Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Long-term clinical outcomes of coronary artery bypass graft surgery compared to those of percutaneous coronary intervention with second generation drug eluting stents in patients with stable angina and an isolated lesion in the proximal left anterior descending artery.

OBJECTIVES: We compared the long-term outcomes of percutaneous coronary intervention with second-generation drug-eluting stents (PCI-DES) and coronary artery bypass graft surgery (CABG) with the left internal mammary artery in stable angina patients with isolated single-vessel proximal left anterior descending artery (pLAD) disease. BACKGROUND: Long-term outcomes of second-generation PCI-DES and CABG in isolated pLAD lesions have not been extensively studied. METHODS: We included 631 PCI-DES patients and 379 CABG patients. Unadjusted and adjusted hazard ratios (HRs) were derived for major adverse cardiac events (MACEs), their components (cardiac death, nonfatal myocardial infarction [MI] not attributed to a non-target vessel, target-lesion revascularization), and patient-related outcome (PRO, composed of all-cause mortality, any MI, any revascularization). RESULTS: In the unadjusted and adjusted analyses, no significant difference was observed between the two groups at follow-up (mean:4.6 ± 2.5 years) for MACEs (HR: 1.45, 95% CI: 0.92-2.28, p = .11; HR:1.43, 95% CI: 0.91-2.26, p = .13), PRO (HR: 1.18, 95%CI: 0.86-1.61, p = .30; HR: 1.18, 95% CI: 0.86-1.62, p = .31), cardiac death (HR: 0.97, 95% CI: 0.46-2.05, p = .93; HR: 0.79, 95% CI: 0.36-1.72, p = .56) and MI (HR: 1.43, 95% CI: 0.49-4.13, p = .51; HR: 1.57, 95% CI: 0.53-4.64, p = .42). Compared with CABG, PCI-DES had a borderline significantly greater risk of repeat revascularization (HR: 1.99, 95% CI: 1.00-3.94, p = .05; HR: 1.95, 95% CI: 0.98-3.9, p = .06). Angina recurred more often after PCI (p < .001), whereas more arrhythmias developed after CABG (p = .02). PCI-DES resulted in fewer in-hospital complications (p < .001) and shorter hospitalizations (p < .001). CONCLUSIONS: The long-term clinical outcomes of second-generation PCI-DES and CABG in patients with stable angina and isolated pLAD disease were comparable.

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.

Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study.

INTRODUCTION: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). METHODS: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. RESULTS: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays. CONCLUSIONS: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.

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.

Incidence and survival of gliomatosis cerebri: a population-based cancer registration study.

Gliomatosis cerebri (GC) comprises a rare widespread infiltrating growth pattern of diffuse gliomas. We explored the incidence patterns and survival rates of GC in a population-based registration sample from the Surveillance, Epidemiology and End, Results database (1973-2012). GC cases (n = 176) were identified based on their International Classification of Diseases in Oncology (ICD-O-3) morphology code (9381). We calculated age-adjusted incidence rates (AIR) and evaluated temporal trends. Survival was assessed with Kaplan-Meier curves and Cox regression models. The annual AIR of GC was 0.1/million. We noted increasing trends in the preceding registration years (1973-2002; annually, + 7%) and a tendency of clinical/radiological approaches to substitute the gold-standard histological assessment for diagnosis. GC was diagnosed in the entire age spectrum (range 1-98 years), but higher incidence rates (0.43/million) were noted among the elderly (≥ 65 years). A slight male preponderance was identified (male-to-female ratio: 1.4). Median overall survival was 9 months with a 5 year survival rate of 18%. Increasing age, primary tumor location not restricted to the cerebral hemispheres and rural residence at diagnosis were identified as negative prognostic factors, whereas receipt of radiotherapy, surgical treatment, race and method of diagnosis were not associated with outcome. This first comprehensive overview of GC epidemiology exemplifies the rarity of the disease, provides evidence for male preponderance and increased incidence among the elderly and shows lower survival rates compared to the published single center reports. Expansion of registration to histological and molecular characteristics would allow emergence of clinical prognostic factors at the population level.

Clinical, neuroimaging and histopathological features of gliomatosis cerebri: a systematic review based on synthesis of published individual patient data.

INTRODUCTION: Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating CNS tumor. As consistent disease features have not been established, the tumor comprises a diagnostic challenge. METHODS: We conducted a systematic literature search for published case reports and case series on patients with histologically confirmed GC. Clinical, diagnostic, neuroimaging, histopathological, and molecular data on individual or summary patient level were extracted and analyzed. RESULTS: A total of 274 studies were identified, including 866 patients with individual-level data and 782 patients with summary data (58.9% males, mean age 43.6 years). Seizures (49.8%) were the most common presenting symptom followed by headache (35.9%), cognitive decline (32.2%), and focal motor deficits (32%). Imaging studies showed bilateral hemisphere involvement in 65%, infratentorial infiltration in 29.9% and a focal contrast-enhanced mass (type II GC) in 31.1% of cases. MRI (extensive hyperintensities in T2/FLAIR sequences) and MR spectroscopy (elevated choline, creatinine, and myoinositol levels; decreased NAA levels) showed highly consistent findings across GC patients. Low-grade and anaplastic astrocytoma were the most prevalent diagnostic categories, albeit features of any histology (astrocytic, oligodendroglial, oligoastrocytic) and grade (II-IV) were also reported. Among molecular aberrations, IDH1 mutation and MGMT promoter methylation were the most commonly reported. Increasing time elapsed from symptom onset to diagnosis comprised the only independent determinant of the extent of CNS infiltration. CONCLUSION: A distinct clinical, neuroimaging, histopathological, or molecular GC phenotype is not supported by current evidence. MRI and MR spectroscopy are important tools for the diagnosis of the tumor before confirmation with biopsy.

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.

Recall of mobile phone usage and laterality in young people: The multinational Mobi-Expo study.

OBJECTIVE: To study recall of mobile phone usage, including laterality and hands-free use, in young people. METHODS: Actual mobile phone use was recorded among volunteers aged between 10 and 24 years from 12 countries by the software application XMobiSense and was compared with self-reported mobile phone use at 6 and 18 months after using the application. The application recorded number and duration of voice calls, number of text messages, amount of data transfer, laterality (% of call time the phone was near the right or left side of the head, or neither), and hands-free usage. After data cleaning, 466 participants were available for the main analyses (recorded vs. self-reported phone use after 6 months). RESULTS: Participants were on average 18.6 years old (IQR 15.2-21.8 years). The Spearman correlation coefficients between recorded and self-reported (after 6 months) number and duration of voice calls were 0.68 and 0.65, respectively. Number of calls was on average underestimated by the participants (adjusted geometric mean ratio (GMR) self-report/recorded = 0.52, 95% CI = 0.47-0.58), while duration of calls was overestimated (GMR=1.32, 95%, CI = 1.15-1.52). The ratios significantly differed by country, age, maternal educational level, and level of reported phone use, but not by time of the interview (6 vs. 18 months). Individuals who reported low mobile phone use underestimated their use, while individuals who reported the highest level of phone use were more likely to overestimate their use. Individuals who reported using the phone mainly on the right side of the head used it more on the right (71.1%) than the left (28.9%) side. Self-reported left side users, however, used the phone only slightly more on the left (53.3%) than the right (46.7%) side. Recorded percentage hands-free use (headset, speaker mode, Bluetooth) increased with increasing self-reported frequency of hands-free device usage. Frequent (≥50% of call time) reported headset or speaker mode use corresponded with 17.1% and 17.2% of total call time, respectively, that was recorded as hands-free use. DISCUSSION: These results indicate that young people can recall phone use moderately well, with recall depending on the amount of phone use and participants' characteristics. The obtained information can be used to calibrate self-reported mobile use to improve estimation of radiofrequency exposure from mobile phones.

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.

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.

Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US.

Pilocytic astrocytomas (PA) comprise the most common childhood central nervous system (CNS) tumor. Exploiting registry-based data from Southern and Eastern Europe (SEE) and SEER, US, we opted to examine incidence, time trends, survival and tentative outcome disparities of childhood PA by sociodemographic and clinical features. Childhood PA were retrieved from 12 SEE registries (N = 552; 1983-2014) and SEER (N = 2723; 1973-2012). Age-standardized incidence rates (ASR) were estimated and survival was examined via Kaplan-Meier and Cox regression analysis. ASR of childhood PA during 1990-2012 in SEE was 4.2/106, doubling in the USA (8.2/106). Increasing trends, more prominent during earlier registration years, were recorded in both areas (SEE: +4.1 %, USA: +4.6 %, annually). Cerebellum comprised the most common location, apart from infants in whom supratentorial locations prevailed. Age at diagnosis was 1 year earlier in SEE, whereas 10-year survival was 87 % in SEE and 96 % in SEER, improving over time. Significant outcome predictors were age <1 year at diagnosis diagnosis (hazard ratio, HR [95% confidence intervals]: 3.96, [2.28-6.90]), female gender (HR: 1.38, [1.01-1.88]), residence in SEE (HR: 4.07, [2.95-5.61]) and rural areas (HR: 2.23, [1.53-3.27]), whereas non-cerebellar locations were associated with a 9- to 12-fold increase in risk of death. The first comprehensive overview of childhood PA epidemiology showed survival gains but also outcome discrepancies by geographical region and urbanization pointing to healthcare inequalities. The worse prognosis of infants and, possibly, females merits further consideration, as it might point to treatment adjustment needs, whereas expansion of systematic registration will allow interpretation of incidence variations.

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.

Incidence and time trends of childhood lymphomas: findings from 14 Southern and Eastern European cancer registries and the Surveillance, Epidemiology and End Results, USA.

PURPOSE: To describe epidemiologic patterns of childhood (0-14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies. METHODS: Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990-2014; incidence rates were estimated and time trends were evaluated. RESULTS: Overall age-adjusted incidence rate was higher in SEE (16.9/106) compared to SEER (13.6/106), because of a higher incidence of Hodgkin (HL, 7.5/106 vs. 5.1/106) and Burkitt lymphoma (BL, 3.1 vs. 2.3/106), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/106 vs. 5.8/106), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE. CONCLUSIONS: Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes.

Comorbidity of Cognitive Impairment and Late-Life Depression Increase Mortality: Results From a Cohort of Community-Dwelling Elderly Individuals in Rural Greece.

OBJECTIVE: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece. METHODS: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders. RESULTS: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI. CONCLUSION: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.

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.