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Background Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). Methods Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. Results As of August 2020, 442,677 (range: 18–185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112–1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. Conclusions Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

This work was supported by the University of Nicosia Medical School (internal funding)., Achilleos S, Quattrocchi A, Gabel J, Heraclides A, Kolokotroni O, Constantinou C, Pagola Ugarte M, Nicolaou N, Rodriguez-Llanes JM, Bennett CM, Bogatyreva E, Schernhammer E, Zimmermann C, Costa AJL, Lobato JCP, Fernandes NM, Semedo-Aguiar AP, Jaramillo Ramirez GI, Martin Garzon OD, Mortensen LH, Critchley JA, Goldsmith LP, Denissov G, Rüütel K, Le Meur N, Kandelaki L, Tsiklauri S, O'Donnell J, Oza A, Kaufman Z, Zucker I, Ambrosio G, Stracci F, Hagen TP, Erzen I, Klepac P, Arcos González P, Fernández Camporro Á, Burström B, Pidmurniak N, Verstiuk O, Huang Q, Mehta NK, Polemitis A, Charalambous A, Demetriou CA.

BackgroundThe COVID-19 pandemic and the widespread adoption of virus control measures have inevitably disrupted efforts to address lifestyle risk factors for non-communicable diseases (NCD). This study aimed to explore the effects of COVID-19 lockdown on all lifestyle medicine pillars, namely diet, physical activity, sleep, stress, social support and use of risky substances.MethodsThis was a cross-sectional study on a convenient sample of adults who resided in Cyprus during the Spring 2020 lockdown. Participants completed an anonymous online questionnaire comprised of six validated tools regarding the following lifestyle behaviours before and during lockdown: adherence to the Mediterranean diet, physical activity, stress and social support levels, sleep pattern and use of risky substances such as smoking and alcohol. Paired before and during lockdown comparisons for each lifestyle pillar were undertaken using Wilcoxon Signed-Rank test and Bowker symmetry Test where response was numerical (non-parametric data) and categorical respectively. Furthermore, stratified analyses for sociodemographic characteristics were performed.ResultsOut of 745 participants, 74% were female and median age was 39 years. Overall participants reported significantly higher perceived stress score (22 v 25,p p p p p trend = 0.03 and ConclusionVarious lifestyle factors were adversely affected by the COVID-19 lockdown in Cyprus. Evidence from this study supports development of holistic lifestyle interventions during and following the pandemic to reduce short and long-term NCD risks by building on lifestyle behaviour strengths and addressing longstanding and emerging gaps and needs.

Coronavirus disease 2019 (COVID-19) has significantly affected the well-being of individuals worldwide. We herein describe the epidemiology of COVID-19 in the Republic of Cyprus during the first epidemic wave (9 March&ndash, 3 May 2020). We analyzed surveillance data from laboratory-confirmed cases, including targeted testing and population screening. Statistical analyses included logistic regression. During the surveillance period, 64,136 tests (7322.3 per 100,000) were performed, 873 COVID-19 cases were diagnosed, and 20 deaths were reported (2.3%). Health-care workers (HCWs) represented 21.4% of cases. Overall, 19.1% of cases received hospital care and 3.7% required admission to Intensive Care Units. Male sex (adjusted Odds Ratio (aOR): 3.04, 95% Confidence Interval (CI): 1.97&ndash, 4.69), increasing age (aOR: 1.56, 95%CI: 1.36&ndash, 1.79), symptoms at diagnosis (aOR: 6.05, 95%CI: 3.18&ndash, 11.50), and underlying health conditions (aOR: 2.08, 95%CI: 1.31&ndash, 3.31) were associated with hospitalization. For recovered cases, the median time from first to last second negative test was 21 days. Overall, 119 primary cases reported 616 close contacts, yielding a pooled secondary attack rate of 12% (95%CI: 9.6&ndash, 14.8%). Three population-based screening projects, and two projects targeting employees and HCWs, involving 25,496 people, revealed 60 positive individuals (0.2%). Early implementation of interventions with targeted and expanded testing facilitated prompt outbreak control on the island.

Background This study aimed to explore socioeconomic factors associated with obesity in the Republic of Cyprus. Methods We interviewed 3021 Greek-Cypriots aged 25-64 years through a multistage survey. We collected self-reported information on demographics, health behaviours (physical activity, smoking, alcohol consumption and dietary intake), socio-economic characteristics (educational attainment, household income and occupational social class) and anthropometric measurements. Obesity was defined as body mass index ≥30 kg/m2. For the association between obesity and each socio-economic indicator, we conducted sex-specific Poisson's regression with robust variance, adjusting for all demographics and health-related behaviours, reporting adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). Results The prevalence of obesity was 22% and 17% among men and women, respectively. There was a significant trend of higher obesity prevalence with increasing age as well as with being widowed in both genders and being a refugee in men. Obesity prevalence decreased with increasing educational attainment (postgraduate vs. none/gymnasium: a PRmen=0.45; 95%CI=0.25-0.82; a PRwomen=0.41; 95%CI=0.18-0.95; p-trends€4000/month vs. ≤€1000/month: a PRmen=0.45; 95%CI=0.26-0.81; a PRwomen=0.45; 95%CI=0.22-0.92; p-trends Conclusions The current study highlights striking social inequalities in obesity among Cypriot men and women, characterised by a linear decrease in obesity prevalence each step up the socioeconomic hierarchy. We recommend that comprehensive and multifaceted public health interventions are considered to address income and education-related barriers resulting in higher obesity rates among specific population sub-groups. Key messages Among Greek Cypriot adults, obesity affects almost one in five whilst obesity prevalence shows gender-specific social inequalities. When investigating social inequalities in health, the choice of socioeconomic indicators should reflect the context of the population and gender-specific differences.

Background A national breast cancer (BC) screening programme, targeting women 50-69 years old, was introduced in Cyprus in 2007. This study aims to assess rural/urban differences in BC incidence, tumour stage at diagnosis (TSD) and mortality, since 2004 and since the introduction of the screening programme. Methods Data were obtained for 6589 new cases of BC (diagnosis 2004-2016) from a national population-based cancer registry (1998-today) in Cyprus. TSD was recorded according to the Surveillance, Epidemiology, and End Results categories. We defined late TSD as regional or distant stage. Unknown stages were excluded. We linked cases to the population census data and place of residence (rural/urban) and calculated incidence and mortality rate ratios (RR) by place of residence. We conducted logistic regression to measure the association between place of residence and TSD or mortality, adjusting for sex, age, ethnicity, smoking and marital status. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. Results Since 2004, 54.7% of BC cases were diagnosed at localised stage, 40.6% at regional stage and 4.7% at distant stage. Incidence, but not mortality, rate for all BC was higher in urban than in rural areas (RRincidece=1.22;95%CI=1.51-1.28 and RRmortality=1.10;95%CI=0.97-1.24). Rural place of residence was associated with higher odds of late TSD (aOR=1.34; 95%CI=1.15-1.58) and death (aOR=1.36; 95%CI=1.11-1.68). After the introduction of the screening programme, for the targeted age group, rural place of residence was still associated with higher odds of late TSD (aOR=1.31; 95%C= 1.03-1.67), but not with death (p > 0.05). Conclusions Even though BC incidence is higher in urban than in rural areas, women residing in rural areas had higher odds of late TSD and death. The introduction of the national BC screening programme only slightly reduced geographical inequalities in TSD. Further studies are needed to understand and reduce the role of inequalities in TSD. Key messages Rural/Urban inequalities in TSD are evident among BC cases in Cyprus, diagnosed between 2004 and 2016. The introduction of the national BC screening programme reduced but did not overcome geographical inequalities in TSD.

Background Despite widespread adoption of lockdown by governments in the COVID-19 response, research on how it affects the individual pillars of Lifestyle Medicine is limited. We aimed to explore the effects of COVID-19 lockdown on healthy eating, physical activity, sleep, stress, social support and use of risky substances. Methods This was a cross-sectional study on a convenient sample of adults who resided in Cyprus during the lockdown. An anonymous questionnaire was completed online in Greek or English comprised of five validated tools in relation to their behaviours before and during the lockdown. We compared median values for each variable/tool before and during lockdown, using Wilcoxon Signed Rank test, and performed stratified analyses for sociodemographic characteristics. Results Out of 745 respondents, 74% were female and median age was 39. Overall scores showed significantly increased sleep quality difficulty (4 v 5, p Conclusions Many aspects of lifestyle were adversely affected by lockdown in Cyprus. As people return to their pre-lockdown routines, the outcomes described provide data to inform the design of lifestyle interventions that support changing or maintaining lifestyle habits. Such interventions can then help decrease people's risk for future poor health outcomes, including the risk for COVID-19 infection. Key messages This study describes aspects of lifestyle affected by the Cyprus COVID-19 lockdown, significant when considering future lockdowns and pre-, during or post-lockdown healthful lifestyle interventions. The outcomes provide data to inform the design of lifestyle interventions to support changing or maintaining healthy lifestyle habits.

During the first quarter of 2020 the world is experiencing a pandemic of Severe Acute Respiratory Syndrome‑Coronavirus‑2 (SARS‑CoV‑2), a novel beta coronavirus that is responsible for the 2019 novel coronavirus disease (COVID‐19). The COVID‐19 pandemic revealed that healthcare systems around the world were not prepared to deal with either the direct effects of the pandemic or with the indirect effects that are imposed on the health of patients with chronic disorders such as cancer patients. Some challenges and dilemmas currently faced during the pandemic include the management of cancer patients during the treatment and follow‐up phases, the assessment of the safety of treatments currently used for the management of SARS‑CoV‑2 for use in cancer patients, the development of psychoeducation and emotional support for cancer patients and the safe conduct of clinical trials involving participation of cancer patients. Evidence from the literature supports the need for the urgent development of a holistic contingency plan which will include clear guidelines for the protection and comprehensive care of cancer patients. The implementation of such a plan is expected to have many beneficial effects by mainly minimizing the increased morbidity and mortality of cancer patients that could result as an adverse consequence of the COVID‐19 or future pandemics., The COVID‐19 pandemic has revealed that health care systems around the world were not prepared to deal with either the direct effects of the pandemic or with the indirect effects that are imposed on the health of cancer patients. The evidence from the literature supports that the development of a contingency plan is as urgent as ever to minimise the increased morbidity and mortality of cancer patients that could result as a consequence of the current COVID‐19 pandemic or any other future pandemics.

There is an ongoing need for solid evidence about the effects of healthy behaviors, and particularly diet, on the quality of life (QoL) among breast cancer survivors. We first conducted a cross-sectional study on 68 Italian stage I-III breast cancer survivors, to investigate the association of adherence to the Mediterranean diet (MD), physical activity and weight status with QoL. Adherence to MD and physical activity was assessed using structured questionnaires. QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality-of-Life tools. We showed that low consumption of red meat and carbonated beverages, daily consumption of wine and high consumption of dishes seasoned with sofrito had beneficial effects on several QoL subscales. By contrast, using olive oil as the main culinary fat, low consumption of commercial sweets and high consumption of nuts were associated with negative effects. Overall, these findings resulted in a null effect of adherence to MD on QoL. Furthermore, we observed better QoL sub-scores among women who performed moderate physical activity (i.e., diarrhea) and those who were underweight/normal weight (i.e., physical functioning and dyspnea) if compared with their counterparts (p-values &le, 0.003 after correction for multiple comparison). Next, we performed a systematic review of nine experimental studies to summarize whether dietary interventions might improve QoL among breast cancer patients. All the studies demonstrated significant improvements in overall QoL and/or its subscales after the interventions. However, differences in study design, interventions and tools used for QoL assessment did not allow us to provide an overall estimate. Moreover, only a single-arm trial evaluated the effect of an exclusive dietary-based intervention, while others combined dietary recommendations with physical activity and weight loss programs. For these reasons, our study encourages more efforts to improve the robustness of current evidence, through more homogenous tools, larger population-based studies and further randomized controlled trials.

Background Until recently, trivalent influenza vaccines (TIV) have contained one influenza B virus, recommended annually by the WHO vaccine selection committee. Quadrivalent Influenza Vaccines (QIV) add protection against a second B lineage; preventing the threat of a vaccine mismatched season, which often occurs in the Northern Hemisphere, leading to reduced vaccine effectiveness (VE) and increased influenza morbidity and mortality. Young children have one of the highest clinical burdens in Ireland, with the highest age-specific rate for influenza cases admitted to critical care units generally in children aged 0–4 years. Additionally, school-aged children are a major source of community transmission. Aim To assess the benefit of a QIV in the Irish paediatric population. Methods A literature review was conducted comparing QIV to TIV, focusing on VE and cost-effectiveness (CE). The VE of live-attenuated influenza vaccine (LAIV) compared to inactivated influenza vaccine (IIV) in children was also studied. The Cochrane database of systematic reviews, the Cochrane Central Register of Controlled Trials, PubMed, the Lancet, and publications from the European projects I-MOVE/I-MOVE+ and VENICE were searched for publications between 2009–2018. Results Recent influenza seasons suggest a higher VE of QIV compared to TIV. Studies have shown that QIV is as effective as TIV for the strains included in both; however QIV has superior immunogenicity for the additional B strain when there is a mismatch season. These results are also reflected in pre-licensing studies of the immunogenicity of QIVs that are now approved. LAIV has been recommended due to higher VE against influenza B strains and the ease and acceptability of the intranasal vaccination compared to the injectable IIV. QIV are more expensive than TIV, however CE analyses indicate that QIV delivers substantial savings in terms of preventing direct healthcare costs through reductions in infection numbers, hospitalisations and deaths; resulting in quality-adjusted life years gained. There are also substantial societal benefits through indirect savings in productivity (preventing employee/caregiver absences). Rolling out QIV to children was the most cost-effective vaccination strategy in the UK (aged 2–11 years) and in European countries (4–16 years) partaking in the I-MOVE+ project, with the exception of Portugal. Conclusion QIV would stabilise the VE across influenza seasons; eliminating the uncertainty of predicting the influenza B lineage, ultimately increasing public confidence in the vaccine, resulting in increased vaccine uptake. Broader protection in the paediatric population would directly reduce influenza transmission and indirectly protect vulnerable populations in the community.

In Ireland seasonal influenza and pertussis vaccination during pregnancy is recommended and every year national campaigns are organised to raise awareness and improve uptake. We estimated influenza and pertussis vaccine uptake and identified factors associated with vaccination status in pregnant women in 2017/18. We conducted a face-to-face omnibus survey, with quota sampling, among women aged 18–55 years and collected socio-demographic characteristics, self-reported vaccination status, awareness of vaccine campaigns, and attitudes towards vaccination. Sample was weighted to ensure representativeness with the target population. We performed univariate and multivariable logistic regression analyses on survey data. Overall, 241 pregnant women were enrolled. Influenza and pertussis vaccine uptake was 61.7% and 49.9%, respectively. Awareness of vaccine campaign and socio-economic status (SES) were associated with both influenza and pertussis vaccine uptake. The association between SES and uptake of vaccines differed by awareness. Women aware of the influenza vaccine campaign and with mid and low SES were less likely to be vaccinated, compared to those with high SES (aOR = 0.46; 95%CI: 0.22–0.97; aOR = 0.27; 95%CI: 0.12–0.60, respectively); women not aware of the pertussis vaccine campaign and with mid and low SES were less likely to be vaccinated, compared to those aware and with high SES (aOR = 0.15; 95%CI: 0.04–0.48; aOR = 0.05; 95%CI: 0.01–0.24, respectively). General practitioner (GP) recommendation was the main reason for receiving influenza vaccine (39.2%), and 71.8% of women were recommended pertussis vaccination from their GPs. The survey reports moderate uptake of vaccines among pregnant women, inequalities in uptake by SES and identifies GPs as primary source for vaccine recommendation. We recommend multifaceted campaigns, by engaging GPs, to target all socio-economic groups.

Antimicrobial resistance (AMR) is one of the biggest issues facing global public health. In 2017, Italy adopted its first National Action Plan on Antimicrobial Resistance 2017&ndash, 2020, which works through the synergy between national, regional, and local levels. In the framework of a Regional Action Plan on healthcare-associated infections and AMR prevention, the Sicilian Health Authority of the Sicilian Region, Southern Italy, has implemented a surveillance system of antibiotic consumption in hospitals, in the community, and of resistance rates (RRs) in hospital settings. Data on antibiotic consumption and on antibiotic RRs have been collected from 2015 to 2017 from pharmacies and laboratories of participating hospitals and from community, respectively. Data on antibiotic consumption showed that the most consumed antibiotics in hospitals were fluoroquinolones in 2015, penicillin in 2016, and beta-lactams in 2017. From 2015 to 2017, data on Klebsiella pneumoniae showed significant increasing RRs to all antibiotic classes, except to carbapenems. RRs of third-generation cephalosporins and carbapenems Escherichia coli showed significant decreasing trends. RRs of the other microorganisms did not change significantly during the study period. The results from the present study show that in Sicily, the use of antibiotics and RRs for selected microorganisms are at a high level. Immediate strategies are needed to decrease the inappropriate usage of antibiotics and control the spread of AMR.

Burden of AMR Collaborative Group:National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal (Prof M Caniça PhD, Vera Manageiro PhD) Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300481/ Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged

The aims of the present study were to: (1) assess surgical site infection (SSI) incidence in a cohort of surgical patients and (2) estimate the compliance with national guidelines for perioperative antibiotic prophylaxis (PAP). SSIs, among the most common health care–associated infections, are an important target for surveillance and an official priority in several European countries. SSI commonly complicates surgical procedures in older people and is associated with substantial attributable mortality and costs. The implementation of PAP guidelines is difficult among surgeons, and failure to comply with the standard of care has been widely reported. A 12-month prospective survey was performed in accordance with the methods, protocols, and definitions of the Hospital in Europe Link for Infection Control through Surveillance (HELICS) protocol. The compliance of the current PAP practices with the published national guidelines was assessed. A total of 249 patients were enrolled. The cumulative SSI incidence was 3.2 per 100 operative procedures. Cumulative compliance for PAP was 12.4%. Overall, only infection risk index ≥1 was confirmed as a significant risk factor for SSI (odds ratio, 6.65; 95% confidence interval, 1.04–42.59; P = 0.045). When only older patients (age >65 years) were considered, no significant risk factors for SSI were identified. Our study indicates an overall inadequate compliance with PAP recommendations, thus highlighting the need to develop multimodal and targeted intervention programs to improve compliance with PAP guidelines.

Specific foods and nutrients help prevent the progression of persistent high-risk human papillomavirus (hrHPV) infection to cervical cancer (CC). The aim of this study was to investigate dietary patterns which may be associated with hrHPV status and the risk of high-grade cervical intraepithelial neoplasia (CIN2+). Overall, 539 eligible women, including 127 with CIN2+, were enrolled in a cross-sectional study, and tested for hrHPV infection. Food intake was estimated using a food frequency questionnaire. Logistic regression models were applied. Using the Mediterranean Diet Score, we demonstrated that, among 252 women with a normal cervical epithelium, medium adherence to the Mediterranean diet decreased the odds of hrHPV infection when compared to low adherence (adjOR = 0.40, 95%CI = 0.22–0.73). Using the principal component analysis, we also identified two dietary patterns which explained 14.31% of the variance in food groups intake. Women in the third and fourth quartiles of the “Western pattern” had higher odds of hrHPV infection when compared with first quartile (adjOR = 1.77, 95% CI = 1.04–3.54 and adjOR = 1.97, 95%CI = 1.14–4.18, respectively). Adjusting for hrHPV status and age, women in the third quartile of the “prudent pattern” had lower odds of CIN2+ when compared with those in the first quartile (OR = 0.50, 95%CI = 0.26–0.98). Our study is the first to demonstrate the association of dietary patterns with hrHPV infection and CC and discourages unhealthy habits in favour of a Mediterranean-like diet.

ObjectivesThe aim of this cross-sectional study was to identify key factors associated with patient delay (PD), health system delay (HSD) and total delay (TOTD) in patients with tuberculosis (TB) to inform control programmes.SettingThe study was conducted in four Italian regions in 2014–2016. Data were obtained using a questionnaire including: sociodemographic and lifestyle data, TB comorbidities, patient knowledge and attitudes towards TB, stigma, access to TB care and health-seeking behaviours.ParticipantsPatients’ inclusion criteria were being diagnosed as a new smear positive pulmonary TB case and living in one of the participating Italian regions. Overall, 344 patients from 30 healthcare centres were invited to participate and 253 patients were included in the analysis (26.5% non-response rate); 63.6% were males and 55.7% were non-Italian born.Outcome measuresRisk factors for PD, HSD and TOTD in patients with TB were assessed by multivariable analysis. Adjusted ORs (aOR) and 95% CIs were calculated.ResultsMedian PD, HSD and TOTD were 30, 11 and 45 days, respectively. Factors associated with longer PD were: stigma (aOR 2.30; 95% CI 1.06 to 4.98), chest pain (aOR 2.67; 95% CI 1.24 to 6.49), weight loss (aOR 4.66; 95% CI 2.16 to 10.05), paying for transportation (aOR 2.66; 95% CI 1.24 to 5.74) and distance to the health centre (aOR 2.46; 95% CI 1.05 to 5.74) (the latter three were also associated with TOTD). Shorter HSD was associated with foreign-born and female status (aOR 0.50; 95% CI 0.27 to 0.91; aOR 0.28; 95% CI 0.15 to 0.53, respectively), dizziness (aOR 0.18, 95% CI 0.04 to 0.78) and seeking care at hospital (aOR 0.35; 95% CI 0.18 to 0.66). Prior unspecific treatment was associated with longer HSD (aOR 2.25; 95% CI 1.19 to 4.25) and TOTD (aOR 2.55; 95% CI 1.18 to 5.82). Haemoptysis (aOR 0.12; 95% CI 0.03 to 0.43) and repeated visits with the same provider (aOR 0.29; 95% CI 0.11 to 0.76) showed shorter TOTD.ConclusionsThis study identifies several determinants of delays associated with patient’s behaviours and healthcare qualities. Tackling TB effectively requires addressing key risk factors that make individuals more vulnerable by the means of public health policy, cooperation and advocacy to ensure that all patients have easy access to care and receive high-quality healthcare.

Several studies showed that altered expression of the miRNA-ome in maternal circulation or in placental tissue may reflect not only gestational disorders, such as preeclampsia, spontaneous abortion, preterm birth, low birth weight, or macrosomia, but also prenatal exposure to environmental pollutants. Generally, the relationships between environmental exposure, changes in miRNA expression, and gestational disorders are explored separately, producing conflicting findings. However, validation of tissue-accessible biomarkers for the monitoring of adverse pregnancy outcomes needs a systematic methodological approach that takes also into account early-life environmental exposure. To achieve this goal, exposure to xenochemicals, endogenous agents, and diet should be assessed. This study has the aim to provide a comprehensive review on the role of miRNAs as potential biomarkers for adverse pregnancy outcomes and prenatal environmental exposure.

Background Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women. Methods Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion. Results Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01–1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%). Conclusions LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.

Summary Background Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become an important healthcare-associated problem, particularly in intensive care units (ICUs). Aim To investigate the emergence of carbapenem- and colistin-resistant A. baumannii infections in two Sicilian hospitals. Methods From October 2008 to May 2011, a period which included two Italian Nosocomial Infections Surveillance in ICUs network (SPIN-UTI) project surveys, all carbapenem-resistant A. baumannii isolates from the ICUs of two hospitals in Catania, Italy, were prospectively collected. Minimum inhibitory concentrations (MICs) were measured by agar dilution, and phenotypic testing for metallo-β-lactamase (MBL) production was performed. Carbapenem resistance genes and their genetic elements were identified by polymerase chain reaction and sequencing. Genotypic relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. Patient-based surveillance was conducted using the SPIN-UTI protocol and previous antibiotic consumption was recorded. Findings Twenty-six carbapenem-resistant A. baumannii were identified. Imipenem and meropenem MICs ranged from 4 to >32 mg/L, and 15 isolates exhibited high-level colistin resistance (MICs >32 mg/L). PFGE demonstrated that all isolates belonged to a unique clonal type and were assigned to ST2 of the international clone II. They harboured an intrinsic bla OxA-51-like carbapenemase gene, bla OxA-82 , which was flanked upstream by IS Aba1. Conclusions The dissemination of clonally related isolates of carbapenem-resistant A. baumannii in two hospitals is described. Simultaneous resistance to colistin in more than half of the isolates is a problem for effective antibiotic treatment. Prior carbapenem and colistin consumption may have acted as triggering factors.

Background/Aims: An important public health issue is monitoring folate inadequacy in women of childbearing potential. The aim of the present study was to investigate associations between folate intake, red blood cell (RBC) folate, total homocysteine (tHcy) and the MTHFR 677T allele. Methods: A total of 204 women were enrolled in a cross-sectional study. Folate intake was assessed by a food frequency questionnaire, and RBC folate, tHcy and MTHFR C677T genotype were determined. Results: About half of the women had a decreased RBC folate level (Conclusions: Our study revealed significant folate deficiency in our Mediterranean population and higher than ideal Hcy concentrations, thus emphasizing that in these groups an improvement in the folate status is needed via a food-based approach or supplement. Consequently, public health policy strategies aiming at improved supplementation are required.

tuberculosis, health-care system, diagnosis

Objective: The aim of the present study was to estimate the preventable proportion of Intubation-Associated Pneumonia (IAP) in the Intensive Care Units (ICUs) participating in the Italian Nosocomial Infections Surveillance in ICUs (SPIN-UTI) network, taking into account differences in intrinsic patients’ risk factors, and additionally considering the compliance with the European bundle for IAP prevention. Methods: A prospective patient-based survey was conducted and all patients staying in ICU for more than 2 days were enrolled in the surveillance. Compliance with the bundle was assessed using a questionnaire for each intubated patient. A twofold analysis by the parametric g-formula was used to compute the number of infections to be expected if the infection incidence in all ICUs could be reduced to that one of the top-tenth-percentile-ranked ICUs and to that one of the ICU with the highest compliance to all five bundle components. Results: A total of 1,840 patients and of 17 ICUs were included in the first analysis showing a preventable proportion of 44% of IAP. In a second analysis on a subset of data, considering compliance with the European bundle, a preventable proportion of 40% of IAP was shown. A significant negative trend of IAP incidences was observed with increasing number of bundle components performed (p Conclusions: The g-formula controlled for time-varying factors is a valuable approach for estimating the preventable proportion of IAP and the impact of interventions, based entirely on an observed population in a real-world setting. However, both the study design that cannot definitively prove a causative relationship between bundle compliance and IAP risk, and the small number of patients included in the care bundle compliance analysis, may represent limits of the study and further and larger studies should be conducted.

Objectives: In order to assess the prevalence of surgical site infections (SSIs) before and after the implementation of a multimodal infection control programme including the realization of a campaign to increase compliance with guidelines for antimicrobial prophylaxis, we designed and conducted the present study involving all 20 of the surgical departments of a large teaching hospital in Catania, Italy. Patients and methods: SSI definitions of the Hospital in Europe Link for Infection Control through Surveillance (HELICS) protocol were used in four 1 day point-prevalence surveys. After the first survey, an infection control programme was implemented involving the active commitment of surgeons and infection control staff. Results: Overall, a total of 600 surgical patients were enrolled. A significant decreasing trend in the SSI rate (from 16.4 to 8.2 per 100 surgical patients, P¼0.018) was shown. After multivariate analysis, significant risk factors for SSI were identified: age .31 years, kidney insufficiency and infection at admission. Taking into account the indication and the timing of administration of antibiotic prophylaxis, in the four surveys prophylaxis was administered inappropriately in 55.3% of surgical procedures. Conclusions: The approach used in this study remains a feasible method of evaluating the burden of SSIs using repeated prevalence surveys. The results provide evidence of a significant decreasing trend in the SSI rate following the infection control intervention. Furthermore, our study underlines the need to develop evidencebased guidelines in collaboration with surgeons, to achieve consensus before implementation in order to improve compliance with antimicrobial prophylaxis and, finally, decrease SSI rates.

DNA methylation, a major epigenetic mechanism, is involved in various biological processes including cancer. Particularly, promoter methylation can inactivate Death-Associated Protein Kinase1 (DAPK...

Several dietary agents, such as micronutrient and non-nutrient components, the so-called bioactive food components, have been shown to display anticancer properties and influence genetic processes. The most common epigenetic change is DNA methylation. Hypomethylation of long interspersed elements (LINE-1) has been associated with an increased risk of several cancers, although conflicting findings have also been observed. The aim of the present study was to test the hypothesis that a low adherence to the Mediterranean diet (MD) and folate deficiency may cause LINE-1 hypomethylation in blood leukocytes of healthy women, and thus genomic instability. One hundred and seventy-seven non-pregnant women were enrolled. Mediterranean diet score (MDS) and folate intake were calculated using a food frequency questionnaire. LINE-1 methylation level was measured by pyrosequencing analysis in three CpG sites of LINE-1 promoter. According to MDS, only 9.6 % of subjects achieved a high adherence to MD. Taking into account the use of supplements, there was a high prevalence of folate deficiency (73.4 %). Women whose consumption of fruit was below the median value (i.e.

Background The overuse and misuse of antibiotics, has contributed to the selection, emergence and dissemination of resistant pathogens. The objective of the study is to provide an overview of changes in antibiotic consumption and resistance data in two Intensive Care Units (ICU1 and ICU2) during a six-years period, from 2008 to 2013. Methods The study used a laboratory-based surveillance approach. Antimicrobial resistance rates (RR) were calculated as the number of resistant isolates divided by the total …

Background DNA methylation, a major epigenetic mechanism, is involved in various biological processes including cancer. Long Interspersed Nuclear Element-1 (LINE-1) hypomethylation, as biomarker of global methylation, was observed in several types of cancer and was associated with a poor prognosis. In the present systematic review, global DNA methylation was evaluated as a biomarker for cancer risk. Methods A literature search, using the PubMED database, was performed to select studies, published up to March …

Background Physical activity (PA) is an important modifiable risk factor for several types of chronic diseases such as obesity. About 35% of European adults did not meet the PA recommendations in 2008. It has been demonstrated that obesity and physical inactivity are closely related, but the direction of this association remains uncertain. Recent data support the effect of Body Mass Index (BMI) on future PA, rather than the effect of activity on future BMI. The objective of …

The mitochondrial DNA (mtDNA) 4977-bp deletion is a biomarker of mitochondrial genomic instability. It is frequently detected in a number of sporadic diseases, and it accumulates in many tissues during aging. Folic acid plays an important role in the maintenance of genomic stability in mammals. The aim of the present cross-sectional study was to characterise the levels of the mtDNA deletion in the lymphocytes of healthy young women, taking into account folate intake, red blood cell (RBC) folate levels and the distribution of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism. Folate intake was estimated by a food frequency questionnaire. Determination of the MTHFR C677T polymorphism and of the mtDNA deletion was performed by real-time polymerase chain reaction analysis. A total of 476 women were enrolled. Low levels of deletion were found (mean ?Ct = 1.24). After multivariate analysis, results did not show any significant relationship between age, smoking habits, pregnancy status, nutritional status, inadequate folate intake, folate deficiency, use of folic acid supplements, MTHFR C677T polymorphism and mtDNA 4977-bp deletions. The lack of association between inadequate folate intake, folate deficiency and mitochondrial genomic instability was confirmed also considering reference values of folate based on DNA damage prevention. Our results indicate that mtDNA 4977-bp deletions are maintained at low levels in lymphocytes of young healthy women despite the wide range of variation of folate intakes and folate status. Future studies, carefully designed to address limits and methodological issues related to variation of this biomarker as an effect of different dietary patterns and of folate status, could provide further insight on the specific mechanisms that are acting in lymphocytes of healthy subjects under observed folate intake. © 2014 © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The present study was conducted in order to (i) characterize the adherence to the Mediterranean diet (MD) pattern and fatty acids (FAs) intakes and (ii) explore interactions betweenTNFA−308 G>A polymorphism and adherence to MD and FAs intakes, respectively, on overweight/obesity risk. From 2010 to 2013, 380 healthy women were enrolled, and MD score (MDS) and FAs intakes were evaluated by a Food Frequencies Questionnaire in relation to nutritional status.TNFA−308 G/A polymorphism was characterized using PCR-RFLP. A total of 32.6% of women were overweight or obese. Lower mean MDS values were more observed in the younger age group than in the older age group (3.60 versus 4.45). The risk of being overweight/obese was 3.5-fold increased due to poor adherence to MD and was about twofold increased in less educated women. Furthermore, younger age was associated with poor adherence to MD. No evidence for an independent effect of the polymorphism on overweight/obesity risk was found. There was no evidence of biological interaction from the gene-diet interaction analyses. Young women, less educated and with poor adherence to MD, are a target group for the nutritional interventions that aimed to control the obesity risk, thus improving the adherence to MD and particularly the intake of unsaturated FAs.

Objective A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk. Methods A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used. Results A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: −6.40, 95% CI: −7.71, −5.09; p

Summary Aim To report an outbreak of extensively drug-resistant (XDR) Acinetobacter baumannii in the neonatal intensive care unit (NICU) of an Italian university hospital. Patient risk profiles for acquisition of A. baumannii and measures used to control the outbreak are described. Methods Antibiotic susceptibility of strains was evaluated by microdilution. Genotyping was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. Carbapenemase genes were analysed by polymerase chain reaction and DNA sequencing. A case–control study was designed to identify risk factors for acquisition of A. baumannii . Findings A. baumannii was isolated from 22 neonates, six of whom were infected. One major PFGE type was identified, assigned to sequence type (ST) 2, corresponding to International Clone II; this was indistinguishable from isolates from the adult ICU in the same hospital. A. baumannii isolates were resistant to aminoglycosides, quinolones and classes of β-lactam antibiotics, but were susceptible to tigecycline and colistin. Carbapenem resistance was associated with the presence of transposon Tn 2006 carrying the bla OxA-23 gene. Length of NICU stay, length of exposure to A. baumannii , gestational age, use of invasive devices and length of exposure to invasive devices were significantly associated with acquisition of A. baumannii on univariate analysis, while length of exposure to central venous catheters and assisted ventilation were the only independent risk factors after multi-variate analysis. Conclusions This XDR A. baumannii outbreak in an NICU was probably caused by intrahospital transfer of bacteria via a colonized neonate whose mother was admitted to the adult ICU. Strengthened infection control measures were necessary to control the outbreak.

Background The overuse of antimicrobials is one of the main factors responsible for the development and spread of antimicrobial resistance, together with other causes, such as intra- and inter-hospital spread of resistant microorganisms and infection control policies and practices. The objective of the present study is to report the trends of Klebsiella pneumoniae and Acinetobacter baumannii antimicrobial resistance indicators in an Italian intensive care unit (ICU) during a six-year period, from 2008 to 2013. Methods Susceptibility data and annual antibiotic consumptions in the ICU were retrospectively obtained from the clinical laboratory and the pharmacy. Trends over time of resistance rates (RRs) and of incidence densities of resistant isolates were determined by linear regression. Results Isolation density of A. baumannii increased significantly from 2008 (20.4 per 1,000 patient-days) to 2013 (58.1 per 1,000 patient-days) and of K. pneumoniae from 2010 (22.3 per 1,000 patient-days) to 2013 (55.9 per 1,000 patient-days). RRs of third-generation cephalosporins (3GCs)-resistant K. pneumoniae (from 2010: 41.9 %, to 2012: 87.0 %), of carbapenem-resistant K. pneumoniae (from 2008: 0 %, to 2013: 59.2 %), and of carbapenem-resistant A. baumannii (from 2008: 87.5 %, to 2013: 96.6 %) showed significant increasing trends. Carbapenems was the main antibiotic class consumed (24.9 % of the total antimicrobial usage density), followed by 3GCs (21.0 %), fluoroquinolones (20.6 %), aminoglycosides (17.3 %), penicillins (15.1 %) and glycopeptides (1.1 %). Carbapenems consumption decreased from 2008 to 2012 and then increased in 2013. Glycopeptides consumption decreased from 2008 to 2011 and then increased in 2013. Aminoglycosides consumption decreased from 2008 to 2010 and increased from 2012 to 2013. Finally, 3GC, penicillins and fluoroquinolones consumptions decreased from 2012 to 2013. Conclusions RRs of carbapenem-resistant A. baumannii and of carbapenem- and 3GC-resistant K. pneumoniae were higher than those for Europe. Our findings highlight the necessity to implement an integrated system for monitoring not only consumption of antibiotics and resistance profiles but also the clonality of alert microorganisms in the ICU for effective infection control.