The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people

Fostering global data sharing: Highlighting the recommendations of the Research Data Alliance COVID-19 working group

© 2020 Austin CC et al. The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community

The association of comorbidities with administration of adjuvant chemotherapy in stage III colon cancer patients: a systematic review and meta-analysis

BACKGROUND: Chemotherapy is an established treatment for stage III colon cancer cases. Older age is known to be associated with less chemotherapy use in these patients, but there might be other relevant factors besides age that influence treatment administration. We summarized evidence on associations between comorbidity and adjuvant chemotherapy administration in stage III colon cancer patients in a systematic review and meta-analysis. METHODS: We searched the PubMed and Web of Science databases up to 2 June 2020 for studies on comorbidities and chemotherapy use in patients with stage III colon cancer. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using random-effects models. Subgroup analyses according to year of colon cancer diagnosis, timing of comorbidity assessment, and geographical region were also conducted. RESULTS: Thirty-three studies were included in this review, including 219,406 stage III colon cancer patients overall. Chemotherapy administration was 60.9% (95% CI: 56.9% to 64.9%), increasing from 57.1% before 2001 to 66.3% after 2010. There were inverse associations between comorbidities and chemotherapy administration. Compared with patients with Charlson comorbidity score 0, those with scores 1 (OR = 0.79, 95% CI = 0.72–0.87) and 2+ (OR = 0.49, 95% CI = 0.42–0.56) received chemotherapy less often. Among comorbidities, the strongest predictors of chemotherapy non-use were dementia (OR = 0.37, 95% CI = 0.33–0.54), followed by heart failure (OR = 0.44, 95% CI = 0.28–0.70) and stroke (OR = 0.56, 95% CI = 0.38–0.81). CONCLUSIONS: Merely 60% of stage III colon cancer patients receive chemotherapy. Comorbidities are strong predictors of chemotherapy non-use, but the association differs by comorbid condition and is strongest with dementia. Given the survival disadvantage of colon cancer patients with comorbidities, further evidence on the risk–benefit ratio of chemotherapy according to the type and severity of comorbidity and on the extent to which the survival disadvantage of comorbidity is explained by less use or lower tolerability of chemotherapy is needed to foster personalized medical care in these patients

Associations between comorbidities and advanced stage diagnosis of lung, breast, colorectal, and prostate cancer: A systematic review and meta-analysis

Comorbidities and advanced stage diagnosis (ASD) are both associated with poorer cancer outcomes, but the association between comorbidities and ASD is poorly understood. We summarized epidemiological evidence on the association between comorbidities and ASD of selected cancers in a systematic review and meta-analysis. We searched PubMed and Web of Science databases up to June 3rd, 2021 for studies assessing the association between comorbidities and ASD of lung, breast, colorectal, or prostate cancer. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Also, potential variations in the associations between comorbidities and ASD by cancer type were investigated using random-effects meta-regression. Thirty-seven studies were included in this review, including 8,069,397 lung, breast, colorectal, and prostate cancer patients overall. The Charlson comorbidity index score was positively associated with ASD (stages III–IV) of breast cancer but was inversely associated with ASD of lung cancer (pinteraction = 0.004). Regarding specific comorbidities, diabetes was positively associated with ASD (OR = 1.17, 95%CI = 1.09–1.26), whereas myocardial infarction was inversely associated with ASD (OR = 0.84, 95%CI = 0.75–0.95). The association between renal disease and ASD differed by cancer type (pinteraction < 0.001). A positive association was found with prostate cancer (OR = 2.02, 95%CI = 1.58–2.59) and an inverse association with colorectal cancer (OR = 0.84, 95%CI = 0.70–1.00). In summary, certain comorbidities (e.g., diabetes) may be positively associated with ASD of several cancer types. It needs to be clarified whether closer monitoring for early cancer signs or screening in these patients is reasonable, considering the problem of over-diagnosis particularly relevant in patients with short remaining life expectancy such as those with comorbidities. Also, evaluation of the cost-benefit relationship of cancer screening according to the type and severity of comorbidity (rather than summary scores) may be beneficial for personalized cancer screening in populations with chronic diseases

Osteoprotegerin and Cardiovascular Events in High-Risk Populations: Meta-Analysis of 19 Prospective Studies Involving 27450 Participants

Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (CVD) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066 CVD events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias (P value from Egger's test=0.013). Correction for publication bias using the trim‐and‐fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03–1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow‐up. Conclusions In populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.peerReviewe

Pesticide contamination and associated risk factors at public playgrounds near intensively managed apple and wine orchards

BACKGROUND: Pesticide levels are generally monitored within agricultural areas, but are commonly not assessed at public places. To assess possible contamination of non-target areas, 71 public playgrounds located next to intensively managed apple and wine orchards were selected in four valleys of South Tyrol (northern Italy). Further, the impact of environmental site characteristics on the number and concentration of pesticides was assessed. Grass samples from the selected playgrounds were collected and screened for 315 pesticide residues using standard gas chromatography and mass spectrometry. RESULTS: Nearly half of the playgrounds (45%) were contaminated by at least one pesticide and a quarter (24%) by more than one. Eleven of the 12 different detected pesticides are classified as endocrine-active substances including the insecticide phosmet and the fungicide fluazinam showing the highest concentrations (0.069 and 0.26 mg kg−1, respectively). Additionally, one disinfectant and one preservation agent was found. Playgrounds in Venosta valley were most often contaminated (76% of all investigated playgrounds), highest concentrations were found in the Low Adige (2.02 mg kg−1). Pesticide concentrations were positively associated with areal proportion of apple orchards in the surroundings, the amount of rainfall and wind speed. In contrast, increasing global irradiance, opposite wind direction, increasing distance to agricultural sites and high wind speeds when pesticide application was not allowed were associated with decreasing pesticide contamination. CONCLUSION: This study is among the first investigating pesticide contamination of public playgrounds together with environmental factors in areas with pesticide-intensive agriculture at the beginning of the growing season. It is likely that playgrounds will be affected by more pesticides and higher concentrations over the course of the crop season. The result, that the majority of the detected pesticides are classified as endocrine active is worrisome as children are especially vulnerable. Hence, we recommend that pesticide risk assessments should better include protection measures for non-target areas

Longitudinal Associations Between Vitamin D Status and Cardiometabolic Risk Markers Among Children and Adolescents

CONTEXT: Vitamin D status has previously been associated with cardiometabolic risk markers in children and adolescents. In particular, it has been suggested that children with obesity are more prone to vitamin D deficiency and unfavorable metabolic outcomes compared with healthy-weight children. OBJECTIVE: To conduct a longitudinal study assessing this association in children and stratify by body mass index (BMI) category. METHODS: Children from the pan-European IDEFICS/I.Family cohort with at least one measurement of serum 25-hydroxyvitamin D [25(OH)D] at cohort entry or follow-up (n = 2171) were included in this study. Linear mixed-effect models were used to assess the association between serum 25(OH)D as an independent variable and z-scores of cardiometabolic risk markers (waist circumference, systolic [SBP] and diastolic blood pressure [DBP], high- [HDL] and low-density lipoprotein, non-HDL, triglycerides [TRG], apolipoprotein A1 [ApoA1] and ApoB, fasting glucose [FG], homeostatic model assessment for insulin resistance [HOMA-IR], and metabolic syndrome score) as dependent variables. RESULTS: After adjustment for age, sex, study region, smoking and alcohol status, sports club membership, screen time, BMI, parental education, and month of blood collection, 25(OH)D levels were inversely associated with SBP, DBP, FG, HOMA-IR, and TRG. The HOMA-IR z-score decreased by 0.07 units per 5 ng/mL increase in 25(OH)D. The 25(OH)D level was consistently associated with HOMA-IR irrespective of sex or BMI category. CONCLUSION: Low serum 25(OH)D concentrations are associated with unfavorable levels of cardiometabolic markers in children and adolescents. Interventions to improve vitamin D levels in children with a poor status early in life may help to reduce cardiometabolic risk

Effects of phytoestrogen supplementation on intermediate cardiovascular disease risk factors among postmenopausal women: a meta-analysis of randomized controlled trials.

IMPORTANCE Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women. OBJECTIVE Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women. EVIDENCE REVIEW Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form. FINDINGS In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (-0.27 mmol/L [-0.41 to -0.13]), low-density lipoprotein (-0.25 mmol/L [-0.37 to -0.13]), triglycerides (-0.20 mmol/L [-0.28 to -0.11]), and apolipoprotein B (-0.13 g/L [-0.23 to -0.03]) and with an increase in serum apolipoprotein A-1 (0.04 g/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (-18.86 ng/mL [-30.06 to -7.65]) and E-selectin (-2.32 ng/mL [-4.05 to -0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34 μm [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled. CONCLUSIONS AND RELEVANCE Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health. : Video Summary: http://links.lww.com/MENO/A593

Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children

Purpose Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. Methods This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. Results Children with 6 years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (beta = -0.11, 95% CI = -0.15 to -0.07). Conclusions IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children