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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

OBJECTIVE: The aim of the present study was to investigate the differences between the consumption of plant-based v. animal-based protein-rich diets on successful ageing, as well as to identify the optimal combination of dietary protein intake for facilitating successful ageing in people aged >50 years. DESIGN: A combined analysis was conducted in older adults of the ATTICA and MEDIS population-based cross-sectional studies. Anthropometrical, clinical and sociodemographic characteristics, lifestyle parameters, dietary habits and level of protein intake were derived through standard procedures. Successful ageing was evaluated using the validated Successful Aging Index (SAI) composed of ten health-related social, lifestyle and clinical characteristics. SETTING: Athens area and twenty Greek islands. PARTICIPANTS: A total of 3349 Greek women and men over 50 years old. RESULTS: Participants with high consumption of plant proteins were more likely to be male, physically active, with higher daily energy intake, higher adherence to the Mediterranean diet and higher level of SAI (P < 0·001). Participants with 'Low animal & High plant' and 'High animal & High plant' protein consumption had a 6 and 7 % higher SAI score, respectively, compared with the other participants (P < 0·001). In contrast, 'Low animal & Low plant' and 'High animal & Low plant' protein intake was negatively associated with SAI as compared to the combination of all other consumption categories (P < 0·02). CONCLUSIONS: The consumption of a plant-based protein-rich diet seems to be a beneficial nutritional choice that should be promoted and encouraged to older people since it may benefit both individual's health and prolong successful ageing.

Objective: The aim of the present study was to investigate the differences between the consumption of plant-based v. animal-based protein-rich diets on successful ageing, as well as to identify the optimal combination of dietary protein intake for facilitating successful ageing in people aged >50 years. Design: A combined analysis was conducted in older adults of the ATTICA and MEDIS population-based cross-sectional studies. Anthropometrical, clinical and sociodemographic characteristics, lifestyle parameters, dietary habits and level of protein intake were derived through standard procedures. Successful ageing was evaluated using the validated Successful Aging Index (SAI) composed of ten health-related social, lifestyle and clinical characteristics. Setting: Athens area and twenty Greek islands. Participants: A total of 3349 Greek women and men over 50 years old. Results: Participants with high consumption of plant proteins were more likely to be male, physically active, with higher daily energy intake, higher adherence to the Mediterranean diet and higher level of SAI (P < 0·001). Participants with 'Low animal & High plant' and 'High animal & High plant' protein consumption had a 6 and 7 % higher SAI score, respectively, compared with the other participants (P < 0·001). In contrast, 'Low animal & Low plant' and 'High animal & Low plant' protein intake was negatively associated with SAI as compared to the combination of all other consumption categories (P < 0·02). Conclusions: The consumption of a plant-based protein-rich diet seems to be a beneficial nutritional choice that should be promoted and encouraged to older people since it may benefit both individual's health and prolong successful ageing. © 2020 The Authors.

Objective: To compare the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets in deterring 10-year CVD. Design: Prospective cohort (n 2020) with a 10-year follow-up period for the occurrence of combined (fatal or non-fatal) CVD incidence (International Classification of Diseases (ICD)-10). Baseline adherence to the Mediterranean and DASH diets was assessed via a semi-quantitative FFQ according to the MedDietScore and DASH scores, respectively. Setting: Attica, Greece. Participants: Two thousand twenty individuals (mean age at baseline 45·2 (sd 14·0) years). Results: One-third of individuals in the lowest quartile of Mediterranean diet consumption, as compared with 3·1 % of those in the highest quartile, developed 10-year CVD (P < 0·0001). In contrast, individuals in the lowest and highest DASH diet quartiles exhibited similar 10-year CVD rates (n (%) of 10-year CVD in DASH diet quartiles 1 v. 4: 79 (14·7 %) v. 75 (15·3 %); P = 0·842). Following adjustment for demographic, lifestyle and clinical confounding factors, those in the highest Mediterranean diet quartile had a 4-fold reduced 10-year CVD risk (adjusted hazard ratio (HR) 4·52, 95 % CI 1·76, 11·63). However, individuals with highest DASH diet quartile scores did not differ from their lowest quartile counterparts in developing such events (adjusted HR 1·05, 95 % CI 0·69, 1·60). Conclusions High adherence to the Mediterranean diet, and not to the DASH diet, was associated with a lower risk of 10-year fatal and non-fatal CVD. Therefore, public health interventions aimed at enhancing adherence to the Mediterranean diet, rather than the DASH diet, may most effectively deter long-term CVD outcomes particularly in Mediterranean populations. ©

BACKGROUND: To explore the effect of household food insecurity on dietary patterns of children and adolescents participating in a school food-aid programme in regions of Greece with low socioeconomic status. METHODS: A cross-sectional study was conducted during the school year 2013-14, among 406 schools in low socioeconomic status regions of Greece. Dietary habits and sociodemographic characteristics of students and their families were recorded. Factor analysis was used in order to derive children's and adolescents' dietary patterns and analysis of covariance was performed to examine the effect of households' food insecurity level on those patterns. A total of 31 399 students participated in the study; 16 652 children (5-11 years) and 14 747 adolescents (12-18 years). RESULTS: Factor analysis identified five dietary patterns in both age groups, explaining the 49.1% (children) and 53.0% (adolescents) of the total variation in intake. After adjusting for various factors, the household's food insecurity was significantly associated with the majority of the derived patterns in both age groups, with most pronounced differences being observed for the consumption of red meat, poultry and fish, fruits, as well as red processed meat, cereals and dairy products, which was lower among children and adolescents with food insecurity. Children with food insecurity consumed significantly more unhealthy food, such as chips, fast food, sugared drinks, sweets, French fries and mayonnaise sauce. CONCLUSIONS: Promotion of healthy eating to households facing food insecurity is of crucial importance, giving emphasis in the design of low cost, yet highly nutritious programmes. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Objective: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. Methods: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. Results: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7–20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7–14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. Conclusion: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS. © 2020 The Authors

BACKGROUND: Uniform international measurement tools for assessing healthy ageing are currently lacking. OBJECTIVES: The study assessed the novel comprehensive global Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) Healthy Ageing Scale, using an Item Response Theory approach, for evaluating healthy ageing across populations. DESIGN: Pooled analysis of 16 international longitudinal studies. SETTING: 38 countries in five continents. SUBJECTS: International cohort (n=355 314), including 44.4% (n=153 597) males, aged (mean±SD) 61.7±11.5 years old. METHODS: The ATHLOS Healthy Ageing Scale (including 41 items related to intrinsic capacity and functional ability) was evaluated in a pooled international cohort (n=355 314 from 16 studies) according to gender, country of residence and age group. It was also assessed in a subset of eight cohorts with =3 waves of follow-up assessment. The independent samples t-test and Mann-Whitney test were applied for comparing normally and skewed continuous variables between groups, respectively. RESULTS: The ATHLOS Scale (range: 12.49-68.84) had a mean (±SD) value of 50.2±10.0, with males and individuals >65 years old exhibiting higher and lower mean scores, respectively. Highest mean scores were detected in Switzerland, Japan and Denmark, while lowest in Ghana, India and Russia. When the ATHLOS Scale was evaluated in a subset of cohorts with =3 study waves, mean scores were significantly higher than those of the baseline cohort (mean scores in =3 study waves vs baseline: 51.6±9.4 vs 50.2±10.0; p

Objectives: To study the clinical, serological and histologic features of primary Sjögren’s syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development. Methods: From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups. Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud’s phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11–3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34–8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years. Conclusion: Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time. © Copyright © 2020 Goules, Argyropoulou, Pezoulas, Chatzis, Critselis, Gandolfo, Ferro, Binutti, Donati, Zandonella Callegher, Venetsanopoulou, Zampeli, Mavrommati, Voulgari, Exarchos, Mavragani, Baldini, Skopouli, Fotiadis, De Vita, Moutsopoulos and Tzioufas.

Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide. Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H). Results: Of 17693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America). Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children., peer-reviewed

Copyright © 2016 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Objectives: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Design: Secondary analysis of a prospective, cross-sectional, point prevalence study. Setting: International, multicenter PICUs. Patients: Pediatric patients with severe sepsis identified on five separate days over a 1-year period. Interventions: None. Measurements and Main Results: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Conclusions: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

The aim was to investigate the association between homocysteine (Hcy) and acute coronary syndrome (ACS) and to test the potential moderating role of Mediterranean diet. An age and gender matched case-control study was conducted among 1491 patients with a first ACS event and 3037 adults free of cardiovascular disease (CVD). Adherence to the Mediterranean diet was measured using the MedDietScore (range 0–55). An increase in Hcy levels was associated with a 1% and 3% higher likelihood of ACS among younger (

Dietary guidelines are an essential policy tool for facilitating optimal dietary patterns and healthy eating behaviours. We report: (i) the methodological approach adopted for developing the National Dietary Guidelines of Greece (NDGGr) for Infants, Children and Adolescents; and (ii) the guidelines for children aged 1-18 years.Design: An evidence-based approach was employed to develop food-based recommendations according to the methodologies of the WHO, FAO and European Food Safety Authority. Physical activity recommendations were also compiled. Food education, healthy eating tips and suggestions were also provided.Setting: The NDGGr encompass food-based nutritional and physical activity recommendations for promoting healthy dietary patterns and eating behaviours and secondarily to serve as a helpful tool for the prevention of childhood overweight and obesity.Results: The NDGGr include food-based recommendations, food education and health promotion messages regarding: (i) fruits; (ii) vegetables; (iii) milk and dairy products; (iv) cereals; (v) red and white meat; (vi) fish and seafood; (vii) eggs; (viii) legumes; (ix) added lipids, olives, and nuts; (x) added sugars and salt; (xi) water and beverages, and (xii) physical activity. A Nutrition Wheel, consisting of the ten most pivotal key messages, was developed to enhance the adoption of optimal dietary patterns and a healthy lifestyle. The NDGGr additionally provide recommendations regarding the optimal frequency and serving sizes of main meals, based on the traditional Greek diet.Conclusions: As a policy tool for promoting healthy eating, the NDGGr have been disseminated in public schools across Greece. © The Authors 2019.

The consumption of dietary fats, which occur naturally in various foods, poses important impacts on health. The aim of this study was to elucidate the association of exclusive use of olive oil for culinary purposes with successful aging in adults aged >50 years old and residing in Greece. Use of olive oil in food preparation and bio-clinical characteristics of the Greek participants enrolled in the ATTICA (n = 1128 adults from Athens metropolitan area) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek islands and Mani) studies, were investigated in relation to successful aging (SA). Participants were divided into the following three categories: (a) no olive oil consumption; (b) combined consumption of olive oil and other dietary fats; and (c) exclusive olive oil consumption. The SA was measured using the previously validated successful aging index (SAI). After adjusting for age, sex, and smoking habits, combined consumption of olive oil and other fats (vs. no olive oil use) was not significantly associated with SAI levels (p = 0.114). However, exclusive olive oil intake (vs. no use of olive oil) was significantly associated with SAI (p = 0.001), particularly among those aged older than 70 years. Therefore, the exclusive consumption of olive oil, as opposed to either combined or no olive oil consumption, beneficially impacts successful aging, particularly among individuals over 70 years of age. Primary public health prevention strategies should seek to encourage the enhanced adoption of such dietary practices in order to promote healthy aging and longevity. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Background/Objectives: Metabolically benign obesity remains a scientific field of considerable debate. The aim of the present work was to evaluate whether metabolically healthy obese (MHO) status is a transient condition which propagates 10-year cardiovascular disease (CVD) onset. Methods: A prospective longitudinal study was conducted during 2001–2012, the ATTICA study studying 1514 (49.8%) men and 1528 (50.2%) women (aged >18 years old) free of CVD and residing in the greater Athens area, Greece. Follow-up assessment of first combined CVD event (2011−2012) was achieved in n = 2020 participants; of them, 317 (15.7%) incident cases were identified. Obesity was defined as body mass index ≥30 kg/m 2 and healthy metabolic status as absence of all NCEP ATP III (2005) metabolic syndrome components (excluding waist circumference). Results: The MHO prevalence was 4.8% (n = 146) with 28.2% of obese participants presenting metabolically healthy status at baseline. Within this group, 52% developed unhealthy metabolic status during the 10-year follow up. MHO vs. metabolically healthy non-obese participants had a higher likelihood of presenting with 10-year CVD events, yet only the subset of them who lost their baseline status reached the level of significance (Hazard Ratio (HR) = 1.43, 95% Confidence Interval (95% CI) 1.02, 2.01). Sensitivity analyses revealed that MHO status was independently associated with elevated CVD risk in women and participants with low adherence to the Mediterranean diet, low grade inflammation, and insulin resistance. Conclusions: MHO status is a transient condition where weight management is demanded to prevent the establishment of unhealthy cardiometabolic features. The existence of obese persons who remain “longitudinally” resilient to metabolic abnormalities is an emerging area of future research. © 2019 Elsevier Inc.

The consumption of dietary fats, which occur naturally in various foods, poses important impacts on health. The aim of this study was to elucidate the association of exclusive use of olive oil for culinary purposes with successful aging in adults aged >50 years old and residing in Greece. Use of olive oil in food preparation and bio-clinical characteristics of the Greek participants enrolled in the ATTICA (n = 1128 adults from Athens metropolitan area) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek islands and Mani) studies, were investigated in relation to successful aging (SA). Participants were divided into the following three categories: (a) no olive oil consumption; (b) combined consumption of olive oil and other dietary fats; and (c) exclusive olive oil consumption. The SA was measured using the previously validated successful aging index (SAI). After adjusting for age, sex, and smoking habits, combined consumption of olive oil and other fats (vs. no olive oil use) was not significantly associated with SAI levels (p = 0.114). However, exclusive olive oil intake (vs. no use of olive oil) was significantly associated with SAI (p = 0.001), particularly among those aged older than 70 years. Therefore, the exclusive consumption of olive oil, as opposed to either combined or no olive oil consumption, beneficially impacts successful aging, particularly among individuals over 70 years of age. Primary public health prevention strategies should seek to encourage the enhanced adoption of such dietary practices in order to promote healthy aging and longevity.

Background: Despite WHO Framework Convention of Tobacco Control (FCTC) adoption, effective implementation of national smoking bans remains pending in several countries. This study quantified the association of second hand smoke (SHS) exposure and 10-year cardiovascular disease (CVD) among never smokers in such settings. Methods: In 2001–2002, a sample of 1514 males and 1528 females (range: 18–89 years old) were randomly selected in Greece. Frequency and duration of SHS exposure (i.e. exposure extending >30 min/day) within the home and/or workplace were assessed by interview. Following a 10-year follow-up period (2002–2012), incidence of non-fatal and fatal CVD (ICD-10) was evaluated among n = 2020 participants. The analytic study sample consisted of all never smokers (n = 910). Results: Despite national smoking ban implementation (2009), 44.6% (n = 406) of never smokers reported SHS exposure. While SHS exposed never smokers exhibited a more favorable profile of CVD-related risk factors at baseline, they subsequently developed similar 10-year CVD incidence rates, at a younger mean age (p = 0.001), than their non-exposed counterparts. Following adjustment for several lifestyle and clinical factors, SHS exposed never smokers exhibited a two-fold elevated 10-year CVD risk (adj. HR: 2.04, 95% CI: 1.43–2.92), particularly among women (adj. HR: 2.45, 95% CI: 1.45–4.06). SHS exposure accounted for 32% excess Population Attributable Risk (PAR) for 10-year CVD events in never smokers, with highest rates (PAR: 52%) being among those exposed in the workplace. Conclusion: The prevention of SHS associated CVD and related healthcare costs mandates additional strategies for securing the effective implementation of comprehensive WHO FCTC based national smoking bans. © 2019 Elsevier B.V.

Background: Obesity in adulthood is associated with decreased leucocyte telomere length (LTL), which is associated with cardiovascular disease and diabetes mellitus type 2. The aim of our study was to investigate whether increased body mass index (BMI) is associated with decreased LTL in children and adolescents, and to identify other risk factors of shorter LTL in this population. Materials and methods: A cross-sectional study was conducted among 919 Greek children aged 9-13 years (The Healthy Growth Study). Participants were classified as obese (n = 124), overweight (n = 276) or of normal BMI (n = 519). LTL was determined by monochrome multiplex quantitative real-time polymerase chain reaction. Univariate and multivariable linear regression analyses were applied to determine the predictive factors of LTL. Results: Both overweight and obese children had significantly shorter LTL than their normal-BMI counterparts. Following adjustment for age, sex, total daily energy intake and average weekly physical activity (average total steps per day), increasing weight category was inversely associated with LTL in children and adolescents (β: −0.110 ± 0.035; P =.002). Conclusion: Overweight and obesity in childhood and adolescence are associated with shorter LTL, even following adjustment for potential confounding effects. Therefore, the increased BMI in childhood and adolescence may be associated with accelerated biological ageing and may have an adverse impact on future health in adulthood. © 2019 Stichting European Society for Clinical Investigation Journal Foundation

The study evaluated the extent to which high normal blood pressure (HNBP), elevated BP, and Stage 1 hypertension predict 10-year incidence of cardiovascular disease (CVD). A population-based, prospective cohort study was conducted among 3042 randomly selected Greek adults, aged 18–89 years. Following 10-years follow-up (2002–2012), incidence of non-fatal and fatal CVD (ICD-10) was achieved in 2020 participants. The analytic sample (n = 1403) excluded hypertensive patients. At baseline, the prevalence rate of HNBP, elevated BP, and Stage 1 hypertension was 44.6% (n = 626), 29.0% (n = 408), and 15.5% (n = 218), respectively. During follow-up, the 10-year combined (fatal or non-fatal) CVD incidence rates in HNBP, elevated BP, and Stage 1 hypertensive individuals were 15.6% (n = 98), 12.0% (n = 49), and 22.5% (n = 49), respectively, as compared to 6.3% (n = 49) in normotensives (all p’s < 0.0001). As compared to normotensives (and following the adjustment for known demographic, lifestyle and clinical confounding factors), HNBP participants had a 1.5-fold (Adjusted Hazard Ratio, Adj. HR: 1.49; 95% CI: 1.00–2.20) increased risk of 10-year CVD events. Similarly, Stage 1 hypertensive participants had an approximately twofold (Adj. HR: 1.90; 95% CI: 1.16–3.08) increased risk for 10-year CVD, particularly among males (Adj. HR: 2.03; 95% CI: 1.08–3.83). However, individuals with elevated BP did not exhibit a differential risk for developing 10-year CVD events (Adj. HR: 1.28; 95% CI: 0.82–2.02). Therefore, since HNBP and Stage 1 hypertension individuals exhibit a notable increased risk of 10-year fatal and non-fatal CVD, the implementation of targeted primary and secondary prevention interventions may deter both CVD and related adverse health outcomes. © 2019, Springer Nature Limited.

Background: Hypertensive nephropathy, a leading cause of declining kidney function, is a multifactorial process not well understood. In order to elucidate biological processes and identify novel macromolecular components crucially involved in the process of kidney damage, the application of system biology approaches, like proteomics, is required. Methods: Proteomic studies were performed using the renal parenchyma of spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls. Animals were sacrificed at early time intervals (6, 13, and 20 weeks after birth), the renal tissue extract was subjected to two-dimensional gel electrophoresis, differential expressed proteins were identified, and altered pathways were evaluated. One specific protein, chloride intracellular channel 4 (CLIC4), not implicated so far in the development of hypertension and nephrosclerosis, was further studied by Western blotting, immunohistochemistry and immunofluorescence. Results: Proteomic analysis identified several pathways/processes and organelles (mitochondria) as being affected from the early stages of hypertension. CLIC4 was overexpressed in SHR at all 3 time intervals examined. This finding was confirmed by Western blotting and by immunohistochemistry and immunofluorescence; these morphological techniques demonstrated that CLIC4 was almost exclusively localized at the apical surface of the proximal tubular epithelial cells. Conclusions: Our studies provide evidence that major changes occur in the renal parenchyma from early stages of the development of hypertension. The overexpression of CLIC4 suggests that alterations in the proximal tubular compartment during hypertension should be further examined and that CLIC4 may be a useful early marker of renal tubular alterations due to elevated blood pressure. © 2017 S. Karger AG, Basel. Copyright: All rights reserved.

Aims To qualitatively evaluate the optimal intervention (food-voucher approach vs. free daily meal distribution), aimed at reducing food insecurity and promoting healthy eating among students attending public schools in socioeconomically disadvantaged areas. Methods We randomly assigned 34 schools to one of the two interventions: students in 17 schools received a daily lunch-box and parents in the other 17 schools received a food voucher of equal value once a month. All students were offered the opportunity to participate. We conducted 30 focus groups in all participating schools (17 in the meal distribution and 13 in the food voucher schools). Eligible participants included parents (n = 106), educators (n = 66) and school principals (n = 34). We qualitatively evaluated their perceptions and attitudes towards the program. Results Important differences were observed between the two approaches, with more favourable perceptions being reported for the meal distribution approach. More specifically, social stigmatization was minimized in the meal distribution approach, through the participation of all students, compared with the food-voucher participants who reported feelings of embarrassment and fear of stigmatization. Secondly, the meal distribution approach alleviated child food insecurity through the provision of the daily meal, while the food-voucher intervention helped manage household food insecurity, as vouchers were mainly used for purchasing food for family meals. Furthermore, the educational and experiential nature of the meal distribution approach intensified healthy eating promotion, while the food-voucher intervention was efficient mainly for conscious parents regarding healthy eating. Conclusions The meal distribution intervention was considered more effective than the food-voucher one. Hence, for interventions aiming at tackling food insecurity of children and adolescents, public health focus could be oriented towards school-based in kind food assistance. © 2017

Objective: Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) demonstrate increased secretion of cortisol precursors following ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic corticotropin-releasing hormone (CRH) secretion. Both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression. We performed an endocrinologic and psychological evaluation in carriers of 21-OHD and matched control subjects. Design: We recruited 29 parents of children with classic CAH (14 males, 15 females; age (mean±SD): 41.8±5.7 yr), and hence 21-OHD carriers, and 13 normal subjects (5 males, 8 females; age: 43.8±6.1 yr). All subjects underwent a formal ovine (o) CRH stimulation test with measurement of ACTH, cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, which was preceded by determination of 24-hour urinary free cortisol (UFC) excretion. Psychometric assessment was performed by administering the State-Anxiety (STAI 1) and Trait-Anxiety (STAI 2) Inventory, Beck Depression Inventory, Symptom Checklist-90R and Temperament and Character Inventory. Results: Carriers of 21-OHD had significantly higher 17-OHP concentrations following oCRH stimulation and higher STAI 1 (47.6±5.6 vs. 43.3±5.4, P=0.023) scores than control subjects. Mean 24-hour UFC concentrations were positively correlated with paranoid (r=0.435; P=0.023) and psychoticism (r=0.454; P=0.017). Stepwise multiple linear regression analysis revealed that the single independent predictor of STAI 1 was peak stimulated 17-OHP concentrations (β: 0.055, SE: 0.023, R2: 0.290, P=0.031). Conclusions: Carriers of 21-OHD may be predisposed to the development of anxiety disorders. © 2017, Hellenic Endocrine Society. All rights reserved.

Background: Stress is defined as a state of threatened or perceived as threatened homeostasis. A broad spectrum of extrinsic or intrinsic, real or perceived stressful stimuli, called ‘stressors’, activates a highly conserved system, the ‘stress system’, which adjusts homeostasis through central and peripheral neuroendocrine responses. Inadequate, excessive or prolonged adaptive responses to stress may underlie the pathogenesis of several disease states prevalent in modern societies. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. Materials and methods: We conducted a systematic review of original articles and reviews published in MEDLINE from 1975 through June 2016. The search terms were ‘childhood stress’, ‘pediatric stress’, ‘stress and disorders’ and ‘stress management’. Results: In this review, we discuss the historical and neuroendocrine aspects of stress, and we present representative examples of paediatric stress system disorders, such as early-life adversity, obesity and bullying. We also discuss the adverse impact of a socio-economic crisis on childhood health. The tremendous progress of epigenetics has enabled us to have a deeper understanding of the molecular mechanisms underlying paediatric stress-related disorders. Conclusions: The need for early successful stress management techniques to decrease the incidence of paediatric stress-related diseases, as well as to prevent the development of several pathologic conditions in adolescence and adulthood, is imperative. © 2017 Stichting European Society for Clinical Investigation Journal Foundation

Copyright © 2016 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Objectives: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. Design: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. Setting: European and U.S. PICUs. Patients: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Conclusions: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions, perhaps related to PICU bed availability, needs to be considered in the design of future international clinical trials in pediatric severe sepsis.

Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide. Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H). Results: Of 17 693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America). Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Herpes zoster (HZ) is an emerging concern for public health officials. The aim of this study was to determine whether universal Varicella immunization implemented in 2004 had an impact on HZ hospitalization in immunocompetent children in Greece. All HZ hospitalizations were recorded during the period 1999–2011. The overall attributable hospitalization rate was 13.89 cases/1000 hospital admissions (95%CI: 11.69–16.38 cases/1000 hospital admissions). HZ hospitalization rate remained unchanged during the study period. These data provide a basis for monitoring HZ hospitalization rate among children following universal toddler immunization. © 2016 Japan Pediatric Society

Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells. © 2015 Elsevier Ltd.

Objective. We aimed to investigate the prevalence of obesity and visceral obesity (VO) within children living on the s mall Greek island of Tinos and their associatedfactors. Methods. Three hundred and fifty two healthy children and pre-adolescents (54% boys) attending the primary schools of Tinos island were evaluated, aged (mean±SD) 8.53±1.72 years (range 6-11), from which 286 (81.25%) were of Greek origin and 65 (18.46%) foreign immigrants. Body weight, height and waist circumference (WC) were measured, plus BMI and WC percentiles were calculated. Children with WC > 90th percentile were categorized as having VO. Results. Among our patients, 235 (66.76%) were of normal weight, 88 (25%) overweight and 29 (8.2%) obese. Obese children, as opposed to their normal weight counterparts, were more likely to be of younger age (p=0.009). VO was found in 65 (18.47%) children, with a higher prevalence among the obese than overweight ones (96.43% vs. 42%, p

OBJECTIVE: To assess interferon-gamma inducible protein 10 (IP-10) as a diagnostic marker for tuberculous infection in children, particularly in relation to its differential diagnostic performance in young children. DES IGN AND RE SULT S: A case-control study was conducted among 161 children and adolescents (mean age 6.3 years 6 standard deviation 1.7; males n = 79, 49%). Fifty-four (33.5%) had active TB, 53 (33%) had latent tuberculous infection (LTBI), and 54 (33.5%) were non-LTBI controls. Unstimulated IP-10 levels did not differ between groups (P > 0.05 for all comparisons). TB-specific antigen stimulated IP-10 levels were more profoundly increased in infected groups than in controls (P < 0.001 for all comparisons). None of the IP-10-based diagnostic indexes demonstrated the ability to discriminate active disease from LTBI. A value of IP-10 ≥ 1222 pg/ml had 83.3% sensitivity, 79.6% specificity, 80.4% positive predictive value and 82.7% negative predictive value for the diagnosis of LTBI. IP-10 based indexes demonstrated a trend towards better performance in the population group aged

Cancer treatment aims to exploit properties that define malignant cells. In recent years, it has become apparent that malignant cells often survive cancer treatment and ensuing cell stress by switching on auxiliary turnover pathways, changing cellular metabolism and, concomitantly, the gene expression profile. The changed profile impacts the material exchange of cancer cells with affected tissues. Herein, we show that pathways of proteostasis and energy generation regulate common transcription factors. Namely, when one pathway of intracellular turnover is blocked, it triggers alternative turnover mechanisms, which induce transcription factor proteins that control expression of cytokines and regulators of apoptosis, cell division, differentiation, metabolism, and response to hormones. We focus on several alternative turnover mechanisms that can be blocked by drugs already used in clinical practice for the treatment of other non-cancer related diseases. We also discuss paradigms on the challenges posed by cancer cell adaptation mechanisms. © 2015 Taylor and Francis.

We determined the rates of community-acquired pneumonia (CAP)-associated hospitalizations and complications in Athens, over a period covering 4 years before and 4 years after the implementation of the 7-valent pneumococcal vaccine (PCV7) in Greece. PCV7 had no impact on pediatric CAP rates, whereas there was an increase in CAP-associated complications. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.