Birth seasonality of childhood central nervous system tumors: Analysis of primary data from 16 Southern-Eastern European population-based registries.

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.

Stillbirth in Greece during the years of economic crisis: a population-based study.

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 (RRGreeks 1.61, 95% CI 1.50, 1.74; RRnon-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.

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US.

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.

Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium.

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 (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I2 = 58%, p = 0.002; ORNCC 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.

Empirical validation of the New Zealand serious non-fatal injury outcome indicator for 'all injury'.

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.

Malignant central nervous system tumors among adolescents and young adults (15-39 years old) in 14 Southern-Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns.

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.

Mortality and survival patterns of childhood lymphomas: geographic and age-specific patterns in Southern-Eastern European and SEER/US registration data.

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 (1.02/106 ), 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.

Towards valid 'serious non-fatal injury' indicators for international comparisons based on probability of admission estimates.

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.

Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis.

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.

Associations of Dietary Factors with Cutaneous Melanoma: A Case-Control Study in Greece with Literature Review.

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.

Fetal growth and childhood acute lymphoblastic leukemia: findings from the childhood leukemia international consortium.

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.

Circulating leptin levels and risk of colorectal cancer and adenoma: a case-control study and meta-analysis.

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.

Nutrition in early life and risk of childhood leukemia: a case-control study in Greece.

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.

Incidence of Disease Recurrence in Patients With Colon and Upper Rectum Adenocarcinoma Stage II and III Receiving Adjuvant Capecitabine Monotherapy: Do Number of Chemotherapy Cycles and Relative Dose Intensity of the Drug Play a Role?

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.

Survival patterns of childhood neuroblastoma: an analysis of clinical data from Southern-Eastern European countries.

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.

In vitro fertilization and risk of childhood leukemia in Greece and Sweden.

BACKGROUND: Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. METHODS: The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1:1 matched controls). The Swedish case-control study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. RESULTS: Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR = 2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR = 1.77; 95% CI: 1.06-2.95) with no sufficient evidence of excess risk for other leukemias (OR = 1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.49-12.37) before age 2 years. CONCLUSIONS: IVF seems to be associated with increased risk of early onset ALL in the offspring.

Survival from breast cancer in relation to access to tertiary healthcare, body mass index, tumor characteristics and treatment: a Hellenic Cooperative Oncology Group (HeCOG) study.

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.

Traumatic hand amputations among children in Greece: epidemiology and prevention potential.

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.

Association of clinical and epidemiological characteristics with COVID-19 BNT162b2 mRNA vaccine short-term adverse reactions in healthcare workers.

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.