Safety of intravitreal chemotherapy in the management of retinoblastoma: A systematic review of the literature.

Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information.

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Orchidopexy for congenital cryptorchidism in childhood and adolescence and testicular cancer in adults: an updated systematic review and meta-analysis of observational studies.

Congenital cryptorchidism is a well-established risk factor of testicular malignancies. However, there is still remarkable variability in the measures of associations between of these two clinical entities. The current meta-analysis investigates the up-to-date risk of testicular cancer in adults with a history of surgically corrected congenital cryptorchidism until adolescence. The meta-analysis was conducted with strict criteria for the identification of the congenital cryptorchidism cases that underwent surgery before adulthood. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed and the Scopus databases was conducted, using a defined strategy, from inception to February 2023. Two independent authors screened the literature and extracted the data, using inclusion and exclusion criteria. Of the 2176 articles identified, 93 articles were fully retrieved, and 6 articles met all the inclusion criteria. The Newcastle-Ottawa scale was applied for the studies' quality assessment. The random-effects model in RevMan 5.4 program was used for the meta-analysis. Three case-control studies and three cohort studies were selected. They included 371,681 patients and 1786 incidents of testicular cancer. The pooled odds ratio (OR) was 3.99 (95% confidence intervals (CI): 2.80-5.71). The heterogeneity was moderate and estimated at 51% with the I-squared statistic. A forest plot and a funnel plot were produced to evaluate the ORs and the probable publication bias, respectively. The mean Newcastle-Ottawa score was 8/9 for all the included reports.  Conclusion: This systematic review and meta-analysis verifies, with an updated estimate, the increased risk of testicular cancer in adults with an orchidopexy history. New evidence on the maldescent laterality supports that the cancer risk remains increased and for the contralateral, unaffected testicle, although to a lesser extent. The orchidopexy in the first year of life prevents the testicular damage and decreases the overall cancer risk. What is Known: • Congenital cryptorchidism is the commonest genitourinary abnormality and a risk factor for testicular cancer. • The most recent meta-analysis reporting this association was in 2013. What is New: • After reviewing literature until February 2023, the association of congenital cryptorchidism with testicular cancer risk in adulthood was verified: odds ratio=3.99 [2.80-5.71], 95% CI. • The meta-analysis highlights the protective role of early orchidopexy and the controversial data about maldescent and testicular cancer laterality.

Treatment With Dupilumab in Patients With Atopic Dermatitis: Systematic Review and Meta-Analysis.

Atopic dermatitis (AD) is a type 2 chronic skin disorder associated with systemic and psychosocial comorbidities decreasing the quality of life for many patients. Dupilumab, a human monoclonal antibody that blocks interleukins IL-4 and IL-13, is a recently added systematic treatment option with an emerging evidence base. Here, we assessed the safety and efficacy of dupilumab in patients with AD. We conducted a systematic review and meta-analysis of placebo-controlled randomized clinical trials evaluating the safety and efficacy of dupilumab on AD-related outcomes including clinical symptoms, quality of life and adverse events (AE). Subgroup analysis was further performed in adults and children/adolescents. Fourteen trials were included: twelve in adults (n = 3,817) and two in children/adolescents (n = 618). Dupilumab decreased the Eczema Area Severity Index (EASI) score [standardized mean difference (SMD) = -0.98; 95% confidence interval (95% CI) = (-1.09, -0.88)], the percent change difference in Scoring Atopic Dermatitis (SCORAD) [mean difference (MD) = -31.56, 95% CI = (-33.75, -29.36)], and in pruritus Numeric Rating Scale (pNRS) [MD = -29.24, 95% CI = (-32.11, -26.37)]. It also achieved a reduction of at least ≥75% in the EASI score [Risk Ratio (RR) = 2.89, 95% CI = (2.47, 3.38)], the Investigator's Global Assessment (IGA) score ≤1 [RR = 3.47, 95% CI = (2.96, 4.06)] and eight additional endpoints with no signs of increased AE compared to placebo. In subgroup analysis, the results were concordant for both groups. Dupilumab improved clinical symptoms and quality of life in adults and children/adolescents with a safety profile comparable to placebo.

Supportive interventions for childhood cancer: An umbrella review of randomized evidence.

Therapeutic advancements have improved pediatric cancer prognosis, shifting the interest towards the management of psychosocial burden and treatment-related morbidity. To critically appraise the available evidence, we conducted an umbrella review of meta-analyses of randomized controlled trials on supportive interventions for childhood cancer. Thirty-four publications (92 meta-analyses, 1 network, 14,521 participants) were included. The most concrete data showed a reduction in procedure-related pain and distress through hypnosis. Moreover, exercise improved the functional mobility of the patients. Regarding pharmacological interventions, most of the meta-analyses pertained to the treatment of nausea/vomiting (ondansetron was effective) and infections/febrile neutropenia [granulocyte-(macrophage) colony-stimulating factors showed benefits]. Substantial heterogeneity was detected in 31 associations. Conclusively, supportive interventions for pediatric cancer are being thoroughly evaluated. However, most of the studies are small and of moderate quality, highlighting the need for more randomized evidence in order to increase precision in improving the quality of life of patients, survivors and their families.

Nutritional Status at Diagnosis as Predictor of Survival from Childhood Cancer: A Review of the Literature.

Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30-50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.

Incidence patterns of childhood non-Wilms renal tumors: Comparing data of the Nationwide Registry of Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST), Greece, and the Surveillance, Epidemiology, and End Results Program (SEER), USA.

BACKGROUND: We used, for the first time, data registered in the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)-Greece to estimate incidence/time trends of the rare childhood (0-14 years) non-Wilms tumors (non-WT), and compared the results of malignant non-WT to those from the Surveillance, Epidemiology, and End Results Program (SEER)-USA. METHODS: Fifty-five cases (n = 33 malignant-only) were extracted from NARECHEM-ST (2001-2020) and 332 malignant cases from SEER (1990-2017). To allow between-country comparisons, age-standardized incidence rates (AIR) of malignant-only non-WT were calculated, and temporal trends were evaluated using Poisson and joinpoint regressions. RESULTS: In NARECHEM-ST, malignant and non-malignant non-WT accounted for 22.6% of all renal tumors. Among malignant tumors, the AIR was 1.0/106 children in Greece, similar to that calculated for SEER, USA (AIR=0.9/106). The proportion of infant malignant and non-malignant non-WT was 27% (20% before 6 months) in NARECHEM-ST. Most common non-WT in Greece were congenital mesoblastic nephromas (CMN) diagnosed mainly in infancy (CIR=7.2/106). The proportion of infant malignant non-WT was 20% in SEER (AIRinfancy=2.5/106), mainly attributed to rhabdoid tumors (CIR=1.6/106). The male-to-female (M:F) ratio of malignant non-WT was 0.9 in NARECHEM-ST vs. 1.2 in SEER, whereas boys outnumbered girls with clear cell sarcoma in NARECHEM-ST (M:F=4.0). Lastly, significantly increasing trends in incidence rates were noted in NARECHEM-ST [+ 6.8%, 95% confidence intervals (CI): 0.5, 13.3] and in SEER (+7.3%, 95%CI: 5.6, 9.0). CONCLUSIONS: Observed incidence, time trends and sociodemographic variations of non-WT may reflect differential registration practices and healthcare delivery patterns including differences regarding surveillance, coding and treatment practices.

Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis.

Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08-2.85; ORpaternal: 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.

Therapeutic interventions for childhood cancer: An umbrella review of randomized evidence.

Treatment advancements in pediatric cancer have improved prognosis, but the strength of supporting evidence has not been thoroughly evaluated. To critically appraise it, we performed an umbrella review of meta-analyses of randomized controlled trials examining the efficacy and safety of therapeutic interventions for pediatric malignancies. Fourteen publications (68 meta-analyses, 31,496 participants) were eligible. Acute lymphoblastic leukemia (ALL) was investigated at most. Substantial heterogeneity was detected in 10 associations, with limited indications for small-study effects and excess-significance bias. The most concrete evidence pertained to the use of methotrexate and vincristine-prednisone pulses for ALL, improving event-free survival. Evidence regarding other cancers was relatively weak. Conclusively, we found few small meta-analyses focusing mainly on ALL. Randomized evidence stemming from adult populations still seems to serve as valuable indirect evidence backup. More randomized evidence and individual patient data meta-analyses are needed to increase certainty and precision in the care of pediatric cancer patients.

Overall and event-free survival of childhood lymphoma in Greece: analysis of harmonized clinical data over a 24-year active registration period.

We assessed event-free (EFS) and overall (OS) survival in 676 incident cases of childhood Hodgkin (HL) and non-Hodgkin (NHL) lymphoma actively registered in Greece (1996-2019). HL-OS5-year was 96% and NHL-OS5-year 85%, whereas HL-EFS5-year was 86% and NHL-EFS5-year was 81%, notably similar to the respective OS rates (HL: 95%, NHL: 85%) in developed countries. For HL, older age at diagnosis, high maternal education and close proximity to treatment centers were linked to remarkably favorable outcomes. By contrast, stage IV patients showed worse OS and EFS. HL patients with low levels of hemoglobin were associated with worse EFS (hazard ratio: 2.81, 95% confidence intervals: 1.09-7.22). OS (76%) and EFS (73%) were poor among high-risk NHL patients and those with increased LDH (71%). The identified predictors of poor disease outcome point to the need for intensification of individualized treatments. Ongoing clinical cancer registration entailing clinical components could contribute to use of state-of-the-art treatments.

Global mapping of overviews of systematic reviews in healthcare published between 2000 and 2020: a bibliometric analysis.

OBJECTIVE: To conduct a bibliometric analysis using a large sample of overviews of systematic reviews (OoSRs) and reveal research trends and areas of interest about these studies. STUDY DESIGN AND SETTING: We searched MEDLINE, Scopus and Cochrane Database of Systematic Reviews from 1/1/2000 to 15/10/2020. We used Scopus meta-data and two authors recorded supplementary information independently. We summarized the data using frequencies with percentages. RESULTS: A total of 1558 studies were considered eligible for analysis. We found that the publications have been increasing yearly and their nomenclature was not uniform (the most frequent label in the title was "overview of systematic reviews"). The largest number of papers and the most cited ones were published by corresponding authors from the UK. The publications were distributed across 737 scholarly journals and many of them were published in the field of complementary/alternative medicine, psychiatry/psychology, nutrition/dietetics, and pediatrics. The co-authorship analysis revealed collaborations among countries. The most common clinical conditions were depression, diabetes, cancer, dementia, pain, cardiovascular disease, stroke, obesity, and schizophrenia. CONCLUSION: OoSRs have recently become a popular approach of evidence synthesis. International collaborations between overview authors from countries with increased research productivity and countries with less research activity should be encouraged.

Social support, adherence to Mediterranean diet and physical activity in adults: results from a community-based cross-sectional study.

There is a growing recognition that social support can potentially exert consistent or opposing effects in influencing health behaviours. The present paper presents a cross-sectional study, including 2,064 adults from Italy, Spain and Greece, who were participants in a multi-centre randomised controlled trial (C4H study), aiming to examine whether social support is correlated with adherence to a healthy Mediterranean diet and physical activity. Social support data were available for 1,572 participants. The majority of the sample reported emotional support availability (84·5 %), financial support availability (72·6 %) and having one or more close friends (78·2 %). Mediterranean diet adherence was significantly associated with emotional support (P = 0·009) and social network support (P = 0·021). No statistically significant associations were found between participant physical activity and the social support aspects studied. In conclusion, emotional and social network support may be associated with increased adherence to the Mediterranean diet. However, further research is needed to evaluate the role of social support in adherence to healthy Mediterranean diet.

A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes.

Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural deterioration. Genetic pleiotropy occurs when a single genetic element is associated with more than one phenotype. We aimed to identify pleiotropic loci associated with bone mineral density (BMD) and nonbone phenotypes in genome-wide association studies. In the discovery stage, the NHGRI-EBI Catalog was searched for genome-wide significant associations (P value < 5 × 10-8), excluding bone-related phenotypes. SNiPA was used to identify proxies of the significantly associated single nucleotide polymorphisms (SNPs) (r 2 = 1). We then assessed putative genetic associations of this set of SNPs with femoral neck (FN) and lumbar spine (LS) BMD data from the GEFOS Consortium. Pleiotropic variants were claimed at a false discovery rate < 1.4 × 10-3 for FN-BMD and < 1.5 × 10-3 for LS-BMD. Replication of these genetic markers was performed among more than 400 000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound data. In the discovery stage, 72 BMD-related pleiotropic SNPs were identified, and 12 SNPs located in 11 loci on 8 chromosomes were replicated in the UK Biobank. These SNPs were associated, in addition to BMD, with 14 different phenotypes. Most pleiotropic associations were exhibited by rs479844 (AP5B1, OVOL1 genes), which was associated with dermatological and allergic diseases, and rs4072037 (MUC1 gene), which was associated with magnesium levels and gastroenterological cancer. In conclusion, 12 BMD-related genome-wide significant SNPs showed pleiotropy with nonbone phenotypes. Pleiotropic associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits.

Is brucellosis a great mimic of tuberculosis? A case report.

Tuberculosis (TB) can manifest prolonged fever or fever of unknown origin, especially when it is located extrapulmonary. We report a case of disseminated TB complicated by iliac bone osteolysis and a gluteal abscess in a 75-year-old female patient with fever and bone marrow dysplasia. Diagnosis of TB was made despite transient false-positive high-titer agglutination tests and ELISA antibodies to Brucella. The case presented shows that in a highly suggestive case of TB, positive agglutination tests or ELISA antibodies to Brucella should be interpreted with caution, and repeated testing should be performed to assess their persistence and fluctuation over time.

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.

Association between blood pressure and risk of cancer development: a systematic review and meta-analysis of observational studies.

With the exception of renal cell carcinoma, studies assessing the association between hypertension and other cancers are inconsistent. We conducted a meta-analysis to assess this evidence. We included observational studies investigating the association between any definition of hypertension or systolic and diastolic blood pressure and risk of any cancer, after searching PubMed until November 2017. We calculated summary relative risks (RR) and 95% confidence intervals (CI) using inverse-variance weighted random effects methods. A total of 148 eligible publications were identified out of 39,891 initially screened citations. Considering only evidence from 85 prospective studies, positive associations were observed between hypertension and kidney, colorectal and breast cancer. Positive associations between hypertension and risk of oesophageal adenocarcinoma and squamous cell carcinoma, liver and endometrial cancer were also observed, but the majority of studies did not perform comprehensive multivariable adjustments. Systolic and diastolic blood pressure were positively associated with risk of kidney cancer but not with other cancers. In addition to the previously well-described association between hypertension and risk of kidney cancer, the current meta-analysis suggested that hypertensive individuals may also be at higher risk of colorectal and breast cancer. However, careful interpretation is required as most meta-analyses included relatively small number of studies, several relative risks had weak or moderate magnitude and maybe affected by residual confounding.

Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium.

BACKGROUND: No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors. METHODS: We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs. We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates. We calculated population attributable fractions for smoking, body-mass index (BMI), physical activity, alcohol intake, type 2 diabetes and parity, use of hormone replacement therapy, and oral contraceptives in women. We calculated summary risk estimates across cohorts with pooled analysis and random-effects meta-analysis methods. FINDINGS: 223 880 men and women were followed up for a mean of 13 years (SD 6). 7724 (3·5%) participants developed an incident hip fracture, of whom 413 (5·3%) died as a result. 5964 DALYs (27 per 1000 individuals) were lost due to hip fractures, 1230 (20·6%) of which were in the group aged 75-79 years. 4150 (69·6%) DALYs were attributed to disability. Current smoking was the risk factor responsible for the greatest hip fracture burden (7·5%, 95% CI 5·2-9·7) followed by physical inactivity (5·5%, 2·1-8·5), history of diabetes (2·8%, 2·1-4·0), and low to average BMI (2·0%, 1·4-2·7), whereas low alcohol consumption (0·01-2·5 g per day) and high BMI had a protective effect. INTERPRETATION: Hip fracture can lead to a substantial loss of healthy life-years in elderly people. National public health policies should be strengthened to reduce hip fracture incidence and mortality. Primary prevention measures should be strengthened to prevent falls, and reduce smoking and a sedentary lifestyle. FUNDING: European Community's Seventh Framework Programme.

Evidence Suggesting the End of Universal Domestic Asbestos Exposure in Metsovo, NW Greece.

BACKGROUND: Inhabitants of Metsovo, NW Greece, had been domestically exposed to asbestos from a gradually abandoned whitewash ("luto") that resulted in a declining epidemic of malignant mesothelioma. OBJECTIVES: We aimed to evaluate whether other sources of asbestos exposure exist following "luto" abandonment. METHODS: Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were used to evaluate residual asbestos exposure in younger Metsovites through the identification of pleural calcifications and asbestos bodies, respectively. In order to provide a historical universally exposed group for comparison, we used the accumulated chest CTs and chest roentgenograms of our previous studies, performed in Metsovites with confirmed exposure but negative chest roentgenogram. As an additional external comparison group, we also assessed CT scans and chest roentgenograms of Metsovites being older than our target group obtained from the records of the Radiology Department between 2009 and 2011. In order to be able to compare our BAL findings, we sought historical controls among BAL studies performed in Metsovites with known exposure to "luto," in the 1980s-1990s, mainly to evaluate alveolitis. Those belonging to individuals of the same age range were used for further comparison. RESULTS: Twenty-two Metsovites born between 1960 and 1980 consented to undergo a chest CT scan, while another 14 CTs were retrieved from the records of the Radiology Department (among 86 of all ages), thus increasing the number of individuals studied to 36. Five of the 36 Metsovites studied were former "luto" users for a short period of time. Minimal pleural calcifications were present in 2 of them, while all chest CTs of nonusers were negative. All 8 BAL studies were negative for asbestos bodies. CONCLUSION: "Luto" use seems to have been the only source of considerable asbestos exposure in Metsovo.

Exposure to pesticides and diabetes: A systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus has a multifactorial pathogenesis with a strong genetic component as well as many environmental and lifestyle influences. Emerging evidence suggests that environmental contaminants, including pesticides, might play an important role in the pathogenesis of diabetes. OBJECTIVES: We performed a systematic review and meta-analysis of observational studies that assessed the association between exposure to pesticides and diabetes and we examined the presence of heterogeneity and biases across available studies. METHODS: A comprehensive literature search of peer-reviewed original research pertaining to pesticide exposure and diabetes, published until 30st May 2015, with no language restriction, was conducted. Eligible studies were those that investigated potential associations between pesticides and diabetes without restrictions on diabetes type. We included cohort studies, case-control studies and cross-sectional studies. We extracted information on study characteristics, type of pesticide assessed, exposure assessment, outcome definition, effect estimate and sample size. RESULTS: We identified 22 studies assessing the association between pesticides and diabetes. The summary OR for the association of top vs. bottom tertile of exposure to any type of pesticide and diabetes was 1.58 (95% CI: 1.32-1.90, p=1.21×10(-6)), with large heterogeneity (I(2)=66.8%). Studies evaluating Type 2 diabetes in particular (n=13 studies), showed a similar summary effect comparing top vs. bottom tertiles of exposure: 1.61 (95% CI 1.37-1.88, p=3.51×10(-9)) with no heterogeneity (I(2)=0%). Analysis by type of pesticide yielded an increased risk of diabetes for DDE, heptachlor, HCB, DDT, and trans-nonachlor or chlordane. CONCLUSIONS: The epidemiological evidence, supported by mechanistic studies, suggests an association between exposure to organochlorine pesticides and Type 2 diabetes.

Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.

OBJECTIVES: To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer. DESIGN: An umbrella review of the evidence across meta-analyses of observational studies of type 2 diabetes with risk of developing or dying from any cancer. DATA SOURCES: PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references. ELIGIBILITY CRITERIA: Meta-analyses or systematic reviews of observational studies in humans that examined the association between type 2 diabetes and risk of developing or dying from cancer. RESULTS: Eligible meta-analyses assessed associations between type 2 diabetes and risk of developing cancer in 20 sites and mortality for seven cancer sites. The summary random effects estimates were significant at P=0.05 in 20 meta-analyses (74%); and all reported increased risks of developing cancer for participants with versus without diabetes. Of the 27 meta-analyses, eventually only seven (26%) compiled evidence on more than 1000 cases, had significant summary associations at P ≤ 0.001 for both random and fixed effects calculations, and had neither evidence of small study effects nor evidence for excess significance. Of those, only six (22%) did not have substantial heterogeneity (I(2)>75%), pertaining to associations between type 2 diabetes and risk of developing breast, cholangiocarcinoma (both intrahepatic and extrahepatic), colorectal, endometrial, and gallbladder cancer. The 95% prediction intervals excluded the null value for four of these associations (breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer). CONCLUSIONS: Though type 2 diabetes has been extensively studied in relation to risk of developing cancer and cancer mortality and strong claims of significance exist for most of the studied associations, only a minority of these associations have robust supporting evidence without hints of bias.