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The burden of tuberculosis (TB) in migrant children and young people (CYP) is commonly overlooked, despite the increasing incidence of TB in migrant populations in the European region. This study aimed to examine the distribution and disease characteristics of TB among migrant and native-born CYP through analysis of data from the European Centre for Disease Prevention and Control (ECDC) surveillance system (TESSy). Retrospective database analysis. A retrospective database analysis was conducted on all CYP TB cases (0–17 years) reported to TESSy (1995–2017), exploring distribution, site of TB, and presence of MDR-TB using multivariate analysis in R statistical software. Of the 73,176 CYP TB cases reported in the EU/EFTA (1995–2017), 24.4% (n = 17,879) occurred in migrant CYP and 75.6% (n = 55,297) occurred in native-born CYP. Migrant CYP were more likely (P < 0.001) to have pulmonary TB (OR: 1.90; 95% CI: 1.74–2.09) and unsuccessful treatment outcomes (OR: 2.05; 95% CI: 1.74–2.40) compared to native-born CYP. The proportion of extrapulmonary TB, compared to pulmonary TB across total CYP cases was higher than the existing evidence base. Overall, there were significant differences in the site of TB and treatment outcomes between migrant and native-born CYP. To improve outcomes, TB screening and detection practices should focus on facilitating care in migrant CYP. However, to better understand the implications of these findings on broader TB control, TB among CYP should be addressed more frequently in reports and research. [ABSTRACT FROM AUTHOR]

• Women with type 2 diabetes and ethnic minorities remain underrepresented across multiple GLP-1RA cardiovascular outcome trials. • GLP-1 receptor agonists significantly reduced MACE in both males and females with type 2 diabetes, among Asians and Whites, and in Asia and Europe. • There was no statistical difference in the reduction of MACE by GLP-1RAs among Blacks and Hispanics. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been pivotal in the management of type 2 diabetes mellitus (T2DM) and in the reduction of major adverse cardiovascular events (MACE). Notably, large cardiovascular outcomes trials (CVOTs) demonstrate significant disparities in inclusion, based on sex, race, ethnicity, and geographical regions. We examined the impact of GLP-1RA on MACE in patients with or without T2DM, based on sex, race, ethnicity, and geography. A literature search for placebo controlled randomized controlled trials on GLP-1RA treatment was conducted. Thorough data extraction and quality assessment were carried out, focusing on key outcome, and ensuring a robust statistical analysis using a random effects model to calculate log odds ratio (OR) with 95% confidence intervals (CIs). A total of 8 CVOTs comprising 71,616 patients were included. Compared with placebo, GLP-1RAs significantly reduced MACE in both sexes (females: logOR -0.19, (95% CI, -0.28 to -0.10), p < 0.01) versus (males: logOR -0.17, (95% CI, -0.23 to -0.10), p < 0.01), (p interaction NS), and among Asians (logOR -34 (95% CI, -0.53 to -0.15), p < 0.01), and Whites (logOR -17 (95% CI, -0.25 to -0.09), p < 0.01), with no difference in MACE among Blacks and Hispanics. Odds of MACE were also reduced in Asia (logOR -31 (95% CI, -0.50 to -0.11), p < 0.01), and Europe (logOR -27 (95% CI, -0.40 to -0.13), p < 0.01), but there was no statistical difference in MACE in North America and Latin America. Significant reductions in MACE with GLP-1RA treatment were demonstrated between both sexes and across certain ethnicities and certain geographical regions. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) and neoplasms have been considered as public health concerns worldwide. This study aimed to estimate the epidemiological patterns of death burden on CVDs and neoplasms and its attributable risk factors in Western Europe from 1990 to 2019 to discuss the potential causes of the disparities. We collected data on CVDs and neoplasms deaths in 24 Western European countries from the Global Burden of Disease Study. We analyzed patterns by age, sex, country, and associated risk factors. The results include percentages of total deaths, age-standardized death rates per 100,000 population, and uncertainty intervals (UIs). Time trends were assessed using annual percent change. In 2019, CVDs and neoplasms accounted for 33.54% and 30.15% of Western Europe's total deaths, with age-standardized death rates of 128.05 (95% UI: 135.37, 113.02) and 137.51 (95% UI: 142.54, 128.01) per 100,000. Over 1990–2019, CVDs rates decreased by 54.97%, and neoplasms rates decreased by 19.54%. Top CVDs subtypes were ischemic heart disease and stroke; top cancers for neoplasms were lung and colorectal. Highest CVD death burdens were in Finland, Greece, Austria; neoplasm burdens in Monaco, San Marino, Andorra. The major risk factors were metabolic (CVDs) and behavioral (neoplasms). Gender differences revealed higher CVDs death burden in males, while neoplasms burden varied by risk factors and age groups. In 2019, CVDs and neoplasms posed significant health risks in Western Europe, with variations in death burdens and risk factors across genders, age groups, and countries. Future interventions should target vulnerable groups to lessen the impact of CVDs and neoplasms in the region. [ABSTRACT FROM AUTHOR]

Reliable information on dietary trends is essential. We compared individual-level dietary estimates for total energy, carbohydrate, fat, and protein intake over time with national supply data from the Global Expanded Nutrient Supply Model (186 paired estimates from 1961 to 2011, 18 countries). We hypothesized that supply data would overestimate individual measures and that the two measures would be weakly correlated. Individual- and supply-level estimates were compared using Spearman correlation coefficients and linear mixed-effect models were used to estimate the differences between measures. Overall, the correlations between individual- and supply-level measures were moderate for energy (r s = 0.34) and carbohydrate (r s = 0.39), strong for fat (r s = 0.85), and protein (r s = 0.69). Trends in total energy measured by individual-level surveys and total energy supply were positively correlated in 38.9% of countries, whereas trends in macronutrients aligned between estimates in most countries. Supply-level dietary data overestimated individual-level intakes, especially in higher income countries in Europe and in the United States. In the United States, supply-level data exceeded individual-level estimates by 26.3% to 29.9% for energy, carbohydrate, and fat, whereas protein estimates were similar between measures. In Europe, supply-level estimates overestimated individual-level intake by 19.9% for energy, 17.0% for carbohydrate, 13.7% for fat, and 7.7% for protein, whereas estimates for energy and macronutrients were similar in Asia. In Asia and lower income countries, our findings generally support the use of supply-level data in the absence of individual-level data, though this finding may be related to smaller sample size and differences in underlying national statistics that inform supply data. This article compares individual-level diet measures of energy, carbohydrate, fat, and protein to national supply-level data in 18 countries. Time trends in macronutrient intake and, to a lesser degree, total energy, align between individual and supply data. Supply data overestimated individual intakes, especially in the United States and higher income countries. Supply data may be an appropriate alternative in Asia and in lower income settings that lack individual data. Abbreviation: 95% CI, 95% confidence interval. [Display omitted] [ABSTRACT FROM AUTHOR]

Although nine of 16 federal states in Germany conduct public health surveillance for Lyme borreliosis (LB), the extent of under-ascertainment is unknown. As a model for European countries that conduct LB surveillance, we sought to estimate the population-based incidence of symptomatic LB after adjusting for under-ascertainment. Estimating seroprevalence-derived under-ascertainment relies on data from seroprevalence studies, public health surveillance, and published literature. The number of symptomatic LB cases in states that conduct LB surveillance was estimated from studies reporting the seroprevalence of antibodies against Borrelia burgdorferi sensu lato, the proportion of LB cases that are asymptomatic, and the duration of antibody detection. The number of estimated incident symptomatic LB cases was compared with the number of surveillance-reported LB cases to derive under-ascertainment multipliers. The multipliers were applied to the number of 2021 surveillance-reported LB cases to estimate the population-based incidence of symptomatic LB in Germany. Adjusting for seroprevalence-based under-ascertainment multipliers, the estimated number of symptomatic LB cases in states that conducted surveillance was 129,870 (408 per 100,000 population) in 2021. As there were 11,051 surveillance-reported cases in 2021 in these states, these data indicate there were 12 symptomatic LB cases for every surveillance-reported LB case. We demonstrate that symptomatic LB is underdetected in Germany and that this seroprevalence-based approach can be applied elsewhere in Europe where requisite data are available. Nationwide expansion of LB surveillance would further elucidate the true LB disease burden in Germany and could support targeted disease prevention efforts to address the high LB disease burden. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the associations of passive (ie, television) and active (ie, electronic games, computer use) screen time (ST) with perceived school performance of adolescents across gender. METHODS: Data were from the 2014 Health Behaviour in School-aged Children survey conducted across 38 European countries and Canada. Perceived school performance was assessed using an item and dichotomized as high (good/very good) versus the remainder (average/below-average as reference). Participants reported hours per day of time spent watching television, playing electronic games, and using a computer in their free time. Multilevel logistic regression was used to estimate the associations. RESULTS: A total of 197,439 adolescents (average age 13.6 [standard deviation 1.63] years; 51% girls) were analyzed. Multivariable modeling showed that engaging in >2 h/d of ST was progressively and adversely associated with high performance in both boys and girls. Adolescents reporting >4 h/d of television time (≤1 h/d as reference) had 32% lower odds in boys (odds ratio [OR] 0.68; 95% confidence interval [CI]: 0.65-0.71) and 39% lower odds in girls (OR 0.61; 95% CI, 0.58-0.65) of reporting high performance. Playing electronic games for >4 h/d was associated with high performance with odds being 38% lower in boys (OR 0.62; 95% CI, 0.59-0.66) and 45% lower in girls (OR 0.55; 95% CI, 0.52-0.57). Sex differences in the estimates were mixed. CONCLUSIONS: High screen use, whether active or passive, was adversely associated with perceived high school performance, with association estimates being slightly stronger in girls than boys, and for mentally active than passive screen use. Discouraging high levels of screen use of any type could be beneficial to school performance. [ABSTRACT FROM AUTHOR]

Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas. Patients aged 12–29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries. Pathological diagnoses were centrally reviewed. Formalin-fixed tissues were analysed by whole exome sequencing, methylation profiling and RNA sequencing and were discussed in a multidisciplinary, international molecular tumour board. Of 71 patients recruited, 48 (median 20 years, range 12–28) met eligibility criteria. Central pathological review confirmed, modified and re-classified the diagnosis in 41, 3, and 4 cases, respectively. Median turnaround time to discussion at molecular tumour board was 8.4 weeks. whole exome sequencing (n = 48), methylation profiling (n = 44, 85%) and RNA sequencing (n = 24, 50%) led to therapeutic recommendations for 81% patients, including 4 with germ line alterations. The most common were for agents targeted towards tyrosine kinases (n = 20 recommendations), DNA repair (n = 18) and the PI3K/mTOR/AKT pathway (n = 15). Recommendations were generally based on weak evidence such as activity in a different tumour type (n = 68, 61%), reflecting the dearth of relevant molecular clinical trial data in the same tumour type. We demonstrate here that comprehensive molecular profiling of AYA patients' samples is feasible and deliverable in a European programme. • AYA cancers have been neglected by molecular profiling initiatives. • Most AYA sarcomas of adequate sample quality have identifiable actionable mutations. • Clinical evidence to support personalised treatment for AYAs is weak or absent. • International molecular profiling is feasible and necessary to fill research gaps. • More effort is needed to enable AYA patients' access to molecularly focused trials. [ABSTRACT FROM AUTHOR]

• Educating new generations of radiation oncologist specialized in brachytherapy is important. • A survey investigating the current status of training among the residents shows interest in brachytherapy, but lack of confidence in starting a practice. • Access to mentors and high case load exposure during training are essential. • A formal and comprehensive logbook and BT curriculum need to be developed. We aim to investigate the current state of brachytherapy (BT) training among the radiation oncology trainees in Europe. A 22-question online survey based on the one by the American Association of Radiation Oncology Residents (2017) with added queries pertinent to training in Europe was sent to 1450 residents in two iterations. These included site-specific training, volume of experience, barriers to training, institutional support, and preferences for further education. Responses to individual statements were given on a 1 to 5 Likert-type scale. The answers were reported by junior (≤3 years of training) and senior years of training (year of training 4/5/6 and junior staff). Descriptive statistics were used to describe frequencies. Residents from 21 European countries participated, 445 (31%) responded. 205 (47%) were senior residents. 60% residents consider that performing BT independently at the end of residency is very or somewhat important. Confidence in joining a brachytherapy practice at the end of residency was high or somewhat high in 34% of senior residents. They reported as barriers to achieving independence in BT to be lack of appropriate didactic/procedural training from supervisors (47%) and decreased case load (31%). 68% reported their program lacks a formal BT curriculum and standardized training assessment. Residents in Europe, feel independent BT practice is very or somewhat important, but do not feel confident they will achieve this goal. To address this gap, efforts are needed to develop and implement a formal and comprehensive BT curriculum with easy access to trained instructors. [ABSTRACT FROM AUTHOR]

IMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC). We generated a prospectively maintained database including patients treated with atezolizumab plus bevacizumab for unresectable HCC across Europe, Asia and USA. Clinico-pathologic characteristics were assessed for their prognostic influence on overall survival (OS) and progression-free survival (PFS) in univariable and multivariate analyses. Overall response rate by RECIST v1.1 and treatment-related adverse events (TRAEs) per CTCAE v.5.0 were reported. Out of 433 patients, 296 Child-Pugh A and ECOG performance status01 patients received atezolizumab plus bevacizumab in first line and were included. Patients were mostly male (82.7%), cirrhotic (75%) with history of viral hepatitis (65.9%). Overall, 68.9% had Barcelona Clinic Liver Cancer C-stage HCC with portal vein tumour thrombosis (PVTT, 35%) and extrahepatic spread (EHS, 51.7%). After a median follow-up of 10.0 months (95% confidence interval (CI): 9.4–10.4), median OS and PFS were 15.7 (95% CI: 14.5-NE) and 6.9 months (95% CI: 6.1–8.3), respectively. In the response-evaluable patients (n = 273), overall response rate was 30.8%. Overall, 221 patients (74.6%) developed TRAEs, with 70 (23.6%) reporting grade 3 or higher TRAEs; 25 (8.4%) patients had bleeding events. OS was independently associated with baseline Albumin-bilirubin (ALBI) grade and PVTT. Shorter PFS was associated with AFP≥ 400 ng/ml, worse ALBI and presence of EHS. This global observational study confirms the reproducible safety and efficacy of atezolizumab plus bevacizumab in routine clinical practice. Within Child-Pugh-A criteria, the presence of PVTT and higher ALBI grade identify patients with poorer survival. • Atezolizumab plus bevacizumab (A + B) is the standard of care for patients with unresectable hepatocellular carcinoma. • We report data from a large cohort of patients treated with A + B in real-life. • Effectiveness and safety of the combination is reproducible in daily practice. • Liver function and macro-vascular invasion is with overall survival. • Radiological response predicts better outcomes. [ABSTRACT FROM AUTHOR]

There is ample evidence documenting the problem of Islamophobia (discrimination and racism against the Muslim community). However, the extent to which the European population is aware of this injustice has not exhaustively been assessed. The aim of this research was to measure in a valid and reliable way the degree of social awareness of Islamophobia in four European countries: Spain, France, United Kingdom and Germany. The sample consisted of 1846 volunteers from these countries. All of them answered a structured protocol on social awareness called Degree of Islamophobia Recognition (DIR). Several cross-cultural analyses based on the Exploratory Factor Analysis (EFA) technique, the ordinal alpha coefficient and the Greatest Lower Bound (GLB) were applied to analyze the dimensionality of the DIR and its reliability. Six sex-differentiated population scales were made based on derived typical scores (TS). The results revealed that the DIR consisted of two cultural dimensions: perceived vulnerability and connection. Both dimensions explained between 51% and 61% of the variance in all countries. Reliability coefficients were acceptable in all cases (>0.7). We propose that public policies combat Islamophobia considering these dimensions and taking into consideration the thresholds of the derived PTs to identify in which regions or social groups these intervention policies are needed. • Measuring social awareness of Islamophobia (SAI) is crucial to establish effective religious conflict prevention policies. • SAI describes the social tendency to recognize unfair or vulnerable situations against the Muslim community. • The DIR (Degree of Islamophobia Recognition) as a valid and reliable measure of SAI is adapted in four Western countries. • Typical derived scores below 40 (out of 100) indicate an absence of social awareness of Islamophobia. [ABSTRACT FROM AUTHOR]

Second-generation Muslims who follow their faith and feel discriminated against tend to maintain their heritage culture and distance themselves from the culture of the country where they grew up, setting the conditions for psychosocial maladjustment. Yet some second generation do find ways to adopt the mainstream culture while remaining attached to their heritage culture. To explain these contradictory observations, we investigated how second-generation Muslims manage to be part of both mainstream and heritage culture although their religion is commonly regarded as incompatible with Western values. To do this, we examined the role of flexibility in existential quest (EQ) in the acculturation of second-generation Muslims. Our hypothesis was that second generation integration is fostered by their ability to be flexible on EQ, which allows them to reflect on cultural and religious issues and to create a safe psychological place where they can practice their faith without feeling they need to withdraw from mainstream society. Two samples of second-generation Muslims, one from Italy (N = 240) and one from Belgium (N = 209), completed an online questionnaire. A multi-group structural equation model was tested. Religiosity, perceived discrimination, and sociodemographic variables were also considered. We noted a positive association between EQ and mainstream culture only for the Italian sample. Our findings suggest that flexibility on EQ is one aspect of the acculturation of second-generation Muslims and that it can provide a resource for coping with the challenge of growing up under dual cultural pressures. [ABSTRACT FROM AUTHOR]

Harmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear. Surgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization. The retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010–2015. The study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes. Resection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment. • Primary treatment of early stage NSCLC varies widely in Europe and the USA. • The Netherlands had the relatively highest SBRT rates and the lowest resection rates for stage I NSCLC. • The USA experienced a significant decreasing trend in Stage I surgical resections. • Higher Age/Stage and unknown histology are strongly associated with lower surgery rates. [ABSTRACT FROM AUTHOR]

To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40–79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life. • A new cure model accounting for higher risk of death from other causes was applied. • We provide the proportion of patients that will not dying from cancer progression. • The impact of ignoring a relative risk of death from other causes> 1 is relevant • Cure indicators are important to decision-making and to improve patients' awareness • Estimates of cancer mortality risk have an impact on patients' quality of life. [ABSTRACT FROM AUTHOR]

Antimicrobial resistances (AMR) present a particularly challenging cross-sectoral policy problem, affecting human and animal health as well as the environment. Compared to the actual problem pressure, the public awareness for AMR is comparatively low and the issue has not been high on the political agenda in most. Given the rising problem pressure, we aim to find out as to what degree and under which conditions political parties bring AMR on the political agenda. By means of multilevel logit regressions based on 173 electoral manifestos in 30 European countries from 2015 to 2020, we explore the conditions that explain whether AMR are taken up in manifestos. The empirical findings indicate firstly that AMR are only addressed by political parties in Northern and Western Europe, in no case in Eastern, and only in one case in Southern Europe, though resistant bacteria are more widely spread in the latter. Secondly, Green parties are those who are most likely to address the AMR challenge. Thirdly, vote share is positively associated with AMR agenda-setting, while EU membership is insignificant and the national average on antibiotics consumption is negatively related to AMR agenda-setting. Finally, AMR are surprisingly mainly perceived as a problem of the agricultural policy subsystem despite its cross-sectoral policy character. The study makes theoretical and empirical contributions: regarding theory, the article shows that typical variables that are used for agenda-setting are less explanatory for complex intersectoral policies. This is also accompanied by the empirical contribution: since problem awareness and complexity of policy problems are correlated, AMR are reduced to an agricultural issue and as such, it is taken over by political parties that have expertise on agricultural-environmental topics. • Antimicrobial resistances (AMR) are a challenging cross-sectoral policy problem. • Public awareness for AMR is low and the issue is not high on the political agenda. • AMR are only addressed by political parties in Northern and Western Europe. • Green parties are most likely to address the AMR challenge. • AMR are mainly perceived as a problem of the agricultural policy subsystem. [ABSTRACT FROM AUTHOR]

Gender-affirming healthcare can carry significant benefits for trans people. However, there are substantial geographical inequalities in the provision of and access to trans-specific healthcare across Europe. Comparative healthcare systems research has typically focused on universal services, neglecting provision which serves specific groups within populations (e.g., trans people). This study aimed to develop a comparative typology of trans-specific healthcare systems across 28 European countries (the EU 27 plus the UK), and to examine country-level correlates which may influence or be influenced by these systems. Using hierarchical and k-means cluster analysis, countries were classified into four types based on measures of trans-specific healthcare provision, regulation and access. Possible country-level correlates (including socio-political climate, medical outcomes, and the general healthcare system) were investigated. The cluster analysis identified four clusters of trans-specific healthcare systems in Europe, characterized as: 1) Centralized conservative (highly centralized, extensive range of treatments, few trans-specific government policies); 2) Centralized reformist (highly centralized, extensive range of treatments, multiple trans-specific government policies); 3) Decentralized marketized (highly decentralized, moderate range of treatments, few trans-specific government policies); 4) Underdeveloped (highly decentralized, limited range of treatments, few or no trans-specific government policies). We found statistically significant differences between the clusters in rates of: public support for trans people; gender identity concealment; treatment access; overall health expenditure; gender inequality. The study develops a novel typology of trans-specific healthcare systems in Europe. It also identifies a range of potential drivers and outcomes of geographical divergences and inequalities in trans-specific healthcare provision. Building on this typology, future comparative research should aim to link the structure of healthcare systems to outcomes for trans people. Comparative healthcare systems research must account for the distinctive forms taken by services and systems that provide healthcare to specific groups within populations. • Develops a novel typology of trans-specific healthcare systems in Europe. • Conceptualizes four distinct types of trans-specific healthcare systems. • Investigates potential drivers and outcomes of inequalities between systems. [ABSTRACT FROM AUTHOR]

Older adults with dementia commonly receive multiple medications and have higher hospitalization rates, elevating the risk of potentially inappropriate prescribing and in-hospital adverse drug reactions (ADRs). There is limited evidence examining ADRs in older adults with dementia during hospitalization. Our aim was to assess the association between dementia and incidence of ADRs during hospitalization and to identify prevalent types of ADRs and medications linked to ADRs. Secondary analysis of the SENATOR trial database, which was a randomized controlled trial of an intervention to reduce ADRs in older inpatients with multimorbidity. A total of 1537 patients (47.2% females) with a mean age of 78.1 years were recruited from 6 European hospitals. Sociodemographic data, functional status, cognitive status, clinical information, and ADR-related outcomes were extracted from the SENATOR database. Inpatients with dementia were identified based on prior International Classification of Diseases, Tenth Revision (ICD-10), dementia diagnosis, receiving acetylcholinesterase inhibitors or memantine, or a Mini-Mental State Examination score ≤24 at admission without concurrent delirium. Among participants, 392 (25.5%) were identified as having dementia. The proportion of patients with probable or certain incident in-hospital ADRs was similar between the groups with and without dementia (22.4% vs 25.4%, P >.05). However, in-hospital rates of probable or certain ADRs from 12 common categories were less frequently identified in patients with dementia compared to those without (19.4% vs 23%, P =.025). Major constipation (6.4% vs 9.9%, P =.03) and acute dyspepsia, nausea, or vomiting (2.8% vs 5%, P =.03) were less commonly observed ADRs in patients with dementia. We did not observe an increased risk of in-hospital ADRs among inpatients with dementia. However, ADRs related to the gastrointestinal tract and identified by subjective symptoms were less frequently identified in this group. This study lays the groundwork for developing new tools for ADR diagnosis for older patients with dementia. [ABSTRACT FROM AUTHOR]

• The GPS is a comprehensive survey of psychedelic use in >6000 consumers worldwide. • Major survey catchments were Canada/US; Australia/NZ, UK/Europe. • Respondents expressed desire for regulated access channels for psychedelics. • Self-exploration was the top motive for use across major survey catchments. • Regional differences were found in psychedelic usage patterns and access sources. Despite advancements in policies governing psychedelic substances globally, our understanding of real-world psychedelic use and its variations across international jurisdictions remains limited. We implemented the Global Psychedelic Survey (GPS) to capture information about psychedelic consumer characteristics, access, and usage patterns around the world. The GPS was administered online in Spring 2023 to English-speaking adults (≥21 years) who use(d) psychedelics. We categorized survey responses into major catchment regions (Canada/US, Europe/UK, Australia/NZ, All Other). We used descriptive and bivariable statistics to characterize consumers' socio-demographic characteristics, psychedelic access sources, and usage patterns. We examined regional differences in psychedelic use patterns using multinomial logistic regression. We analyzed 6379 responses from 85 countries including Canada/US (n = 4434), Europe/UK (n = 771), Australia/NZ (n = 864), and Other (n = 310). Psilocybin, LSD, and MDMA were the most used psychedelics and personal growth was the most common use motive across all catchments. There were significant regional differences in psychedelic use patterns, including types of psychedelics used (e.g., less ibogaine use in Europe/UK and Australia/NZ relative to Canada/US), frequency of use (e.g., lower frequency use in Australia/NZ relative to Canada/US), motivations for use (e.g., less therapeutic use in Europe/UK and Other relative to Canada/US), and types of dosing regimens (e.g., more "micro"-dosing in Canada/US). In this large sample of adult psychedelic consumers from regions around the world, infrequent psychedelic use centered around life enhancement was common. Respondents indicated preference for legal access via quality-controlled sources. Jurisdictional differences in access and usage patterns likely reflect region-specific regulations and traditional practices. Further research should explore opportunities to increase representation of non-White respondents in psychedelic research via translation of studies into several languages and incorporation of culturally reflective, community-based study development. [ABSTRACT FROM AUTHOR]

• Low hand grip strength is negatively associated with the risk of developing Parkinson's disease. • The usual walking pace may increase the risk of sarcopenia. • No evidence of an inverse causal relationship of Parkinson's disease to sarcopenia. To explore the causal association between sarcopenia-related traits and Parkinson's disease by Mendelian randomization (MR) approach. A genome-wide association study (GWAS) of sarcopenia-related traits was done at the UK Biobank (UKB). The traits were appendicular lean mass, low hand grip strength (including the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) criteria and usual walking pace. The International Parkinson's Disease Genomics Consortium (IPDGC) gave us GWAS data for Parkinson's disease (PD). We used three different types of MR analyses: including Inverse-variance weighted (IVW), Mendelian randomized Egger regression (MR-Egger), and weighted median methods (both weighted and simple modes). The MR analysis showed that low hand grip strength was negatively associated with the risk of developing Parkinson's disease, including EWGSOP criterion (odds ratio (OR) = 0.734; 95% confidence interval (CI) = 0.575–0.937, P = 0.013) and FNIH criterion (OR = 0.619; 95% CI = 0.419–0.914, P = 0.016), and usual walking pace was also a risk factor for Parkinson's disease (OR = 3.307, 95% CI = 1.277–8.565, P = 0.014). In European population, low hand grip strength is negatively associated with the risk of developing Parkinson's disease, and usual walking pace is also a risk factor for Parkinson's disease. Further exploration of the potential genetic mechanisms underlying hand grip strength and Parkinson's disease and the potential relationship between walking pace, balance, and falls in Parkinson's patients may help to reduce the burden of sarcopenia and Parkinson's disease. [ABSTRACT FROM AUTHOR]

ICU nurses are most frequently at the patient's bedside, providing care for both patients and family members. They perform an essential role and are involved in decision-making. Despite this, research suggests that nurses have a limited role in the end-of-life decision-making process and are occasionally not involved. Explore global ICU nurse involvement in end of life decisions based on the physician's perceptions and sub-analyses from the ETHICUS-2 study. This is a secondary analysis of a prospective multinational, observational study of the ETHICUS-2 study. End of life decision-making processes in ICU patients were studied during a 6-month period between Sept 1, 2015, and Sept 30, 2016, in 199 ICUs in 36 countries. None. The ETHICUS II study instrument contained 20 questions. This sub-analysis addressed the four questions related to nurse involvement in end-of-life decision-making: Who initiated the end-of-life discussion? Was withholding or withdrawing treatment discussed with nurses? Was a nurse involved in making the end-of-life decision? Was there agreement between physicians and nurses? These 4 questions are the basis for our analysis. Global regions were compared. Physicians completed 91.8 % of the data entry. A statistically significant difference was found between regions (p < 0.001) with Northern Europe and Australia/New Zealand having the most discussion with nurses and Latin America, Africa, Asia and North America the least. The percentages of end-of-life decisions in which nurses were involved ranged between 3 and 44 %. These differences were statistically significant. Agreement between physicians and nurses related to decisions resulted in a wide range of responses (27–86 %) (p < 0.001). There was a wide range of those who replied "not applicable" to the question of agreement between physicians and nurses on EOL decisions (0–41 %). There is large variability in nurse involvement in end-of-life decision-making in the ICU. The most concerning findings were that in some regions, according to physicians, nurses were not involved in EOL decisions and did not initiate the decision-making process. There is a need to develop the collaboration between nurses and physicians. Nurses have valuable contributions for best possible patient-centered decisions and should be respected as important parts of the interdisciplinary team. Wide global differences were found in nurse end of life decision involvement, with low involvement in North and South America and Africa and higher involvement in Europe and Australia/New Zealand. [ABSTRACT FROM AUTHOR]

• We analyzed the relationship between suicide rate and GCI in nine former Soviet countries and nine European and Asian countries. • Suicide rate was related to GCI in six of the nine former Soviet Union countries and in three of the nine European and Asian countries. • Attention should be paid to poor or worsening GCI values for suicide prevention in countries of the former Soviet Union. Investigations of suicide in countries of the former Soviet Union, which broke into 15 different countries in the early 1990s, require examinations of a combination of economic, social, and health factors. It is important to address these factors individually and to examine the various composite indicators for each. Moreover, it would be worthwhile to explore the potential applicability of a comprehensive worldwide index. We analyzed data from nine of the former Soviet countries for which both the annual suicide rate and the Global Competitiveness Index (GCI) were available for the years 2006–2017. We determined the precise relationships between the suicide rate and the GCI during this period in these nine countries as well as in nine countries with high suicide rates in Europe and Asia. The results indicated the following: (i) In six of the nine former Soviet countries with complete data, the suicide rate showed a relationship with the GCI. Notably, this relationship was inverse in all but one country. (ii) Among the nine European and Asian countries with high suicide rates, three exhibited a correlation between the suicide rate and the GCI. Measures to prevent suicide should be devised especially in countries of the former Soviet Union through collaboration among multiple fields and organizations, as necessary, with particular attention paid to countries with worse or worsening GCI values. [ABSTRACT FROM AUTHOR]

The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour. With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials. • High-quality, protocol compliant radiotherapy is essential in clinical trials. • QUARTET is a platform for centralised prospective radiotherapy quality assurance. • QUARTET facilitates a strong collaborative network for paediatric radiation oncology. • QUARTET improves equity in access to paediatric radiotherapy expertise across Europe. • QUARTET supports central review of diagnostic imaging for treatment failure analysis. [ABSTRACT FROM AUTHOR]

Many intratumoural (IT) immunotherapies are currently developed in the clinic with the aim of overcoming primary and secondary resistance and/or to limit on-target/off-tumour toxicities of immune checkpoint targeted therapies. This study aimed to describe the feasibility, safety and efficacy of IT immunotherapy treatments. This retrospective single-centre study included the first 100 consecutive patients enrolled in Gustave Roussy's Human IntraTumoral-ImmunoTherapy (HIT-IT) program. Patient characteristics, target description, image guidance, safety and response according to iRECIST (Response Evaluation Criteria in Solid Tumours for immunotherapy trials) were recorded. Predictive factors of complications and responses were analysed. Survival was also reported. From 09/2015 to 05/2020, 100 patients had 115 tumours injected during 423 treatment cycles. Most frequent primary tumour arose from the skin (n = 49), digestive track (n = 4) or head and neck (n = 8). Injected tumours' mean diameter was 37 ± 23 mm, and a median number of 4 IT injections per patient (interquartile range:3–5) were performed. Targeted tumours for IT injections were superficial lymph nodes (36.5%), subcutaneous lesions (25.2%), liver tumours (20.9%) and others (17.4% including tumour sites such as deep lymph nodes or lung). Most patients (72%) received systemic immunotherapy in combination with HIT-IT. Procedure- and drug-related adverse events (AEs) occurred in 11.3% and 33.3% of the treatment cycles, respectively. Only 3 procedure-related AEs were grade-3 (0.7%); and no grade-4 or 5 occurred. Among all cycles, 7 grade-3 and 1 grade-5 drug-related AEs were reported. Complete and partial responses were achieved for 5% and 18% of patients, respectively, while stable disease was the best response for 11%. Patients receiving HIT-IT as a 1st-line treatment (24%), or not previously pre-treated with immunotherapy (53%) responded better, p = 0.001 and p = 0.004, respectively. From 1st cycle of IT, 12-month overall progression-free survival and overall survival were 21% (14–31%) and 57% (47–68%), respectively. This retrospective study, conducted on patients with cancer and treated within clinical trials at Gustave Roussy, demonstrates the feasibility and safety of the IT immunotherapy strategy. [Display omitted] • Image-guided intratumoural immunotherapy is feasible for both superficial and deep lesions. • No procedure-related grade 4 or 5 adverse events were observed. • A high response rate of injected tumours has been observed. [ABSTRACT FROM AUTHOR]

In the context of new targeted therapies and immunotherapy as well as screening modalities for lung cancer patients, detailed mortality trends in Europe and Northern America are unknown. Time-trend analysis using vital registration data of Northern America and Europe from the WHO Mortality Database (years 2000/2017). To assess improvements in lung cancer mortality, we performed a population-averaged Poisson autoregressive analysis. The average annual percent change (AAPC) was used as a summary measure of overall and country-specific trends in mortality. Second, we studied time trends of lung cancer incidence and smoking prevalence rates. In the total population of 872·5 million people between 2015 and 2017, the average annual age-standardised mortality from lung cancer was 54·6 deaths per 100 000, with substantial differences across countries. Lung cancer was reported as the primary cause of death in 5·4 cases per 100 deaths. The age-standardised mortality rate decreased constantly (AAPC –1·5%) between 2000 and 2017. While mortality in men dropped annually by an average of −2·3%, mortality in women decreased by an average of −0·3%. This slight decline was driven exclusively by the USA. In contrast, 21 out of 31 countries registered a significant increase in female lung cancer mortality between 2000 and 2017, with Spain (AAPC 4·1%) and France (AAPC 3·6%) leading the list. Despite overall decreases in lung cancer mortality trends, female mortality remained unchanged or increased significantly in all countries except the USA. National mortality outcomes reflect variabilities in tobacco control, screening, therapeutic advances, and access to health care. • Lung cancer mortality decreased with an AAPC of −1·5%. • Female mortality trends remained stable or increased in all countries except the USA. • In Northern America, lung cancer mortality declined more than in Europe. [ABSTRACT FROM AUTHOR]

We retrospectively investigated the role of (neo)adjuvant chemotherapy in patients with primary, localized angiosarcoma. We selected all patients with primary, localized angiosarcoma, who had received radical surgery between January 2005 and December 2019 at 33 European sarcoma reference centers. The primary objective was to compare the outcome of patients who received (neo)adjuvant chemotherapy versus those who did not, in terms of overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS). To reduce the risk of confounding due to imbalance, a propensity-score matching(PSM) was performed. Finally, subgroups analysis was performed according to tumor site, tumor size (< 50 mm or ≥ 50 mm) and patients predicted 10-years OS according to the nomogram sarculator (two different cutoff-values were applied: ≤ 33% or > 33% and < 60% or ≥ 60%). 362 patients were analyzed: 149 (41.2%; treated group) received (neo) adjuvant chemotherapy and 213 (58.6%; control group) did not. The median follow-up for the OS endpoint was 5.1 years (95% CI: 4.0–5.5). The OS-HR was 0.58 (95%CI: 0.40–0.83; p-value = 0.003) in the univariate analysis and 0.74 (95% CI: 0.38–1.43; p = 0.367) in the PSM analysis. The DFS-HR was 0.75 (95% CI: 0.57–0.98; p-value = 0.036) in the univariate analysis, and 0.91 (95% CI:0.56–1.48; p-value = 0.7) in the PSM analysis. The DMFS-HR was 0.75 (95% CI: 0.55–1.02; p-value = 0.065) in univariate analysis and 0.92 (95% CI: 0.53–1.61; p-value = 0.769) in the PSM analysis. Subgroup analysis revealed no heterogeneity of results in strata of tumor site. On the contrary, there was a trend for heterogeneity according to tumor size and patient's risk of death. For all the endpoints analyzed, patients with tumors smaller than 50 mm or at lower risk of death seem to have no benefit from chemotherapy, while patients with larger tumors or at higher risk of death at 10 years seem to derive substantial benefit. This large, retrospective study suggests that patients affected by > 50 mm and/or high-risk primary, localized angiosarcoma could benefit from (neo)adjuvant chemotherapy. • Localized angiosarcoma of any site. • Effectiveness of (neo)adjuvant chemotherapy. • High risk angiosarcoma. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials. • Major progress in the diagnosis of Merkel cell carcinoma by immunohistochemistry/molecular pathogenesis. • The management of primary tumour was mostly based on retrospective studies. • Breakthrough in advance disease management with the approval of immunotherapy. [ABSTRACT FROM AUTHOR]

Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4–12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies. • The efficacy of immunotherapy for melanoma in-transit metastases is unknown. • An international multicenter retrospective cohort study. • Systemic immunotherapy is an effective treatment for melanoma in-transit metastases. [ABSTRACT FROM AUTHOR]

Pediatric obesity is a primary public health concern, and designing effective programs for managing it is of the utmost importance. The objective of this study was to describe the protocol study of a three-arm, parallel, randomized controlled trial aimed at assessing the efficacy of a family-system-based intervention ("ENTREN-F" program) for managing childhood obesity, compared to the "ENTREN" program (no "F" - without specific family-system-based workshop) and a control group (behavioral monitoring). The ENTREN-F program was a multicomponent family-system-based intervention carried out by a multidisciplinary team in the primary health care setting. The program targeted children between 8 and 12 years with overweight and obesity (P ≥ 85th). Parents were actively involved in the process. The contents were designed using the Cognitive Behavioral Therapy (CBT) principles. The program comprised individual behavioral monitoring, a healthy habits workshop for children and their parents, a CBT workshop for children, and a family-system-based workshop for parents, enhancing parental management skills plus family functioning. The trial's primary outcomes included changes in child body mass index (BMI) z-scores, child's psychological well-being, and family functioning over six months. Secondary outcomes included changes in eating behavior, physical activity, self-esteem, parental distress, parental feeding practices, and parental modeling. To our knowledge, this is one of the few randomized controlled trials to assess the efficacy of a multicomponent program that considers health from a comprehensive perspective, trying to improve children's psychological well-being and family functioning besides weight loss. This study, therefore, addresses a gap in the literature. If found to be efficacious, it suggests a new potential health service for translation into National Primary Health Care services in Spain, one of the ten countries with the highest prevalence of obesity in Europe. [ABSTRACT FROM AUTHOR]

Football clubs operate as a global business and need to have a connection with stakeholders. Nowadays the main and the most effective way to interact are social media which have the ability to connect us with almost anyone in the world. This article shows how important is the role of social media followers in the commercial aspects of a club's business. The aim of this article is to investigate the relationship between the number of followers on social media and revenue. For this purpose, there was used the correlation coefficient. The analysis was preceded by the determination of descriptive statistics. The research sample included the top 20 football clubs from Europe covered data for the 2019/20 and 2020/21 football seasons and the corresponding financial year. There was used the data for the number of social media followers (Facebook, Instagram, Twitter, YouTube, TikTok) and the matchday, broadcast, and commercial income. The research has revealed a strong relationship between social media following and clubs' revenues. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockers (ICBs) in combination with antiangiogenic drugs showed synergistic efficacy in several tumour types. New patterns of progression have recently been defined upon treatment with ICB alone including atypical responses such as pseudoprogression (PsPD), dissociated response and hyperprogressive disease (HPD). This study aimed to describe the patterns of response observed in patients treated with combination ICB with antiangiogenic drugs. We conducted a monocentric retrospective analysis of patients (pts) enrolled in phase I trials at Gustave Roussy assessing the combination of ICB and antiangiogenic drugs. Radiological CT scans were centrally reviewed by a senior radiologist according to iRECIST criteria including progressive disease (PD), partial response (PR) and stable disease (SD). HPD was defined as a progression at the first evaluation with a delta tumour growth rate exceeding 50%. PsPD was defined as initial progression followed by stabilisation or decrease of tumour size, DisR as a concomitant size decrease in some tumour lesions and size increase in others. Both PsPD and DisR are defined as atypical responses. Overall response rate included PR and complete response (CR) and disease control rate included PR, CR and SD. Between December 2016 and June 2020, 111 pts were included. The median follow up was 12.8 months (11.3–15.1). The most common tumour types were lung and pleura (20%), kidney (18%) and bladder (17%). The overall response rate and disease control rate were 21.6% (n = 24) and 59% (n = 65), respectively. Twenty-one patients (19%) experienced PD as the best response. PsPD, DisR and HPD were observed in 4 (3.6%), 11 (9.9%) and 7 (6.3%) pts, respectively. DisR and PsPD were associated with longer iProgression Free Survival (median: 6.9 and 18.9 months, respectively) and iOverall Survival (median: 28.4 and 31.1 months, respectively) than a median of SD in immune progression-free survival (median: 4.2 months) and immune overall survival (median: 12.7 months). Patients treated with ICBs and antiangiogenic agents display atypical responses. Survival might be longer in patients with DisR responses and PsPD disease than patients with HPD, PD and SD. [Display omitted] • Patients treated with immune checkpoint blockers and antiangiogenic agents display atypical responses. • Atypical responses were pseudoprogression, dissociated response and hyperprogressive disease and were observed in 6%, 10% and 6% pts. • Survival might be longer in patients with dissociated response and pseudoprogression than patients with stable disease. [ABSTRACT FROM AUTHOR]

Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised. Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR / BRAF / KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA. Out of 323 patients included, 43 patients had one dGA: KRAS m (n = 26; 8 G12C), EGFR m (n = 8; 6 del19/ex21), BRAF m (n = 5; 4 V600E) and ALK r (n = 4). The median age was 66 years [39–84], gender ratio 1:1, with 98% performance status (PS) 0–1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2–24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4–28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRAS m G12C vs. 8.1 mo (5.8-NR) in the EGFR m del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAF m V600E/ ALK r (P = 0.02). We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAF m and ALK r but not for those harbouring KRAS m. Larger prospective studies are needed to confirm these findings. • Similar treatment outcomes to PACIFIC phase III trial. • Different benefits of durvalumab consolidation based on oncogenic alterations. • Significant increase in PFS with durvalumab in patients with KRAS mutations. • ALK- rearranged NSCLC seem to benefit the least to durvalumab consolidation. • Largest retrospective study evaluating durvalumab in oncogenic addicted stage III NSCLC. [ABSTRACT FROM AUTHOR]

This study aimed to understand how politics, economics, and public health restrictions affected each other during the COVID-19 pandemic. We use seemingly unrelated regressions on a monthly data set of government approval ratings, the stringency index, the time-dependent reproduction number (R), and unemployment, allowing the residuals in each regression to be correlated with each other. We also conduct sensitivity tests using weekly data and the growth in polls. The study covers 27 European countries from April 2020 to April 2021. A unit increase in the R and COVID-19 cases per million increases the stringency index by 23.742 and 4.207, respectively; a unit increase in stringency boosts the incumbent's popularity by 0.384; the poll positively affects the stringency index; stringency has negative effects on the R; and the poll and stringency index have opposite effects on unemployment. Political and economic pressures did not hinder the government from introducing stronger measures. [ABSTRACT FROM AUTHOR]

There is an alarming delay in Europe for anticancer medicines becoming accessible for children. Following a paediatric European Union marketing authorisation, national Health Technology Assessment (HTA) agencies evaluate effectiveness, and safety of medicines to support decision on their cost and reimbursement. This study (a SIOPE Access to Medicines project) aimed to evaluate how these HTA evaluations take place for anticancer medicines indicated for paediatric use in Europe and to explore where the delays for market access originate. We obtained HTA reports from the public domain for nine European countries for blinatumomab, dinutuximab beta and tisagenlecleucel. We evaluated the time elapsed between marketing authorisation for a paediatric indication and a national HTA decision and the nature of the decision. Out of 23 HTA decisions (four countries without blinatumomab report), 18 were positive, two with restrictions, three negative. For blinatumomab, tisagenlecleucel and dinutuximab beta, the median time to an HTA decision after regulatory approval for paediatric use was 353 days (range 193–751), 141 days (range 77–517) and 515 days (range 0–780), respectively, with variability between countries. Dinutuximab beta and tisagenlecleucel were first introduced in children, but did not result in shorter time to HTA decision. For blinatumomab, marketing authorisation followed 1008 days after the indication in adults, with HTA applications submitted a median of 167 days later, and a recommendation after 145 days. This study reveals ample variability in HTA decision making in nine European Union countries. Collaboration and alignment of required evidence is needed to facilitate robust scientific HTA assessments, also considering methodological challenges in paediatric oncology. • Health technology assessments of paediatric oncology drugs vary greatly within Europe. • The timing of HTA evaluation adds to the delay of patient access. • Differences between adult and paediatric trial methodology should be considered. • Multistakeholder collaboration between EMA, academia, pharmaceutical companies, patients advocates and HTAs is needed. [ABSTRACT FROM AUTHOR]

Over the last three decades, cancer mortality has shown favourable patterns in Europe. Patterns and trends however have been less favourable for most eastern countries. We computed cancer mortality rates in western (WE) and eastern European (EE) countries using the official mortality database of the World Health Organisation, using joinpoint regression models to identify significant changes in trends over time. Cancer mortality declined by 1–1.4% annually in WE since 1990, to reach an age-standardised rate (world standard) of 125.4/100,000 men and 81.3/100,000 women in 2016. In contrast, EE rates only started to decline around the 2000s in men and remained stable in women, to reach 171.9/100,000 men and 98.2/100,000 women. Lung cancer rates were 30.8/100,000 men and 14/100,000 women in WE versus 47.1/100,000 men and 15.2/100,000 women in EE. In relative terms, the mortality excess in EE increased from 32 to 37% in men and from 15 to 21% in women, compared with WE. The largest percent excesses were for cancers of the upper respiratory tract, stomach, intestines and lung in men and uterus in women. Prostate cancer rates increased in EE to reach 12.7/100,000 in 2016, whereas they decreased to 10.2/100,000 in WE. Compared with rates in 1990, over the period 1991–2016, about 3.9 million cancer deaths were avoided in WE, but no notable improvements was seen in EE. If cancer mortality rates in EE had been those observed in WE, over 55,000 deaths would have been avoided in 2016. Differences in lifestyle patterns, mainly smoking and alcohol, besides different roll-out of improvements in cancer diagnosis and management are the key determinants of the persisting difference in cancer mortality between western and eastern Europe. There is no evidence for the gap to close. • There is a persistent cancer mortality excess in central-eastern versus western Europe. • The gap between eastern and western has increased in relative terms. • Between 1990 and 2016, 3.9 million cancer deaths were avoided in western Europe. • In the same period, no material advancement was observed in eastern Europe. • In 2016, over 55,000 (18%) cancer deaths would have been avoided in eastern Europe by closing the gap. [ABSTRACT FROM AUTHOR]

• A cross-sectional study on 1913 European aged ≥50 years. • First study to explore the association between COVID-19 vaccination and long COVID according to the status of chronic multimobidity. • Chronic multimorbidity might expand the influence of unvaccination on developing long COVID among European aged ≥50 years. We aimed to explore the association between coronavirus disease-19 (COVID-19) vaccination and long COVID according to the status of chronic multimobidity. A total of 1913 participants were recruited in the cross-sectional study on the basis of the Survey of Health and Retirement in Europe. COVID-19 vaccination was defined as vaccination within the last 12 months. Chronic multimorbidity was defined as history of 2 + chronic disease. The study outcome was long COVID during the 12-month follow-up. Multivariable logistic models were performed to estimate the influence of chronic multimorbidity on the association of vaccination with long COVID. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. Chronic multimorbidity significantly modified the association of COVID-19 vaccination with long COVID (P interaction = 0.024). The rates of study outcome were significantly lower among vaccinated participants in the chronic multimorbidity subgroup, but not in the other subgroup. Multivariable odds ratios (95 % confidence intervals) of study outcome for unvaccination vs. vaccination were 1.494 (1.013–2.203) in those with multimorbidity and 0.915 (0.654–1.280) in those without multimorbidity, respectively. Adding COVID-19 vaccination to a model containing conventional risk factors significantly improved risk reclassification for study outcome among those with chronic multimobidity (continuous NRI was 25.39 % [ P = 0.002] and IDI was 0.42 % [ P = 0.075]) An inverse association of COVID-19 vaccination with long COVID was found among participants with chronic multimorbidity, but not among those without chronic multimorbidity. Chronic multimorbidity might expand the influence of unvaccination on developing long COVID among European aged ≥50 years. [ABSTRACT FROM AUTHOR]

Magnet hospitals, a concept developed in the U.S., have been associated with improved nurse recruitment and retention, and better patient outcomes. Magnet principles may be useful to address workforce challenges in European hospitals, but they have not been implemented or evaluated on a large scale in the European hospital context. This study aims to explore the initial phase of implementing Magnet principles in 11 acute care hospitals in six European countries. The specific objectives of the study were to investigate the type of work that characterises the early phase of implementation and how implementation leaders engage with their context. A multinational qualitative study was conducted, with data from 23 semi-structured, one-to-one interviews with implementation leaders in 11 acute care hospitals in six European countries. Thematic analyses guided the analysis of data. Three themes of core work processes during the early phase of implementing Magnet principles in European hospitals were identified. The first theme, 'Creating space for Magnet', describes how work was directed towards creating both political and organisational space for the project. The second theme, 'Framing to fit: understanding and interpreting Magnet principles', describes the translational work to understand what the Magnet model entails and how it relates to the local hospital context. Finally, the third theme, 'Calibrating speed and dose', describes the strategic work of considering internal and external factors to adjust the process of implementation. The first phase of implementation was characterised by conceptual and relational work; translating the Magnet concepts, considering the fit into existing structures and practices and making space for Magnet in the local context. Understanding the local context played an important role in shaping and guiding the navigation of professional and organisational tensions. Hospitals employed diverse strategies to either emphasise or downplay the role of nurses and nursing to facilitate progress in the implementation. [ABSTRACT FROM AUTHOR]

We used the comprehensive definition of AYA (age 15 to 39 years) to update 5-year relative survival (RS) estimates for AYAs in Europe and across countries and to evaluate improvements in survival over time. We used data from EUROCARE-6. We analysed 700,000 AYAs with cancer diagnosed in 2000–2013 (follow-up to 2014). We focused the analyses on the 12 most common cancers in AYA. We used period analysis to estimate 5-year RS in Europe and 5-year RS differences in 29 countries (2010–2014 period estimate) and over time (2004–06 vs. 2010–14 period estimates). 5-year RS for all AYA tumours was 84%, ranging from 70% to 90% for most of the 12 tumours analysed. The exceptions were acute lymphoblastic leukaemia, acute myeloid leukaemia, and central nervous system tumours, presenting survival of 59%, 61%, and 62%, respectively. Differences in survival were observed among European countries for all cancers, except thyroid cancers and ovarian germ-cell tumours. Survival improved over time for most cancers in the 15- to 39-year-old age group, but for fewer cancers in adolescents and 20- to 29-year-olds. This is the most comprehensive study to report the survival of 12 cancers in AYAs in 29 European countries. We showed variability in survival among countries most likely due to differences in stage at diagnosis, access to treatment, and lack of referral to expert centres. Survival has improved especially for haematological cancers. Further efforts are needed to improve survival for other cancers as well, especially in adolescents. • Tumours of adolescents and young adults can be treated effectively. • Application of paediatric protocols to AYAs with ALL improves outcomes. • We highlighted survival differences between European countries for most AYA tumours. • Survival improved over time for most cancers in the 15- to 39-year-old age group. • Survival improved over time for fewer cancers in those aged 15 to 29. [ABSTRACT FROM AUTHOR]

Background Early-life development plays a key role in adult type 2 diabetes (T2D), but the extent to which this can be attenuated by lifestyle is unknown. Objectives The aim was to investigate the independent relevance of genetic predisposition to low birth weight and childhood obesity for T2D, and their attenuation, by adherence to a healthy lifestyle in adulthood. Methods Genetic risk scores (GRSs) were estimated for birth weight and childhood BMI with genetic risk categories according to their quintiles in 90,029 and 321,225 participants from the China Kadoorie Biobank (CKB; mean age, 53.0 y) and UK Biobank (UKB; 56.1 y). Healthy lifestyle scores were defined on noncurrent smoking, moderate alcohol consumption, healthy diet, regular physical activity, and nonobesity, and categorized into healthy (4∼5 factors), intermediate (2∼3 factors), and unhealthy (0∼1 factor) lifestyle. Results GRSs for low birth weight and childhood BMI were associated with higher T2D risks. Healthy lifestyle was related to lower T2D risk, and there was an additive interaction with increasing childhood BMI GRS and decreasing healthy lifestyle factors on T2D risk, whereas no additive interaction was observed for birth weight. Participants with a healthy compared with an unhealthy lifestyle had a 68% (HR: 0.32; 95% CI: 0.22, 0.47) and 77% (0.23; 0.19, 0.28) lower T2D risk among participants at high genetic risk (lowest quintile) of low birth weight in the CKB and UKB. Among participants with high genetic risk (highest quintile) of childhood obesity, compared with those with an unhealthy lifestyle, adherence to a healthy lifestyle was associated with a 69% (0.31; 0.22, 0.46) and 80% (0.20; 0.17, 0.25) lower risk of T2D in the CKB and UKB. Conclusions Genetic predisposition to low birth weight and childhood obesity were associated with higher risk of adult T2D and these excess risks were attenuated by adherence to a healthy lifestyle in adulthood, particularly among those at high genetic risk of childhood obesity. [ABSTRACT FROM AUTHOR]

Financial discrimination may affect an increasing number of cancer survivors in Europe as a consequence of the improvement of cancer management. According to the latest projections, Europe counts around 20 million cancer survivors. In the few years, the issue raised the attention of the European policymakers. The goal of this study is to promote political and legal solutions taking into consideration the need to stop discrimination against cancer survivors. The article also aims to implement legal principles on patients' rights and social values at the national and European levels, emphasising EU competence on the matter. The article reviews the current legal aspects concerning the right to be forgotten (RTBF) for cancer survivors in Europe, and it analyses the EU competency for its implementation. The legislative initiatives in force in France, Belgium, Luxembourg, the Netherlands, and Portugal provide concrete examples of an effective solution for former patients that should be extended throughout the EU. Under these circumstances, the European Legislator could lead on multiple initiatives to implement at the European level the RTBF, as our research has demonstrated the EU competency for these matters. A Pan-European solution based on the implementation of the RTBF is feasible within current treaties and seems the best approach to tackle the issue. The EU Action would provide a common and harmonised regulatory framework among the Member States to avoid discrimination and ensure equality among EU citizens being cured of cancer. • About 20 million citizens survive cancer, with +45% in the period from 2010 to 2020. • Restrictions to get financial services are neglected issues for cancer survivors. • 5 EU Member States implemented the right to be forgotten for cancer survivors. • Europe has the competence to tackle the issue endorsing the right to be forgotten. [ABSTRACT FROM AUTHOR]

Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease. • Dural infiltration is prognostic and integrated into the Kadish-INSICA staging system (International Network for Sinonasal Cancer and Skull Base Tumours (www.insica.org). • Adjuvant radiotherapy is beneficial across all stage groups, including early stage. • Prophylactic neck irradiation prevents neck nodal recurrence. • 82.4% express Somatostatin Receptor 2 (SSTR2) protein which can be used for SSTR2-targeted imaging. • SSTR2-targeted peptide receptor radionuclide therapy is useful in metastatic disease. [ABSTRACT FROM AUTHOR]

Survey Study. To investigate recent practice changes with respect to the provision of virtual visits by hand therapists due to the COVID-19 pandemic by asking about changes in the frequency of virtual visits, the assessments and treatments currently provided virtually, and the opinions of therapists on the future on virtual visits in hand therapy practice. The survey was distributed to the American Society of Hand Therapists (ASHT), the Australian Hand Therapy Association (AHTA), the Canadian Society of Hand Therapists (CSHT), and the European Federation for the Societies of Hand Therapy (EFSHT). Of the 819 responses, there were 573 therapists (70%) who reported that they currently use virtual visits in their practice. Only 38 therapists (4.6%) were providing virtual visits prior to COVID-19, representing a 15-fold increase in virtual visits since the beginning of the pandemic. Only 26% (n = 213) reported that they used patient-reported outcome measures (PROM) in conjunction with their virtual visits. Approximately 78% (n = 638) said that they thought there is a sustainable future for this method of care in hand therapy practice. This survey has helped identify the changing landscape in the provision of rehabilitation and established some of the common assessments and interventions currently utilized by hand therapists in the virtual environment. Next, steps for research are to investigate the reliability and validity of some of the assessments and interventions used, to establish whether virtual care will provide good outcomes for patients, and ultimately understand the optimal combination of conventional therapy and virtual care. • From a survey of 819 therapists from across the world, 573 therapists, 70% reported that they currently use virtual visits in their practice. Less than 5% of therapists were providing virtual visits prior to COVID-19, representing a 15-fold increase in virtual visits since the beginning of the pandemic. • Only 26% of therapists who responded to the survey reported that they used patient-reported outcome measures (PROM) in conjunction with their virtual visits. • Approximately 78% of therapists who responded said that they thought there is a sustainable future for this method of care in hand therapy practice. • This survey has helped identify the changing landscape in the provision of rehabilitation and established some of the common assessments and interventions currently utilized by hand therapists in the virtual environment. • Clinicians and researchers now need to improve the implementation of outcome measures in virtual care and develop methods for improving assessments within the virtual environment. [ABSTRACT FROM AUTHOR]

The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI); however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). We derived a cohort of 406 patients with unresectable/advanced HCC receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. We tested whether the development of clinically significant trAE (i.e. graded ≥2, trAE2) predicted improved overall survival (OS), progression-free survival (PFS), and objective response rates (ORR) following ICI. We established an international consortium of 10 tertiary-care referral centres located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to validate this association. In the FDA dataset of 406 patients, 325 (80%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 258, 64%), trAE2 were reported in 228 patients (56.1%). Development of trAE2 was associated with longer OS (16.7 versus 11.2 months) and PFS (5.5 versus 2.2 months) and persisted as an independent predictor of outcome after adjusting for viral aetiology, gender, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy. In a multi-institutional cohort of 357 patients with similar characteristics mostly treated with ICI monotherapy (n = 304, 85%), the development of trAE2 was associated with longer OS (23.3 versus 12.1 months) and PFS (9.6 versus 3.9 months). TrAE2 were confirmed predictors of improved OS (HR 0.43; 95% CI:0.25–0.75) and PFS (HR 0.48; 95% CI: 0.31–0.75), with multivariable analyses confirming their association with outcome independent of clinicopathologic features of interest. Additional time-varying multivariable analyses also indicated that trAEs were associated with a decreased risk of progression (HR 0.56, 95% CI: 0.46–0.67) in the FDA dataset and death (HR 0.55; 95% CI: 0.32–0.95) in the multi-institutional dataset. Development of trAE2 correlates with improved outcomes in patients with HCC receiving ICI in clinical trials and in routine practice. Prospective studies aimed at understanding the underlying immunologic foundations of such relationships are warranted to identify predictive biomarkers of toxicity and response. • Treatment-related adverse events (trAEs) may affect immunotherapy outcomes in HCC. • We correlated trAEs with response and survival in independent datasets. • trAEs predict for better response and survival in trials and clinical practice. [ABSTRACT FROM AUTHOR]

In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft-tissue sarcomas. An update is provided for leiomyosarcoma (LMS). Clinical trials with advanced or metastatic LMS were identified via literature review in PubMed (published 2003–2018, ≥10 adult LMS patients). End-points were 3- and 6-month progression-free survival rates (PFSR-3m and PFSR-6m). When estimates could not be derived from publications, data requests were sent out. Treatments were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guidelines. A random effects meta-analysis was used to pool trial-specific estimates for first-line (1L) or pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale was used to guide the treatment effect to target in future trials. From 47 studies identified, we obtained information on 7 1L and 16 2L+ trials for 1500 LMS patients. Overall, in 1L, PFSR-3m and PFSR-6m were 74% (95% confidence interval [CI] 64–82%) and 58% (95% CI 50–66%), respectively. For 2L+, PFSR-3m was 48% (95% CI 41–54%), and PFSR-6m was 28% (95% CI 22–34%). No difference was observed between R-T and NR-T for first or later lines. Under the alternative that the true benefit amounts to a hazard ratio of 0.65, a PFSR-6m ≥70% can be considered to suggest drug activity in 1L. For 2L+, a PFSR-3m ≥62% or PFSR-6m ≥44% would suggest drug activity. Specific results are also provided for uterine LMS. This work provides a new benchmark for designing phase II studies for advanced or metastatic LMS. • A novel random effects meta-analysis of 29 clinical trials (2003–2018). • More than 1500 patients with advanced/metastatic leiomyosarcoma (LMS). • Treatment classification according to the ESMO 2018 guidelines. • ESMO Magnitude of Clinical Benefit Scale (MCBS) to target treatment effects. • New benchmark for all LMS and specifically for uterine LMS patients. [ABSTRACT FROM AUTHOR]

Background Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking. Objectives We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA. Methods We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models. Results Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g. protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: β = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed. Conclusions Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function. [ABSTRACT FROM AUTHOR]

Increasingly, cancer drugs are being approved based on surrogate measurements of efficacy. Clinically meaningful data, such as overall survival (OS) and quality of life, are often only presented in subsequent publications. We examined if the clinical benefit of cancer drugs, as measured by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), improves post-European Medicines Agency (EMA) approval as more data emerges. Cancer drug indications approved by the EMA from January 2006 to December 2016 were reviewed and trials cited for efficacy were identified. Primary and subsequent publications (up to December 2019) of scorable trials were included. Changes in benefit over time were measured using ESMO-MCBS thresholds for non-curative (≥4 for substantial, =3 for intermediate and ≤2 for low benefit) and curative intent (A or B for major benefit) scoring. Fifty-five non-curative and two curative intent trials were included. At approval, 29.1% of non-curative trials were substantial, 45.5% intermediate and 25.5% low benefit. For curative intent trials, one displayed major benefit and one displayed no major benefit. We identified 82 subsequent publications for reassessment. A change in ESMO-MCBS classification was seen in 34.5% of non-curative trials (11 raised and 8 lowered). At 3-year reassessment, 36.4% of non-curative trials were substantial, 34.5% intermediate and 29.1% low benefit. Both curative trials showed no major benefit at reassessment. As over a third of trials changed classification, in either direction, reassessing the ESMO-MCBS score of approved cancer drugs may help to inform patients and ensure ongoing relevance of regulatory and reimbursement decisions. • When reassessed, most cancer drugs did not exhibit substantial benefit. • Over a third of drug trials changed benefit classification at 3-year reassessment. • However, a nearly equal number of trials increased and decreased their benefit. • Thus, it may be useful to regularly reassess the benefit of approved cancer drugs. [ABSTRACT FROM AUTHOR]

Background Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance. Objectives The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations. Methods We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n  = 1249 healthy older adults (aged 65–79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models. Results Intake of vitamin B-6 was related to lower chair rise test time [β: –0.033 ± 0.016 s (log); P  = 0.043]. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (β: 1.5 ± 0.8 kg; P  = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (β: –1.4 ± 0.7 kg; P  = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations. Conclusions Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012. [ABSTRACT FROM AUTHOR]

Cross-sectional studies from Eastern Asia have indicated a positive association between parental phubbing (snubbing via smartphones) and adolescent problematic gaming (PG). Longitudinal research is needed to evaluate the specific impact of maternal and paternal phubbing on adolescent PG in Europe. This study used a two-wave longitudinal design (with a six-month time interval) to test a theoretical model in which maternal and paternal phubbing at Wave 1 (W1) predicted adolescent PG at Wave 2 (W2), with maternal and paternal indifference (W2) as mediators. Gender differences in the hypothesized associations were also explored. Data were collected in Italy via online surveys, and the sample comprised 557 adolescent gamers (M age = 15.62 ± 1.54; 69% males). The mediation model was tested using path analysis, and multi-group comparisons were performed. The results showed that parental phubbing (W1) increased parental indifference (W2) in both mothers and fathers. Maternal phubbing (W1) indirectly predicted adolescent PG (W2) via increased maternal indifference (W2) in both males and females, whereas paternal phubbing (W1) directly and indirectly predicted adolescent PG (W2) via paternal indifference (W2) only in females. Parents and adolescents should be aware of the potentially detrimental effects associated with the dysfunctional use of digital technology. • Parental phubbing increased parental indifference of both mothers and fathers over time, as perceived by adolescent gamers. • A crossover effect between phubbing and indifference of the parents emerged. • Maternal phubbing indirectly predicted later adolescent PG via increased maternal indifference in both males and females. • Paternal phubbing, both directly and indirectly, predicted later adolescent PG via paternal indifference in females. [ABSTRACT FROM AUTHOR]

The uncertainty brought about by COVID-19 in times of mass migration adds an extra layer of perceived threat and competition for resources among host residents in migrant-receiving societies. This convergence of perceived threat potentially exacerbates implicit stereotypes about immigrants and can increase intergroup discord. We used panel data and a linear structural equation model to assess the distinct indirect effects of prejudice, as well as positive and negative intergroup emotions, within the associations of contact with immigrants and perceived COVID-19 threat (not directly related to immigrants) among host residents from 7 European countries, the United States, and Colombia (total N = 13,645). In addition, we examined potential underlying explanations regarding the role that implicit stereotypes of immigrants as disease carriers/spreaders (spillover effect) may play within the aforementioned associations. We introduce the concept of incidental intergroup threat to refer to the spillover of implicit immigrant stereotypes as disease spreaders onto emotional responses related to the presence of newcomers and pandemic threat perceptions. Our findings offer novel evidence that intergroup emotions exert indirect effects, above and beyond the effects of prejudice, vis-à-vis the association between intergroup contact and incidental pandemic threat. These results also suggest that, during global health disasters, spillover effects may yield incidental intergroup threats. Future interventions designed to address intergroup exclusionary reactions during disease pandemics could benefit from integrating threat regulation strategies into efforts to prevent spillover effects and incidental intergroup threats within immigrantreceiving societies. [ABSTRACT FROM AUTHOR]

National programs that reduce adolescent cannabis use warrant renewed attention in light of current discussions to reform cannabis legislation, including the possibility of legalization for recreational use. This study measures the size of a decrease in a country's prevalence of adolescent cannabis use that accompanies a decrease in its prevalence of adolescents who had ever smoked a cigarette. Data are from the European School Survey Project on Alcohol and Other Drugs (ESPAD), which is a collaborative effort of more than 40 European countries to surveil adolescent substance use. This study uses data from the seven survey administrations in 1995, 1999, 2003, 2007, 2011, 2015, and 2019. The main analysis is a fixed-effect regression analysis of country-level, four-year changes in adolescent lifetime cannabis use prevalence on country-level, four-year changes in adolescent lifetime cigarette use prevalence. Decreases in the national prevalence of adolescents who had ever smoked a cigarette were accompanied by decreases half as large in national prevalence of adolescent lifetime cannabis use. For European countries considering the legalization of adult recreational cannabis use, tobacco control can offer a tool to help counter potential increases in cannabis use among adolescents. [ABSTRACT FROM AUTHOR]

• Methamphetamine use is high among MSM: Across prevalence periods, the pooled prevalence were 15% and 23%, which demands urgent interventions. • High heterogeneity was found across study designs, subgroups of MSM, and regions. • Addressing adverse effects in MSM is critical: Research, policy, and collaboration are needed for prevention, education, healthcare, and harm reduction. International efforts have reduced the availability of methamphetamine precursors, but its distribution and use continue to rise. Methamphetamine use can lead to short- and long-term adverse effects, including addiction, physical and psychosocial health problems, socioeconomic troubles, incarceration, overdose, and death. Gay, bisexual, and other men who have sex with men (MSM) have been shown to have an elevated prevalence of methamphetamine use. We conducted a systematic review and meta-analysis to estimate the prevalence of methamphetamine use among MSM. We searched electronic databases, such as PubMed, for peer-reviewed literature published between 2011 and 2022. Data on methamphetamine use were extracted, including study features, location, study design, sampling method, recruitment period, specific MSM subgroups, prevalence period, and demographics. Employing a random-effects model, we computed the pooled prevalence of methamphetamine use among MSM across two prevalence periods: recent use (i.e., one month, three months, six months, one year) and lifetime use. The systematic review included 56 studies with a total of 25,953 MSM who use methamphetamine. Most studies were conducted in Europe, with the highest prevalence reported in the United Kingdom. The studies primarily used cross-sectional or cohort study designs with convenience sampling. The pooled prevalence rates across recent use (i.e., past month, past three months, past six months, and past year) was 15% (95% CI [11-19%]). Additionally, we pooled lifetime use, which was 23% (95% CI [9-38%]). High heterogeneity (I2 > 99%) was observed, indicating significant variation. This systematic review and meta-analysis provide a pooled prevalence of methamphetamine use among MSM. The analysis accounts for study design, prevalence period, specific MSM subgroups, and geographical areas to estimate methamphetamine use in diverse settings and populations. The review highlights the need for targeted interventions and harm reduction strategies focused on prevention, education, healthcare access, and stakeholder collaboration to address the multifaceted challenges of methamphetamine use among MSM. [ABSTRACT FROM AUTHOR]

An increasing proportion of colorectal cancer (CRC) cases in Europe are detected by screening with faecal immunochemical testing (FIT). Previous studies showed that population screening with FIT leads to a decrease in CRC incidence and to detection at an earlier stage. However, approximately twenty percent of patients with CRC without metastases at initial diagnosis still develop metachronous metastases. We investigated the association between detection mode of the primary tumor and overall survival (OS) after metachronous metastasis in patients with CRC. Nationwide registry-based data was obtained of 794 patients who developed metachronous metastases after being diagnosed with stage I-III CRC between January and June 2015. With multivariable Cox PH regression modelling, we analyzed the (causal) association between detection mode of the primary tumor (FIT screen-detected versus non-screen-detected) and OS after metachronous metastasis while adjusting for potential confounders. Median OS and five-year OS after metachronous metastasis were significantly higher for patients with screen-detected (n = 152) vs. non-screen-detected primary tumors (n = 642): 38.3 vs. 19.2 months, and 35.4% vs. 18.8%, respectively, p < 0.0001). After adjustment for potential confounders, the association between detection mode and OS after metachronous metastasis remained significant (HR 0.70 [95% CI 0.56–0.89]). Screen-detection of the primary tumor was independently associated with longer OS after metachronous metastasis. This may support the clinical utility of the population screening program and it shows the prognostic value of detection mode of the primary tumor once metachronous metastasis is diagnosed. • More CRC cases in Europe are detected by population screening. • Study on the consequences of screening for prognosis after metachronous metastases. • mOS after metastases was 19.1 months longer for screen-detected primary CRC tumors. • 5-year OS after metastases was 16.6% higher for screen-detected primary CRC tumors. • The association remained in multivariable and sensitivity analyses. [ABSTRACT FROM AUTHOR]