National Institute for Health Development

Recent studies have suggested the involvement of brain RNA m6A methylation in stress response. One of the key players in the RNA m6A regulation is the demethylation catalysed by the fat mass and obesity-associated protein FTO, encoded by the fat mass and obesity-associated gene. Based on findings that experimental manipulation of the RNA m6A methylation in animal experiments can affect anxiety, and given that the C-allele of FTO rs1421085 had a significant association with indicators of overweight and obesity in our previous study, we have examined the possible association of FTO rs1421085 genotype with neuroticism in the same longitudinally observed sample. Data analysis included both birth cohorts of the Estonian Children Personality, Behaviour and Health Study (ECPBHS) that started in 1998/1999 when participants were 9 or 15 years old, respectively. Follow-ups were conducted at age 15, 18 and 25. Neuroticism at different ages was assessed with questionnaires of the five factor model. Statistically significant assocation between the FTO rs1421085 genotype and neuroticism emerged by age 25, with an additive effect of each T-allele. This association was largely based on females and was prominent in the older birth cohort at age 25, sampled during the Great Recession of 2007-2009. Conclusively, an overweight and obesity-related variant of FTO, the gene encoding an RNA m6A demethylase, was associated with lower neuroticism, this association being subject to gender and cohort effects.

Important questions remain regarding differences in geographical and age-specific mortality patterns as the COVID-19 pandemic evolved in consecutive waves, and how COVID-19 mortality compares to seasonal influenza. In a pandemic situation, excess all-cause mortality provides a more complete and robust measure than cause-specific mortality. Data submitted by 26 countries participating in the European Mortality Monitoring (EuroMOMO) network between 2020 and 2023 was analysed to quantify excess all-cause mortality during the COVID-19 pandemic. Excess mortality from this period was compared to previous influenza seasons from 2014 to 2019. Pooled estimates of excess mortality showed four main waves during the COVID-19 pandemic period, most markedly in people aged 65 years and above, with timing and magnitude that varied between countries. Here we show that prior to implementation of control measures and COVID-19 vaccination, excess mortality greatly exceeded typical seasonal influenza mortality, but later during the pandemic was at levels comparable to influenza.

IntroductionPrevalence of high risk human papillomavirus (hrHPV) and its subtypes by sociodemographic factors and the related cytological findings in the Estonian cancer screening population were examined, with the aim to improve cancer prevention.MethodsThis cross-sectional study included all women who participated in the Estonian cervical cancer screening programme from January 1, 2021 to January 31, 2022 and had a valid HPV test result reported to the Estonian Cancer Screening Registry (n = 37 537, aged 30, 35, 40, 45, 50, 55, 60, and 65). Limited sample (N = 18 784) within the total sample consisted of women who used self-sampling (N = 3535) or whose clinician collected sample was analysed using lab methodology that differentiates HPV16, 18, and 45. Data on HPV and cytology results were obtained from the Estonian Cancer Screening Registry, whereas data on education, nationality, and marital status were obtained from the Estonian Population Registry.ResultshrHPV was detected in the samples of 3307 (8.8%) women, and the prevalence was significantly higher in age groups under 40, in women with lower education, of Estonian nationality, and with no partner. The overall prevalence of HPV16 was 1.8%, ranging from 4.4% in 30-year-old women to 0.9% in 55-year-old women. The proportion of normal cytology was 50% among all hrHPV positive women and 35% in all HPV16 positive women, while it was 47% for HPV16 alone and 24% for HPV16 plus other hrHPV subtypes. The probability of normal cytology was significantly higher in women aged 50 and older compared to women aged 30 and 35 for total hrHPV and HPV16.ConclusionAll countries should monitor HPV prevalence across different age groups. As different HPV genotypes have a different oncogenic risk profile, extended or complete genotyping would help personalised risk-based screening approaches, with less health care costs, less harms, and a bigger net benefit. In addition, lab methodology should be harmonised.

Renal cancer (RC) presents a challenge with increasing incidence and mortality. This study compares RC cancer-specific survival (CSS) and overall survival (OS) based on histological type. This population-based retrospective cohort study covers 1995-2017, utilizing cases from the Finnish Cancer Registry. Comorbidity, procedure and treatment information from 1995-2018 were obtained from the national health care registry, while death data originated from the national death certificate registry. RC cases were categorized by histology to analyze CSS and OS via Fine and Gray's proportional sub-hazards model and Cox regression (adjusting for age, tumor extent, Charlson comorbidity index and treatment). The final cohort included 14,413 patients, predominantly ccRCC (75.5%), followed by papillary RCC (pRCC),5.8% and chromophobe RCC (chRCC) 2.1%. Univariate analysis showed better OS for non-ccRCC patients, with 5-year survival (5ySR) of 72.6% (95% CI 70.3-74.7%), compared to ccRCC (62.7%, 95%CI 61.8-63.5). Among non-ccRCC, the 5ySRs were as follows: pRCC 74.3% (95%CI 71.2-77.2), chRCC 82.2% (95% CI 77.2-86.1), sarcomatoid variants (sarcRC) 29.2% (95% CI 20.6-38.3), and collecting duct carcinoma (CDC) 23.5% (95%CI 7.3-44.9). Non-ccRCC showed improved CSS compared to ccRCC (sHR 0.69, 95% CI 0.60-0.78). Favorable CSS for chRCC (sHR 0.28, 95% CI 0.18-0.43) and pRCC (sHR 0.66, 95% CI 0.56-0.78), while sarcRC (sHR 1.83, 95% CI 1.36-2.46) and CDC (sHR 3.19, 95% CI 2.01-5.08) showed poorer CSS. Overall, non-ccRCC had a better prognosis, driven by pRCC and chRCC, whereas sarcRC and CDC had poor prognoses. CSS has improved over time, with a 62% reduction in death risk since 1995. Our results demonstrate that the histological subtype is a powerful predictor of survival. Histology should be used more in clinical decision-making. Having a histological confirmation would tailor the selection of treatment: surgical management for aggressive and ccRCC and conservative management for less aggressive histological types.

BackgroundSocioeconomic disparities in dietary behaviors are well-known, but underlying mechanisms are not fully understood. We investigated whether consumer attitudes toward dietary behaviors mediate the relationship between socioeconomic factors and diet quality.MethodsThis analysis included 4051 adult participants from eight European countries of the I.Family study (2013/2014). Dietary intake was assessed using a food frequency questionnaire, and diet quality was measured by adherence to dietary recommendations using the Healthy Dietary Adherence Score. Socioeconomic factors included education, income, and social vulnerabilities (migrant background, experiencing unemployment in the household, single parenthood). Structural equation modeling was used to model pathways between predictors, outcome, and mediators, which also allowed for accounting of the clustered study design, incorporating random intercepts for country.ResultsEducation and income were positively, and unemployment was negatively associated with diet quality. Attitudes reflecting favorable dietary behaviors were positively associated with diet quality, while unfavorable attitudes were inversely associated. Analysis of the path between socioeconomic factors and attitudes revealed a heterogeneous association pattern. Trusting food advertisements and frequently using ready-to-eat foods partially mediated the association between education, income, and diet quality. The association between single parenthood and diet quality was fully mediated by comparing food labels, valuing organic products, and using ready-to-eat foods.ConclusionOur findings suggest a mediating role of consumer attitudes in the association between socioeconomic factors and diet quality, but results were not consistent across socioeconomic factors. Our findings may inform the development of interventions and regulations promoting healthy diet, such as restricting food advertisments.

Understanding factors influencing clinical biomarkers is important for the prevention of chronic disease. This study aimed to estimate transitions of biomarker status from childhood to adolescence and to identify determinants of biomarker status in early life in a prospective children cohort. Our sample comprised 1295 children participating in the baseline (2007/08) and second follow-up examination (2013/14) of the multi-center IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS)/I.Family study. Clinical blood biomarkers including glycated hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, C-reactive protein (CRP), interleukin 6, ferritin, leptin and insulin-like growth factor 1 (IGF-1) were repeatedly measured in 2007/2008 (age range: 3.0 to <10.0 years) and in 2013/2014. Latent transition analysis was used to estimate biomarker statuses and transition probabilities; determinants of biomarker status were estimated using mixed-effects models. Four distinct biomarker statuses were identified: (1) "normal" (all biomarkers low/medium; except HDL-cholesterol; reference), (2) "low leptin/IGF-1/HbA1c", (3) "dyslipidemia/high leptin" and (4) "inflammation". Children classified as "low leptin/IGF-1/HbA1c" at baseline were most likely to stay in this status (89.8%) or to change to the "normal" status (10%) during follow-up. Compared to "normal" children, children classified as "low leptin/IGF-1/HbA1c" were less likely to have a family history of diabetes (0.26 [0.08;0.86]; odds ratio (OR) and 95% confidence interval) or hypertension (0.53 [0.29;0.99]) and the children (0.32 [0.27;0.38]) as well as their mothers (0.93 [0.88;0.98]) had a lower BMI. Children from families with low/medium education had a 55% [9%-119%] higher risk of being in the "dyslipidemia/high leptin" and 49% [1%-121%] higher risk of being in the "inflammation" status as compared to children in the "normal" status. Membership in a sports club reduced the latter risks by 28% [2%-47%] and 40% [17%-56%], respectively. European children showed distinct phenotypes for the investigated biomarkers. Especially parental characteristics like a family history of diabetes or hypertension, a high maternal BMI, or low/medium education were associated with unfavorable biomarker status in children.

Plant-based dietary patterns may reduce the risk of chronic diseases, but their benefits and risks in younger populations remain unclear due to variations in diet quality and nutrient adequacy. Robust tools to assess adherence to these patterns are essential. The aim of this study was to develop and validate three plant-based diet propensity (PBDP) scores - overall, healthy and unhealthy - to capture plant-based dietary patterns and assess their associations with nutrient intakes and health indicators in children, adolescents and adults. This cross-sectional study of children, adolescents and adults used data from the I.Family study (n = 15,780 participants) from eight European countries. Dietary intake was assessed using a food frequency questionnaire. The overall PBDP score was constructed by categorising all plant-based food groups as positive and animal-based food groups as negative. The healthy PBDP emphasised healthy plant-based food groups, whereas the unhealthy PBDP emphasised less healthy plant-based food groups. Validity was assessed through correlations with nutrient intakes and comparison across demographic groups. Associations with health indicators were also analysed. PBDP scores showed expected associations with nutrient intakes. Higher overall and healthy PBDP scores were observed in females, adults, individuals with higher parental educational levels and those from Belgium and Spain. The healthy PBDP score was associated with higher HDL cholesterol, improved bone stiffness and lower triglycerides. The unhealthy PBDP score was associated with lower HDL cholesterol in adults, but not in children or adolescents. PBDP scores describe plant-based dietary patterns across demographic groups and are valid and reliable in adults. The findings highlight challenges in assessing dietary patterns in children and adolescents. Future research should address these challenges to enhance the validity of PBDP scores in younger populations and further explore their potential in guiding dietary recommendations across all age groups.

Abstract Background: In comparative effectiveness research, treatment retention - i.e., the time from treatment start to treatment discontinuation - is an important indicator of treatment effectiveness for chronic illnesses. There is no agreement on the event that defines discontinuation. Commonly used are “last dose received”, “decision to discontinue”, or “first dose missed”, as well as mixtures of these in multi-source studies. For drugs administered less frequently than once daily as is the case for many disease-modifying anti-rheumatic drugs (DMARDs) used for the treatment of spondyloarthritis, retention as determined by these events can vary considerably. Our goal was to quantify the impact of the different definitions of discontinuation on conclusions drawn from treatment comparisons and to recommend a standardised definition. Methods: We utilised model-based simulations and real-world data from spondyloarthritis patients treated with tumour necrosis factor (TNF) inhibitors, DMARDs with a wide range of dosing intervals, in Europe. We compared the estimation of the hazard ratio of discontinuation between treatments with varying differences in dosing intervals for the different definitions of discontinuation. To accommodate interval-censored events we used linear transformation models. Results: The simulation revealed increasing differences in the estimated treatment hazard ratio based on time to “last dose received” or “first dose missed” compared to “decision to discontinue” with increasing differences in the dosing interval (up to 55 days). These differences were, however, small and further diminished with mixed events. No bias was observed when the time to “decision to discontinue” was analysed as interval-censored between the times to “last dose received” and “first dose missed” instead of as exactly observed. No clinically meaningful differences in estimated hazard ratios between TNF inhibitors with different dosing intervals (56 versus 7 days) were observed in the real-world data. Conclusions: The impact of the different treatment discontinuation definitions on comparative retention were found to be negligible. Nonetheless, we recommend to define retention as the time from treatment start to the decision to discontinue treatment. Is the timing of the decision unknown, retention can be analysed as interval-censored between the last dose received and the first dose missed using transformation models. Trial registration: Not applicable.