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Simple Summary: Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertion mutations (Exon20ins) used to have poor outcomes after the failure of platinum-based therapies. Amivantamab, a drug that targets two proteins involved in NSCLC (EGFR/MET), was developed and studied in the CHRYSALIS clinical trial. This paper summarizes an analysis comparing outcomes for amivantamab from CHRYSALIS to the outcomes for a mix of treatments that were used in real-world clinical practice (real-world physician's choice [RWPC]). RWPC data were collected from hospitals across Europe in the CATERPILLAR real-world evidence (RWE) study. The outcomes of 114 patients from CHRYSALIS were compared to 55 lines of treatment (LOTs) from CATERPILLAR-RWE, accounting for differences in patient characteristics between the two populations. Overall, the results show that amivantamab was at least twice as good as RWPC for platinum pre-treated patients in terms of tumor response and survival rates. Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths in Europe, with low survival rates primarily due to late-stage diagnosis. Early detection can significantly improve survival rates, but lung cancer screening is not currently implemented in Italy. Many countries have implemented lung cancer screening programs for high-risk populations, with studies showing a reduction in mortality. This review aimed to identify key areas for establishing a lung cancer screening program in Italy. A literature search was conducted in October 2022, using the PubMed and Scopus databases. Items of interest included updated evidence, approaches used in other countries, enrollment and eligibility criteria, models, cost-effectiveness studies, and smoking cessation programs. A literature search yielded 61 scientific papers, highlighting the effectiveness of low-dose computed tomography (LDCT) screening in reducing mortality among high-risk populations. The National Lung Screening Trial (NLST) in the United States demonstrated a 20% reduction in lung cancer mortality with LDCT, and other trials confirmed its potential to reduce mortality by up to 39% and detect early-stage cancers. However, false-positive results and associated harm were concerns. Economic evaluations generally supported the cost-effectiveness of LDCT screening, especially when combined with smoking cessation interventions for individuals aged 55 to 75 with a significant smoking history. Implementing a screening program in Italy requires the careful consideration of optimal strategies, population selection, result management, and the integration of smoking cessation. Resource limitations and tailored interventions for subpopulations with low-risk perception and non-adherence rates should be addressed with multidisciplinary expertise. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis. Methods: We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared amitriptyline with placebo for migraine prophylaxis in adults. Our outcomes of interest were informed by the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in migraine days per month, migraine days per month, and adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB 2.0 tool and the certainty of evidence by using the GRADE approach. Results: Our search yielded 10.826 unique records, of which three trials (n = 622) were eligible for data synthesis and analysis. We found moderate certainty evidence that amitriptyline increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo (relative risk: 1.60 (95% CI 1.17 to 2.19); absolute risk difference: 165 more per 1,000 (95% CI 47 more to 327 more). We found moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.05 (95% CI 0.01 to 0.10); absolute risk difference: 50 more per 1,000 (95% CI 10 more to 100 more). Conclusions: Our meta-analysis showed that amitriptyline may have a prophylactic role in migraine patients, however these results are far from robust. This warrants further large-scale research to evaluate the role of amitriptyline in migraine prevention. [ABSTRACT FROM AUTHOR]

Background WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level. Methods We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rateor time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years. Results The overall pooled influenza-associated hospitalisation rate was 40.5 (95% confidence interval (CI) = 24.3-67.4) per 100 000 persons, with rates varying substantially by age: 224.0 (95% CI = 118.8-420.0) in children aged 0-4 years and 96.8 (95% CI = 57.0-164.3) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates). Conclusions Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years. [ABSTRACT FROM AUTHOR]

Background To address social inequalities in adolescent substance use and consequent disparities in health, it is important to identify the mechanisms of the association between substance use and academic performance. We study the role of health literacy (HL) in the association between academic performance and weekly smoking, monthly alcohol use and cannabis ever-use among adolescents in Europe. Methods SILNE-R school survey data, which was collected in 2016–17 with paper-and-pencil-method from Hanover (GE), Amersfoort (NL) and Tampere (FI), were used (N  = 5088, age 13–19). Health Literacy for School-aged Children instrument was used to assess students' HL. Logistic regression analyzed the association of substance use with academic performance and HL, separately and in the same model. Linear and multinomial logistic regression analyzed the association between academic performance and HL. Results Poor academic performance compared with high was associated with smoking [odds ratio (OR) 3.94, 95% confidence interval (CI) 2.83–5.49], alcohol use (OR: 2.94, 95% CI: 2.34–3.68) and cannabis use (OR: 2.56, 95% CI: 1.89–3.48). Poor HL was also associated with each substance use (with ORs of 2.32, 1.85 and 1.29). HL was positively associated with academic performance (β = 1.04, 95% CI: 0.89–1.20). The associations between academic performance and substance use were only slightly attenuated after controlling for HL. Conclusions Academic performance and HL were both determinants of substance use, confirming their role in tackling the disparities in substance use. However, HL did not demonstrably mediate the association between academic performance and substance use. A wider set of factors needs to be tackled to address emerging social inequalities in adolescent substance use. [ABSTRACT FROM AUTHOR]

Background Diabetes is more prevalent among overweight/obese individuals, but has become a significant public health challenge among normal-weight populations. In this meta-analysis, we aimed to estimate diabetes/prediabetes incidence and its temporal trends by weight status. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched until 8 December 2021. Prospective cohort studies reporting diabetes incidence by baseline body mass index (BMI) categories in adults were included. The median year of data collection was used to assess the temporal trends. Subgroup analyses and meta-regression were also performed. Results We included 94 studies involving 3.4 million adults from 22 countries. The pooled diabetes incidence in underweight, normal-weight, and overweight/obese adults was 4.5 (95% confidence interval (CI)=2.8-7.3), 2.7 (95% CI=2.2-3.3), and 10.5 (95% CI=9.3-11.8) per 1000 person-years, respectively. The diabetes incidence in low- and middle-income countries (LMICs) was higher than in high-income countries among normal-weight (5.8 vs 2.0 per 1000 person-years) or overweight/obese (15.9 vs 8.9 per 1000 person-years) adults. European and American regions had a higher diabetes incidence than the non-Western areas, regardless of weight status. Underweight diabetes incidence decreased significantly from 1995-2000 to 2005-2010. Diabetes incidence in normal-weight populations has increased continuously since 1985 by an estimated 36% every five years. In overweight/obese adults, diabetes incidence increased between 1985-1990 and 1995-2000, stabilised between 2000 and 2010, and spiked suddenly after 2010. Conclusions Diabetes incidence and its temporal trends differed by weight status. The continuous upward trend of diabetes incidence among overweight/obese individuals requires urgent attention, particularly in LMICs. Furthermore, diabetes among normal-weight individuals is becoming a significant public health problem. [ABSTRACT FROM AUTHOR]

Background: Elevated rates of suicidal behavior were reported during the COVID-19 pandemic. However, information is scarce on patients' profiles during this period. Studies evoke the potential adverse effects of the mandatory lockdown, but they remain relatively speculative. Methods: We monitored fluctuations in suicide attempts (SA) in six European countries. We gathered data, retrospectively for under 18-year-old SA episodes (1 January 2018 to 31 December 2021), through records of psychiatric emergency services. We collected clinical profiles individually. We extracted environmental indicators by month, as provided by Oxford COVID-19 Government Response Tracker (OxCGRT). We used the Pruned Exact Linear Time (PELT) method to identify breakpoints in SA episodes reported for each country, and logistic regressions to estimate changes in patients' characteristics after the breakpoints. Finally, we used a univariate and multivariate negative binomial model to assess the link between SA and OxCGRT indicators, accounting for the delay (lag) between the interventions and their impact on SA. Results: The study comprised 2,833 children and adolescents (mean age = 15.1 years (SD 1.6); M: F sex-ratio = 1:5.4). A significant increase in SA was found either 6 or 10 months after the beginning of the pandemic, varying by country. Patients were more likely to be girls (aOR = 1.77 [1.34; 2.34]) and used SA methods "other than self-poisoning" (aOR = 1.34 [1.05; 1.7]). In the multivariate model, an association was found between SA and the contact tracing indicator with an 11 months delay, and the number of COVID-19 deaths with a 3-months delay. Conclusions: Findings confirmed a delayed increase in SA during the COVID-19 pandemic in children and adolescents as well as changes in patients' profiles. The duration and severity of the pandemic emerged as the strongest predictor in the rise of SA. If faced with a similar pandemic in the future, the gap between the onset of pandemic and the increase in suicide attempts presents an opportunity for prevention. [ABSTRACT FROM AUTHOR]

Background Social inequalities in multimorbidity may occur due to familial and/or individual factors and may differ between men and women. Using population-based multi-generational data, this study aimed to (1) assess the roles of parental and individual education in the risk of multimorbidity and (2) examine the potential effect modification by sex. Methods Data were analysed from 62 060 adults aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 European countries. Intergenerational educational trajectories (exposure) were High–High (reference), Low–High, High–Low and Low–Low, corresponding to parental–individual educational attainments. Multimorbidity (outcome) was ascertained between 2013 and 2020 as self-reported occurrence of ≥2 diagnosed chronic conditions. Inequalities were quantified as multimorbidity-free years lost (MFYL) between the ages of 50 and 90 and estimated via differences in the area under the standardized cumulative risk curves. Effect modification by sex was assessed via stratification. Results Low individual education was associated with higher multimorbidity risk regardless of parental education. Compared to the High–High trajectory, Low–High was associated with −0.2 MFYL (95% confidence intervals: −0.5 to 0.1), High–Low with 3.0 (2.4–3.5), and Low–Low with 2.6 (2.3–2.9) MFYL. This pattern was observed for both sexes, with a greater magnitude for women. This effect modification was not observed when only diseases diagnosed independently of healthcare-seeking behaviours were examined. Conclusions Individual education was the main contributor to intergenerational inequalities in multimorbidity risk among older European adults. These findings support the importance of achieving a high education to mitigate multimorbidity risk. [ABSTRACT FROM AUTHOR]

Background: Performing cardiovascular and cancer screenings in target populations can reduce mortality. Visiting a General Practitioner (GP) once a year is related to an increased likelihood of preventive care. The aim of this study was to analyse the influence of visiting a GP in the last year on the delivery of preventive services based on sex and household income. Methods: Cross-sectional study using data collected from the European Health Interview Survey 2013–2015 of individuals aged 40–74 years from 29 European countries. The variables included: sociodemographic factors (age, sex, and household income (HHI) quintiles [HHI 1: lowest income, HHI 5: more affluent]), lifestyle factors, comorbidities, and preventive care services (cardiometabolic, influenza vaccination, and cancer screening). Descriptive statistics, bivariate analyses and multilevel models (level 1: citizen, level 2: country) were performed. Results: 242,212 subjects were included, 53.7% were female. The proportion of subjects who received any cardiometabolic screening (92.4%) was greater than cancer screening (colorectal cancer: 44.1%, gynaecologic cancer: 40.0%) and influenza vaccination. Individuals who visited a GP in the last year were more prone to receive preventive care services (cardiometabolic screening: adjusted OR (aOR): 7.78, 95% CI: 7.43–8.15; colorectal screening aOR: 1.87, 95% CI: 1.80–1.95; mammography aOR: 1.76, 95% CI: 1.69–1.83 and Pap smear test: aOR: 1.89, 95% CI:1.85–1.94). Among those who visited a GP in the last year, the highest ratios of cardiometabolic screening and cancer screening benefited those who were more affluent. Women underwent more blood pressure measurements than men regardless of the HHI. Men were more likely to undergo influenza vaccination than women regardless of the HHI. The highest differences between countries were observed for influenza vaccination, with a median odds ratio (MOR) of 6.36 (under 65 years with comorbidities) and 4.30 (over 65 years with comorbidities), followed by colorectal cancer screening with an MOR of 2.26. Conclusions: Greater adherence to preventive services was linked to individuals who had visited a GP at least once in the past year. Disparities were evident among those with lower household incomes who visited a GP. The most significant variability among countries was observed in influenza vaccination and colorectal cancer screening. [ABSTRACT FROM AUTHOR]

Meal timing has been associated with metabolic markers in adults, but not in children or adolescents. The aim of this study was to investigate associations of meal timing patterns (MTPs) with insulin resistance (IR) and triglyceride levels in children and adolescents. In this cross-sectional study, we included 2,195 participants aged 8–15 years from the European I.Family study (2013/14). Habitual diet exposures were derived using 24-hr dietary recalls and HOMA-IR, HbA1c, and triglycerides were used as metabolic outcome variables. We applied k-means cluster analysis on five dietary exposures (energy proportion in the morning and evening, eating window, pre-sleep fasting and eating frequency), which revealed the following three MTPs: "early-often", "late-long" and "late-infrequent-short". We used linear mixed models to estimate the associations between MTPs and the z-scores of the metabolic outcome variables. The association analysis revealed differences between MTPs in HOMA-IR but not in HbA1c or triglyceride z-scores. The "late-infrequent-short" pattern was associated with a 0.19 (95%-CI: (0.01, 0.36)) higher HOMA-IR z-score compared to the "early-often" pattern in the model adjusted for age, BMI z-score, education, sex, country, and family membership. These findings suggest that the timing of meals may influence IR already in childhood and adolescence. Therefore, the time of meals should be considered in future nutrition research and dietary advice for children and adolescents. [ABSTRACT FROM AUTHOR]

Simple Summary: Females with PTEN Hamartoma Tumor Syndrome (PHTS) have very high hereditary breast cancer risks up to 76%. The aim of this European cohort study was to the describe the lifestyle in PHTS patients and to assess associations between physical activity, alcohol consumption, tobacco smoking, BMI and breast cancer in female adult PHTS patients. It was observed that of 125 patients who completed the questionnaire, 81% were ≥2 times/week physically active, 86% consumed on average <1 glass of alcohol/day, 78% never smoked and most patients were overweight or obese (72%). In total, 39 developed breast cancer (31%). No indications were found that associations between lifestyle and breast cancer in PHTS patients are different from the general population. These findings suggest that awareness about lifestyle among PHTS patients is important, as a healthier lifestyle could potentially decrease their breast cancer risk in a similar way as for the general population. Females with PTEN Hamartoma Tumor Syndrome (PHTS) have breast cancer risks up to 76%. This study assessed associations between breast cancer and lifestyle in European female adult PHTS patients. Data were collected via patient questionnaires (July 2020–March 2023) and genetic diagnoses from medical files. Associations between lifestyle and breast cancer were calculated using logistic regression corrected for age. Index patients with breast cancer before PHTS diagnosis (breast cancer index) were excluded for ascertainment bias correction. In total, 125 patients were included who completed the questionnaire at a mean age of 44 years (SD = 13). This included 21 breast cancer indexes (17%) and 39 females who developed breast cancer at 43 years (SD = 9). Breast cancer patients performed about 1.1 times less often 0–1 times/week physical activity than ≥2 times (ORtotal-adj = 0.9 (95%CI 0.3–2.6); consumed daily about 1.2–1.8 times more often ≥1 than 0–1 glasses of alcohol (ORtotal-adj = 1.2 (95%CI 0.4–4.0); ORnon-breastcancer-index-adj = 1.8 (95%CI 0.4–6.9); were about 1.04–1.3 times more often smokers than non-smokers (ORtotal-adj = 1.04 (95%CI 0.4–2.8); ORnon-breastcancer-index-adj = 1.3 (95%CI 0.4–4.2)); and overweight or obesity (72%) was about 1.02–1.3 times less common (ORtotal-adj = 0.98 (95%CI 0.4–2.6); ORnon-breastcancer-index-adj = 0.8 (95%CI 0.3–2.7)). Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients' breast cancer risk is important. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether a hypothetical intervention targeting either psychosocial well-being or emotion-driven impulsiveness is more effective in reducing unhealthy food choices. Therefore, we aimed to compare the (separate) causal effects of psychosocial well-being and emotion-driven impulsiveness on European adolescents' sweet and fat propensity. Methods: We included 2,065 participants of the IDEFICS/I.Family cohort (mean age: 13.4) providing self-reported data on sweet propensity (score range: 0 to 68.4), fat propensity (range: 0 to 72.6), emotion-driven impulsiveness using the UPPS-P negative urgency subscale, and psychosocial well-being using the KINDLR Questionnaire. We estimated, separately, the average causal effects of psychosocial well-being and emotion-driven impulsiveness on sweet and fat propensity applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). Further, we investigated a potential indirect effect of psychosocial well-being on sweet and fat propensity mediated via emotion-driven impulsiveness using a causal mediation analysis. Results: If all adolescents, hypothetically, had high levels of psychosocial well-being, compared to low levels, we estimated a decrease in average sweet propensity by 1.43 [95%-confidence interval: 0.25 to 2.61]. A smaller effect was estimated for fat propensity. Similarly, if all adolescents had high levels of emotion-driven impulsiveness, compared to low levels, average sweet propensity would be decreased by 2.07 [0.87 to 3.26] and average fat propensity by 1.85 [0.81 to 2.88]. The indirect effect of psychosocial well-being via emotion-driven impulsiveness was 0.61 [0.24 to 1.09] for average sweet propensity and 0.55 [0.13 to 0.86] for average fat propensity. Conclusions: An intervention targeting emotion-driven impulsiveness, compared to psychosocial well-being, would be marginally more effective in reducing sweet and fat propensity in adolescents. [ABSTRACT FROM AUTHOR]

Background: Emerging research suggests that physical activity among children and adolescents decreased during the COVID-19 pandemic. However, a differentiated overview of European youth is lacking. In particular, no systematic analysis has been conducted to date on the impact of heterogeneous pandemic restrictions and school closures within European countries, and with regard to potentially vulnerable groups. Methods: We searched seven databases and included studies for children and adolescents (≤ 19 years) of the WHO European Region that compared physical activity during the COVID-19 pandemic with a pre-pandemic baseline using validated measurement instruments. We used the Oxford Stringency Index and School Closure Index as indicators of restriction stringency. Screening for eligibility, data extraction, assessment of the study risk of bias (using the 'Risk of Bias in Non-randomized Studies - of Exposure' [ROBINS-E]) and certainty grading of evidence (using the GRADE approach), were all done in duplicate. Unpublished data was requested from study authors. Data were pooled in random effects models. An a priori protocol was published, reporting is carried out in accordance with the 'Preferred Reporting Items for Systematic Review and Meta-Analyses' (PRISMA) statement. Results: Of 14,897 non-duplicate records, 26 publications (n = 15,038 pre-pandemic, n = 13,041 during pandemic) met full inclusion criteria. Comparison before and during the COVID-19 pandemic revealed a significant reduction in total physical activity (standardized mean difference [SMD], -0.57 [95%CI, -0.95; -0.20]) and moderate-to-vigorous physical activity (SMD, -0.43 [95% CI, -0.75; -0.10]), corresponding to a decrease of 12 min per day (a 20% reduction of the WHO recommendation). A decrease in sporting activity was also recorded. Subgroup analyses suggested that middle childhood (aged 8–12) and adolescents were particularly affected by the decline. School closures were associated with a reduction in physical activity. The certainty of evidence for all outcomes was low. Conclusions: A sharp decline in all forms of physical activity was recorded among European children and adolescents during the COVID-19 pandemic. This decline was higher during periods of school closure and mainly affected younger schoolchildren and adolescents. Immediate action by policy-makers and practitioners, as well as evidence-based public health strategies, are imperative in reversing this trend. Trial registration: PROSPERO: CRD42023395871 [ABSTRACT FROM AUTHOR]

Background Many countries have sought to incentivise soft drinks manufacturers to reduce sugar in their products as part of efforts to address a growing prevalence of obesity. Are their policies effective? Methods Using a difference-in-differences design, we compared trends in the sugar content of 10 695 new sugar-sweetened beverages (SSB) launched between 2010 and 2019 in six European markets, including the UK and France (taxes designed to incentivise reformulation), the Netherlands (policy based on voluntary agreements to reduce sugar), Germany, Italy and Spain (no national policies). Results The announcement in 2016 and adoption in 2018 of the UK tax led to yearly reductions in average sugar content of 17% (95% CI: 15–19%) to 31% (13–48%) between 2016 and 2019, compared to 2015, while the 2018 French tax produced a 6% (95% CI: 5–7%) sugar reduction only in 2018, compared to 2017, shortly after it was redesigned to provide a stronger incentive for reformulation. Voluntary agreements implemented in the Netherlands in 2014 led to an 8% (95% CI: 4–13%) sugar reduction only in 2015, compared to 2013. Conclusion The analysis supports the conclusions that sugar reductions in new SSBs have been greater in countries that have adopted specific policies to encourage them; a sugar-based tax design encourages more sugar reductions than a volume-based tax design; the tax rate and the amount of the tax reduction from switching to the next lower tier in a sugar-based tax design may be critical to incentivize reformulation. [ABSTRACT FROM AUTHOR]

Background Governments across Europe deployed non-pharmaceutical interventions to mitigate the spread of coronavirus disease 2019 (COVID-19), which not only showed clear benefits but also had negative consequences on peoples' health. Health inequalities increased, disproportionally affecting people with higher age or lower education. This study analyzed associations between social factors and worsened self-rated health of elderly people in the course of the COVID-19 pandemic, taking different stringencies of government mandates as well as infection rates into account. Methods Data stem from the European SHARE survey. The main outcome was a binary indicator of worsened self-rated health. Analyses included data from two waves (2020 and 2021) during the pandemic (N  = 48 356 participants, N = 96 712 observations). Predictors were age, sex, education and living together with a partner, and two macro indicators that reflected the stringency of government response mandates and COVID-19 infection rates. Data were analyzed using logistic mixed-effects regression models. Results Older age [odds ratio (OR) 1.73, confidence interval (CI) 1.65–1.81] and female sex (OR 1.26, CI 1.20–1.32) were positively associated and higher education (OR 0.74, CI 0.70–0.79) was negatively associated with worsened self-rated health. Not living together with a partner showed higher odds of worsened self-rated health (OR 1.30, CI 1.24–1.36). Inequalities increased from 2020 to 2021. Associations between worsened self-rated health and government response mandates or infection rates were inconsistent. Conclusion Self-rated health worsened in the course of the pandemic and health disparities increased. Possible future pandemics require targeted interventions to minimize adverse health outcomes, in particular among old, potentially isolated, and deprived people. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible. METHODS: We harmonized the study populations to individuals 65+ years of age, applied the same satellite-derived PM2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF). RESULTS: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5-μg/m³ increase in PM2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. [ABSTRACT FROM AUTHOR]

Background: The SLC30A8 gene encodes zinc transporter-8 (ZnT8), highly expressed in insulin-secreting pancreatic beta cells, and may contribute to insulin processing and secretion. The SNP 13266634C/T (R325W change) in the SLC30A8 gene has been associated with type 2 diabetes (T2D) development. Genome-wide association studies and subsequent population studies including Europeans and Asians have demonstrated that the rare allele T (Trp325) of SNP 13266634 in the SLC30A8 gene is protective against T2D. Aim: We aimed to investigate whether the SNP rs13266634C/T is associated with T2D and its phenotypes in Turkey, which geographically connects Asia and Europe. Materials and methods: In our study, 650 nonobese individuals (366 T2D and 284 healthy individuals) were enrolled. Target SNP was genotyped by real-time PCR using the LightSNiP Genotyping Assay System. Results: The frequency of the T allele was lower in the T2D group than in the healthy control group (14.6% vs. 24.5%, respectively). The rare variant T of SNP rs13266634 in SLC30A8, located in the last exon of the gene, is associated with an increased c-peptide level, and it was 47.2% protective against type 2 diabetes compared to the C allele (OR = 0.528, 95% CI: 0.399–0.699, p <.001). Conclusions: Our findings indicate consistently with other studies that a rare variant of rs13266634C/T is protective against T2D, as the related first report in the nonobese Turkish population. Comprehensive studies to better understand the envisaged vital molecular role of SLC30A8 in pancreatic beta cells may contribute to developing therapeutic approaches. [ABSTRACT FROM AUTHOR]

We describe a new method for presenting and interpreting linear trends in health inequalities, and present a proof-of-concept analysis of inequalities in smoking among adolescents in Europe. We estimated the regression line of the assumed linear relationship between smoking prevalence in low– and high–socioeconomic status (SES) youth over time. Using simulation, we constructed a 95% confidence interval (CI) for the smoking prevalence in low-SES youth for when this would be 0% in high-SES youth, and we calculated the likelihood of eradicating smoking inequality (<5% for both low and high SES). This method was applied to data on adolescents aged 15–16 years (n  = 250,326) from 23 European countries, derived from the 2003–2015 European Survey Project on Alcohol and Other Drugs. Smoking prevalence decreased more slowly among low- than among high-SES adolescents. The estimated smoking prevalence was 9.4% (95% CI: 6.1, 12.7) for boys and 5.4% (95% CI: 1.4, 9.2) for girls with low SES when 0% with high SES. The likelihood of eradicating smoking inequality was <1% for boys and 37% for girls. We conclude that this novel methodological approach to trends in health inequalities is feasible in practice. Applying it to trends in smoking inequalities among adolescents in Europe, we found that Europe is currently not on track to eradicate youth smoking across SES groups. [ABSTRACT FROM AUTHOR]

Background: The databases of children's anthropometric parameters are often outdated, rarely representative and are not always available at an international level. Objectives: To present children's anthropometric parameters in six European countries that contributed to the Feel4Diabetes project and find country-specific differences. Design/Setting: The Feel4Diabetes study was performed between 2016 and 2018, targeting children in Belgium, Bulgaria, Finland, Greece, Hungary and Spain. The current study presents data from the baseline and the yearly follow-up anthropometric measurements. Subjects: In total, 20,832 measurements of children (48.7% boys) between 6 and 10 years of age were conducted. Main outcome measure: weight, height, BMI. Results: Belgian boys had the lowest body weight and height, while Greek boys had the highest body weight, and Finnish had the highest body height. The highest proportion of overweight (percentile above 85%) and obese boys (percentile above 95%) was in Greece, followed by Hungarian, Spanish, Bulgarian and Finnish boys. In contrast, Belgian boys had the lowest ratio in both categories. Among girls, Greece had the highest; Belgium had the lowest body weight; Finland was the highest in all age categories. The ratio in the overweight range was the highest in Greece, followed by Spanish, Bulgarian and Hungarian girls, who were second in the obese category. Finnish girls had lower and Belgian girls had the lowest ratio in both BMI categories. All the detailed data are presented in tables, and the trends are figures. Conclusions: Our study presents fresh and comparable anthropometric data of children between 6 and 10 years of age in six European countries, supporting the need for appropriate obesity prevention. [ABSTRACT FROM AUTHOR]

This meta-analysis (random effects) studies the self-perceived digital competence of university lecturers in university teaching, using 7470 lecturers from Europe and Latin America collected in K = 31 samples, with teaching experience of between 6 and 15 years. The effect size obtained from a moderate random effects model of r = −0.21 with a 99% confidence interval is significant, negative, and moderate, confirming the low competence level. The meta-regression results show that the area of knowledge plays an important role. The systematic review of the literature shows that the perception of ICTs is positive, while the level of competence is low, and there are institutional and training challenges to be solved. [ABSTRACT FROM AUTHOR]

Higher dietary protein, alone or in combination with physical activity (PA), may slow the loss of age-related muscle strength in older adults. We investigated the longitudinal relationship between protein intake and grip strength, and the interaction between protein intake and PA, using four longitudinal ageing cohorts. Individual participant data from 5584 older adults (52 % women; median: 75 years, IQR: 71·6, 79·0) followed for up to 8·5 years (mean: 4·9 years, SD: 2·3) from the Health ABC, NuAge, LASA and Newcastle 85+ cohorts were pooled. Baseline protein intake was assessed with food frequency questionnaires and 24-h recalls and categorized into < 0·8, 0·8–<1·0, 1·0–<1·2 and ≥ 1·2 g/kg adjusted body weight (aBW)/d. The prospective association between protein intake, its interaction with PA, and grip strength (sex- and cohort-specific) was determined using joint models (hierarchical linear mixed effects and a link function for Cox proportional hazards models). Grip strength declined on average by 0·018 SD (95 % CI: –0·026, –0·006) every year. No associations were found between protein intake, measured at baseline, and grip strength, measured prospectively, or rate of decline of grip strength in models adjusted for sociodemographic, anthropometric, lifestyle and health variables (e.g., protein intake ≥ 1·2 v· < 0·8 g/kg aBW/d: β = –0·003, 95 % CI: –0·014, 0·005 SD per year). There also was no evidence of an interaction between protein intake and PA. We failed to find evidence in this study to support the hypothesis that higher protein intake, alone or in combination with higher PA, slowed the rate of grip strength decline in older adults. [ABSTRACT FROM AUTHOR]

The management of atrial fibrillation (AF), the most common sustained arrhythmia, impacts healthcare resource utilization (HCRU). This study aims to estimate global resource use in AF patients, using the GARFIELD-AF registry. A prospective cohort study was conducted to characterize HCRU in AF patients enrolled in sequential cohorts from 2012 to 2016 in 35 countries. Components of HCRU studied were hospital admissions, outpatient care visits, and diagnostic and interventional procedures occurring during follow-up. AF-related HCRU was reported as the percentage of patients demonstrating at least one event and was quantified as rate-per-patient-per-year (PPPY) over time. A total of 49,574 patients was analyzed, having an overall median follow-up of 719 days. Almost all patients (99.5%) had at least one outpatient care visit, while hospital admissions were the second most frequent medical contact, with similar proportions in North America (37.5%) and Europe (37.2%), and slightly higher in the other GARFIELD-AF countries (42.0%; namely Australia, Egypt, and South Africa). Asia and Latin America showed lower percentages of hospitalizations, outpatient care visits, and diagnostic and interventional procedures. Analyses of GARFIELD-AF highlighted the vast AF-related HCRU, underlying significant geographical differences in the type, quantity, and frequency of AF-related HCRU. These differences were likely attributable to health service availability and differing models of care. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic Macular Œdema (DME) and Age‐related Macular Degeneration (nAMD) are the leading causes of vision loss in developed nations. Anti‐Vascular Endothelial Growth Factor (aVEGF) has revolutionized the treatment of both conditions, but access is limited by costs. Biosimilars of aVEGF can cut costs, but prescriber concerns over the lack of clinical data can slow uptake. This paper reports all biosimilar aVEGF in development for Europe and the USA, and pools the results of clinical confirmatory trials to provide statistically greater reassurance in the similarity of outcomes. Methods: Biosimilars in the clinical development phase were identified from US and EU trial registries. Results: There are 13 biosimilars of ranibizumab and aflibercept in final clinical comparative trial stage of development in Europe and the USA, recruiting 6126 patients. Five studies of intravitreal bevacizumab biosimilars are recruiting 772 patients. Equivalence outcomes are typically based on Best‐Corrected Visual Acuity (BCVA) with 90% confidence limits of −3 to +3 letters between reference and biosimilar medicines. Completed trials to date with 1166 participants analysed together show BCVA outcomes of ≤1 letter between Originator Reference Products and Biosimilars; for serious adverse events the risk ratio is 1.17, with 95% confidence intervals of 0.85–1.63, p = 0.32. Conclusions: Biosimilars of aVEGF are expected soon. There are likely sufficient brands expected to create meaningful price competition. To date, the EU/US regulatory pathway is delivering biosimilars with close equivalence of safety and efficacy outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the experienced barriers of care for treatment-seeking trans individuals (TSTG) in three large European clinics. Methods: An online follow-up questionnaire was filled out by 307 TSTG individuals as part of the research protocol of the European Network for the Investigation of Gender Incongruence (ENIGI). Data was collected during follow-up in 2017/2018, around 5 years after participants had their initial clinical appointments in Ghent (Belgium), Amsterdam (the Netherlands), or Hamburg (Germany). Background characteristics, country, treatment characteristics and mental health were analyzed in relation to experienced barriers of care (EBOC, measured though agreement with statements). Results: The majority of participants reported various EBOC, oftentimes more than one. The most-frequently reported EBOCs pertained to the lack of family and friends' support (28.7%, n = 88) and travel time and costs (27.7%, n = 85), whereas around one-fifth felt hindered by treatment protocols. Also, a significant share expressed the feeling that they had to convince their provider they needed care and/or express their wish in such way to increase their likelihood of receiving care. A higher number of EBOCs reported was associated with more mental health problems, lower income and female gender. Conclusions: A substantial number of TSTG individuals within three European health care systems experiences EBOCs. EBOCs relate to both personal and systemic characteristics. These findings can help health care providers and centers to improve care. More research must be done to better understand the diversity among TSTG individuals and the corresponding barriers experienced. Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1964409 [ABSTRACT FROM AUTHOR]

Understanding a woman's future contraceptive needs and enhancing her chances of putting those needs into action depend heavily on her intentions to use contraceptive methods. However, there is little information about global perspectives of intention to utilise contraceptives among fecund sexually active women. This study examines the patterns and determinants of contraception intention of fecund sexually active women. The most recent Demographic and Health Surveys (DHS) from 59 countries were used for secondary data analysis. The DHSs applied a cross-sectional survey design to collect data from women between the ages of 15 and 49. The study comprises a sample of 697,590 fecund sexually active women in the reproductive ages. The desire to utilise contraceptive methods was examined using a multivariable binary logistic regression analysis. All analyses were weighted to allow for a complex survey design. A pooled prevalence of intention to utilise contraception was 42.8% (95% CI: 42.5, 43.1) at the global level. Eastern and Southern Europe had the lowest prevalence, 17.3% (95% CI: 16.4, 18.2), and the highest prevalence was observed in countries from Latin America and the Caribbean, 68.0% (95% CI: 67.5, 69.9). Attaining secondary-level education (adjusted odds ratio (aOR) = 1.68; 95% CI: 1.62–1.72) or higher (aOR = 1.71; 95% CI: 1.63–1.80), working (aOR = 1.21; 95% CI: 1.18–1.24), experience of a pregnancy loss (aOR = 1.06; 95% CI: 1.03–1.09), or being exposed to media family planning messages (aOR = 1.51; 95% CI: 1.48–1.55) were factors associated with an increased likelihood of intent to use contraceptives. The study has established that contraceptive use intention was low in many developing countries. Education, age, employment status, fertility preference, and exposure to family planning messages influenced contraceptive use intention. Health policy-makers ought to consider these factors when designing sexual and reproductive health strategies in developing countries. [ABSTRACT FROM AUTHOR]

With pet ownership on the rise, millions of individuals are exposed to this environmental exposure. Although the subject has been largely studied, more evidence is needed to clarify the potential association of pet ownership with human health. The aim of this research is to study the potential association of pet exposure (any pet, cat, dog, bird, fish) with all-cause, cardiovascular and cancer mortality of older (≥ 50 years) European residents. To this end, a total of 23,274 participants from the Survey of Health Ageing and Retirement in Europe (SHARE) were employed (median follow-up 119 months). All-cause mortality (5163 events), as well as cardiovascular (CVD) (1832 events), and cancer mortality (1346 events) were examined using Cox Proportional Hazards models for their relation with pet exposure at baseline. Stratified analyses were also performed by gender and for single or multi-person households. No significant association was observed for any of the pets with all-cause mortality on the whole sample and the fully adjusted models. In stratified analyses, bird exposure significantly increased the risk of all-cause mortality in women [Hazard Ratio (HR) = 1.23 ; 95% CI 1.04–1.44] as well as women living alone (HR = 1.38 ; 95% CI 1.02–1.85). Cause-specific models revealed an increased risk of death for women bird owners for causes other than cancer and CVD (HR = 1.40 ; 95% CI 1.05–1.99). In conclusion, bird ownership may be negatively associated with survival of older women in Europe. [ABSTRACT FROM AUTHOR]

We investigated the association between perceived neighbourhood characteristics and falls in community-dwelling adults, using data from Wave 5 and 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE). We included 25,467 participants aged 50 to 103 years (mean age 66.2 ± 9.6, 58.5% women), from fourteen European countries (Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Israel, Italy, Luxembourg, Slovenia, Spain, Sweden, Switzerland). At baseline, we recorded individual-level factors (socio-demographic, socio-economic and clinical factors), contextual-level factors (country, urban versus rural area, European region) and perceived neighbourhood characteristics (vandalism or crime, cleanliness, feeling part of neighbourhood, helpful neighbours, accessibility to services) for each participant. We recorded falls in the six months prior to the baseline and 2-year follow-up interviews. The associations between neighbourhood characteristics and falls were analysed by binary logistic regression models; odds ratios (95% confidence intervals) were calculated. Participants reporting-versus not reporting-vandalism or crime had an increased falls risk of 1.16 (1.02–1.31) at follow-up, after full adjustment; lack of cleanliness, feeling part of the neighbourhood, perceiving neighbours as helpful and difficult accessibility to services were not associated with falls. Vandalism or crime was consistently associated with increased falls risks in women, adults without functional impairment and urban areas residents. In conclusion, adverse neighbourhood environments may account for inequality in falls risk among middle-aged and older adults and could be added to fall risk stratification tools. [ABSTRACT FROM AUTHOR]

Using data from the first wave of the SHARE COVID-19 Survey and additional information collected from the previous waves of SHARE (Survey of Health Ageing and Retirement in Europe), we explore the effects of job characteristics on two outcomes: (i) the probability of work interruptions and (ii) the length of such interruptions during the first phase of the Coronavirus Pandemic. In order to assess the relationship between job features and labour market outcomes, we define two indexes proxying the pre-COVID-19 technical remote work feasibility as well as the level of social interaction with other people while working. Moreover, we use an indicator that classifies ISCO-08 3-digit job titles based on the essential nature of the good or service provided. We find that job characteristics have been major determinants of the probability of undergoing work interruptions and their duration. In addition, we show that women have been negatively affected by the Pandemic to a much larger extent than men, suggesting the relevance of the intrinsic characteristics of jobs they are mainly involved in, and the role of gender selection into specific activities. Not only females were more likely to have undergone work interruptions but they also exhibited larger probabilities of longer work breaks. A similar impact is seen for self-employed and less-educated workers. [ABSTRACT FROM AUTHOR]

A growing body of research suggests that adult child educational attainment benefits older parents' cognitive outcomes via financial (e.g. direct monetary transfers) and nonfinancial (e.g. psychosocial) mechanisms. Quasi-experimental studies are needed to circumvent confounding bias. No such quasi-experimental studies have been completed in higher-income countries, where financial transfers from adult children to aging parents are rare. Using data on 8,159 adults aged ≥50 years in the Survey for Health, Aging and Retirement in Europe (2004/2005), we leveraged changes in compulsory schooling laws as quasi-experiments. Each year of increased schooling among respondents' oldest children was associated with better verbal fluency (β = 0.07, 95% CI: 0.02, 0.12) scores; overall associations with verbal memory scores were null, with mixed and imprecise evidence of association in models stratified by parent gender. We also evaluated associations with psychosocial outcomes as potentially important mechanisms. Increased schooling among respondents' oldest children was associated with higher quality-of-life scores and fewer depressive symptoms. Our findings present modest albeit inconsistent evidence that increases in schooling may have an "upward" influence on older parents' cognitive performance even in settings where financial transfers from adult children to their parents are uncommon. Associations with parents' psychosocial outcomes were more robust. [ABSTRACT FROM AUTHOR]

Background. The problem of the ageing population has resulted in attitudes towards aging in different age groups becoming a subject of increased academic interest. Objectives. To provide comparative characteristics of the prevalence of manifestations of gerontological ageism among university students in five European countries. Material and methods. The sample consisted of university students (n = 2493) aged 18–25 from Belarus (n = 827), Russia (n = 528), Poland (n = 798), Lithuania (n = 223) and Ukraine (n = 117). The prevalence of gerontological ageism among respondents was evaluated according to the Fraboni Ageism Scale. Results. The prevalence and manifestations of gerontological ageism vary depending on the country. The maximum total indicator, displaying the highest overall level of ageism, was noted among Belarusian students, the minimum – in Lithuania (p < 0.05). The final indicators of gerontological ageism were found to be the following: the level of age discrimination and negative emotional attitude towards the elderly was increased in one fifth of the respondents in all five groups. The observation found the level of ageism averaging at 60%, evenly distributed in all groups. The predominant attitudes towards older people were found to be neutral or positive (84.6%). Conclusions. The manifestations of ageism are international in nature and can explain 20% of the total variety of answers characterising the differences in ranked attributes and degree of ageism. The total indicator showed the highest degree of gerontological ageism among students in Belarus, the lowest – among those in Lithuania, with levels of gerontological ageism among students in Russia, Poland and Ukraine distributed in between. [ABSTRACT FROM AUTHOR]

Objective: Prevention of osteoarthritis (OA) remains important, as there are no disease‐modifying treatments. A personalized approach has the potential to better target prevention strategies. In the present study, we used recently identified genetic risk variants from genome‐wide association analysis for advanced OA to calculate polygenic risk scores (PRS) for knee and hip OA and assessed PRS performance in an independent population of older community‐dwelling adults. Methods: PRS were calculated in 12,093 individuals of European genetic descent ages ≥70 years who were enrolled in the Aspirin in Reducing Events in the Elderly trial. The outcome measure was knee and hip replacement (hospitalizations during the trial and self‐reported joint replacements before enrollment). PRS were considered as continuous (per SD) and categorical (low risk [0–20%], medium risk [21–80%], high risk [81–100%]) variables. Logistic regression was used to examine associations between PRS and risk of joint replacement, adjusted for age, sex, body mass index, and socioeconomic status. Results: Among the participants, 1,422 (11.8%) had knee replacements and 1,297 (10.7%) had hip replacements. PRS (per SD) were associated with a risk of knee replacement (odds ratio [OR] 1.13 [95% confidence interval (95% CI) 1.07–1.20]) and hip replacement (OR 1.23 [95% CI 1.16–1.30]). Participants with high PRS had an increased risk of knee replacement (OR 1.44 [95% CI 1.20–1.73]) and hip replacement (OR 1.88 [95% CI 1.56–2.26]), compared to those with low PRS. Associations were stronger for PRS and hip replacement risk in women than in men. Associations were similar in sensitivity analyses that examined joint replacements before and during the trial separately. Conclusion: PRS have the potential to improve prevention of severe knee and hip OA by providing a personalized approach and identifying individuals who may benefit from early intervention. [ABSTRACT FROM AUTHOR]

Introduction: Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. Methods: Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann–Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan–Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). Results: 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3–5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). Conclusion: Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS). [ABSTRACT FROM AUTHOR]

Background Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. Objectives We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. Methods A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. Results Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55–0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. Conclusions In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones. [ABSTRACT FROM AUTHOR]

Background mixed evidence exists on the association between muscle strength and mortality in older adults, in particular for cancer mortality. Aim to examine the dose–response association of objectively handgrip strength with all-cause and cancer mortality. Study Design and Setting data from consecutive waves from the Survey of Health, Ageing and Retirement in Europe comprising 27 European countries and Israel were retrieved. Overall, 54,807 men (45.2%; 128,753 observations) and 66,576 women (54.8%; 159,591 observations) aged 64.0 (SD 9.6) and 63.9 (SD 10.2) years, respectively, were included. Cox regression and Fine-Grey sub-distribution method were conducted. Results during the follow-up period (896,836 person-year), the fully adjusted model showed the lowest significant risk estimates for the highest third of handgrip strength when compared with the first third (reference) in men (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.34–0.50) and women (HR, 0.38; 95% CI, 0.30–0.49) for all-cause mortality. We identified a maximal threshold for reducing the risk of all-cause mortality for men (42 kg) and women (25 kg), as well as a linear dose–response association in participants aged 65 or over. No robust association for cancer mortality was observed. Conclusion these results indicate an inverse dose–response association between incremental levels of handgrip and all-cause mortality in older adults up to 42 kg for men and 25 kg for women, and a full linear association for participants aged 65 years or over. These findings warrant preventive strategies for older adults with low levels of handgrip strength. [ABSTRACT FROM AUTHOR]

Background: Spain has been hit hard by COVID-19 since March 2020, especially in its metropolitan areas. We share experiences from Barcelona in measuring socioeconomic inequalities in the incidence of COVID-19 in the different waves, and in implementing coordinated and equity-oriented public health policy responses. Methods: We collected daily data on confirmed COVID-19 cases, geocoded the address of residence to assign each case to one of the 73 neighborhoods and 1068 census tracts, and calculated the cumulative incidence of COVID-19 by neighborhood and five income groups (quintiles of census tracts) by sex across four waves of the pandemic. We adjusted hierarchical Bayesian spatial models to obtain the relative risk (RR) of cumulative incidences in each quintile compared with the richest areas. A variety of public health policies implemented to tackle the pandemic and especially these inequalities in COVID-19 incidence and vaccination are selected and described. Results: Area-level income inequalities in the incidence of COVID-19 were present at different degree in all four waves. In the second wave (10/1/2020 to 12/6/2020), RR for the poorest income quintile census tracts compared with the richest was 1.43 (95% credible interval-CI-: 1.22–1.67) for men and 1.58 (95% CI: 1.35–1.83) for women. Later, inequalities in vaccination coverage also arose. Equity-oriented policy responses included: "health hotels" or home delivery of basic products for individuals with COVID-19 and without adequate conditions for isolation; new emergency facilities for homeless people, including those with active drug use; mass screening in high incidence areas; contingency plans for nursing homes and schools; adapting community health programs for their early reactivation; digital self-appointment support points and community vaccination days. Conclusion: COVID-19 hit Barcelona neighborhoods unequally, with variations between waves. The rapid availability of geolocalized data and by socioeconomic level helped public authorities to implement targeted policies and collaborative interventions for the most vulnerable populations. Further studies would be needed to evaluate their impact. [ABSTRACT FROM AUTHOR]

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤−5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72–2.99) and 1.43 (95% CI: 0.67–3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association. [ABSTRACT FROM AUTHOR]

Studies show that older migrants have poorer health than native populations in Western Europe. To date, little systematic research has explored the differences between men and women within older populations with migration backgrounds. This article examines gender-specific aspects and mediating mechanisms of self-reported health among older migrants from Turkey. Using a mixed method approach, data and results from a quantitative survey and a qualitative study conducted in Berlin, Germany, are analysed and integrated at the interpretive level. Standardised face-to-face interviews were carried out with the help of a network approach with 194 older migrants from Turkey (93 women, 101 men, mean age: 68). Potential mediators showing significant gender differences are included in a parallel multiple mediation analysis. The documentary method is used to analyse 11 semi-structured narrative interviews with first-generation labour migrants from Turkey. Women reported significantly worse subjective health than men (c = 0.443, bCI [0.165–0.736]), conveyed through greater functional limitations (ab = 0.183, bCI [0.056–0.321]) and emotional loneliness (ab = 0.057, bCI [0.008–0.128]). Respondents to the qualitative study perceived that women age earlier and have poorer health due to the burden of performing a greater variety of social roles. Higher levels of emotional loneliness among women could be caused by their experiences of negatively assessed partnerships. Our results show that as a group, older female migrants have an elevated health vulnerability. A broader scientific foundation regarding gender differences in the health of older migrants and their causes is needed to promote gender-sensitive prevention and care for this group. [ABSTRACT FROM AUTHOR]

Background: Media use may influence metabolic syndrome (MetS) in children. Yet, longitudinal studies are scarce. This study aims to evaluate the longitudinal association of childhood digital media (DM) use trajectories with MetS and its components. Methods: Children from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden participating in the IDEFICS/I.Family cohort were examined at baseline (W1: 2007/2008) and then followed-up at two examination waves (W2: 2009/2010 and W3: 2013/2014). DM use (hours/day) was calculated as sum of television viewing, computer/game console and internet use. MetS z-score was calculated as sum of age- and sex-specific z-scores of four components: waist circumference, blood pressure, dyslipidemia (mean of triglycerides and HDL-cholesterol−1) and homeostasis model assessment for insulin resistance (HOMA-IR). Unfavorable monitoring levels of MetS and its components were identified (cut-off: ≥ 90th percentile of each score). Children aged 2–16 years with ≥ 2 observations (W1/W2; W1/W3; W2/W3; W1/W2/W3) were eligible for the analysis. A two-step procedure was conducted: first, individual age-dependent DM trajectories were calculated using linear mixed regressions based on random intercept (hours/day) and linear slopes (hours/day/year) and used as exposure measures in association with MetS at a second step. Trajectories were further dichotomized if children increased their DM duration over time above or below the mean. Results: 10,359 children and adolescents (20,075 total observations, 50.3% females, mean age = 7.9, SD = 2.7) were included. DM exposure increased as children grew older (from 2.2 h/day at 2 years to 4.2 h/day at 16 years). Estonian children showed the steepest DM increase; Spanish children the lowest. The prevalence of MetS at last follow-up was 5.5%. Increasing media use trajectories were positively associated with z-scores of MetS (slope: β = 0.54, 95%CI = 0.20–0.88; intercept: β = 0.07, 95%CI = 0.02–0.13), and its components after adjustment for puberty, diet and other confounders. Children with increasing DM trajectories above mean had a 30% higher risk of developing MetS (slope: OR = 1.30, 95%CI = 1.04–1.62). Boys developed steeper DM use trajectories and higher risk for MetS compared to girls. Conclusions: Digital media use appears to be a risk factor for the development of MetS in children and adolescents. These results are of utmost importance for pediatricians and the development of health policies to prevent cardio-metabolic disorders later in life. Trial registration: ISRCTN, ISRCTN62310987. Registered 23 February 2018- retrospectively registered. [ABSTRACT FROM AUTHOR]

Background Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. Objective To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. Design Prospective cohort study. Setting 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. Subjects Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. Methods Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. Results Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09–1.25, P  < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14–1.17, P  < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18–1.51, P  < 0.0001). Conclusions There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis. [ABSTRACT FROM AUTHOR]

Objectives To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA. Methods All patients with PsA starting secukinumab or a TNFi in 2015–2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+). Results We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar. Conclusion No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective. [ABSTRACT FROM AUTHOR]