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Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19 that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical, and laboratory characteristics of children diagnosed with MIS-C who were admitted to the PICU and those who did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Demographic, clinical, and laboratory data were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR: 12.89, 95%CI: 1.35-123.41, p -value = 0.03) and cardiological involvement (OR: 34.55, 95%CI: 2.2-541.91, p -value = 0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 h from admission, D-dimer levels higher than 4 μg/mL and decreased Left Ventricular Ejection Fraction (LVEF) were associated with an increased risk of PICU admission (OR: 7.95, 95%CI: 1.48-42.78, p -value = 0.02 and OR = 1.28, 95%CI: 1.07-1.53, p -value = 0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p -value = 0.005) and were hospitalized for more days than children in the pediatric ward (median length of stay (IQR): 20 (15, 28) days vs. 8.5 (6, 14) days, p -value < 0.001). Conclusions: The findings of this study indicate that cardiovascular and hepatic involvement and increased D-dimer levels in children with MIS-C might be associated with admission to the PICU.

The COVID-19 pandemic modified the epidemiology and the transmission of respiratory syncytial virus (RSV). We collected data on RSV positivity and incidence from children hospitalized in the largest tertiary paediatric hospital in Greece before (2018-2020, period A), during (2020-2021, period B), and after (2021-2023, period C) the COVID-19 lockdown. A total of 9,508 children were tested for RSV. RSV positivity (%) was 17.6% (552/3,134) for period A, 2.1% (13/629) for period B, and 13.4% (772/5,745) for period C (p < 0.001). The mean age (±SD) of RSV-positive children among the three periods was A: 5.9(±9.3), B: 13.6 (±25.3), and C: 16.7 (±28.6) months (p < 0.001). The peak of RSV epidemiology was shifted from January-March (period A) to October-December (period C). RSV in-hospital incidence per 1,000 hospitalizations in paediatric departments was A:16.7, B:1.0, and C:28.1 (p < 0.001), and the incidence in the intensive care unit was A: 17.3, B: 0.6, and C: 26.6 (p < 0.001). A decrease in RSV incidence was observed during the COVID-19 lockdown period, whereas a significant increase was observed after the lockdown. A change in epidemiological patterns was identified after the end of the lockdown, with an earlier seasonal peak and an age shift of increased RSV incidence in older children.

Introduction: It has been postulated that nutrition may influence the risk for cutaneous melanoma (CM); therefore, we aimed to assess the associations of food groups and individual nutrient intakes with CM in a Greek population., Methods: In this case-control study, 151 patients with histologically confirmed CM, newly diagnosed and treated in the Oncology Department of the "Laikon" University Hospital (Athens, Greece), and 151 age- and sex-matched healthy individuals residing in the Athens metropolitan area, recruited among participants for routine health examinations, were included. All participants completed a questionnaire comprising anthropometric measurements, sociodemographic, lifestyle, and health-related variables. A validated, semiquantitative food frequency questionnaire was used to assess average consumption of 136 food items during the 12 months preceding the onset of disease. Multivariate conditional regression models were used to derive odds ratios (ORs) with 95% confidence intervals (95% CI) regarding the association of nine food groups and seven macronutrients with CM., Results: Statistically significant positive associations with CM were found with higher energy intake (OR: 1.67, 95% CI: 1.22-2.30) and intake of saturated fatty acids (OR: 2.28, 95% CI: 1.00-5.28), after adjusting for sun sensitivity, major depression history, and alcohol intake. Inverse associations with higher intake of milk and dairy products (OR: 0.65, 95% CI: 0.48-0.88), fruits (OR: 0.68, 95% CI: 0.51-0.90), added lipids (OR: 0.65, 95% CI: 0.47-0.91), and sugars and syrups (OR: 0.70, 95% CI: 0.53-0.93) were also observed., Conclusions: Beyond intrinsic risk factors, our results support associations of CM with multiple food groups and nutrients; if confirmed by prospective studies, these findings can add further knowledge about this fatal cancer., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction/background: Adjuvant capecitabine monotherapy is an option for colon and upper rectum adenocarcinoma patients, providing they have stage II disease with an intermediate risk of recurrence, or stage III but they are above 70's or they have comorbidities. We wanted to examine whether the number of chemotherapy cycles and the relative dose intensity (RDI) of capecitabine monotherapy in the adjuvant setting are affecting disease recurrence., Patients and Methods: We included patients with completely resected stage II and III colon and upper rectum cancer who received adjuvant capecitabine monotherapy, from 2003 until May 2020. Patients with early relapse, i.e. during chemotherapy or within 6 months after the completion of adjuvant chemotherapy, and those with rectal cancer who received radiotherapy were excluded. Patients were divided into 3 groups based on the number of chemotherapy cycles received and the RDI. Group A included patients with ≤4 cycles of chemotherapy, group B patients with >4 cycles of chemotherapy and RDI ≤80%, and group C patients with >4 cycles of chemotherapy and RDI >80%. Study's endpoint, was recurrence free survival (RFS)., Results: Two hundred twenty six patients with stage II and III disease (164 and 62 respectively) were included. Sixteen, 166 and 44 were included in groups A, B and C respectively. After a median follow-up of 41 months, 21 patients (9,3%) had relapsed. Patients belonging to group C were found to have a trend for lower relapse rate compared to patients belonging to group A or group B., Conclusion: Number of adjuvant capecitabine cycles and RDI might play a role in RFS in patients with stage II and III colon and upper rectum adenocarcinoma., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years: 91%; EFS 5-year; <1.5 years: 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS : 18.12, 95% confidence intervals, CI: 3.47-94.54), N-myc amplification (HR OS : 2.16, 95% CI: 1.40-3.34), no surgical excision (HR OS : 3.27, 95% CI: 1.91-5.61) and relapse/progression (HR OS : 5.46, 95% CI: 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS : 0.11, 95% CI: 0.02-0.79; HR EFS : 0.19, 95% CI: 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The aim of the study was to investigate the prevalence and severity of adverse reactions (ARs) after immunization of healthcare workers (HCWs) with BNT162b2 vaccine and to associate them with clinical and epidemiological characteristics., Methods: A form containing demographic and clinical data as well as ARs after both doses of the vaccine was completed, and statistical association analysis was performed., Results: A total of 502 HCWs (females 78.3%) with mean age (±SD) 48.17 years (±12.97) participated. After the first dose, 404 (80.5%) HCWs reported at least one local AR (LAR) and 366 (72.9%) after the second dose ( p -value=0.004). After the first dose, 121 (24.1%) HCWs reported at least one systemic AR (SAR) and 275 (54.8%) after the second dose ( p -value<0.0001).In the logistic regression analysis, there was no association of gender or medical history of underlying disease with LARs. There was a negative association of age with the cumulative score (CS) of LARs (OR: 0.82, 95% CI: 0.69-0.96) after the first dose. Females had a positive association with CS of SARs following both doses (OR, 95% CI: 2.57, 1.39-4.73 and 2.71, 1.76-4.19, respectively). Age was negatively associated with CS of SARs (OR: 0.66, 95% CI: 0.57-0.76) after the second dose. Severe ARs included Bell's palsy (1) and tinnitus with temporary hearing loss (1)., Conclusion: The administration of the BNT162b2 vaccine in our HCWs cohort had a good safety profile with the most common ARs being self-limited. An increasing rate of SARs following the second vaccine dose was noticed. Rare but severe possible ARs should be further investigated.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys <5 years born during summer seemed to be at a lower risk of embryonal tumors (IRR: 0.73, 95% CI: 0.54-0.99). A clustering of astrocytomas was also found among girls (0-14 years) born during spring (IRR: 1.23, 95% CI: 1.03-1.46). Although the present exploratory results are by no means definitive, they provide some indications for age-, gender- and histology-related seasonal variations of CNS tumors. Expansion of registration and linkage with cytogenetic reports could refine if birth seasonality is causally associated with CNS tumors and shed light into the complex pathophysiology of this lethal disease., (© 2020 UICC.)

Background: Little is known about the etiology of childhood Wilms tumor (WT) and potentially modifiable maternal risk factors, in particular., Methods: Unpublished data derived from the hospital-based, case-control study of the Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) were included in an ad hoc conducted systematic literature review and meta-analyses examining the association between modifiable maternal lifestyle risk factors and WT. Eligible data were meta-analysed in separate strands regarding the associations of WT with (a) maternal folic acid and/or vitamins supplementation, (b) alcohol consumption and (c) smoking during pregnancy. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale., Results: Effect estimates from 72 cases and 72 age- and sex-matched controls contributed by NARECHEM-ST were meta-analysed together with those of another 17, mainly medium size, studies of ecological, case-control and cohort design. Maternal intake of folic acid and/or other vitamins supplements during pregnancy was inversely associated with WT risk (6 studies, OR: 0.78; 95 %CI: 0.69-0.89, I 2 = 5.4 %); of similar size was the association for folic acid intake alone (4 studies, OR: 0.79; 95 %CI: 0.69-0.91, I 2 = 0.0 %), derived mainly from ecological studies. In the Greek study a positive association (OR: 5.31; 95 %CI: 2.00-14.10) was found for mothers who consumed alcohol only before pregnancy vs. never drinkers whereas in the meta-analysis of the four homogeneous studies examining the effect of alcohol consumption during pregnancy the respective overall result showed an OR: 1.60 (4 studies, 95 %CI: 1.28-2.01, I 2 = 0.0 %). Lastly, no association was seen with maternal smoking during pregnancy (14 studies, OR: 0.93; 95 %CI: 0.80-1.09, I 2 = 0.0 %)., Conclusions: In the largest to-date meta-analysis, there was an inverse association of maternal folic acid or vitamins supplementation with WT risk in the offspring, derived mainly from ecological studies. The association with maternal alcohol consumption found in our study needs to be further explored whereas no association with maternal smoking was detected. Given the proven benefits for other health conditions, recommendations regarding folic acid supplementation as well as smoking and alcohol cessation should apply. The maternal alcohol consumption associations, however, should be further explored given the inherent limitations in the assessment of exposures of the published studies., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020. Published by Elsevier Ltd.)

The recent economic crisis has been linked with declines in population health. Evidence on the impact of the crisis on stillbirth rates is scarce. The aim of this study was to assess trends of stillbirth rates in Greece during the pre-crisis (2004-2008) and crisis period (2009-2015) and explore risk factors. Nationwide data (n = 1,276,816 births; 5023 stillbirths) were used to assess rates and trends through Poisson and joinpoint regressions. Multivariable Poisson regressions by nationality were fitted. The overall annual stillbirth rate was 3.9/1000 births with higher rates among non-Greeks (5.0/1000) than Greeks (3.7/1000). Non-significant decreasing trends were noted for Greeks (- 0.5%, 95% confidence interval [CI] - 1.4, 0.4%) versus non-significant increasing trends in non-Greeks (1.4%, 95% CI - 0.5, 3.3%). After adjusting for possible confounders, the relative stillbirth risk (RR) increased during the crisis versus the pre-crisis period (RR Greeks 1.61, 95% CI 1.50, 1.74; RR non-Greeks 1.92, 95% CI 1.64, 2.26). Multiplicity, birth order, birth size, maternal education, marital status, and parental age were risk factors.Conclusions: Bidirectional stillbirth trends were observed among Greeks and non-Greeks, whereas the RR increased by 2-fold during the crisis. Persisting disparities require tailored employment of preventive measures ensuring optimal quality of the child's and maternal health.What is Known:• Stillbirth rate is a key population health indicator reflecting economic development and health care services within a population.• The recent economic crisis has been linked with declines in population health.What is New:• Economic crisis, ethnic minorities, and several modifiable factors seem to be significant determinants of stillbirth risk.

Aim: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases., Methods: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed., Results: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers., Conclusions: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms., Competing Interests: Conflict of interest statement The authors state that there is no personal, financial or other conflict of interest related to this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Dietary habits during pregnancy have been inconsistently linked to childhood acute myeloid leukemia (AML), given the putative intrauterine onset of the disease as a result of triggering events during the critical period of fetal hematopoiesis. We investigated the potential association of maternal coffee and tea consumption during pregnancy with childhood AML risk, pooling primary data from eight case-control studies participating in the Childhood Leukemia International Consortium., Methods: Information on coffee and/or tea consumption was available for 444 cases and 1255 age- and sex-matched controls, on coffee consumption for 318 cases and 971 controls and on tea consumption for 388 cases and 932 controls. Categories for cups of daily coffee/tea consumption were created in order to explore potential dose-response associations. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression., Results: Associations were found neither in the analysis on coffee or tea nor in the analysis on coffee only consumption (any versus no). A positive association with increasing coffee intake was observed (>1 cup per day; OR: 1.40, 95% CI: 1.03-1.92, increment of one cup per day; OR: 1.18, 95% CI: 1.01-1.39). No associations were observed with tea consumption. Interaction analyses showed non-significant associations between coffee/tea and smoking. Hyperdiploidy was inversely associated with tea consumption, with other cytogenetic markers having no association with coffee/tea., Conclusion: Given the widespread consumption of caffeinated beverages among pregnant women, our finding is of important public health relevance, suggesting adverse effects of maternal coffee consumption during pregnancy in the offspring., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: To study trends of infant mortality rate (IMR) and neonatal mortality rate in Greece during the period 2004-2016 and explore the role of sociodemographic factors in the years of crisis., Design: Nationwide individual data for live births and infant (0-11 months) deaths provided by the Hellenic Statistical Authority were examined using Poisson, joinpoint regression and interrupted time series (ITS) analyses., Setting: Greece., Participants: All infant deaths (n=4862) over the 13-year period, of which 87.2% were born to Greek mothers, and respective live births., Main Outcome Measures: Evolution of IMR (0-364 days), early (<7 days) neonatal mortality rate (ENMR), late (7-27 days) neonatal mortality rate (LNMR) and post neonatal (28-364 days) mortality rate (PNMR) trends, by maternal nationality, place of residence and Human Development Index (HDI)., Results: By Poisson regression, overall, during the study period, among infants of Greek mothers, IMR and PNMR declined significantly (-0.9%; 95% CI -1.7% to -0.1% and -1.6%; -3.0% to -0.2% annually, respectively), although differentially by place of residence (IMR urban : -2.1%; -2.9% to -1.3%, IMR rural : +10.6%; 7.6% to 13.6%). By contrast, among infants of non-Greek mothers, the low starting IMR/ENMR/LNMR/PNMR increased significantly (max ENMR:+12.5%; 8.6% to 16.5%) leading to a non-significant time-trend pattern overall in Greece. The inverse associations of HDI with IMR, ENMR and PNMR were restricted to Greek mothers' infants. Joinpoint regression analyses among Greek mothers' infants indicated non-significant increasing trends of IMR and ENMR following the crisis (+9.3%, 2012-2016, p=0.07 and +10.2%, 2011-2016, p=0.06, respectively). By contrast, the high (+17.1%; 8.1% to 26.9%, p=0.002) IMR increases among non-Greek infants were restricted to 2004-2011 and equalised to those of Greek mothers' infants thereafter. ITS analyses in preset years (2008, 2010, 2012) identified significantly increasing trends in IMR, LNMR and PNMR after 2012, and in ENMR after 2010, among Greek mothers' infants., Conclusions: HDI and rural residence were significantly associated with IMR. The strongly decreasing IMR trends among Greek-mothers' infants were stagnated after a lag time of ~4 years of crisis approximating the previously sharply increasing trends among non-Greeks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Wilms tumour (WT) management represents a success story in pediatric oncology. We aimed to assess, for the first time, the event-free survival (EFS) vs. overall survival (OS) in Southern and Eastern Europe (SEE) using harmonised clinical data collected by childhood cancer registries and to identify respective prognostic factors., Methods: From 1999 to 2017, data for incident WT cases aged 0-14 years from 3 nationwide (Greece, Belarus and Slovenia) and one regional (Greater Poland) SEE registries were collected following common coding. Kaplan-Meier curves were constructed, and EFS vs. OS values were derived from Cox proportional hazard models by study variables., Results: A total of 338 WT cases (45.6% males; median age, 3.19 years; age<5 years, 75%) were included in the analyses. Bilateral were 21 tumours (6.2%). Among the 317 unilateral cases, the majority (93.7%) received International Society of Pediatric Oncology-based protocols; EFS 5-year was 85.1%, and OS 5-year 91.1%; both outcomes were significantly worse in stage IV patients or in those with high-risk/unfavourable histology. Relapse rate among high-risk/unfavourable histology cases was 2.3 times higher than among low-intermediate risk/favourable histology cases, with respective death rate 5.6 times higher. Both relapse and death rates increased significantly in patients with advanced anatomical stage and high-risk/unfavourable histology. Finally, significantly worse was the outcome in bilateral tumours (OS 5-year : 76.3%) vs. unilateral non-metastatic tumours (OS 5-year : 94.7%)., Conclusions: Our results delineate the potential of high-quality childhood cancer registration entailing clinical data to assess predictors of WT outcome over and beyond those derived from enrolment into clinical trials. Specifically, outcomes among children with WT residing in the four participating SEE countries were comparable with those reported by major cooperative international groups, albeit somehow inferior. Despite the excellent overall prognosis, however, subgroups of patients with advanced or bilateral disease and/or high-risk histology still suffer poor outcomes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The childhood peak of brain tumors suggests that early-life exposures might have a role in their etiology. Hence, we examined in the Greek National Registry for Childhood Hematological Malignancies and Solid tumors (NARECHEM-ST) whether perinatal and early-life risk factors influence the risk of childhood brain tumors., Methods: In a nationwide case-control study, we included 203 cases (0-14 years) with a diagnosis of brain tumor in NARECHEM-ST (2010-2016) and 406 age-, sex-, and center-matched hospital controls. Information was collected via interviews with the guardians and we analyzed the variables of interest in multivariable conditional logistic regression models., Results: Instrument-assisted delivery was associated with higher (OR: 7.82, 95%CI: 2.18-28.03), whereas caesarean delivery with lower (OR: 0.67, 95%CI: 0.45-0.99) risk of childhood brain tumors, as compared to spontaneous vaginal delivery. Maternal alcohol consumption during pregnancy (OR: 2.35, 95%CI: 1.45-3.81) and history of living in a farm (OR: 4.98, 2.40-10.32) increased the odds of childhood brain tumors. Conversely, higher birth order was associated with lower risk (OR for 2nd vs. 1st child: 0.60, 95%CI: 0.40-0.89 and OR for 3 rd vs. 1 st : 0.34, 95%CI: 0.18-0.63). Birth weight, gestational age, parental age, history of infertility, smoking during pregnancy, allergic diseases, and maternal diseases during pregnancy showed no significant associations., Conclusions: Perinatal and early-life risk factors, and specifically indicators of brain trauma, exposure to toxic agents and immune system maturation, might be involved in the pathogenesis of childhood brain tumors. Larger studies should aim to replicate our findings and examine associations with tumor subtypes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (OR CC 1.05, 95% CI 1.00-1.11; OR NCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (OR CC 0.99, 95% CI 0.91-1.07, heterogeneity I 2  = 58%, p = 0.002; OR NCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.

Background: Despite recent therapeutic advancements, Wilms tumour (WT) presents remarkable survival variations. We explored mortality and survival patterns for children (0-14 years) with WT in 12 Southern and Eastern European (SEE) countries in comparison with the United States of America (USA)., Methods: A total of 3966 WT cases (0-14 years) were registered by a network of SEE childhood cancer registries (N:1723) during available registration periods circa 1990-2016 and surveillance, epidemiology, and end results program (SEER) (N:2243; 1990-2012); mortality data were provided by the respective national statistical services. Kaplan-Meier curves and Cox proportional hazards models were used to assess the role of age, sex, year of diagnosis, urbanisation and Human Development Index (HDI) on overall survival (OS)., Results: Persisting regional variations shape an overall 78% 5-year OS in the participating SEE countries, lagging behind the USA figure (92%, p=0.001) and also reflected by higher SEE mortality rates. Worth mentioning is the gradually escalating OS in SEE (hazard ratio [HR] 5-year increment :0.67, 95% confidence interval [CI]:0.60, 0.75) vs. a non-significant 10% improvement in the SEER data, which had a high starting value. OS differentials [two-fold less favourable among children aged 10-14 years, boys and those living in rural SEE areas (HR:1.37; CI:1.10-1.71) or countries with inferior HDI (2-3-fold)] were minimal in the USA., Conclusions: Children with WT residing in SEE countries do not equally enjoy the substantial survival gains, especially for those living in rural areas and in lower HDI countries. Noteworthy are steep and sizeable survival gains in SEE along with the newly presented Greek data pointing to achievable survival goals in SEE despite the financial crisis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Our purpose was to empirically validate the official New Zealand (NZ) serious non-fatal 'all injury' indicator. To that end, we aimed to investigate the assumption that cases selected by the indicator have a high probability of admission. Using NZ hospital in-patient records, we identified serious injury diagnoses, captured by the indicator, if their diagnosis-specific survival probability was ≤0.941 based on at least 100 admissions. Corresponding diagnosis-specific admission probabilities from regions in Canada, Denmark and Greece were estimated. Aggregate admission probabilities across those injury diagnoses were calculated and inference made to New Zealand. The admission probabilities were 0.82, 0.89 and 0.90 for the regions of Canada, Denmark and Greece, respectively. This work provides evidence that the threshold set for the official New Zealand serious non-fatal injury indicator for 'all injury' captures injuries with high aggregate admission probability. If so, it is valid for monitoring the incidence of serious injuries., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Despite advances in the management of nephroblastoma (Wilms' tumor, WT), the etiology of the tumor remains obscure. We aimed to compare nephroblastoma incidence rates and time trends among children (0-14 years) in 12 Southern and Eastern European (SEE) countries and the Surveillance, Epidemiology, and End Results Program (SEER), USA, in relation to the human development index (HDI)., Methods: In total 1776 WT cases were recorded in 13 SEE collaborating registries (circa 1990-2016), whereas data on 2260 cases (1990-2012) were extracted from the SEER database. Age-standardized incidence rates (AIRs) were calculated and correlated with HDI, whereas temporal trends were evaluated using Poisson regression and Joinpoint analyses., Results: The overall SEE AIR (9.2/10 6 ) was marginally higher than that of the SEER (8.3/10 6 ), whereas significant differences were noted among the 13 SEE registries which comprised mainly Caucasian populations. A statistically significant temporal increase in incidence was noted only in Belarus. Most cases (∼75%) were diagnosed before the fifth year of life, with rates steadily declining thereafter; median age at diagnosis was similar in SEE countries and SEER. A slight male preponderance in the first year of life (male:female = 1.1) was followed by a female preponderance in the older age groups (male:female = 0.7). Lastly, a statistically significant positive association between higher HDI and increasing nephroblastoma incidence was noted (regression coefficient: +3.25, 95%CI: +1.35, +5.15)., Conclusions: Variations in incidence and time trends across the examined registries, changing male-to-female patterns with advancement in age, and positive associations with the HDI imply a plausible role for environmental and genetic factors in disease etiology, and these need to be explored further., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: Neuroblastoma outcomes vary with disease characteristics, healthcare delivery and socio-economic indicators. We assessed survival patterns and prognostic factors for patients with neuroblastoma in 11 Southern and Eastern European (SEE) countries versus those in the US, including-for the first time-the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumours (NARECHEM-ST)/Greece., Methods: Overall survival (OS) was calculated in 13 collaborating SEE childhood cancer registries (1829 cases, ∼1990-2016) and Surveillance, Epidemiology, and End Results (SEER), US (3072 cases, 1990-2012); Kaplan-Meier curves were used along with multivariable Cox regression models assessing the effect of age, gender, primary tumour site, histology, Human Development Index (HDI) and place of residence (urban/rural) on survival., Results: The 5-year OS rates varied widely among the SEE countries (Ukraine: 45%, Poland: 81%) with the overall SEE rate (59%) being significantly lower than in SEER (77%; p < 0.001). In the common registration period within SEE (2000-2008), no temporal trend was noted as opposed to a significant increase in SEER. Age >12 months (hazard ratio [HR]: 2.8-4.7 in subsequent age groups), male gender (HR: 1.1), residence in rural areas (HR: 1.3), living in high (HR: 2.2) or medium (HR: 2.4) HDI countries and specific primary tumour location were associated with worse outcome; conversely, ganglioneuroblastoma subtype (HR: 0.28) was associated with higher survival rate., Conclusions: Allowing for the disease profile, children with neuroblastoma in SEE, especially those in rural areas and lower HDI countries, fare worse than patients in the US, mainly during the early years after diagnosis; this may be attributed to presumably modifiable socio-economic and healthcare system performance differentials warranting further research., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress., (© 2017 UICC.)

Childhood (0-14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern-Eastern European (SEE) countries and those in the United States. Average age-standardized mortality rates and time trends of Hodgkin (HL) and non-Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990-2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990-2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan-Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/10 6 ), which presented a sizeable (-4.8%, P = .0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non-HL was associated with a poorer outcome and an amphi-directional age-specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28-1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46-0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype-specific, and age-specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs., (Copyright © 2016 John Wiley & Sons, Ltd.)

We explored the potential association of depression history and personality, evaluated through a robust questionnaire tool, namely the Eysenck Personality Scale, with disease risk and progression among Greek patients. A total of 106 melanoma patients and their 1 : 1 sex-matched controls were interviewed on the basis of a questionnaire comprising phenotypic, sociodemographic, lifestyle and medical history variables, as well as information on history of lifetime major depression. The Eysenck Personality Questionnaire, measuring the four personality dimensions (extraversion, neuroticism, psychoticism, lie), was thereafter completed. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses, whereas potential predictors of survival were explored using Cox proportional hazards models. Sun sensitivity score [OR: 1.55, 95% confidence interval (CI): 1.16-2.06] and major depression history (OR: 5.72, 95% CI: 1.38-23.73) were significantly associated with melanoma, whereas inverse associations of extraversion (OR: 0.90, 95% CI: 0.83-0.97) and psychoticism score (OR: 0.88, 95% CI: 0.78-1.00) were noted. These associations were more pronounced and remained solely among female patients; notably, decreased extraversion (OR: 0.86, 95% CI: 0.76-0.98) and psychoticism score (OR: 0.63, 95% CI: 0.43-0.91), as well as increased depression history (OR: 10.69, 95% CI: 1.43-80.03) were evident. Cox-derived hazard ratios showed nonsignificant associations of depression history and personality with disease outcome. Our data support the hypotheses that depression history and personality are associated with melanoma risk. No effect on survival after cancer diagnosis was observed. If confirmed in future studies, these associations may contribute toward better understanding the etiology of melanoma, enhancing health-related quality of life.

Background: Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15-39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern-Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program., Methods: Malignant CNS tumors diagnosed in AYAs during the period spanning 1990-2014 were retrieved from 14 population-based cancer registries in the SEE region (n = 11,438). Age-adjusted mortality rates were calculated and survival patterns were evaluated via Kaplan-Meier curves and Cox regression analyses, and they were compared with respective 1990-2012 figures from SEER (n = 13,573)., Results: Mortality rates in SEE (range, 11.9-18.5 deaths per million) were higher overall than the SEER rate (9.4 deaths per million), with decreasing trends in both regions. Survival rates increased during a comparable period (2001-2009) in SEE and SEER. The 5-year survival rate was considerably lower in the SEE registries (46%) versus SEER (67%), mainly because of the extremely low rates in Ukraine; this finding was consistent across age groups and diagnostic subtypes. The highest 5-year survival rates were recorded for ependymomas (76% in SEE and 92% in SEER), and the worst were recorded for glioblastomas and anaplastic astrocytomas (28% in SEE and 37% in SEER). Advancing age, male sex, and rural residency at diagnosis adversely affected outcomes in both regions., Conclusions: Despite definite survival gains over the last years, the considerable outcome disparities between the less affluent SEE region and the United States for AYAs with malignant CNS tumors point to health care delivery inequalities. No considerable prognostic deficits for CNS tumors are evident for AYAs versus children. Cancer 2017;123:4458-71. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Aim: To present incidence of central nervous system (CNS) tumours among adolescents and young adults (AYAs; 15-39 years) derived from registries of Southern and Eastern Europe (SEE) in comparison to the Surveillance, Epidemiology and End Results (SEER), US and explore changes due to etiological parameters or registration improvement via evaluating time trends., Methods: Diagnoses of 11,438 incident malignant CNS tumours in AYAs (1990-2014) were retrieved from 14 collaborating SEE cancer registries and 13,573 from the publicly available SEER database (1990-2012). Age-adjusted incidence rates (AIRs) were calculated; Poisson and joinpoint regression analyses were performed for temporal trends., Results: The overall AIR of malignant CNS tumours among AYAs was higher in SEE (28.1/million) compared to SEER (24.7/million). Astrocytomas comprised almost half of the cases in both regions, albeit the higher proportion of unspecified cases in SEE registries (30% versus 2.5% in SEER). Similar were the age and gender distributions across SEE and SEER with a male-to-female ratio of 1.3 and an overall increase of incidence by age. Increasing temporal trends in incidence were documented in four SEE registries (Greater Poland, Portugal North, Turkey-Izmir and Ukraine) versus an annual decrease in Croatia (-2.5%) and a rather stable rate in SEER (-0.3%)., Conclusion: This first report on descriptive epidemiology of AYAs malignant CNS tumours in the SEE area shows higher incidence rates as compared to the United States of America and variable temporal trends that may be linked to registration improvements. Hence, it emphasises the need for optimisation of cancer registration processes, as to enable the in-depth evaluation of the observed patterns by disease subtype., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0-14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies. Observational studies examining the association between parental alcohol consumption and childhood leukemia were considered eligible. Data extracted from 39 case-control studies (over 16 000 leukemia cases and 30 000 controls) were pooled and summary-effect estimates were calculated. Subgroup analyses were carried out by main acute leukemia type [lymphoblastic or myeloid), cytogenetics/genetic polymorphisms, and specific alcohol beverages. We found a statistically significant dose-response association of any level of maternal alcohol consumption compared with nondrinking during pregnancy exclusively with acute myeloid leukemia (AML) [odds ratio (OR)moderate consumption: 1.64, 95% confidence intervals (CIs): 1.23-2.17 and ORhigh consumption: 2.36, 95% CI: 1.60-3.49]. In contrast, no association of paternal preconception consumption with any leukemia type was noted. In beverage-specific analyses, only a positive association of maternal wine drinking with childhood AML was found, which was more pronounced in analyses including only studies on infant leukemia (ORwine: 2.12, 95% CI: 1.16-3.90). The largest ever meta-analysis shows a sizeable, statistically significant dose-response association of maternal alcohol consumption during index pregnancy with AML risk. Future research exploring the role of genetic polymorphisms is anticipated to shed light on the underlying pathophysiology.

Purpose: History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted., Methods: Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken., Results: Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60)., Conclusions: In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.

Background: Exploring the effect of maternal and/or childhood diet on offspring leukemogenesis is challenging, given differences in food group categories, their potentially variable impact depending on time window of exposure and the multiple leukemia subtypes. We opted to quantitatively synthesize published data on the association of maternal/child diet with leukemia risk., Methods: Medline was searched until June 30th, 2016 for eligible articles on the association of childhood leukemia with consumption of (i) food groups, excluding alcoholic and non-alcoholic beverages, and (ii) specific dietary supplements before/during index pregnancy and childhood., Results: Eighteen studies of case-control design (N=11,720 cases/18,721 controls) were included, of which nine assessed maternal dietary components, five index child's and four both, mainly focusing on acute lymphoblastic leukemia (ALL). Statistically significant inverse estimates for ALL were found (2 studies, 413 cases, 490 controls) for fruit (OR: 0.81, 95% CI: 0.67, 0.99); vegetables (OR: 0.51, 95% CI: 0.28, 0.94); legumes (OR: 0.76, 95% CI: 0.62, 0.94); fish (OR: 0.27, 95% CI: 0.14, 0.53, among the 0-4year old; 2 studies 215 cases, 215 controls); preconception folic acid supplementation (OR: 0.69, 95%CI: 0.50-0.95; published meta analysis plus 2 studies, 3511 cases, 6816 controls); and use of vitamins during pregnancy (OR: 0.81, 95%CI: 0.74-0.88; published meta analysis plus one study, 5967 cases, 8876 controls). The associations (2 studies) of the remaining food groups and maternal dietary supplements consumption during pregnancy as well as of childhood diet and supplements intake (2-4 studies) were non significant., Conclusions: Maternal consumption of specific food groups comprising"healthy" items of the Mediterranean diet, preconception use of folic acid and intake of vitamins during pregnancy were associated with decreased ALL risk. Further research is needed, however preferably with homogeneous dietary information and data on immunophenotypic/cytogenetic subtypes to also explore the interaction of specific macro- and micronutrients intake with gene polymorphisms., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Governments wish to compare their performance in preventing serious injury. International comparisons based on hospital inpatient records are typically contaminated by variations in health services utilisation. To reduce these effects, a serious injury case definition has been proposed based on diagnoses with a high probability of inpatient admission (PrA). The aim of this paper was to identify diagnoses with estimated high PrA for selected developed countries., Methods: The study population was injured persons of all ages who attended emergency department (ED) for their injury in regions of Canada, Denmark, Greece, Spain and the USA. International Classification of Diseases (ICD)-9 or ICD-10 4-digit/character injury diagnosis-specific ED attendance and inpatient admission counts were provided, based on a common protocol. Diagnosis-specific and region-specific PrAs with 95% CIs were calculated., Results: The results confirmed that femoral fractures have high PrA across all countries studied. Strong evidence for high PrA also exists for fracture of base of skull with cerebral laceration and contusion; intracranial haemorrhage; open fracture of radius, ulna, tibia and fibula; pneumohaemothorax and injury to the liver and spleen. Slightly weaker evidence exists for cerebellar or brain stem laceration; closed fracture of the tibia and fibula; open and closed fracture of the ankle; haemothorax and injury to the heart and lung., Conclusions: Using a large study size, we identified injury diagnoses with high estimated PrAs. These diagnoses can be used as the basis for more valid international comparisons of life-threatening injury, based on hospital discharge data, for countries with well-developed healthcare and data collection systems., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: To systematically review and meta-analyse existing evidence on the association between folate/B12, and depression among the aged people., Methods: Following PRISMA/STROBE guidelines, the Medline abstracts were retrieved using an algorithm comprising relevant MeSH terms. Publications on the association of folate/B12 serum measurements with depression were abstracted independently by two reviewers and included in both gender and gender-specific meta-analyses, following recarculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies., Results: Both gender data were contributed by 11 folate-related (7949 individuals) and 9 B12-related studies (6308 individuals), whereas gender-specific data by 4 folate-related (3409 individuals) and 3 B12-related studies (1934 individuals). A statistically significant overall association between both exposures of interest (low folate and B12 levels) and depression was observed (ORfolate:1.23, 95%CI:1.07-1.43, ORB12:1.20, 95%CI:1.02-1.42). Gender-specific estimates pointed to a statistically significant positive association between low B12 levels and depression only among women (OR:1.33, 95%CI:1.02-1.74); the gender specific associations of low folate levels with depression were, however, non-significant and of counter-direction (ORfemales:1.37, 95%CI:0.90-2.07; ORmales:0.84, 95%CI:0.57-1.25)., Conclusion: Low folate and B12 serum levels seem to be associated with depression in the aged. The gender-specific analyses are confined to a positive association of low B12 with depression among older women and call for further research in this direction.

The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (≤3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996-2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0-14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10-2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13-2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15-2.40 and ORprelaborCD=1.79, 95% CI: 1.21-2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor.

Aim: Childhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region., Methods: Average age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan-Meier curves were derived for the maximum and the more recent (10 and 5 year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants., Results: Variations in mortality (8-16 per million) and survival (5-year: 35-69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (-2.4%, p=0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1-1.4)., Conclusion: Cross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This Swedish nationwide cohort study aims to examine the role of maternal characteristics (maternal age, education, smoking, BMI, diabetes, and preeclampsia) and multiple intrauterine growth measures on the risk of childhood lymphomas. A total of 3 444 136 singleton live births registered in the Swedish Medical Birth Register were analyzed, among whom there were 515 incident non-Hodgkin lymphoma (NHL) cases and 169 Hodgkin lymphoma (HL) cases aged 0-14 years at diagnosis (1973-2007) identified through linkage with the Swedish Cancer Register. Proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) of NHL and HL. Male sex (HR=2.00, 95% CI: 1.66-2.41), older maternal age (HR=1.03, 95% CI: 1.00-1.06, per 1-year increase), and large for gestational age compared with appropriate for gestational age (AGA) birth weight (HR=1.83, 95% CI: 1.20-2.79) were correlated with the risk of NHL; of note, in subanalysis by sex, the latter association was confined to girls (HR=3.37, 95% CI: 1.90-5.97, Pinteraction by sex=0.008). The risk of childhood HL overall was more evident among boys (HR=2.03, 95% CI: 1.46-2.81), whereas indices of accelerated fetal growth were not convincingly associated with the risk of HL. Apart from the established association with sex, the findings point to accelerated intrauterine growth as a risk factor for childhood NHL that may differ by sex. Given the rarity of this condition at birth, however, further studies with more elaborate indices are needed to conclude on its association with rare diseases such as HL.

Background: Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML)., Methods: One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders., Results: Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged., Conclusion: Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes., (© 2015 John Wiley & Sons Ltd.)

Clustering patterns, among health-care personnel, of excessive concerns pertaining to perceived electromagnetic field-related health impacts, as contrasted to those from other environmental factors, were explored. Knowledge/excessive concerns of 722 health-care personnel were assessed using a 22-item structured questionnaire along with a double-phase qualitative study comprising semistructured interviews and focus groups. Over 75 percent of the participants had high perceived knowledge, whereas accuracy was limited to <20 percent and correctness to 8 percent. An "excessive concern" group was clearly distinguished from a "relaxed attitude" one. Clustering of excessive concerns may derive from personal beliefs, suggesting a risk governance issue for health education policies., (© The Author(s) 2013.)

Aim: Following completion of the first 5-year nationwide childhood (0-14 years) registration in Greece, central nervous system (CNS) tumour incidence rates are compared with those of 12 registries operating in 10 Southern-Eastern European countries., Methods: All CNS tumours, as defined by the International Classification of Childhood Cancer (ICCC-3) and registered in any period between 1983 and 2014 were collected from the collaborating cancer registries. Data were evaluated using standard International Agency for Research on Cancer (IARC) criteria. Crude and age-adjusted incidence rates (AIR) by age/gender/diagnostic subgroup were calculated, whereas time trends were assessed through Poisson and Joinpoint regression models., Results: 6062 CNS tumours were retrieved with non-malignant CNS tumours recorded in eight registries; therefore, the analyses were performed on 5191 malignant tumours. Proportion of death certificate only cases was low and morphologic verification overall high; yet five registries presented >10% unspecified neoplasms. The male/female ratio was 1.3 and incidence decreased gradually with age, apart from Turkey and Ukraine. Overall AIR for malignant tumours was 23/10(6) children, with the highest rates noted in Croatia and Serbia. A statistically significant AIR increase was noted in Bulgaria, whereas significant decreases were noted in Belarus, Croatia, Cyprus and Serbia. Although astrocytomas were overall the most common subgroup (30%) followed by embryonal tumours (26%), the latter was the predominant subgroup in six registries., Conclusion: Childhood cancer registration is expanding in Southern-Eastern Europe. The heterogeneity in registration practices and incidence patterns of CNS tumours necessitates further investigation aiming to provide clues in aetiology and direct investments into surveillance and early tumour detection., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To estimate the level of awareness of prenatal screening (PS) and explore the underlying demographic, lifestyle and medical history parameters of Greek and non-Greek pregnant women undergoing prenatal diagnosis., Patients and Methods: A structured questionnaire was answered by 354 women at the time of receiving the results of invasive prenatal testing. Summary statistics and multiple logistic regression analyses were performed., Results: Adequate knowledge of the effectiveness of PS tests was reported by 50.8% of women. Popular press reading was associated with more than 2-fold higher level of awareness [odds ratio (OR)=0.51, p=0.0004]. Inadequate awareness was recorded among pregnant women of non-Greek nationality (OR=2.07, p=0.04), as well as among those also unaware of the effects of smoking during pregnancy (OR=2.39, p=0.004)., Conclusion: Pre-gestational prenatal counseling is essential in order to improve knowledge and attitudes of women towards PS and reduce the health gap between different cultural and social groups., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Positive associations have been reported between the measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth-weight-for-gestational-age and proportion of optimal birth weight (POBW)-were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI: 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one-standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI: 0.77, 0.95), respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin-like growth factors. © 2013 UICC., (Copyright © 2013 UICC.)

Purpose: Equivocal results regarding the role of leptin in colorectal cancer (CRC) and adenoma (CRA) have been reported. A case-control study investigating the association of leptin with CRC risk and clinicopathological characteristics along with meta-analysis of published data on both CRC and CRA were conducted., Methods: Pubmed and Embase were searched for the meta-analysis, comprising 28 case-control studies amounting 3,614 CRC and 1,215 CRA cases, along with 5,220 controls. Meticulous contact with the authors of individual studies was undertaken for the provision of additional data. Pooling of standardized mean differences (SMD), relative risks (RR) and 95 % CI (random effects models), subgroup, sensitivity, and meta-regression analyses were conducted., Results: The meta-analysis suggested positive association of serum leptin with CRA (RR, 95 % CI 1.35, 1.03 to +1.76), but not CRC either at the pooled analysis on SMDs or RRs (SMD, 95 % CI 0.18, -0.04 to +0.40; RR, 95 % CI 1.04, 0.65 to +1.65). Significant heterogeneity between studies on CRC as well as between studies on CRA providing SMD was noted. Subgroup, meta-regression and sensitivity analyses highlighted potential methodology-, design-, size- and quality-related effect modifiers., Conclusions: Meta-analysis of current evidence suggests positive association of serum leptin with CRA but not with CRC risk. Given the case-control nature of available studies, the limited number of studies on serum leptin and CRA, and the heterogeneity of CRC studies, carefully designed, prospective studies preferably reporting RRs adjusted for a variety of confounders may be warranted.

The aim of the present nationwide Greek study is to assess whether survival from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is modified by socioeconomic status (SES) and area remoteness. Detailed precoded information derived from a personal interview conducted by specially trained health personnel with the child guardians was available for 883 ALL and 111 AML incident childhood cases registered in the Nationwide Registry for Childhood Hematological Malignancies during the period 1996-2010. Parental socioprofessional category was recorded on the basis of ISCO68 and ISCO88 codes; the exact traveling distance between residence and the treating hospital was ad hoc calculated. Multivariate Cox's proportional hazards models were applied to examine the mutually adjusted associations between survival and potential predictors. Children from a lower parental socioprofessional category experienced 40% worse survival (P=0.02) independent of age, sex, and ALL subtype, whereas those whose parents were married had better outcomes (rate ratio: 0.47, P=0.01). Urbanization of residence at diagnosis or 'residence to treating hospital' distance was not nominally associated with survival from ALL. By contrast, no noteworthy associations implicating SES were found for AML survival, probably because of the burden of the disease and small numbers. Lower SES indicators and a single-parenthood family milieu seem to be independently associated with unfavorable outcomes from childhood ALL. Area remoteness might not be a significant outcome predictor during recent years, following considerable improvements in the motorway infrastructures and care delivery patterns. This study may provide a valuable snapshot capturing the impact of socioeconomic covariates before the burst of the Greek financial crisis.

Objective: To summarize existing evidence on the effect of serum folate and vitamin B12 levels on cognitive impairment among elders via a meta-analysis, also including unpublished data from a cross-sectional study of seniors ( > 65 years) residing in Velestino, Greece., Method: Serum measurements and Mini-Mental State Examination (MMSE) assessments were available for 593 Velestinians. In addition, 12 studies availing data on folate blood levels (N = 9,747) and 9 on B12 (N = 8,122) were identified following a search algorithm; pooled effect estimates were derived., Results: Cognitive impairment (MMSE < 24) among Velestenians was associated with lower education level in both genders; decreased social activity, depressive symptoms and low folate levels in males; older age in females. Meta-analyses showed an adverse effect of low-folate levels on cognition (OR: 1.66, 95% CI: 1.40-1.96); B12 was nonsignificantly associated (OR: 1.11, 95% CI: 0.88-1.40)., Discussion: Low folate levels are associated with cognitive impairment of seniors; underlying pathophysiological mechanisms should be further explored.

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case-control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene-environment interactions., Objectives: The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene-environment interactions and subtype-specific associations through the pooling of data from independent studies., Methods: By September 2012, CLIC included 22 studies (recruitment period: 1962-present) from 12 countries, totaling approximately 31000 cases and 50000 controls. Of these, 19 case-control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child-parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens., Conclusions: CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene-environment interactions and associations among specific leukemia subtypes in different ethnic groups., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Hand/finger amputations though rare account for significant disability and health-related costs; yet, information on underlying causes, springing mostly from physicians' reports, is rather anecdotal. We sought to draw attention to the high preventable fraction of hand/finger amputations among adults in Greece., Patients and Methods: Data on external cause of injury and short-term outcome, recorded over nine years in the Emergency Department Injury Surveillance System (EDISS) were analysed, whereas sample weights were used for nationwide extrapolations., Results: Hand/finger injuries accounted for 20.4% (N = 57,986) among 284,705 injuries recorded in patients >14-year-old (3% annual probability); 728 (1.3%) resulted in amputations; the estimated incidence rate (IR) was 39.3/100,000 person-years, reaching a high 92.6/100,000 among males aged 45-64 years. As expected, the vast majority of victims were males (90%), frequently young immigrants; ∼two-thirds sustained occupational injuries during working hours. Objects most frequently involved included: machinery (57% overall/69% occupational), means of transport (10.4%), materials (9.5%), parts of buildings/furniture (5%). Wood-working was the most common risk factor (20% overall/28% occupational) whereas 6% of victims accepted own inattention. 30% of amputations were hospitalised whereas 10% transferred to specialised units., Discussion: Specialised registries reveal the magnitude and specific causes of disabling hand injuries and point to tailored national injury prevention programs; specifically in Greece, as they occur in more controlled occupational environments among middle-aged males, woodworkers, and are caused mainly by machinery., Conclusions: Increased management of safety in the workplace could play a role in reduction in hand amputations., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Several reports point to inverse associations between allergies and ALL; yet, no study has explored this link using both self-reported-data on allergic history and biomarkers of atopic sensitization., Methods: Clinical information for the variables of interest was available for 252 out of 292 cases of childhood (0-14 years) ALL, newly diagnosed across Greece over a 4.5 year period as well as for 294 hospital controls. Allergen-specific-IgEs, as markers of allergic predisposition, against 24 most prevalent respiratory and food allergens, were determined, using an enzyme immunoassay procedure for 199 children with ALL and 113 controls. Cases were compared with controls through frequency distributions and unconditional multiple logistic regression models to estimate odds ratios (ORs) and 95% confidence-intervals (CIs) regarding associations of allergy with childhood ALL., Results: Self-reported-allergic history overall (OR: 0.49, 95% CI: 0.34-0.72) and practically each one of its main components (respiratory, food, any other clinical allergy) were strongly and inversely associated with ALL. Likewise, the serum IgE inverse association was of the same magnitude (OR: 0.43, 95% CI: 0.22-0.84) mainly contributed by food IgE (OR: 0.39, 95% CI: 0.18-0.83)., Conclusion: Beyond the already established inverse association of allergic history with childhood ALL, a same magnitude association is evident when serologic markers of allergic predisposition are used as an alternative measure of allergy. Further research with more appropriate study designs is needed to better understand possible associations between prior allergy and childhood ALL risk., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

To investigate the association of dietary habits with cognitive function among elders (>65 years). Complete sociodemographic, dietary information, serum measurements, and Mini-Mental State Examination (MMSE) assessments were available for 237 elderly men and 320 women residing in Velestino, Greece (a rural Greek town). All models were adjusted for age, education, social activity, smoking, depression symptomatology (using the Geriatric Depression Scale), MedDietScore (range 0-55), and metabolic syndrome. About 49.8% men and 66.6% women had MMSE scores <24, with a mean MMSE score of 22.7±4.43 and 21.1±4.73, respectively. Adherence to the Mediterranean diet was moderate (mean MedDietScore of 34.1±3.25 in men and 35.1±2.48 in women). Indicative cognitive impairment (MMSE score <24) was positively associated with age and low education in women and with depressive symptoms, low education status, and low social activity in men. Adherence to the Mediterranean diet was positively associated with MMSE score in men (P=.02), but inversely associated in women (P=.04). Concerning the food groups studied, intake of pulses, nuts, and seeds was associated with lower likelihood of having MMSE score<24 in men (P=.04). Only the Mediterranean dietary pattern showed a significant association with MMSE score positive for cognitive impairment (i.e., protective in men, but not in women), while individual food groups or nutrients did not achieve significance. The latter findings support the role of whole diet in the prevention of mental disorders, and state a research hypothesis for a sex-diet interaction on cognitive function among elders.

Purpose: There is a paucity of findings concerning the role of diet in childhood leukemogenesis, whereas the results are equivocal and the studies heterogeneous with regard to food items examined. This case-control study investigates the association of childhood leukemia with food groups, macronutrient consumption, total energy intake and adherence to Mediterranean diet among children aged 5-14 years in Greece., Methods: A total of 139 consecutive, incident leukemia cases out of which 121 were acute lymphoblastic leukemia were derived from the Nationwide Registry for Childhood Hematological Malignancies along with one : one age- and gender-matched hospital controls. Information on socio-demographic, maternal and child variables and dietary habits was obtained through in-person interviews with the guardians/children. Multiple logistic regression was performed with adjustment for birth weight and possible confounding variables., Results: Higher consumption of added lipids was associated with an increased risk of childhood leukemia, whereas consumption of milk and dairy products with reduced risk. From the macronutrient analysis, a borderline trend linking high protein intake with reduced childhood leukemia risk was observed., Conclusion: Consumption of milk and dairy products in the first year of life may protect against childhood leukemia possibly through vitamin D actions, while added lipids may increase the risk through various mechanisms. These results offer a holistic evaluation of children's nutrition and suggest that dietary habits in the early years of life may contribute to the prevention of childhood leukemia.

Apart from tumour, treatment and patient characteristics at diagnosis, access to healthcare delivery may as well play a significant role in breast cancer prognosis. This study aimed to assess the additional impact exerted on survival by travel burden-a surrogate indicator of limited access to healthcare- expressed as geographical distance and/or time needed to reach the tertiary healthcare center from the patient's residence. Between 1997 and 2005, 2,789 women participated in therapeutic clinical trials conducted by the Hellenic Cooperative Oncology Group. The effect of geographical distance and travel time between patient's residence and treating hospital on survival was estimated using Cox proportional hazards regression adjusting for age, menopausal status, tumour size/grade, positive nodes (number), hormonal receptor status, HER2 overexpression, surgery type/treatment protocol as well as for body mass index>30 kg/m2. More aggressive tumour features, older treatment protocols and modifiable patient characteristics, such as obesity (HR: 1.27) adversely impacted on breast cancer survival. In addition, less studied indicators of access to healthcare, such as geographic distance>350 km and travel time>4 h were independently and significantly associated with worse outcomes (HR=1.43 and 1.34 respectively). In conclusion, to address inequalities in breast cancer survival, improvements in access to healthcare services related to increased travel burden especially for patients of lower socioeconomic status should be considered, more than ever at times of financial crisis and independently of already known modifiable patient characteristics.

Background: Traumatic hand and finger amputations frequently lead to permanent disability., Objective: To investigate their epidemiological characteristics and estimate the prevention potential among children 0-14 years old, through a cross-sectional survey., Methods: Nationwide extrapolations were produced based on data recorded between 1996 and 2004 in the Greek Emergency Department Injury Surveillance System and existing sample weights. Incident and injury related characteristics were analysed to identify preventable causes., Results: Among 197,417 paediatric injuries, 28,225(14%) involved the hand and fingers resulting in 236 amputations (∼1% of hand injuries). The annual probability to seek emergency department care for a hand injury was 3%. The estimated incidence rate (IR) of hand amputations was 19.7/100,000 person-years. Over 50% concerned children 0-4 years old (male:female=2:1), peaking at 12-24 months. Male preschoolers suffered the highest IR (38.7/100,000). Migrant children were overrepresented among amputees. Of all amputations, 64% occurred in the house/garden and 14% in day-care/school/sports activities, usually between 08:00 and 16:00 (61%). Doors were the product most commonly involved (55% overall; 72% in day-care/school/gym) followed by furniture/appliances (15%) and machinery/tools (7%). Crushing was the commonest mechanism. Inadequate supervision and preventive measures were also frequently reported. 5% of the amputees were referred to specialised units for replantation/reconstructive surgery., Conclusions: The majority of paediatric hand and finger amputations could be prevented in Greece, particularly among preschoolers, by a single product modification, namely door closure systems, coupled with improved supervision. Paediatricians should incorporate this advice into their routine child-safety counselling. This country-specific profile supports the need for maintaining similar databases as an indispensable tool for assisting decision-making and preventing disabling and costly injuries.

An increase of the prevalence of childhood allergic diseases and the incidence of childhood Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL) were reported in the late 20th century. Among adults, several studies point to an inverse association with lymphoma; it remains to be confirmed whether allergy is also related to childhood lymphomas and whether the association, if any, is of an aetiologic nature. Between 1996 and 2008, 277 children (aged 0-14 years) with HL (N = 111) or NHL (N = 166) were enrolled in Nationwide Registry for Childhood Hematological Malignancies (NARECHEM), a Greek hospital-based-registry of childhood hematological malignancies. Hospital controls were individually matched to cases on age and sex. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95%confidence intervals (CIs) for associations of allergic diseases and other covariates with childhood HL or NHL risk. Subsequently, we combined our results with those of a French case-control study in a meta-analysis amounting to a total of 330 NHL cases/1478 controls and 239 HL cases/959 controls. After controlling for sociodemographic, perinatal and environmental factors, childhood NHL was less prevalent among children with allergy-associated symptoms overall (OR:0.50, 95%CI:0.27-0.92) or a history of asthma (OR:0.43, 95%CI:0.21-0.88). By contrast, allergy did not seem to be associated with childhood HL risk, although statistical power was limited. Fewer seaside holidays and higher birth weight were also associated with increased childhood NHL risk. The combined OR of the two studies for the association of asthma with NHL risk was: 0.52, 95%CI:0.32-0.84, whereas for HL: 0.86, 95%CI:0.51-1.45. Allergy seems to be strongly and inversely associated with childhood NHL. It remains to be elucidated in future investigations comprising larger populations, focusing on specific disease subtypes and employing more pertinent study-designs, whether this association is genuinely protective., (Copyright © 2011 Elsevier Ltd. All rights reserved.)