Epidemic intelligence in Europe: a user needs perspective to foster innovation in digital health surveillance.

BACKGROUND: European epidemic intelligence (EI) systems receive vast amounts of information and data on disease outbreaks and potential health threats. The quantity and variety of available data sources for EI, as well as the available methods to manage and analyse these data sources, are constantly increasing. Our aim was to identify the difficulties encountered in this context and which innovations, according to EI practitioners, could improve the detection, monitoring and analysis of disease outbreaks and the emergence of new pathogens. METHODS: We conducted a qualitative study to identify the need for innovation expressed by 33 EI practitioners of national public health and animal health agencies in five European countries and at the European Centre for Disease Prevention and Control (ECDC). We adopted a stepwise approach to identify the EI stakeholders, to understand the problems they faced concerning their EI activities, and to validate and further define with practitioners the problems to address and the most adapted solutions to their work conditions. We characterized their EI activities, professional logics, and desired changes in their activities using NvivoⓇ software. RESULTS: Our analysis highlights that EI practitioners wished to collectively review their EI strategy to enhance their preparedness for emerging infectious diseases, adapt their routines to manage an increasing amount of data and have methodological support for cross-sectoral analysis. Practitioners were in demand of timely, validated and standardized data acquisition processes by text mining of various sources; better validated dataflows respecting the data protection rules; and more interoperable data with homogeneous quality levels and standardized covariate sets for epidemiological assessments of national EI. The set of solutions identified to facilitate risk detection and risk assessment included visualization, text mining, and predefined analytical tools combined with methodological guidance. Practitioners also highlighted their preference for partial rather than full automation of analyses to maintain control over the data and inputs and to adapt parameters to versatile objectives and characteristics. CONCLUSIONS: The study showed that the set of solutions needed by practitioners had to be based on holistic and integrated approaches for monitoring zoonosis and antimicrobial resistance and on harmonization between agencies and sectors while maintaining flexibility in the choice of tools and methods. The technical requirements should be defined in detail by iterative exchanges with EI practitioners and decision-makers.

[Selected aspects regarding social factors in skin diseases]. / Ausgewählte Aspekte sozialer Faktoren bei Hautkrankheiten.

Skin diseases are complex and cannot be explained solely by genetic or environmental factors but are also significantly shaped by social influences. This review illuminates the bidirectional relationship between social factors and skin diseases, demonstrating how social determinants such as socioeconomic status, living environment, and psychosocial stress can influence the onset and progression of skin conditions. Simultaneously, it explores how skin diseases can affect individuals' social lives and work capability, leading to a cycle of social withdrawal and further deterioration of the condition. The paper describes the need for a holistic approach in dermatology that goes beyond the biomedical perspective and incorporates social factors to develop effective prevention and treatment strategies. The increasing prevalence of skin diseases in Europe and the expected rise in allergies due to climate change make the consideration of social determinants even more urgent. The findings of this review aim to raise awareness of the complex interconnections between social factors and skin health and contribute to reducing social disparities in skin health.

From the creation of the European research area in 2000 to a Mission on cancer in Europe in 2021-lessons learned and implications.

In the year 2000, cancer research in Europe had the potential to make a difference as it had several unique strengths, such as a strong foundation in biomedical science, good patient registries, infrastructures that spanned from biological repositories to bioinformatic hubs as well as thriving Comprehensive Cancer Centers (CCCs) and basic/preclinical cancer research institutions of high international standing. Research, however, was fragmented and lacked coordination. As a result, Europe could not harness its potential for translating basic research discoveries into a clinical setting for the patients' benefit. What was needed was a paradigm shift in cancer research that addressed the translational research continuum. Along these lines, in 2000, European Union (EU) Commissioner Philippe Busquin established the European Research Area (ERA) and in 2002 the European Cancer Research Area (ECRA), and their political approval was a powerful catalyst for the increased involvement of scientists in science policy in the EU. In this report, we briefly describe the actions embraced by the cancer community and cancer organizations in response to Busquin's proposals that led to the creation of the EU Mission on Cancer (MoC) in Horizon 2020 in 2021.

Risk and sex-specific trends of dementia and stroke in Italy Compared to European and high-income countries and the world: global implications.

BACKGROUND: Understanding the increasing trends in Italy may inform new prevention strategies and better treatments. We investigated trends and risk factors of dementia, stroke, and ischemic heart disease (IHD) in Italy with the second-oldest population globally, compared to European and high-income countries and the world. METHODS: We analyzed the Global Burden of Disease Study (GBD) 2019 estimates on incidence and burden (i.e., disability and death combined) of the three conditions in both sexes. We also analyzed the burden attributable to 12 modifiable risk factors and their changes during 1990-2019. RESULTS: In 2019, Italy had 186,108 new dementias (123,885 women) and 94,074 new strokes (53,572 women). Women had 98% higher crude dementia and 24% higher crude stroke burdens than men. The average age-standardized new dementia rate was 114.7 per 100,000 women and 88.4 per 100,000 men, both higher than Western Europe, the European Union, high-income countries, and the world. During 1990-2019, this rate increased in both sexes (4%), despite a decline in stroke (- 45%) and IHD (- 17%) in Italy. Dementia burden attributable to tobacco decreased in both sexes (- 12.7%) during 1990-2019, while high blood glucose and high body mass index combined burden increased (25.4%). Stroke and IHD had similar trends. CONCLUSIONS: While decreases in new strokes and IHDs are encouraging, new approaches to their joint prevention are required to reverse the rising dementia trends, especially among women. Life course approaches to promoting holistic brain health should be implemented at the community, national, and international levels before the growing trends become overwhelming.

Editors' highlight picks from 2023 in ESC heart failure.

Heart failure is a devastating syndrome affecting an increasingly high number of patients worldwide. Its aetiology and pathogenesis are complex with the involvement of factors ranging from the genetic material through valvular dysfunctions to numerous organs beyond the entire cardiovascular system. Based on continuous efforts of the heart failure scientific community we have witnessed major advances in many related disciplines during the last year. For example, epidemiological aspects-paving the road for improved risk prevention-have been thoroughly analysed for various geographical regions. Additionally, evidence-based approaches now allow the introduction of novel guideline recommended medical therapies (i.e. sodium-glucose transporter 2 inhibitors, and iron supplementation) while basic and translational research aim to explore additional molecular targets for future heart failure diagnostics and medications. All above aspects are addressed in this article, where a selection of articles published in the ESC Heart Failure journal in 2023 are highlighted. The editors are confident that the scientific contributions of ESC Heart Failure effectively served a highly relevant area of cardiovascular research last year.

Redefining the treponemal history through pre-Columbian genomes from Brazil.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3-6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

Long-Term Exposure to Low-Level PM2.5 and Mortality: Investigation of Heterogeneity by Harmonizing Analyses in Large Cohort Studies in Canada, United States, and Europe.

BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible. METHODS: We harmonized the study populations to individuals 65+ years of age, applied the same satellite-derived PM2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF). RESULTS: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5-µg/m3 increase in PM2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141.

Tuberculosis in prehistory in Eastern Central Europe (Hungary) - Chronological and geographical distribution.

Tuberculosis (TB) has long been a major scourge of humankind. Paleopathological and paleomicrobiological studies have revealed the past presence of the disease on a large spatial and temporal scale. The antiquity of the disease has extensively been studied in the Carpathian Basin, given its dynamic population and cultural changes since prehistory. These studies, however, have mainly focused on the populations living during the Common Era. The aim of this paper is to present the published and the recently discovered cases of prehistoric TB, from the Neolithic (6000-4500/4400 BCE) to the Bronze Age (2600/2500-800 BCE) Central Carpathian Basin (Hungary). We summarize 18 published cases and present new cases dating to the Neolithic period and introduce 3 newly discovered Bronze Age cases of TB. Despite extensive research, TB has not yet been identified from the Copper and Iron Ages in the Carpathian Basin. Considering the state of TB research, and supplemented by our prehistoric dataset, the spatio-temporal pattern of the disease can be further elucidated, thus advancing future molecular and paleopathological studies. Our dataset offers comprehensive spatial and temporal information on the spread of the disease in the Carpathian Basin, along with a detailed biological profile of the demonstrated cases and extensive paleopathological descriptions of the observed lesions, complemented by photographic evidence. This invaluable resource paves the way for enhanced understanding and progress in the field.

The role of primary care during the pandemic: shared experiences from providers in five European countries.

BACKGROUND: The COVID-19 pandemic necessitated wide-ranging adaptations to the organisation of health systems, and primary care is no exception. This article aims to collate insights on the role of primary care during the pandemic. The gained knowledge helps to increase pandemic preparedness and resilience. METHODS: The role of primary care during the pandemic in five European countries (Austria, Denmark, France, Hungary, Italy) was investigated using a qualitative approach, namely case study, based on document analysis and semi-structured interviews. In total, 31 interviews were conducted with primary care providers between June and August 2022. The five country case studies were subjected to an overarching analysis focusing on successful strategies as well as gaps and failures regarding pandemic management in primary care. RESULTS: Primary care providers identified disruptions to service delivery as a major challenge emerging from the pandemic which led to a widespread adoption of telehealth. Despite the rapid increase in telehealth usage and efforts of primary care providers to organise face-to-face care delivery in a safe way, some patient groups were particularly affected by disruptions in service delivery. Moreover, primary care providers perceived a substantial propagation of misinformation about COVID-19 and vaccines among the population, which also threatened patient-physician relationships. At the same time, primary care providers faced an increased workload, had to work with insufficient personal protective equipment and were provided incongruous guidelines from public authorities. There was a consensus among primary care providers that they were mostly sidelined by public health policy in the context of pandemic management. Primary care providers tackled these problems through a diverse set of measures including home visits, implementing infection control measures, refurbishing used masks, holding internal meetings and relying on their own experiences as well as information shared by colleagues. CONCLUSION: Primary care providers were neither well prepared nor the focus of initial policy making. However, they implemented creative solutions to the problems they faced and applying the learnings from the pandemic could help in increasing the resilience of primary care. Attributes of an integrated health system with a strong primary care component proved beneficial in addressing immediate effects of the pandemic.

Obesity-related complications, healthcare resource use and weight loss strategies in six European countries: the RESOURCE survey.

BACKGROUND: Obesity-related complications (ORCs), such as type 2 diabetes (T2D) and cardiovascular disease, contribute considerably to the clinical and economic impacts of obesity. To obtain a holistic overview of health and weight management attempts for people with obesity in Europe, we designed the cross-sectional RESOURCE survey to collect data on comorbidities, healthcare resource use (HCRU) and weight loss strategies from people with obesity in France, Germany, Italy, Spain, Sweden and the UK. METHODS: Adults (≥18 years old) with self-reported body mass index (BMI) ≥30 kg/m2 who reported interacting with primary or secondary healthcare services in the past 12 months, but had not been pregnant during this time, were recruited from an existing consumer research panel. All data were self-reported via an online survey (May-June 2021). Weight changes over the past year were calculated from participants' estimated weights. RESULTS: Of the 1850 participants in the survey, 26.3% reported that they had ≥3 ORCs from a set of 15 conditions of interest. The most frequently reported ORCs were hypertension (39.3% of participants), dyslipidaemia (22.8%) and T2D (17.5%). Participants in obesity class III (BMI 40 to <70 kg/m2) were more likely to report multiple ORCs than those in lower obesity classes. The presence of multiple ORCs was linked to various types of HCRU, including a significantly increased chance of reporting hospitalization in the past year. Most participants (78.6%) had attempted to lose weight in the past year, but of those who also reported estimated weight changes, 73.4% had not experienced clinically meaningful weight loss of ≥5%. CONCLUSIONS: ORCs are common in people with obesity, and are linked to increased HCRU. Together with the low reported success rate of weight loss attempts, this highlights an unmet need in Europe for enhanced weight management support for people with obesity.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

1000 Days: The "WeCare Generation" Program-The Ultimate Model for Improving Human Mental Health and Economics: The Study Protocol.

INTRODUCTION: The COVID-19 pandemic stressed the necessity of a new resilience of the human population and health system. The "WeCare Generation" program is a new proposal of territorial intervention, with a new paradigm, on the diseases of the human body and mind. BACKGROUND: In recent decades, the independent strands of investigation on brain plasticity and early trauma consequences have demonstrated that traumatic experiences in the period from pregnancy to the age of 3 years have an enormous impact on an individual's future development, and both physical and mental health. Research shows that adverse child experiences (ACEs) are associated with a strong risk of conditions such as: harmful alcohol use, smoking, illicit drug use, high body-mass index, depression, anxiety, interpersonal violence, cancer, type 2 diabetes, cardiovascular diseases, stroke respiratory diseases and, as a consequence, to a high financial cost in Italy and also across Europe (1-9% GDP) and the USA (total annual costs estimated to be USD 581 billion in Europe and USD 748 billion in North America). All this suggests that an early intervention on that traumatized-slice of population leads to multiplied savings. METHODS: A multi-center, randomized, controlled trial was designed. The parents of the future neonatal population (from pregnancy to delivery) with trauma will be enrolled, and randomized to treatment, or control arm. The article describes in detail how the primary outpoint (cost to the national health system), and some secondary outpoints, will be collected. DISCUSSION: An overall rate of return on investment (ROI) statistically significant 13.0% per annum with an associated benefit/cost ratio (BCR) of 6.3 is expected as the primary outcome of the "WeCare Generation" program. Our proposed model predicts a new medical paradigm aiming to empower new generations, with a strong return on economy and health.

Anaphylaxis across Europe: are pollen food syndrome and lipid transfer protein allergy so far apart?

PURPOSE OF REVIEW: Traditionally pollen-food syndrome (PFS) is considered to be a mild cross-reacting food allergy affecting only Northern Europe, with lipid transfer protein (LTP) allergy being more severe and mainly occurring in Southern Europe. This review seeks to update the reader on both types of plant food allergy and to determine whether the stereotypical presentations of these plant food allergies remain the same, with a particular focus on reaction severity. RECENT FINDINGS: Recent findings suggest that both these types of plant food allergy occur in children and adults. Although it is true that PFS allergy is more prevalent in Northern Europe and LTP allergy is more well known in Southern Europe, these conditions are not hidebound by geography, and the increasing spread and allergenicity of pollen due to global warming continues to change their presentation. Both conditions have a spectrum of symptom severity, with PFS sometimes presenting with more severe symptoms, including anaphylaxis and LTP allergy with milder reactions. SUMMARY: It is important to consider that in many parts of Europe, reactions to plant foods, especially fruits or vegetables, could be mediated either by pollen cross-reactivity or primary sensitization to LTP allergens. All those presenting with symptoms to plant foods will benefit from a detailed clinical history and appropriate tests so that an accurate diagnosis can be made, and correct management implemented.

Improving treatment of patients with psychosis in low-and-middle-income countries in Southeast Europe: Results from a hybrid effectiveness-implementation, pragmatic, cluster-randomized clinical trial (IMPULSE).

BACKGROUND: In Southeast Europe (SEE) standard treatment of patients with psychosis is largely based on pharmacotherapy with psychosocial interventions rarely available. DIALOG+ is a digital psychosocial intervention designed to make routine care therapeutically effective. This trial simultaneously examined effectiveness of DIALOG+ versus standard care on clinical and social outcomes (Aim 1) and explored intervention fidelity (Aim 2). METHODS: A hybrid type II effectiveness-implementation, cluster-randomized trial was conducted in five SEE countries: Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, and Serbia. The intervention was offered to patients six times across 12 months instead of routine care. The outcomes were subjective quality of life (primary), clinical symptoms, satisfaction with services, and economic costs. Intervention fidelity was operationalized as adherence to the protocol in terms of frequency, duration, content, and coverage. Data were analyzed using multilevel regression. RESULTS: A total of 81 clinicians and 468 patients with psychosis were randomized to DIALOG+ or standard care. The intervention was delivered with high fidelity. The average number of delivered sessions was 5.5 (SD = 2.3) across 12 months. Patients in the intervention arm had better quality of life (MANSA) at 6 months (p = 0.03). No difference was found for other outcomes at 6 months. Due to disruptions caused by the COVID-19 pandemic, 12-month data were not interpretable. CONCLUSIONS: DIALOG+ improved subjective quality of life of individuals with psychosis at 6 months (after four sessions), albeit with small effect size. The intervention has the potential to contribute to holistic care of patients with psychosis.

Prescribing Patterns of Codeine and Alternative Medicines in Children in Europe.

INTRODUCTION: Concerns over serious respiratory depression in children led to two European Union (EU) referral procedures (in 2013 and 2015) to review the benefit-risk balance of codeine in this population when used for pain relief, cough or cold. Consequently, codeine should no longer be used in children aged < 12 years and restrictions were introduced for treatment in children ≥ 12 years. OBJECTIVE: This multinational collaborative study aimed to assess the effectiveness of these risk minimisation measures by evaluating changes in prescribing of codeine and alternative treatments. METHOD: Children under 12 and 12-18 years old were followed between 2010 and 2017 to analyse quarterly trends in prescribing of codeine and alternative treatments in electronic health records from France, Germany, Norway, Spain and the United Kingdom using interrupted time series analysis. RESULTS: Overall prescribing of codeine in children decreased in all five countries, reaching near zero prevalence in children under 12 years of age. This was accompanied by an increase in use of other opioid analgesics in France (from 0.15 to 0.56 prevalence per 100 person-years immediately after the first referral), Norway (from 0.0006 to 0.0013 at the end of the study), the United Kingdom (from 0.018 to 0.05 at the end of the study), and an increase in non-opioid analgesics in Norway (from 0.045 to 0.075 at the end of the study) after the referral on pain relief indication. The referral on cough/cold indication led to a decrease in use of opioid and non-opioid antitussives in children aged < 12 years in France (from 10 to 7 and 20 to 16, respectively) and had no impact in other countries. Overall prescribing trends for codeine and alternatives were similar across both age groups within each country. CONCLUSION: The decrease in use of codeine shows that healthcare professionals followed the adopted measures and switched prescribing practices for pain management in children aged < 18 years towards opioid or non-opioid analgesics depending on national clinical and reimbursement settings. Whist the magnitude of the first referral on pain differed between countries, the second referral on cough/cold had only a minimal impact on the use of codeine and antitussives.

'Value-based methodology for person-centred, integrated care supported by Information and Communication Technologies' (ValueCare) for older people in Europe: study protocol for a pre-post controlled trial.

BACKGROUND: Older people receive care from multiple providers which often results in a lack of coordination. The Information and Communication Technology (ICT) enabled value-based methodology for integrated care (ValueCare) project aims to develop and implement efficient outcome-based, integrated health and social care for older people with multimorbidity, and/or frailty, and/or mild to moderate cognitive impairment in seven sites (Athens, Greece; Coimbra, Portugal; Cork/Kerry, Ireland; Rijeka, Croatia; Rotterdam, the Netherlands; Treviso, Italy; and Valencia, Spain). We will evaluate the implementation and the outcomes of the ValueCare approach. This paper presents the study protocol of the ValueCare project; a protocol for a pre-post controlled study in seven large-scale sites in Europe over the period between 2021 and 2023. METHODS: A pre-post controlled study design including three time points (baseline, post-intervention after 12 months, and follow-up after 18 months) and two groups (intervention and control group) will be utilised. In each site, (net) 240 older people (120 in the intervention group and 120 in the control group), 50-70 informal caregivers (e.g. relatives, friends), and 30-40 health and social care practitioners will be invited to participate and provide informed consent. Self-reported outcomes will be measured in multiple domains; for older people: health, wellbeing, quality of life, lifestyle behaviour, and health and social care use; for informal caregivers and health and social care practitioners: wellbeing, perceived burden and (job) satisfaction. In addition, implementation outcomes will be measured in terms of acceptability, appropriateness, feasibility, fidelity, and costs. To evaluate differences in outcomes between the intervention and control group (multilevel) logistic and linear regression analyses will be used. Qualitative analysis will be performed on the focus group data. DISCUSSION: This study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people, their informal caregivers, and health and social care practitioners in seven different European settings. TRIAL REGISTRATION: ISRCTN registry number is 25089186 . Date of trial registration is 16/11/2021.

Summary of key guidelines for locoregional treatment of HCC in Asia, Europe, South and North America.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide accounting for over 800,000 new cases in 2018, with the highest incidence in Asia and Africa where hepatitis B is the most common risk factor. In Europe, Japan, and the United States, hepatitis C chronic alcohol abuse and non-alcoholic fatty liver disease are more common risk factors. Five-year survival is low, less than 20% worldwide. HCC is a particularly challenging disease to treat because therapeutic options and prognosis must also consider hepatitis or cirrhosis independent of the malignancy. Locoregional therapies (LRT) including ablation, arterially directed therapy and external beam radiation are the preferred treatments for patients with good performance status, unresectable disease limited to the liver and preserved liver function. In practice, patients with portal vein tumor thrombus and limited extrahepatic disease may also be considered candidates for LRT. There are several guidelines developed by expert panels provide recommendations on treating this challenging disease including the Barcelona Clinic Liver Cancer, European Association for the Study of the Liver, European Society for Medical Oncology, American Association for the Study of the Liver Diseases, and the National Comprehensive Cancer Network. The purpose of this paper is to review the guidelines as they are applied clinically in regions with high incidence of HCC.

Dairying, diseases and the evolution of lactase persistence in Europe.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

Vitamin D food fortification in European countries: the underused potential to prevent cancer deaths.

BACKGROUND: Meta-analyses of randomized controlled trials have shown that vitamin D supplementation reduces cancer mortality by 13%. Vitamin D fortification of foods may increase vitamin D levels in a similar manner as vitamin D supplementation and could achieve similar reductions in cancer mortality. Whereas some European countries already implemented widespread fortification of foods with vitamin D, in other countries only few or no foods are fortified. In this study, we estimated the reduction in cancer mortality presumably already achieved by current fortification policies in 2017 and the potential for further reductions if all countries had effective fortification. METHODS: We reviewed scientific literature, publicly available information, and contacted health authorities to obtain information on current vitamin D food fortification policies in 34 European countries. Together with country-specific cancer death statistics from Eurostat, information on life expectancy, and country-specific fortification policies, we used data from studies on supplementation and serum 25(OH)D increases and cancer mortality to estimate numbers of probably already prevented cancer deaths and numbers of potentially further preventable deaths and years of life lost. RESULTS: Current vitamin D fortification is estimated to prevent approximately 11,000 in the European Union and 27,000 cancer deaths in all European countries considered per year. If all countries considered here would implement adequate vitamin D fortification of foods, an estimated additional 129,000 cancer deaths (113,000 in the European Union) could be prevented, corresponding to almost 1.2 million prevented years of life lost (1.0 million in the EU) or approximately 9% of cancer deaths (10% in the EU). INTERPRETATION: Systematic fortification of foods might considerably reduce the burden of cancer deaths in Europe.