Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Cryptosporidium sp. infection in solid organ transplant recipients: A systematic review and meta-analysis.

(1) Background: Organ transplant recipients (OTRs) are vulnerable groups at risk of parasitic infections. This systematic review and meta-analysis aimed to evaluate the overall prevalence of Cryptosporidium sp. in OTRs and shed light on this potentially serious complication of organ transplantation. (2) Methods: We systematically searched studies on Cryptosporidium sp. infections in OTRs in four databases (Academia, PubMed, Scopus, and Science Direct). Random effects models were used to calculate pooled prevalence estimates with 95% confidence intervals (CIs). Sub-group and meta-regression analyses were conducted. A quality assessment of the included studies was also performed. (3) Results: Among 876 articles retrieved, 21 were included, accounting for 2,642 OTRs. Twenty studies were cross-sectional in design, of which seven reported data on a comparison group, and one was a retrospective cohort. The pooled prevalence of Cryptosporidium sp. in OTRs was 15% (95% CI: 7.4-24.6). Subgroup analysis revealed that the prevalence of Cryptosporidium sp. infection was higher in adults, symptomatics and developing countries and in studies using only non-molecular methods. However, substantial heterogeneity was reported. Low to moderate heterogeneity was observed in subgroups reporting lower prevalence Cryptosporidium sp. including children (5.8; 95% CI: 2.8-9.6), studies conducted in developed countries (5.8; 95% CI: 3.0-9.4) and studies using both molecular and non-molecular diagnostics (11.4; 95% CI: 6.4-17.4). The majority of the listed research reported low-medium quality scores. (4) Conclusion: Cryptosporidium sp. infection is a significant complication in OTRs with underreported prevalence. Preventive strategies to reduce the burden should include Cryptosporidium sp. routine screening for OTRs, particularly post-transplantation in patients with diarrhea. Additional well-designed research studies are required to determine the extent of the Cryptosporidium sp. burden in OTRs.

Diagnostic Performance of Toluidine Blue Stain for Direct Wet Mount Detection of Cryptosporidium Oocysts: Qualitative and Quantitative Comparison to the Modified Ziehl-Neelsen Stain.

(1) Background: The wet mount staining technique is a simple, economical, and rapid method for detecting parasitic stages. The objective of the current study was to evaluate wet mount diagnostic stains for Cryptosporidium infection in human faecal samples and to compare the sensitivity and qualitative performance of toluidine blue (TolB) and modified Ziehl-Neelsen (mZN) stain. (2) Methods: The collection, purification, and molecular amplification of Cryptosporidium oocysts were performed. TolB, malachite green, trypan blue, and crystal violet were evaluated qualitatively to diagnose Cryptosporidium oocysts. The outperforming stain was compared to mZN using a quantitative evaluation and qualitative scoring system. (3) Results: The oocysts of Cryptosporidium parvum were effectively purified and utilized for spiking. TolB was the most effective diagnostic stain among wet mount stains for detecting Cryptosporidium oocysts. TolB outperformed mZN in terms of sensitivity, with 100% versus 79% at a concentration of 104 and 49% versus 23% at a concentration of 102. TolB had the most favourable qualitative stain characteristics against mZN; however, sample freshness and being a temporary stain were crucial considerations. (4) Conclusions: This study emphasizes that TolB, as a routine wet mount technique for screening Cryptosporidium infection, will provide a more sensitive and faster method than mZN staining.

Barriers and facilitators for adopting healthy lifestyles in breast cancer survivors: a scoping review protocol.

OBJECTIVE: This scoping review will identify barriers and facilitators for the adoption of 7 healthy lifestyle components by female breast cancer survivors. This will be achieved by mapping the World Cancer Research Fund/American Institute for Cancer Research recommendations and the Lifestyle Medicine pillars. INTRODUCTION: Adherence to healthy lifestyle components (including weight management, physical activity, healthy diet, restorative sleep, avoidance of risky substances, forming and maintaining healthy relationships, and stress management) may improve the quality of life of breast cancer survivors and reduce the risk of adverse patient outcomes. However, cancer survivors' adherence to recommendations of multiple healthy lifestyle components is low, and decreases over time. INCLUSION CRITERIA: The review will consider peer-reviewed studies investigating barriers and facilitators for adopting any of the 7 healthy lifestyle components by female adult (18+ years old) breast cancer survivors (ie, from the time of diagnosis) in community, hospital, and/or cancer care settings, without any geographical restrictions. All study designs and articles published in English will be included. METHODS: The review will follow the JBI methodology for scoping reviews. Databases to be searched will include MEDLINE (PubMed), Embase, CINAHL (EBSCOhost), PsycINFO (Ovid), and the Cochrane Library databases. Articles published from 2007 to the present will be considered since this was the year in which the World Cancer Research Fund/American Institute for Cancer Research recommendations were published. Two independent reviewers will screen the retrieved articles and extract the data. Barriers and facilitators for each lifestyle component will be grouped according to the Theoretical Domain Framework. A narrative summary will explicate the charted data. REVIEW REGISTRATION: Open Science Framework https://osf.io/cn3va.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Hospital Surge Capacity Preparedness in Disasters and Emergencies: Protocol for a Systematic Review.

Hospitals' medical surge preparedness or surge capacity preparedness plays a significant role in reducing mortalities and in the treatment of severe injuries in disasters and emergencies. Though actions or activities for surge capacity preparedness of hospitals are discussed in several studies, they remain fragmented and need to be compiled. This systematic review will provide a comprehensive synthesis of evidence of actions or steps taken to strengthen hospitals' medical surge preparedness in disasters and emergencies, which will eventually help develop surge capacity programs and relevant policies. All the studies published in peer-reviewed journals between 1 January 2016 and 30 July 2022, with full text available, will be included in this review. Seven electronic databases-PubMed, Scopus, MEDLINE, CINAHL, Embase, PsycINFO, and Ovid-will be searched. Two reviewers will independently screen the titles and abstracts using the eligibility criteria, review full-text articles, and extract data with the help of CADIMA software. A third reviewer will help resolve any discrepancies during the whole process. The extracted data will be narratively synthesized with the key characteristics and findings of the studies. The NIH quality assessment tools will be used to scale up the the quality of the retrieved quantitative studies. Moreover, the mixed methods appraisal tool (MMAT) and Noyes et al. guidelines will be used to assess the mixed methods studies and qualitative studies quality assessment, respectively.

Effect of vaccination on SARS-CoV-2 reinfection risk: a case-control study in the Republic of Cyprus.

OBJECTIVES: We explored the effectiveness of COVID-19 vaccines in preventing reinfection in the Republic of Cyprus. STUDY DESIGN: This was a matched case-control study (1:2). METHODS: Cases were adults with a first episode of SARS-CoV-2 infection in 2020 and a second episode (i.e. reinfection) between June and August 2021. Controls were adults with only one infection episode in 2020 (i.e. not reinfected). Matching was performed by age, gender, and week of diagnosis for the first episode. The reinfection date of a case was applied to the matched controls for estimating full or partial vaccination status. Cases and controls were classified as unvaccinated, partially vaccinated (i.e. vaccination series not completed or final dose received ≤14 days before the reinfection date), or fully vaccinated (i.e. final dose received >14 days before the reinfection date). Conditional logistic regression was performed to calculate odds ratios and 95% confidence intervals for full or partial vaccination, against no vaccination, between controls and cases. RESULTS: This study showed that controls were more likely to be vaccinated (odds ratio for full vaccination: 5.51, 95% confidence interval: 2.43-12.49) than cases. CONCLUSIONS: This finding answers a pressing question of the public and supports the offer of vaccination to people with previous SARS-CoV-2 infection.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

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.

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

Effect of public health interventions during the first epidemic wave of COVID-19 in Cyprus: a modelling study.

BACKGROUND: Cyprus addressed the first wave of SARS CoV-2 (COVID-19) by implementing non-pharmaceutical interventions (NPIs). The aims of this study were: a) to estimate epidemiological parameters of this wave including infection attack ratio, infection fatality ratio, and case ascertainment ratio, b) to assess the impact of public health interventions and examine what would have happened if those interventions had not been implemented. METHODS: A dynamic, stochastic, individual-based Susceptible-Exposed-Infected-Recovered (SEIR) model was developed to simulate COVID-19 transmission and progression in the population of the Republic of Cyprus. The model was fitted to the observed trends in COVID-19 deaths and intensive care unit (ICU) bed use. RESULTS: By May 8th, 2020, the infection attack ratio was 0.31% (95% Credible Interval [CrI]: 0.15, 0.54%), the infection fatality ratio was 0.71% (95% CrI: 0.44, 1.61%), and the case ascertainment ratio was 33.2% (95% CrI: 19.7, 68.7%). If Cyprus had not implemented any public health measure, the healthcare system would have been overwhelmed by April 14th. The interventions averted 715 (95% CrI: 339, 1235) deaths. If Cyprus had only increased ICU beds, without any social distancing measure, the healthcare system would have been overwhelmed by April 19th. CONCLUSIONS: The decision of the Cypriot authorities to launch early NPIs limited the burden of the first wave of COVID-19. The findings of these analyses could help address the next waves of COVID-19 in Cyprus and other similar settings.

Lifestyle habits of adults during the COVID-19 pandemic lockdown in Cyprus: evidence from a cross-sectional study.

BACKGROUND: The 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. METHODS: This 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. RESULTS: Out of 745 participants, 74% were female and median age was 39 years. Overall participants reported significantly higher perceived stress score (22 v 25, p <  0.01), lower social support score (71 v 68, p <  0.001), and worse sleep quality score (4 v 5, p <  0.01) during lockdown. Mediterranean diet (MD) adherence was moderate and increased significantly only in those practicing religious fasting (score of 6 v 7, p <  0.01). Total minutes spent sitting increased (120 v 180, p <  0.01) although overall physical activity score did not significantly change. Smoking intensity increased during lockdown whilst frequency of alcohol consumption decreased (ptrend = 0.03 and <  0.01, respectively). CONCLUSION: Various 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.

Extensive Testing and Public Health Interventions for the Control of COVID-19 in the Republic of Cyprus between March and May 2020.

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-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): 1.97-4.69), increasing age (aOR: 1.56; 95%CI: 1.36-1.79), symptoms at diagnosis (aOR: 6.05; 95%CI: 3.18-11.50), and underlying health conditions (aOR: 2.08; 95%CI: 1.31-3.31) 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: 9.6-14.8%). 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.

Developing a holistic contingency plan: Challenges and dilemmas for cancer patients during the COVID-19.

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 "Obiettivo Antibiotico" Campaign on Prudent Use of Antibiotics in Sicily, Italy: The Pilot Phase.

The issue of antimicrobial resistance (AMR) is a focus of the World Health Organization, which proposes educational interventions targeting the public and healthcare professionals. Here, we present the first attempt at a regionwide multicomponent campaign in Sicily (Italy), called "Obiettivo Antibiotico", which aims to raise the awareness of prudent use of antibiotics in the public and in healthcare professionals. The campaign was designed by an interdisciplinary academic team, and an interactive website was populated with different materials, including key messages, letters, slogans, posters, factsheets, leaflets, and videos. The campaign was launched in November 2018 and, as of 21 December 2018, the website had a total of 1159 unique visitors, of which 190 became champions by pledging to take simple actions to support the fight against AMR. Data from social media showed that the audience was between 18 and 54 years of age, with a high proportion of female participants (64%). Interestingly, the LinkedIn page received more than 1200 followers, and Facebook 685 followers. The number of actions taken (pledges) by the audience was 458, evenly divided between experts (53%) and the general public (47%). Additional efforts are needed to reach more people, thus future efforts should focus on further promotion within the Sicilian region to sustain the engagement with the campaign.

The Effects of Diet and Dietary Interventions on the Quality of Life among Breast Cancer Survivors: A Cross-Sectional Analysis and a Systematic Review of Experimental Studies.

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 ≤ 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.

Dietary Patterns are Associated with Leukocyte LINE-1 Methylation in Women: A Cross-Sectional Study in Southern Italy.

Bioactive food compounds have different effects on global DNA methylation, an epigenetic mechanism associated with chromosomal stability and genome function. Since the diet is characterized by a mixture of foods, we aimed to identify dietary patterns in women, and to evaluate their association with long interspersed nuclear elements (LINE-1) methylation, a surrogate marker of global DNA methylation. We conducted an observational cross-sectional study of 349 women from Southern Italy, with no history of severe diseases. Dietary patterns were derived by food frequency questionnaire and principal component analysis. LINE-1 methylation of leukocyte DNA was assessed by pyrosequencing. We observed that intake of wholemeal bread, cereals, fish, fruit, raw and cooked vegetables, legumes, soup, potatoes, fries, rice, and pizza positively correlated with LINE-1 methylation levels. By contrast, vegetable oil negatively correlated with LINE-1 methylation levels. Next, we demonstrated that adherence to a prudent dietary pattern-characterized by high intake of potatoes, cooked and raw vegetables, legumes, soup and fish-was positively associated with LINE-1 methylation. In particular, women in the 3rd tertile exhibited higher LINE-1 methylation level than those in the 1st tertile (median = 66.7 %5mC; IQR = 4.67 %5mC vs. median = 63.1 %5mC; IQR = 12.3 %5mC; p < 0.001). Linear regression confirmed that women in the 3rd tertile had higher LINE-1 methylation than those in the 1st tertile (ß = 0.022; SE = 0.003; p < 0.001), after adjusting for age, educational level, employment status, smoking status, use of folic acid supplement, total energy intake and body mass index. By contrast, no differences in LINE-1 methylation across tertiles of adherence to the Western dietary pattern were evident. Interestingly, women who exclusively adhered to the prudent dietary pattern had a higher average LINE-1 methylation level than those who exclusively or preferably adhered to the Western dietary pattern (ß = 0.030; SE = 0.004; p < 0.001; ß = 0.023; SE = 0.004; p < 0.001; respectively), or those with no preference for a specific dietary pattern (ß = 0.013; SE = 0.004; p = 0.002). Our study suggested a remarkable link between diet and DNA methylation; however, further mechanistic studies should be encouraged to understand the causal relationship between dietary intake and DNA methylation.

Antibiotic Consumption and Resistance during a 3-Year Period in Sicily, Southern Italy.

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 2017-2020, 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.

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis.

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 <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. INTERPRETATION: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. FUNDING: European Centre for Disease Prevention and Control.

Mediterranean Diet and Particulate Matter Exposure Are Associated With LINE-1 Methylation: Results From a Cross-Sectional Study in Women.

Emerging evidence suggests that air pollution increases the risk of cardiovascular disease (CVD) and metabolic disorders, adding to the global burden of disease attributable to lifestyle and behavioral factors. Although long interspersed nucleotide elements 1 (LINE-1) methylation has been associated with these disorders, no studies have simultaneously examined the effects of diet and air pollution exposure on DNA methylation. Herein, we evaluated the association of particulate matter (PM with aerodynamic diameters of less than 10 mm) exposure and adherence to Mediterranean Diet (MD) with LINE-1 methylation. Healthy women (n = 299), aged 15 to 80 years, were enrolled in a cross-sectional study. Dietary data and adherence to MD were assessed by a Food Frequency Questionnaire (FFQ) and Mediterranean Diet Score (MDS). PM10 levels during 1-month before recruitment were recorded by monitoring stations and assigned to each woman based on their residential address and day of recruitment. LINE-1 methylation in blood samples was assessed by pyrosequencing and reported as percentage of 5-methylcytosine (5mC). The Mann-Whitney U test, Spearman's rank correlation test and linear regression models were applied. Our results demonstrated, for the first time, an inverse association between adherence to MD and exposure to PM10 with LINE-1 methylation: while higher monthly PM10 exposure decreases LINE-1 methylation level (ß = -0.121; p = 0.037), the adherence to MD increases it (ß = 0.691; p < 0.001). MDS seemed to interact with PM10 levels (p = 0.002) on LINE-1 methylation, as such we confirmed that the effect of MD decreased with increasing PM10 levels (ß = 0.657; p < 0.001 in the first tertile; ß = 0.573; p < 0.001 in the second tertile; ß = 0.551; p < 0.001 in the third tertile). Thus, we suggest that LINE-1 methylation is a possible mechanism underpinning environment-related health effects, and encourage further research to evaluate whether the adherence to the MD could counteract the negative effect of PM10 exposure.

Determinants of patient and health system delay among Italian and foreign-born patients with pulmonary tuberculosis: a multicentre cross-sectional study.

OBJECTIVES: The 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. SETTING: The 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. PARTICIPANTS: Patients' 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 MEASURES: Risk factors for PD, HSD and TOTD in patients with TB were assessed by multivariable analysis. Adjusted ORs (aOR) and 95% CIs were calculated. RESULTS: Median 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. CONCLUSIONS: This 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.