Safety and Efficacy of the Consumption of the Nutraceutical "Red Yeast Rice Extract" for the Reduction of Hypercholesterolemia in Humans: A Systematic Review and Meta-Analysis.

Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing hypercholesterolemia in humans. A systematic review and meta-analysis was conducted from January 2012 to May 2022. The search was strictly focused on clinical trials that examined the association between RYR extract consumption and parameters of the lipid profile in humans. Fourteen double-blinded clinical trials were identified. The interventions lasted 4-24 weeks. In most studies, there was one intervention group and one control group. RYR extract consumption statistically significantly reduced total cholesterol (mean absolute reduction: 37.43 mg/dL; 95% confidence interval [CI]: -47.08, -27.79) and low-density lipoprotein cholesterol (LDL-C; mean absolute reduction: 35.82 mg/dL; 95% CI: -43.36, -28.29), but not high-density lipoprotein cholesterol, triglycerides and apolipoproteins A-I and B. As regards the safety, RYR extract was considered a safe choice with neither threatening nor frequent side effects. The consumption of RYR extract by people with hypercholesterolemia was associated with statistically significant reduction in total cholesterol and LDL-C, whereas it was not associated with an increase in life-threatening side effects. Further research on specific subpopulations and outcomes could establish a consensus on determining the clinical benefits and potential risks, if any, of this nutraceutical.

Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality: a multiregister nationwide matched cohort study in Sweden.

BACKGROUND: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). METHODS: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. RESULTS: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. CONCLUSIONS: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. TRIAL REGISTRATION DETAILS: Not applicable.

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.

Fertility status in childhood cancer survivors of hematological malignancies: a systematic review.

Stunning advances in treatment modalities implemented in children with hematological malignancies have led to 5-year overall survival rates exceeding 85%. However, this growing population of long-term survivors has raised significant concerns about their fertility status throughout adulthood, while specific treatment- and non-treatment-related factors appear to possibly affect fertility through distinct mechanisms. We aimed to comprehensively review the published literature on the association between treatment-related factors and risk of impaired fertility in childhood hematological cancer survivors. We searched PubMed up to March 2021 to identify eligible studies published during the last two decades. A narrative synthesis of the results was performed, although no meta-analysis was feasible due to the small number of studies and the large heterogeneity of evidence. Five studies on 2020 survivors of childhood leukemia were deemed eligible. The qualitative data synthesis showed significant fertility deficits in survivors treated with cranial radiotherapy and chemotherapy for childhood leukemia. Two studies examined biochemical measures of reduced ovarian reserve, providing some evidence that the levels of anti-Müllerian hormone can be used as a proxy for diminished ovarian reserve. The current findings should facilitate the delivery of age- and gender-appropriate interventions to optimize reproductive outcomes in childhood hematological cancer survivors.

Earlier Age at Menarche Is Associated with Body Fat and Negative Body Image in Adult Life.

Earlier age at menarche is one of the well-documented antecedents of a range of adverse health effects in adulthood including obesity and psychopathological effects. Yet, few researchers have examined the potential association of menarcheal age with body fat distribution, self-perception, and body image. We retrospectively tested a sample (N = 392) of adult women (18-80 years) to examine the associations of age at menarche with body composition and body image indices. Analyses of covariance and multivariable logistic and linear regression were fitted adjusting for age, physical activity level, smoking, and alcohol consumption. Further adjustment was made for body mass index (BMI) and percentage of fat mass. Earlier age at menarche was associated with slightly increased odds of higher BMI and abdominal fat percentage; of note is the positive correlation with lower body composition indices including hip and calf circumferences/skinfolds. Additionally, earlier age at menarche was associated with higher scores in the negative body image scales, namely overweight preoccupation and self-classified weight, whereas lower risks were found for higher scores in the positive body image scales, namely appearance evaluation and body area satisfaction scales. These findings remained significant after correcting for body fat percentage. The present results showed positive associations for earlier age at menarche with gross indices of obesity with the associations mainly confined to distribution of body fat in the lower part of the body, whereas an increased risk of negative body image was also found. Future research could refine our understanding of the biological and psychological mechanisms underlying these associations.

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.

The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia.

BACKGROUND: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development. METHODS: Cases comprised 1,126 children (0-12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002-2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models. RESULTS: C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04-1.15; ORBCP-ALL: 1.09; 95% CI, 1.03-1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P < 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40-4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27-4.24; ORBCP-ALL: 2.37; 95% CI, 1.18-4.76). CONCLUSIONS: Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL. IMPACT: These findings encourage the exploration of potential preventive interventions. See related commentary by Wiemels and Gallant, p. 292.

Prevalence of visceral leishmaniasis among people with HIV: a systematic review and meta-analysis.

Leishmaniasis is a parasitic infection expressing different clinical phenotypes. Visceral leishmaniasis (VL) is considered an opportunistic infection among people with human immunodeficiency virus (HIV). The objective of this review was to identify published data on the prevalence of Leishmania spp. infection among PWH and to define particular determinants that affect critically the epidemiological characteristics of VL-HIV coinfection and, potentially, its burden on public health. Two independent reviewers conducted a systematic literature search until June 30, 2022. Meta-analyses were conducted using random-effects models to calculate the summary prevalence and respective 95% confidence intervals (CI) of leishmaniasis among PWH. Meta-regression analysis was performed to investigate the impact of putative effect modifiers, such as the mean CD4 cell count, on the major findings. Thirty-four studies were eligible, yielding a summary prevalence of 6% (95%CI, 4-11%) for leishmaniasis (n = 1583) among PWH (n = 85,076). Higher prevalence rates were noted in Asia (17%, 95%CI, 9-30%) and America (9%, 95%CI, 5-17%) than in Europe (4%, 95%CI, 2-8%). Prevalence rates were significantly mediated by the age, sex, and CD4 cell count of participants. Heterogeneity remained significant in all meta-analyses (p < 0.0001). In the majority of included studies, people were coinfected with HIV and Leishmania species associated with VL, as opposed to those associated with cutaneous leishmaniasis. No sign of publication bias was shown (p = 0.06). Our summary of published studies on leishmaniasis among PWH is important to provide prevalence estimates and define potential underlying factors that could guide researchers to generate and further explore specific etiologic hypotheses.

Differentiated mental health patterns in pregnancy during COVID-19 first two waves in Sweden: a mixed methods study using digital phenotyping.

To utilize modern tools to assess depressive and anxiety symptoms, wellbeing and life conditions in pregnant women during the first two waves of the COVID-19 pandemic in Sweden. Pregnant women (n = 1577) were recruited through the mobile application Mom2B. Symptoms of depression, anxiety and wellbeing were assessed during January 2020-February 2021. Movement data was collected using the phone's sensor. Data on Google search volumes for "Corona" and Covid-related deaths were obtained. Qualitative analysis of free text responses regarding maternity care was performed. Two peaks were seen for depressive symptoms, corresponding to the two waves. Higher prevalence of anxiety was only noted during the first wave. A moderating effect of the two waves in the association of depression, anxiety, and well-being with Covid deaths was noted; positive associations during the first wave and attenuated or became negative during the second wave. Throughout, women reported on cancelled healthcare appointments and worry about partners not being allowed in hospital. The association of mental health outcomes with relevant covariates may vary during the different phases in a pandemic, possibly due to adaptation strategies on a personal and societal/healthcare level. Digital phenotyping can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, and to adjust the support offered.

Central nervous system cystic echinococcosis: a systematic review.

Central nervous system (CNS) cystic echinococcosis (CE) is a rare disease caused by Echinococcus which especially exists in agricultural endemic areas. This condition is more frequent in the pediatric and adolescent population and it can be associated with hydatid cyst in other localizations. A literature search was conducted up to April 28, 2021 by two independent reviewers. This study focused on clinical, imaging, therapeutic features as well as on complications of CNS CE among children and adults. Fifteen studies from seven different countries were included. A significant prevalence in males (ranging from 51% to 100%) was observed with an average rate of 60%. CNS CE was mainly single and located in the parietal region. The predominant symptoms were those of increased intracranial pressure. All patients were treated surgically, and the most common post-surgical complication was cyst rupture (prevalence: [3.3-37.5%], average: 12.9%). Furthermore, the outcomes were worse amongst patients with cyst ruptures and multiple recurrences. The average proportion of deaths due to CNS CE was 5.6% (range: 2.5-14.8%). This review highlights the necessity of including CNS CE in the differential diagnosis of patients with cystic lesions, especially in those residing in endemic areas. Early gross total cyst removal is the mainstay of treatment yielding the best outcomes.

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.

Catheter-Associated Urinary Tract Infections, Bacteremia, and Infection Control Interventions in a Hospital: A Six-Year Time-Series Study.

Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections. Urine catheters are often reservoirs of multidrug-resistant (MDR) bacteria and sources of pathogens transmission to other patients. The current study was conducted to investigate the correlation between CAUTIs, MDR bacteremia, and infection control interventions, in a tertiary-care hospital in Athens, from 2013 to 2018. The following data were analyzed per month: 1. CAUTI incidence; 2. consumption of hand hygiene disinfectants; 3. incidence of isolation of MDR carrier patients, and 4.incidence of bacteremia/1000 patient-days [total resistant a.Gram-negative: carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae; b.Gram-positive: vancomycin-resistant Enterococci and methicillin-resistant Staphylococcus aureus]. The use of scrub disinfectant solutions was associated with decreased CAUTI rate in Total Hospital Clinics (OR: 0.97, 95% CI: 0.96−0.98, p-value: <0.001) and in Adults ICU (OR: 0.79, 95% CI: 0.65−0.96, p-value:0.018) while no correlation was found with isolation rate of MDR-carrier pathogens. Interestingly, an increase in total bacteremia (OR: 0.81, 95% CI: 0.75−0.87, p-value:<0.001) or carbapenem-resistant bacteremia correlated with decreased incidence of CAUTIs (OR: 0.96, 95% CI: 0.94−0.99, p-value: 0.008). Hand hygiene measures had a robust and constant effect on infection control, reducing the incidence of CAUTIs.

Gender dysphoria in twins: a register-based population study.

Both genetic and environmental influences have been proposed to contribute to the variance of gender identity and development of gender dysphoria (GD), but the magnitude of the effect of each component remains unclear. We aimed to examine the prevalence of GD among twins and non-twin siblings of individuals with GD, using data derived from a large register-based population in Sweden over the period 2001-2016. Register data was collected from the Statistics Sweden and the National Board of Health and Welfare. The outcome of interest was defined as at least four diagnoses of GD or at least one diagnosis followed by gender-affirming treatment. A total of 2592 full siblings to GD cases were registered, of which 67 were twins; age at first GD diagnosis for the probands ranged from 11.2 to 64.2 years. No same-sex twins that both presented with GD were identified during the study period. The proportion of different-sex twins both presenting with GD (37%) was higher than that in same-sex twins (0%, Fisher's exact test p-value < 0.001) and in non-twin sibling pairs (0.16%). The present findings suggest that familial factors, mainly confined to shared environmental influences during the intrauterine period, seem to contribute to the development of GD.

Ventilator-Associated Pneumonia, Multidrug-Resistant Bacteremia and Infection Control Interventions in an Intensive Care Unit: Analysis of Six-Year Time-Series Data.

Ventilator-associated pneumonia (VAP) occurs more than 48h after mechanical ventilation and is associated with a high mortality rate. The current hospital-based study aims to investigate the association between VAP rate, incidence of bacteremia from multidrug-resistant (MDR) pathogens, and infection control interventions in a single case mix ICU from 2013 to 2018. Methods: The following monthly indices were analyzed: (1) VAP rate; (2) use of hand hygiene disinfectants; (3) isolation rate of patients with MDR bacteria; and (4) incidence of bacteremia/1000 patient-days (total cases, total carbapenem-resistant cases, and carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae cases separately). Results: Time trends of infection control interventions showed increased rates in isolation of patients with MDR pathogens (p <0.001) and consumption of hand disinfectant solutions (p =0.001). The last four years of the study an annual decrease of VAP rate by 35.12% (95% CI: −53.52 to −9.41; p =0.01) was recorded, which significantly correlated not only with reduced trauma and cardiothoracic surgery patients (IRR:2.49; 95% CI: 2.09−2.96; p <0.001), but also with increased isolation rate of patients with MDR pathogens (IRR: 0.52; 95% CI: 0.27−0.99; p = 0.048), and hand disinfectants use (IRR: 0.40; 95% CI: 0.18−0.89; p =0.024). Conclusions: Infection control interventions significantly contributed to the decrease of VAP rate. Constant infection control stewardship has a stable time-effect and guides evidence-based decisions.

Cardiovascular outcomes in transgender individuals in Sweden after initiation of gender-affirming hormone therapy.

AIMS: We compared the incidence of cardiovascular disease (CVD) in transgender participants with a diagnosis of gender dysphoria (GD) with and without gender-affirming hormone therapy (GAHT) to the incidence observed in the general population. METHODS AND RESULTS: The population-based cohort included all individuals >10 years in Sweden linked to Swedish nationwide healthcare Registers (2006-16). Two comparator groups without GD/GAHT were matched (1:10) on age, county of residence, and on male and female birth-assigned sex, respectively. Cox proportional models provided hazard ratios (HRs) and 95% confidence intervals (CI) for CVD outcomes. Among 1779 transgender individuals [48% birth-assigned males (AMAB), 52% birth-assigned females (AFAB)], 18 developed CVD, most of which were conduction disorders. The incidence of CVD for AFAB individuals with GD was 3.7 per 1000 person-years (95% CI: 1.4-10.0). Assigned male at birth individuals with GD had an incidence of CVD event of 7.1 per 1000 person-years (95% CI: 4.2-12.0). The risk of CVD event was 2.4 times higher in AMAB individuals (HR: 2.4, 95% CI: 1.3-4.2) compared with cisgender women, and 1.7 higher compared with cisgender men (HR: 1.7, 95% CI: 1.0-2.9). Analysis limited to transgender individuals without GAHT yielded similar results to those with GAHT treatment. CONCLUSION: The incidence of CVD among GD/GAHT individuals was low, although increased compared with matched individuals without GD and similar to the incidence among GD/no GAHT individuals, thus not lending support for a causal relationship between treatment and CVD outcomes. Larger studies with longer follow-up are needed to verify these findings, as well as possible effect modification by comorbidity.

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

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.

Maternal lifestyle factors and risk of neuroblastoma in the offspring: A meta-analysis including Greek NARECHEM-ST primary data.

The etiology of childhood neuroblastoma remains largely unknown. In this systematic review and meta-analysis, we summarized and quantitatively synthesized published evidence on the association of maternal modifiable lifestyle factors with neuroblastoma risk in the offspring. We searched MEDLINE up to December 31, 2020 for eligible studies assessing the association of maternal smoking, alcohol consumption and nutritional supplementation during pregnancy with childhood (0-14 years) neuroblastoma risk. Random-effects models were run, and summary odds ratios (OR) and 95% confidence intervals (95% CI) on the relevant associations were calculated, including estimates derived from primary data (n = 103 cases and n = 103 controls) of the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) case control study (2009-2017) in Greece. Twenty-one eligible studies amounting 5163 cases participating in both case-control and cohort/linkage studies were included in the meta-analysis. Maternal smoking and alcohol consumption were not statistically significantly associated with neuroblastoma risk (summary ORsmoking: 1.08, 95% CI: 0.96-1.22, I2 =12.0%, n = 17 studies; summary ORalcohol: 1.01, 95% CI: 0.82-1.18, I2 =0.0%, n = 8 studies). By contrast, maternal vitamin intake during pregnancy was associated with significantly lower neuroblastoma risk (summary OR: 0.57, 95% CI: 0.34-0.95, I2 =58.9%, n = 4 studies). The results of the largest to-date meta-analysis point to an inverse association between vitamin intake during pregnancy and childhood neuroblastoma risk. Future longitudinal studies are needed to confirm and further specify these associations as to guide preventive efforts on modifiable maternal risk factors of childhood neuroblastoma.

Perinatal mental health: how nordic data sources have contributed to existing evidence and future avenues to explore.

PURPOSE: Perinatal mental health disorders affect a significant number of women with debilitating and potentially life-threatening consequences. Researchers in Nordic countries have access to high quality, population-based data sources and the possibility to link data, and are thus uniquely positioned to fill current evidence gaps. We aimed to review how Nordic studies have contributed to existing evidence on perinatal mental health. METHODS: We summarized examples of published evidence on perinatal mental health derived from large population-based longitudinal and register-based data from Denmark, Finland, Iceland, Norway and Sweden. RESULTS: Nordic datasets, such as the Danish National Birth Cohort, the FinnBrain Birth Cohort Study, the Icelandic SAGA cohort, the Norwegian MoBa and ABC studies, as well as the Swedish BASIC and Mom2B studies facilitate the study of prevalence of perinatal mental disorders, and further provide opportunity to prospectively test etiological hypotheses, yielding comprehensive suggestions about the underlying causal mechanisms. The large sample size, extensive follow-up, multiple measurement points, large geographic coverage, biological sampling and the possibility to link data to national registries renders them unique. The use of novel approaches, such as the digital phenotyping data in the novel application-based Mom2B cohort recording even voice qualities and digital phenotyping, or the Danish study design paralleling a natural experiment are considered strengths of such research. CONCLUSIONS: Nordic data sources have contributed substantially to the existing evidence, and can guide future work focused on the study of background, genetic and environmental factors to ultimately define vulnerable groups at risk for psychiatric disorders following childbirth.