporal surveillance/monitoring of quantitative and qualitative indicators associated with the urban external and internal domains that shape up the quality of life and the health of urban populations, using small city areas, i.e. neighborhoods, quarters, or smaller administrative districts, as the point of reference. Research should focus on the urban exposome's measurable units at different levels, i.e. the individuals, small, within-city areas and the populations. The urban exposome framework applied in the city of Limassol, Cyprus combines three elements: (i) a mixed-methods study on stakeholders' opinions about quality of life in the city; (ii) a systematic assessment of secondary data from the cancer and death registries, including city infrastructure data; and (iii) a population health and biomonitoring survey. Continuous assessment of environmental and health indicators that are routinely collected, and the incorporation of primary data from population studies, will allow for the timely identification of within-city health and environmental disparities to inform policy making and public health interventions. The urban exposome could facilitate evidence-based public health response, offering researchers, policy-makers, and citizens effective tools to address the societal needs of large urban centers.

Abiding by the exposome paradigm, incorporation of external and internal exposure metrics using metabolomics tools is warranted to refine the etiology of type II diabetes (T2D). A small (n = 51) age-and sex matched case-control study was conducted in Cyprus coupling urinary trihalomethanes (THMs) with T2D. The objectives were to (i) perform a comparative assessment of different deconvolution parameters in compound identification and (ii) evaluate the association between differentially expressed metabolites and either urinary THM or T2D status. Untargeted urinary metabolomics was performed with a GC MS triple quadrupole mass spectrometry system. Results of three deconvolution searches each yielding >130 metabolites were used in subsequent analyses. The number of differentially expressed compounds by T2D status or the urinary THM levels (above or below median) differed among the three searches. The identity of these compounds was also confirmed using known standards (level 1 identification). In multivariate logistic regression, 3-aminoisobutyric acid was an important predictor of lower odds of T2D after adjusting for known risk factors. The widespread incorporation of metabolomics in population studies accounting for environmental exposures will eventually pave the way for the exposome characterization, also improving our understanding of,the disease process.

Increased disinfectant use commonly takes place in hospitals and other health care settings. A cross-sectional study among active nurses in two Cypriot public hospitals (n = 179) was conducted to examine the prevalence of exposure to disinfection byproducts (DBPs), such as trihalomethanes (THMs) using both self-reported information and biomarker measurements. The objectives of this study were to: i) quantify the magnitude and variability of occupational exposure to disinfectants/DBPs in nurses, ii) generate job exposure matrices (JEM) and job task exposure matrices (JTEM) for disinfectants, and iii) assess the major determinants of urinary THMs in nurses. End of shift urinary total THM values showed high variability among the nurses, but did not differ between hospitals. The disinfectant group of alcohols/phenols was used by > 98% of nurses, followed by octenidine (82%), iodine and chlorine (39%, each), chlorhexidine (25%), formaldehyde (12%), hydrogen peroxide (11%), and peracetic acid/ammonia/quaternary ammonium compounds (QACs), all being < 8% each. Chlorine use during the past 24 hr was associated with significantly (p < 0.05) lower brominated THMs (BrTHMs) after adjusting for age, gender and BMI, while a positive association was shown for TCM and the sum of all THMs (TTHMs), albeit not significant. Nurses were exposed to nearly double the levels of TTHMs and BrTHMs (median and IQR, 1027 [560, 2475] ng/g and 323 [212, 497] ng/g, respectively) when compared to those of the general population (552 [309,989] ng/g and 152 [87,261] ng/g, respectively). This was the first occupational health dataset reporting measurements of biomarkers of end of shift exposures to disinfectants/DBPs.

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11–12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world, commonly diagnosed in the majority of obese patients with type 2 diabetes mellitus (T2DM). Metabolic disrupting chemicals with short half-lives, such as those of halogenated structure (trihalomethanes, THM) have been linked with hepatic insulin resistance phenomena in animal studies. However, human studies evaluating the role of THM exposure on liver pathogenesis and T2DM disease process are scarce. The objectives of this study were to: i) determine the association of urinary brominated THM (BrTHM) levels and T2DM disease status, and ii) investigate the association between urinary BrTHM levels and serum alanine aminotransferase (ALT) concentrations, often used as surrogate markers of NAFLD. A pilot case–control study was conducted in Nicosia, Cyprus (n = 95). Cases were physician-diagnosed T2DM patients and controls were healthy individuals. Liver enzymes, leptin and TNF-α were measured in sera, while urinary THM levels were measured using tandem mass spectrometry. Diabetics had higher levels of serum leptin, body mass index and ALT than the controls. Among all study participants those with serum ALT levels above the median (17 IU/L) had higher mean tribromomethane (TBM) concentrations compared to those with serum ALT below 17 IU/L. A significant increase in the odds of having above the median serum ALT levels [OR 6.38, 95% CI: 1.11, 42.84 (p = 0.044)] was observed for each unit increase in creatinine-unadjusted urinary TBM levels, along with BMI and past smoking, after adjusting for possible confounders, such as urinary creatinine, age, sex, and leptin; no other THM compound showed a significant association with serum ALT. Logistic regression models for T2DM using the urinary BrTHM as exposure variables did not reach the predetermined level of significance. The interplay between exposures to BrTHM and the initiation of key pathophysiological events relating to hepatic injury (ALT) and inflammation (leptin) was recognized via the use of selected biomarkers of effect. Our evidence that THM could act as hepatic toxins with a further initiation of diabetogenic effects call for additional studies to help us better understand the disease process of the two co-morbidities (NAFLD and T2DM). Keywords: Brominated trihalomethanes, Fatty liver, Non-alcoholic, Diabetes, Disinfection byproducts, Inflammation, Obesity

The increased comparative prevalence rates of thyroid cancer in Cyprus (>EU average) led us to conduct this study on possible risk factors of thyroid nodules. Romania served as a reference with a comparative thyroid cancer prevalence < EU average. This study aimed to assess the association between urinary iodine (UI) and thyroid nodules in adult females (n = 208) from Cyprus and Romania. Study design A case-control study (n = 208). Methods Cases were females with ultrasound-confirmed thyroid nodules and controls with confirmed absence of nodules. In both countries, subjects underwent ultrasound medical examinations, completed a questionnaire and offered a spot urine sample. Results Median UI level in Cyprus was 94 μg/L, whereas 32% of the Cypriot UI was < 50 μg/L, classifying the population as mildly iodine deficient. In Romania, both cases and controls were iodine sufficient. No significant differences (P > 0.05) in serum free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were found between cases and controls. Cases had lower median TSH levels compared with controls (1.4 mIU/L and 1.7 mIU/L, P = 0.060), but serum TSH and free thyroxin levels were within normal range. Albeit non-significant, participants with inadequate UI (

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Although the increasing prevalence of thyroid nodular disease (TND) has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to thyroid-disrupting chemicals may contribute to TND and altered thyroid function. We investigated the association between exposures to bisphenol A (BPA), its chlorinated derivatives (ClxBPA), and bisphenol F (BPF) with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212) was conducted, where cases were those with thyroid nodules (diameter 0.05) association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or ClxBPA. A larger study would be justified.

Background and aims. The most common thyroid disorders, with an increasing detection worldwide, are the thyroid nodules and thyroiditis, which leads to an increase of thyroid cancer incidence . In two different countries with a different exposure to risk factors for thyroid cancer, such as Cyprus and Romania, the rank of thyroid cancer among other neoplasms is very different: the 3rd most prevalent cancer among females in Cyprus and the 12th in Romania, respectively. Environmental chemicals, such as bisphenol A have a proven effect on the thyroid function. However, the relation between the exposure to the endocrine disruptor and the development of thyroid nodules, with a potential of malignant transformation has not been previously studied. The aim of the study was to investigate the potential factors that lead to the difference of thyroid nodules incidence in the mentioned countries.Methods. A pilot case-control study has been conducted in 2014-2015 in the “Prof. Dr. Ion Chiricuță” Institute of Oncology, Cluj-Napoca, Romania and the Endocrinology Department of Archbishop Makarios III Hospital, Nicosia, Cyprus. Females older than 20 years with no medical history were recruited. Cases were women with ultrasound-confirmed thyroid nodules of size >3mm. Controls were women without thyroid nodules after ultrasound confirmation. All participants provided blood samples for measurements of the thyroid stimulating hormone (TSH), free thyroxin (FT4), anti- thyroglobulin (ATg) and anti-thyroid peroxidase (ATPO); urine samples. Demographics, anthropometrics and other relevant information were provided through the administration of a questionnaire.Results. In Romania we selected 51 patients with thyroid nodules (case group) and 41 without thyroid nodules (control group) and in Cyprus 57 cases, respectively 65 controls. After the statistical analysis of the data collected we observed statistically significant differences between the populations of the two countries regarding BMI and the value of the thyroid hormones and antibodies.Conclusions. Using the data observed in this study, differences were found between Cyprus and Romania among females with thyroid nodules the BMI, and the level of thyroid hormones had statistically significant differences. This study reports preliminary data, further analysis of environmental exposures to chemical factors that might have a certain influence over the thyroid in the two countries will follow.

Evidence for the association of bisphenol A (BPA) with type II diabetes mellitus (T2DM) has been inconsistent in human studies. In-vitro and animal studies indicate that chlorinated BPA derivatives aggravate BPA health effects via higher estrogenic activity and alteration of membrane-initiating signaling pathways. We evaluated the association between urinary monochlorinated BPA (mono-ClBPA) concentrations and the incidence of T2DM. In our cross-sectional study, we identified 20 adult participants (≥18 yr) who reported having T2DM (doctor-diagnosed) and 131 adults with normal health. First morning void urine samples were analyzed for total BPA and mono-ClBPA. Detection limits of the analytical method were 95 ng L−1 for BPA and 32 ng L−1 for mono-ClBPA. Multivariable logistic regression analyses and additive Bayesian network modeling were performed. After adjusting for age, gender, BMI, urinary total BPA and other confounders, the odds of having T2DM was 3.29 times higher (95% confidence interval, CI: 1.10, 11.4; P < 0.05) per unit increase in log-transformed and creatinine-adjusted urinary mono-ClBPA levels (n = 151); this relation did not hold for total BPA. The globally optimum Bayesian model corroborated the results of the logistic regression by expressing mono-ClBPA in the pathway of T2DM, and not for total BPA. An age-matched sensitivity analysis confirmed the increase in OR of T2DM by 3.04 times (95% CI: 1.10, 11.0; P < 0.05) per unit increase in log-transformed and creatinine-adjusted urinary mono-ClBPA concentration (n = 68). The urinary monochlorinated BPA derivative was significantly associated with T2DM, whereas the parent compound (total BPA) was not. Caution should be applied in interpreting these findings, as this is the first study to report this association and the sample size of participants with T2DM is small. Additional research with a larger sample size coupled with relevant toxicological studies is warranted.

A complex network of sources and routes of exposure to disinfection by-products (DBP), such as trihalomethanes (THM) has been driving the wide variability of daily THM intake estimates in environmental epidemiological studies. We hypothesized that the spatiotemporal variability of THM exposures could be differentially expressed with their urinary levels among residents whose households are geographically clustered in district-metered areas (DMA) receiving the same tap water. Each DMA holds unique drinking-water pipe network characteristics, such as pipe length, number of pipe leaking incidences, number of water meters by district, average minimum night flow and average daily demand. The present study assessed the spatial and seasonal variability in urinary THM levels among residents (n=310) of geocoded households belonging to two urban DMA of Nicosia, Cyprus, with contrasting water network properties. First morning urine voids were collected once in summer and then in winter. Results showed that the mean sum of the four urinary THM analytes (TTHM) was significantly higher during summer for residents of both areas. Linear mixed effects models adjusted for age, season and gender, illustrated spatially-resolved differences in creatinine-adjusted urinary chloroform and TTHM levels between the two studied areas, corroborated by differences observed in their pipe network characteristics. Additional research is warranted to shed light on the contribution of spatially-resolved and geographically-clustered environmental exposures coupled with internal biomarker of exposure measurements towards better understanding of health disparities within urban centers.