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Objectives Research among older adults reveals that the loss of core network members is a risk factor for loneliness. Still, it is not clear whether all such losses induce similar levels of loneliness, particularly as network members are distributed at varied geographic distances. Neither is it clear whether tie addition—the other ubiquitous aspect of network turnover in later life—offsets the loneliness that arises from different network loss scenarios. Methods This paper scrutinized core network losses across multiple relationship–distance scenarios. We used the fourth and sixth waves of data from the Survey of Health, Ageing, and Retirement in Europe and estimated fixed-effect models. Results The loss of a child from a core network increases feelings of loneliness across variant distances, especially when not complemented by additional connections. Losing relatives or nonkin core connections in proximity (within 1 km and 5 km radius, respectively) is also associated with increased loneliness, yet such effects are also largely mitigated by the addition of new core network members. Discussion The relationship between core network member losses and loneliness can significantly differ based on the nature of the lost connection and its geographic distance. Active rebalancing of one's core network following losses and proactive network expansion can serve as pivotal strategies to prevent loneliness for the aging population. [ABSTRACT FROM AUTHOR]

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

Study Question: How many twins are born in human populations and how has this changed over recent decades?Summary Answer: Since the 1980s, the global twinning rate has increased by a third, from 9.1 to 12.0 twin deliveries per 1000 deliveries, to about 1.6 million twin pairs each year.What Is Known Already: It was already known that in the 1980s natural twinning rates were low in (East) Asia and South America, at an intermediate level in Europe and North America, and high in many African countries. It was also known that in recent decades, twinning rates have been increasing in the wealthier parts of our world as a result of the rise in medically assisted reproduction (MAR) and delayed childbearing.Study Design, Size, Duration: We have brought together all information on national twinning rates available from statistical offices, demographic research institutes, individual survey data and the medical literature for the 1980-1985 and the 2010-2015 periods.Participants/materials, Setting, Methods: For 165 countries, covering over 99% of the global population, we were able to collect or estimate twinning rates for the 2010-2015 period. For 112 countries, we were also able to obtain twinning rates for 1980-1985.Main Results and the Role Of Chance: Substantial increases in twinning rates were observed in many countries in Europe, North America and Asia. For 74 out of 112 countries the increase was more than 10%. Africa is still the continent with highest twinning rates, but Europe, North America and Oceania are catching up rapidly. Asia and Africa are currently home to 80% of all twin deliveries in the world.Limitations, Reasons For Caution: For some countries, data were derived from reports and papers based on hospital registrations which are less representative for the country as a whole than data based on public administrations and national surveys.Wider Implications Of the Findings: The absolute and relative number of twins for the world as a whole is peaking at an unprecedented level. An important reason for this is the tremendous increase in medically assisted reproduction in recent decades. This is highly relevant, as twin deliveries are associated with higher infant and child mortality rates and increased complications for mother and child during pregnancy and during and after delivery.Study Funding/competing Interest(s): The contribution of CM was partially supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant No 681546, FAMSIZEMATTERS), Nuffield College, and the Leverhulme Trust. The contribution of GP was partially supported by the French Agence Nationale de la Recherche (grant No ANR-18-CE36-0007-07). The authors declare no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: For better supporting the science-governance interface, the potential of health assessments appears underrated. Aims: To identify what various types of health assessment have in common; how they differ; which assessment(s) to apply for which purpose; and what needs and options there are for future joint development. Methods: This review is based on five types of health assessment: monitoring/surveillance/reporting, assessment of health impact, of health technology, of health systems performance, health-related economic assessment. The approach is exploratory and includes: applying an agreed set of comparative criteria; circulating and supplementing synoptic tables; and interpreting the results. Results: Two of the assessments deal with the question 'Where do we stand?', two others with variants of 'What if' questions. Economic Assessment can take place in combination with any of the others. The assessments involve both overall 'procedures' and a variety of 'methods' which inescapably reflect some subjective assumptions and decisions, e.g. on issue framing. Resources and assistance exist for all these assessments. The paper indicates which type of assessment is appropriate for what purpose. Conclusions: Although scientific soundness of health assessments is not trivial to secure, existing types of health assessment can be interpreted as a useful 'toolkit' for supporting governance. If current traces of 'silo' thinking can be overcome, the attainability of a more unified culture of health assessments increases and such assessments might more widely be recognized as a prime, 'tried and tested' way to voice Public Health knowledge and to support rational governance and policy-making. [ABSTRACT FROM AUTHOR]

Context/problem: Comparative analysis of relative and absolute mortality differentials between socioeconomic groups are now available. These show consistently increasing relative increases in mortality differentials but complex trends in absolute mortality differentials. Objective: This paper provides an analysis of relative and absolute trends in mortality by cause of death and socioeconomic group (SEG) from 1984 to 2008 among men and active women aged 30-64 years in Ireland and compares these results with recent European and US studies to give an overview of trends. Methods: This paper uses mortality data from the Irish Central Statistics Office from 1984 to 2008 to calculate standardized death rates by age, sex, socioeconomic status and cause of death showing trends in SEG inequalities in mortality in Ireland. These show which specific causes of death are driving all-cause mortality trends. Results: SEG differentials in all-cause mortality among men and women have been increasing since the 1980s. Some of this increase reflects larger falls in cardiovascular causes among advantaged groups, but the trend is largely accounted for by increasing inequalities in mortality in digestive, neoplasm and external causes of deaths. Conclusions: These findings are in line with international findings that show that socioeconomic differentials in digestive, neoplasm and external cause deaths are driving general socioeconomic differentials in all-cause mortality. External cause deaths may have been influenced by levels of economic activity, particularly in construction, during the economic boom among manual workers. Furthermore, deaths from digestive diseases during the 1990s and 2000s may well be the result of increases in liver disease associated with excessive alcohol consumption. [ABSTRACT FROM AUTHOR]

Background The Nordic countries represent a unique case study for the COVID-19 pandemic due to socioeconomic and cultural similarities, high-quality comparable administrative register data and notable differences in mitigation policies during the pandemic. We aimed to compare weekly excess mortality in the Nordic countries across the three full pandemic years 2020–2022. Methods Using data on weekly all-cause mortality from official administrative registers in Denmark, Finland, Norway and Sweden, we employed time series regression models to assess mortality developments within each pandemic year, with the period 2010–2019 used as reference period. We then compared excess mortality across the countries in 2020–2022, taking differences in population size and age- and sex-distribution into account. Results were age- and sex-standardized to the Danish population of 2020. Robustness was examined with a variety of sensitivity analyses. Results While Sweden experienced excess mortality in 2020 [75 excess deaths per 100 000 population (95% prediction interval 29–122)], Denmark, Finland and Norway experienced excess mortality in 2022 [52 (14–90), 130 (83–177) and 88 (48–128), respectively]. Weekly death data reveal how mortality started to increase in mid-2021 in Denmark, Finland and Norway, and continued above the expected level through 2022. Conclusion Although the Nordic countries experienced relatively low pandemic excess mortality, the impact and timing of excess mortality differed substantially. These estimates—arguably the most accurate available for any region in capturing pandemic-related excess deaths—may inform future research and policy regarding the complex mortality dynamics in times of a health crisis such as the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background Type-2 diabetes (T2D) and hypertension (HTN) are two of the most prevalent non-communicable diseases (NCDs): they both cause a relevant number of premature deaths worldwide and heavily impact the national health systems. This study illustrates the impact of HTN and T2D in four European countries (Albania, Bulgaria, Greece and Spain) and compares their policies towards the monitoring and management of HTN and T2D and the prevention of NCDs as a whole. This analysis is conducted throughout the DigiCare4You Project (H2020)—which implements an innovative solution involving digital tools for the prevention and management of T2D and HTN. Methods The analysis is implemented through desk research, and it is enriched with additional information directly provided by the local coordinators in the four countries, by filling specific semi-structured forms. Results The countries exhibit significant differences in the prevalence of HTN and T2D and available policies and programs targeted to these two chronic conditions. Each country has implemented strategies for HTN and T2D, including prevention initiatives, therapeutic guidelines, educational programs and children's growth monitoring programs. However, patient education on proper disease management needs improvement in all countries, registries about patients affected by HTN and T2D are not always available, and not all countries promoted acts to contain the increasing rates of risk factors related to NCDs. Conclusions While political awareness of the risks associated with HTN, T2D and NCDs in general is growing, there is a collective need for countries to strengthen their policies for preventing and managing these chronic diseases. [ABSTRACT FROM AUTHOR]

Background Resilience of national health systems in Europe remains a major concern in times of multiple crises and as more evidence is emerging relating to the indirect effects of the COVID-19 pandemic on health care utilization (HCU), resulting from de-prioritization of regular, non-pandemic healthcare services. Most extant studies focus on regional, disease specific or early pandemic HCU creating difficulties in comparing across multiple countries. We provide a comparatively broad definition of HCU across multiple countries, with potential to expand across regions and timeframes. Methods Using a cross-country federated research infrastructure (FRI), we examined HCU for acute cardiovascular events, elective surgeries and serious trauma. Aggregated data were used in forecast modelling to identify changes from predicted European age-standardized counts via fitted regressions (2017–19), compared against post-pandemic data. Results We found that elective surgeries were most affected, universally falling below predicted levels in 2020. For cardiovascular HCU, we found lower-than-expected cases in every region for heart attacks and displayed large sex differences. Serious trauma was the least impacted by the COVID-19 pandemic. Conclusion The strength of this study comes from the use of the European Population Health Information Research Infrastructure's (PHIRI) FRI, allowing for rapid analysis of regional differences to assess indirect impacts of events such as pandemics. There are marked differences in the capacity of services to return to normal in terms of elective surgery; additionally, we found considerable differences between men and women which requires further research on potential sex or gender patterns of HCU during crises. [ABSTRACT FROM AUTHOR]

Background: Tier 1 exposure tools recommended for use under REACH are designed to easily identify situations that may pose a risk to health through conservative exposure predictions. However, no comprehensive evaluation of the performance of the lower tier tools has previously been carried out. The ETEAM project aimed to evaluate several lower tier exposure tools (ECETOC TRA, MEASE, and EMKG-EXPO-TOOL) as well as one higher tier tool (STOFFENMANAGER®). This paper describes the results of the external validation of tool estimates using measurement data. Methods: Measurement data were collected from a range of providers, both in Europe and United States, together with contextual information. Individual measurement and aggregated measurement data were obtained. The contextual information was coded into the tools to obtain exposure estimates. Results were expressed as percentage of measurements exceeding the tool estimates and presented by exposure category (non-volatile liquid, volatile liquid, metal abrasion, metal processing, and powder handling). We also explored tool performance for different process activities as well as different scenario conditions and exposure levels. Results: In total, results from nearly 4000 measurements were obtained, with the majority for the use of volatile liquids and powder handling. The comparisons of measurement results with tool estimates suggest that the tools are generally conservative. However, the tools were more conservative when estimating exposure from powder handling compared to volatile liquids and other exposure categories. In addition, results suggested that tool performance varies between process activities and scenario conditions. For example, tools were less conservative when estimating exposure during activities involving tabletting, compression, extrusion, pelletisation, granulation (common process activity PROC14) and transfer of substance or mixture (charging and discharging) at nondedicated facilities (PROC8a; powder handling only). With the exception of STOFFENMANAGER® (for estimating exposure during powder handling), the tools were less conservative for scenarios with lower estimated exposure levels. Conclusions: This is the most comprehensive evaluation of the performance of REACH exposure tools carried out to date. The results show that, although generally conservative, the tools may not always achieve the performance specified in the REACH guidance, i.e. using the 75th or 90th percentile of the exposure distribution for the risk characterisation. Ongoing development, adjustment, and recalibration of the tools with new measurement data are essential to ensure adequate characterisation and control of worker exposure to hazardous substances. [ABSTRACT FROM AUTHOR]

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue.Methods: The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries.Results: A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90).Conclusion: Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined. [ABSTRACT FROM AUTHOR]

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

There are several measures that summarize the mortality experience of a population. Of these measures, life expectancies are generally preferred based on their simpler interpretation and direct age standardization, which makes them directly comparable between different populations. However, traditional life expectancy estimations are highly inaccurate for smaller populations and consequently are seldom used in small-area applications. In this paper, the authors compare the relative performance of traditional life expectancy estimation with a Bayesian random-effects approach that uses correlations (i.e., borrows strength) between different age groups, geographic areas, and sexes to improve the small-area life expectancy estimations. In the presented Monte Carlo simulations, the Bayesian random-effects approach outperforms the traditional approach in terms of bias, root mean square error, and coverage of the 95% confidence intervals. Moreover, the Bayesian random-effects approach is found to be usable for populations as small as 2,000 person-years at risk, which is considerably smaller than the minimum of 5,000 person-years at risk recommended for the traditional approach. As such, the proposed Bayesian random-effects approach is well-suited for estimation of life expectancies in small areas. [ABSTRACT FROM AUTHOR]

This paper has contributed to confirming the link between education and health in developed countries. The analysis is based on 11 European Union countries. We estimate country-specific health functions, where the dependent variable is self-reported health status and the education attainment is one of the main inputs. All eight waves (1994–2001) of the European Community Household Panel are deployed. A random effects ordered probit is estimated in order to control, to a given extent, for unobserved heterogeneity. Explanatory variables are both time invariant (education attainment and gender) and time varying (gross wages, hours of work, age and living alone). Results confirm the positive impact of secondary education on health in most cases and tertiary education in all cases, even after controlling for other inputs in the health function and taking unobserved heterogeneity into account. Secondary education has an impact on health in all countries in the sample except for The Netherlands and UK. The effect does not differ between secondary and tertiary education in France, Ireland and Greece. The correlation between education and health is interpreted in different but complementary ways by diverse approaches and we may not disentangle the precise mechanism that connects health with education from our results. Anyway, it seems clear that better coordination is needed between education and health policies to effectively improve health literacy. Other relevant results from our study are that women register poorer health than men, age contributes to worsening health status and wages contribute positively to health. [ABSTRACT FROM AUTHOR]

Despite its relevance for research funding, few comparable data are available in official R&D statistics on the amount and composition of project funding. This paper discusses in detail the methodology developed in the European Network of Excellence on Research and Innovation Policies PRIME for systematically producing indicators on public project funding which allow for comparative analysis between different countries and across periods of time. We introduce the design of the methodology, and discuss delimitation problems and how to develop suitable classifications of project funding instruments, as well as data availability and limitations. We present examples of our quantitative results for six European countries and of the questions they raise for comparative policy analysis. [ABSTRACT FROM AUTHOR]

Background In Europe, more than 15 million people live with heart failure (HF). It imposes an enormous social, organizational and economic burden. As a reaction to impending impact on healthcare provision, different country-specific structures for HF-care have been established. The aim of this report is to provide an overview and compare the HF-care approaches of Germany, Ireland, the Netherlands and the UK, and to open the possibility of learning from each other's experience. Methods A mixed methods approach was implemented that included a literature analysis, interviews and questionnaires with HF-patients and caregivers, and expert interviews with representatives from healthcare, health service research and medical informatics. Results The models of HF-care in all countries analyzed are based on the European Society of Cardiology guidelines for diagnosis and treatment of HF. Even though the HF-models differed in design and implementation in practice, key challenges were similar: (i) unequal distribution of care between urban and rural areas, (ii) long waiting times, (iii) unequal access to and provision of healthcare services, (iv) information and communication gaps and (v) inadequate implementation and financing of digital applications. Conclusion Although promising approaches exist to structure and improve HF-care, across the four countries, implementation was reluctant to embrace novel methods. A lack of financial resources and insufficient digitalization making it difficult to adopt new concepts. Integration of HF-nurses seems to be an effective way of improving current models of HF-care. Digital solutions offer further opportunities to overcome communication and coordination gaps and to strengthen self-management skills. [ABSTRACT FROM AUTHOR]

Background Employees have witnessed rising trend in work stress over the last few decades. However, we know a little about country differences in those trends. Our article fills this gap in the literature by examining heterogeneities in trends in working conditions by country groups defined by their amount of investment into labor market policy (LMP) programs. Additionally, we provide findings on differences in occupational inequalities between country groups. Methods We use comparative longitudinal data of the European Working Conditions Surveys including cross-sectional information on employees from 15 countries surveyed in Waves 1995, 2000, 2005, 2010 and 2015. Estimation results are provided by three-way multilevel models with employees nested within country-years nested within countries. Our work stress measure is the proxy version of job strain based on the demand-control model. Results Our regression results indicate that for employees in countries with the least LMP spending job strain increased by 10% from 1995 to 2015 compared to a smaller and insignificant change in middle- and high-LMP countries. In low-LMP countries, inequalities in job strain also widened during the studied period: the gap in job strain between the highest- and lowest-skilled increased by 60% from 1995 to 2015. This contrasts a stable gap in middle- and high-LMP countries. Conclusions Our results direct the attention to the vulnerable position of the least skilled and highlight that LMP investments may buffer some of the adverse impacts of globalization and technological changes and effectively improve the labor market situation of the least skilled. [ABSTRACT FROM AUTHOR]

Background: Intimate partner violence (IPV) is a prevalent yet underdiagnosed health issue, and primary care practitioners are in a unique front-line position to provide care and counsel for the victims.Objective: To identify the signs and symptoms of women exposed to IPV who attended primary care, regardless motive of consultation.Methods: Systematic review and meta-analysis on Cochrane, PubMed, Embase and CINAHL between 1946 and 2020. Eligible studies had to be original quantitative research, on women aged >15 years, attending primary care settings in Europe, North America and Australia and interviewed on their status as victims of IPV and on their signs and symptoms.Results: Of 1791 articles identified, 57 were selected. Associations were found between IPV and signs and symptoms of depression [19 studies: overall odds ratio (OR) = 3.59, 95% confidence interval (CI; 2.7-4.7, I2 = 94.6%)], anxiety [9 studies: overall OR = 2.19, 95% CI (1.75-2.73, I2 = 84%)], gynaecological and/or sexually transmitted infections [6 studies: overall OR = 2.82, 95% CI (2.1-3.8, I2 = 41%)] and combination of somatic symptoms [5 studies: standard mean deviation = 0.795, 95% CI (0.62-0.97, I2 = 0%)].Conclusions: Women exposed to IPV may present with clinical symptoms and signs other than bodily injury. Policy implications knowing these symptoms presented by women victims of IPV can help GPs identify and treat them.Systematic Review Registration: PROSPERO CRD42018089857. [ABSTRACT FROM AUTHOR]

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

Background As populations age, the possible consequences of increased frailty are a major concern for the health sector. Here, we investigate how life expectancy with and without frailty has changed during a 10–11-year-period across Europe. Methods The Sullivan method was used to investigate changes in life expectancy with and without frailty in 10 European countries. Frailty status (non-frail, pre-frail and frail) was determined by use of the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI). Data on frailty prevalence was obtained from 21 698 individuals in wave 1 (2004–05) and 38 859 individuals in wave 6 (2015) of the SHARE. Information on mortality was obtained from the Eurostat Database. Results In 2015, women aged 70 spent 25.0% (95% CI: 24.0–26.1) of their remaining life expectancy in a frail state, and the number for men was 11.5% (95% CI: 10.7–12.3). Southern Europeans spent 24.2% (95% CI: 22.9–25.4) of their remaining life expectancy in a frail state and the numbers for Central Europeans and Northern Europeans were 17.0% (95% CI: 16.0–17.9) and 12.2% (95% CI: 10.9–13.5), respectively. From 2004–05 to 2015, life expectancy increased by 1.1 years (from 15.3 to 16.4 years) for 70-year-old Europeans. Similarly, non-frail life expectancy increased by 1.1 years (95% CI: 0.8–1.4), whereas no significant changes in life expectancy in frail states were observed. Conclusions This study suggests that Europeans today spend more years in a non-frail state than Europeans did 10–11 years ago. Our findings reflect a considerable inequality by gender and region. [ABSTRACT FROM AUTHOR]

Background The quality of life (QoL) of older adults is a key aspect of healthy ageing, and older adults' socioeconomic status (SES), the neighbourhood they live in and their social networks (SN) are known to impact QoL. However, little is known about the interaction between these concepts. The aim was to examine how SN, SES and neighbourhood type are associated with QoL in older adults. Methods : Wave 4 (year 2011) and wave 6 (year 2015) data from the longitudinal Survey of Health, Ageing and Retirement in Europe were used for the analysis. Multilevel regression models estimated the associations including 34 792 participants from wave 4 and 67 334 participants from wave 6 from 16 countries (mean age = 66.45 years). The outcome variable was QoL, independent variables were SES (education and making end meet) and neighbourhood type (housing type and housing area), and SN variables (satisfaction and size) were the moderators. Results : SES and SN variables were positively associated with QoL. Living in a house or duplex was positively associated with QoL compared with living in a farmhouse. SN moderated the association between education and QoL. The effect of area type on QoL was moderated by SN size. SN satisfaction was an independent correlate of QoL. Conclusion : Older adults' satisfaction with their SN may be more important than having a large SN. Low SES older adults may be more prone to having weak SN. Maintaining and creating supportive SN may attenuate the negative effects of low SES or less favourable neighbourhood characteristics. [ABSTRACT FROM AUTHOR]

Background: Smoking, obesity and alcohol abuse greatly affect mortality and exhibit a distinct time dynamic, with their prevalence and associated mortality rates increasing and (eventually) declining over time. Their combined impact on secular trends in life expectancy is unknown but is relevant for understanding these trends. We therefore estimate the combined impact of smoking, obesity and alcohol on life-expectancy trends in Europe.Methods: We used estimated national age-specific smoking-, obesity- and alcohol-attributable mortality fractions for 30 European countries by sex, 1990-2014, which we aggregated multiplicatively to obtain lifestyle-attributable mortality. We estimated potential gains in life expectancy by eliminating lifestyle-attributable mortality and compared past trends in life expectancy at birth (e0) with and without lifestyle-attributable mortality. We examined all countries combined, by region and individually.Results: Among men, the combined impact of smoking, obesity and alcohol on e0 declined from 6.6 years in 1990 to 5.8 years in 2014, mainly due to declining smoking-attributable mortality. Among women, the combined impact increased from 1.9 to 2.3 years due to mortality increases in all three lifestyle-related factors. The observed increase in e0 over the 1990-2014 period was 5.0 years for men and 4.0 years for women. After excluding lifestyle-attributable mortality, this increase would have been 4.2-4.3 years for both men and women.Conclusion: Without the combined impact of smoking, obesity and alcohol, the increase over time in life expectancy at birth would have been smaller among men but larger among women, resulting in a stable increase in e0, parallel for men and women. [ABSTRACT FROM AUTHOR]

Context: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.Objective: This work aimed to study cortisol metabolism during DR-HC and TID-HC.Design: A randomized, 12-week, crossover study was conducted.Intervention and Participants: DC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n = 50) vs healthy individuals (n = 124) as controls.Main Outcome Measures: Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections.Results: Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < .001) and reached control values (P = .089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < .05), but remained increased vs controls (P < .001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC vs controls (P < .01) but normalized with DR-HC (P = .358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.Conclusions: The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change toward normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy. [ABSTRACT FROM AUTHOR]

Study Question: Were Neanderthals and Denisovans (referred here also as extinct hominidae) carrying deleterious variants in genes regulating reproduction?Summary Answer: The majority of extinct hominidae analyzed here, presented a considerable number of deleterious variants per individual in proteins regulating different aspects of reproduction, including gonad and uterine function, and gametogenesis.What Is Known Already: Neanderthals, Denisovans and extant humans were interfertile and hybridized while occupying geographically overlapping areas in Europe and Asia. This is evidenced by the small archaic genome component (average ∼2%) present in non-African extant humans.Study Design, Size, Duration: The genome of eight extinct hominidae, together with five human genome databases, plus 44 mothers and 48 fathers (fertile controls), were screened to look for deleterious variants in 1734 protein-coding genes regulating reproduction.Participants/materials, Setting, Methods: Ancient DNA from six Neanderthals and two Denisovans dated between ∼82 000 and 43 000 calibrated years was retrieved from the public European Nucleotide Archive. The hominins analyzed include Altai, Vindija 33.15, 33.19, 33.25 and 33.26, El Sidron 1253, Denisova 3 and 11. Their DNA was analyzed using the CLC Genomics Workbench 12, by mapping overlapping paired-end reads (Illumina, FASTQ files) to the human genome assembly GRCh37 (hg19) (Vindija 33.19, 33.25, 33.26, Denisova 3 and Denisova 11) or by analyzing BAM files (Altai, El Sidron 1253 and Vindija 33.15) (human genome reference, GRCh37 (hg19)). Non-synonymous reproductive variants were classified as deleterious or tolerated (PolyPhen-2 and SIFT analyses) and were compared to deleterious variants obtained from extant human genome databases (Genome Aggregation Database (GnomAD), 1000 Genomes, the Haplotype Map (HapMap), Single Nucleotide Polymorphism Database (dbSNPs)) across different populations. A genetic intersection between extant or extinct DNA variants and other genetic disorders was evaluated by annotating the obtained variants with the Clinical Variant (ClinVar) database.Main Results and the Role Of Chance: Among the eight extinct hominidae analyzed, a total of 9650 non-synonymous variants (only coverage ≥20 reads included; frameshift mutations were excluded) in 1734 reproductive protein-coding genes were found, 24% of which were classified as deleterious. The majority (73%) of the deleterious alleles present in extant humans that are shared between extant humans and extinct hominidae were found to be rare (<1%) in extant human populations. A set of 8044 variants were found uniquely in extinct hominidae. At the single-gene level, no extinct individual was found to be homozygous for deleterious variants in genes necessary for gamete recognition and fusion, and no higher chance of embryo-lethality (calculated by Mendelian Genetics) was found upon simulated mating between extant human and extinct hominidae compared to extant human-extant human. However, three of the eight extinct hominidae were found to be homozygous for 48-69 deleterious variants in 55 genes controlling ovarian and uterine functions, or oogenesis (AKAP1, BUB1B, CCDC141, CDC73, DUSP6, ESR1, ESR2, PATL2, PSMC3IP, SEMA3A, WT1 and WNT4). Moreover, we report the distribution of nine Neanderthal variants in genes associated with a human fertility phenotype found in extant human populations, one of which has been associated with polycystic ovarian syndrome and primary congenital glaucoma.Limitations, Reasons For Caution: While analyzing archaic DNA, stringent filtering criteria were adopted to screen for deleterious variants in Neanderthals and Denisovans, which could result in missing a number of variants. Such restraints preserve the potential for detection of additional deleterious variants in reproductive proteins in extinct hominidae.Wider Implications Of the Findings: This study provides a comprehensive overview of putatively deleterious variants in extant human populations and extinct individuals occurring in 1734 protein-coding genes controlling reproduction and provides the fundaments for future functional studies of extinct variants in human reproduction.Study Funding/competing Interest(s): This study was supported by the Department of Biological Science and by the Office of Research and Sponsored Programs at the University of Tulsa (Faculty Research Grant and Faculty Research Summer Fellowship) to M.A. and the University of Tulsa, Tulsa Undergraduate Research Challenge (TURC) program to E.L.; no conflict of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: A farm upbringing has been associated with lower risk of asthma and methylation of asthma-related genes. As such, a farm upbringing has the potential to transfer asthma risk across generations, but this has never been investigated. We aimed to study the generational effects from a parental farm upbringing on offspring asthma.Methods: Our study involved three generations: 5759 participants from the European Community Respiratory Health Survey (ECRHS) study (born 1945-1971, denoted G1), their 9991 parents (G0) and their 8260 offspring (G2) participating in RHINESSA (Respiratory Health In Northern Europe, Spain and Australia). Questionnaire data were collected on G0 and G1 from G1 in 2010 and on G2 from themselves in 2013. The parental/grandparental place of upbringing was categorized: (i) both parents from farm; (ii) mother from farm, father from village/city; (iii) father from farm, mother from village/city; (iv) both parents from village or one parent from village and one from city; (v) both parents from city (reference group). Grandparental upbringing was equivalently categorized. Offspring asthma was self-reported and data were analysed using Cox-regression models with G2 age as the time scale.Results: A parental farm upbringing was not associated with offspring asthma when compared with city upbringing [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.74-1.69]. Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. A grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67-1.65) or paternal line (HR 1.02, 95% CI 0.62-1.68).Conclusions: This multigenerational analysis suggests no evidence of an association between parental/grandparental farm upbringing and offspring asthma. [ABSTRACT FROM AUTHOR]

Study Question: Is one cycle of IVM non-inferior to one cycle of conventional in IVF with respect to live birth rates in women with high antral follicle counts (AFCs)?Summary Answer: We could not demonstrate non-inferiority of IVM compared with IVF.What Is Known Already: IVF with ovarian hyperstimulation has limitations in some subgroups of women at high risk of ovarian stimulation, such as those with polycystic ovary syndrome. IVM is an alternative ART for these women. IVM may be a feasible alternative to IVF in women with a high AFC, but there is a lack of data from randomized clinical trials comparing IVM with IVF in women at high risk of ovarian hyperstimulation syndrome.Study Design, Size, Duration: This single-center, randomized, controlled non-inferiority trial was conducted at an academic infertility center in Vietnam from January 2018 to April 2019.Participants/materials, Setting, Methods: In total, 546 women with an indication for ART and a high AFC (≥24 follicles in both ovaries) were randomized to the IVM (n = 273) group or the IVF (n = 273) group; each underwent one cycle of IVM with a prematuration step versus one cycle of IVF using a standard gonadotropin-releasing hormone antagonist protocol with gonadotropin-releasing hormone agonist triggering. The primary endpoint was live birth rate after the first embryo transfer. The non-inferiority margin for IVM versus IVF was -10%.Main Results and the Role Of Chance: Live birth after the first embryo transfer occurred in 96 women (35.2%) in the IVM group and 118 women (43.2%) in the IVF group (absolute risk difference -8.1%; 95% confidence interval (CI) -16.6%, 0.5%). Cumulative ongoing pregnancy rates at 12 months after randomization were 44.0% in the IVM group and 62.6% in the IVF group (absolute risk difference -18.7%; 95% CI -27.3%, -10.1%). Ovarian hyperstimulation syndrome did not occur in the IVM group, versus two cases in the IVF group. There were no statistically significant differences between the IVM and IVF groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications.Limitations, Reasons For Caution: The main limitation of the study was its open-label design. In addition, the findings are only applicable to IVM conducted using the prematuration step protocol used in this study. Finally, the single ethnicity population limits the external generalizability of the findings.Wider Implications Of the Findings: Our randomized clinical trial compares live birth rates after IVM and IVF. Although IVM is a viable and safe alternative to IVF that may be suitable for some women seeking a mild ART approach, the current study findings approach inferiority for IVM compared with IVF when cumulative outcomes are considered. Future research should incorporate multiple cycles of IVM in the study design to estimate cumulative fertility outcomes and better inform clinical decision-making.Study Funding/competing Interest(s): This work was partly supported by Ferring grant number 000323 and funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) and by the Fund for Research Flanders (FWO). LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; RJN has received conference and scientific board fees from Ferring, is a minor shareholder in an IVF company, and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant; RBG reports grants and fellowships from the NHMRC of Australia; JS reports lecture fees from Ferring Pharmaceuticals, Biomérieux, Besins Female Healthcare and Merck, grants from Fund for Research Flanders (FWO), and is co-inventor on granted patents on CAPA-IVM methodology in the US (US10392601B2) and Europe (EP3234112B1); TDP, VQD, VNAH, NHG, AHL, THP and RW have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.Trial Registration Number: NCT03405701 (www.clinicaltrials.gov).Trial Registration Date: 16 January 2018.Date Of First Patent’s Enrolment: 25 January 2018. [ABSTRACT FROM AUTHOR]

Introduction: The smoking epidemic greatly affected mortality levels and trends, especially among men in low-mortality countries. The objective of this article was to examine similarities and differences between sexes and low-mortality countries in the mortality imprint of the smoking epidemic. This will provide important additions to the smoking epidemic model, but also improve our understanding of the differential impact of the smoking epidemic, and provide insights into its future impact.Methods: Using lung-cancer mortality data for 30 European and four North American or Australasian countries, smoking-attributable mortality fractions (SAMF) by sex, age (35-99), and year (1950-2014) were indirectly estimated. The timing and level of the peak in SAMF35-99, estimated using weighting and smoothing, were compared.Results: Among men in all countries except Bulgaria, a clear wave pattern was observed, with SAMF35-99 peaking, on average, at 33.4% in 1986. Eastern European men experienced the highest (40%) and Swedish men the lowest (16%) peak. Among women, SAMF35-99 peaked, on average, at 18.1% in 2007 in the North American/Australasian countries and five Northwestern European countries, and increased, on average, to 7.5% in 2014 in the remaining countries (4% in Southern and Eastern Europe). The average sex difference in the peak is at least 25.6 years in its timing and at most 22.9 percentage points in its level.Conclusions: Although the progression of smoking-attributable mortality in low-mortality countries was similar, there are important unexpected sex and country differences in the maximum mortality impact of the smoking epidemic driven by cross-country differences in economic, political, and emancipatory progress.Implications: The formal, systematic, and comprehensive analysis of similarities and differences between sexes and 34 low-mortality countries in long-term time trends (1950-2014) in smoking-attributable mortality provided important additions to the Global Burden of Disease study and the descriptive smoking epidemic model (Lopez et al.). Despite a general increase followed by a decline, the timing of the maximum mortality impact differs more between sexes than previously anticipated, but less between regions. The maximum mortality impact among men differs considerably between countries. The observed substantial diversity warrants country-specific tobacco control interventions and increased attention to the current or expected higher smoking-attributable mortality shares among women compared to men. [ABSTRACT FROM AUTHOR]

Objectives: To determine the spread of ESBLs and carbapenemases in Enterobacterales and Pseudomonas aeruginosa in Europe.Methods: 45 335 Gram-negative bacilli were collected in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2013 to 2017. Antimicrobial susceptibility was determined using broth microdilution, and 9546 isolates were screened for β-lactamase genes by PCR and sequencing.Results: ESBLs were identified in 35.5% of Klebsiella pneumoniae and 18.5% of Escherichia coli. ESBL carriage was lowest among isolates in Northern/Western Europe and highest in Eastern Europe. CTX-M-15 was the dominant ESBL in all countries except Greece, where SHV-type ESBLs were more common. Carbapenemases (KPC, OXA-48-like, GES, NDM and VIM) were found in 3.4% of Enterobacterales and were most common among K. pneumoniae (10.5% of those collected). Carbapenemase carriage was lowest in Northern/Western and highest in Southern Europe. KPC-positive Enterobacterales were most abundant but the percentages of OXA-48-like-, NDM- and VIM-positive isolates increased over time and were correlated with an increase in meropenem non-susceptibility. Carbapenemases (VIM, IMP, NDM and GES) were also identified in 5.1% of P. aeruginosa and were commonly found in Eastern Europe. Carbapenemase carriage and meropenem non-susceptibility among P. aeruginosa fluctuated over the 5 years studied and were not well correlated.Conclusions: ESBL and carbapenemase carriage varied by species and European subregion. Meropenem non-susceptibility in European isolates of Enterobacterales can be attributed to carbapenemase carriage and is increasingly caused by MBLs and OXA-48-like carbapenemases. Carbapenemases or other β-lactamases are not a common cause of meropenem non-susceptibility in P. aeruginosa in Europe. [ABSTRACT FROM AUTHOR]

Background The purpose of this article is to report on a comparative analysis of the official food-based dietary guidelines (FBDG) that were applicable in 2015 in 25 EU Member States. We assess FBDG in relation to the main guidelines established by the FAO/WHO, the EURODIET project and the EFSA, with a particular focus on identifying strengths and limitations of current FBDG in Europe towards addressing diet-related health inequalities. Methods This is a review research, in which a mixed-methods sequenced procedure was utilized. In each EU country key informants, including sociologists, economists, dietitians and nutritionists were asked to provide data regarding: (i) current dietary guidelines and national health priorities, (ii) model of health promotion currently available, (iii) results of the latest food consumption survey. All documents were reviewed by the coordinating team. Full data were analysed by two nutritionists, using a tabulated sheet to organize and compare the results. Results While all countries have national FBDG, the level of detail and quality varies substantially with regard to: time of last update; availability of recommendations for specific target groups; specification of frequency and portion size; the graphical representation; recommended amounts and limits of foods consumed; and recommendations regarding physical activity. Conclusions European countries have great opportunities to improve FBDG to better serve Public Health policy through a more consistent foundation of how these guidelines are developed, the inclusion of different population subgroups as a target for recommendations and the implementation of monitoring systems. [ABSTRACT FROM AUTHOR]

Study Question: Are progesterone vaginal pessaries 400 mg twice a day (bid) non-inferior to progesterone vaginal gel (90 mg) once a day (od) in the primary endpoint of clinical pregnancy rate after 38 days of luteal phase support in women undergoing in vitro fertilisation (IVF)?Summary Answer: Non-inferiority of progesterone vaginal pessaries 400 mg bid to progesterone 8% vaginal gel (90 mg od) was shown for clinical pregnancy rate after 38 days of luteal phase support.What Is Known Already: To maximise successful embryo transfer after IVF, additionally administered progesterone is used for proper endometrium transformation in the luteal phase. Vaginally administered progesterone results in adequate secretory transformation of the endometrium.Study Design, Size, Duration: This multicentre, multinational, open, randomised, two-parallel group, non-inferiority Phase 3 clinical trial was carried out at 17 study sites in five European countries (Belgium, Bulgaria, Czech Republic, Hungary and Serbia) between October 2013 and August 2014. An interactive web response system (IWRS) was implemented for treatment allocation at the sites. Power analysis, based on the assumptions of a non-inferiority margin of -9%, a significance level of α 2.5% (one-sided), power 90%, at a reference pregnancy rate for the progesterone vaginal gel group of 30%, as well as applying a dropout rate of 10%, yielded a total number of 766 patients to be randomised.Participants/materials, Setting, Methods: Women aged between 18 and 40 years with a clinical indication for IVF/intracytoplasmic sperm injection (ICSI) and embryo transfer were eligible to participate. The clinical pregnancy rate was assessed by fetal heart movement measured by transvaginal ultrasound at day 38 (D38) (primary endpoint) and D70. Also assessed were biochemical pregnancy rate (assessed by serum β-hCG ≥25 IU/L), clinical implantation rates at D38, patient evaluation of vaginal bleeding and discharge (assessed by diary) and adverse event (AE) incidence, severity and relationship to study medication.Main Results and the Role Of Chance: A total of 769 female patients were randomised to progesterone 400 mg vaginal pessaries bid (n = 385, 50.1%) or progesterone 90 mg vaginal gel od (n = 384, 49.9%). Patients receiving progesterone vaginal pessaries and progesterone vaginal gel were comparable in demographics, baseline characteristics and number of retrieved oocytes. In the full analysis set (FAS; n = 369 progesterone vaginal pessaries and n = 368 progesterone vaginal gel), clinical pregnancy rates on D38 were 38.3% for progesterone vaginal pessaries and 39.9% for progesterone vaginal gel. In the per protocol analysis set (PP; n = 357 progesterone vaginal pessaries and n = 356 progesterone vaginal gel), clinical pregnancy rates on D38 were 38.1% for progesterone vaginal pessaries and 40.4% for progesterone vaginal gel. For the differences in pregnancy rates between the progesterone vaginal pessaries group and the progesterone vaginal gel, the lower limit of the 97.5% CI was -8.6 and -9.5% for the FAS and PP datasets, respectively. The original prespecified non-inferiority margin of -9% was thus met in the FAS dataset but was marginally below this in the PP dataset. However, the pregnancy rate of the comparator was higher than the anticipated rate of 30%, and a predetermined logistic regression model including treatment group, country and age group effects without interaction terms showed non-inferiority of progesterone vaginal pessaries to progesterone vaginal gel for both the FAS and PP populations, in that the lower limits of the 95% CIs were above 0.7 for both analyses. As a result of this, the relevant authorities accepted to widen the acceptable non-inferiority margin to -10%, and as such both the FAS and PP populations succeeded in showing non-inferiority. Biochemical pregnancy and clinical implantation rates were comparable for both treatments. Both treatment groups showed similar high compliance throughout the study, and the safety profiles were also comparable between the groups. Drug-related AEs occurred with frequencies of 15.1% with progesterone vaginal pessaries and 14.4% with progesterone vaginal gel.Limitations, Reasons For Caution: Clinical pregnancy rate is a surrogate for the outcome of live birth rate.Wider Implications Of the Findings: Progesterone 400 mg pessaries bid for luteal phase support is an effective, safe and tolerable treatment option for women undergoing IVF during ART.Study Funding/competing Interest(s): This work was funded by Actavis Group PTC ehf., Iceland, part of Teva Pharmaceuticals, and by L.D. Collins & Co. Ltd. Gedeon Richter plc has recently entered into a license and distribution agreement to commercialise the vaginal pessaries in the European Union (except Ireland/UK). The progesterone vaginal pessaries studied are now marketed as Cyclogest®, Amelgen®, Cyclovita®, Luteum and Cygest® throughout the EU, Asia and Middle East & North Africa. The competing interests are as follows. H.S.: employee of Gedeon Richter plc/PregLem S.A. C.K.: consultant to L.D. Collins & Co. Ltd and received consulting fees for work performed. T.D.H.: at the initiation and completion of this study, full professor at KU Leuven and Head of Leuven University Fertility Center at the University Hospital Gasthuisberg, Leuven, Belgium. In October 2015, T.D.H. became vice president of Global Medical Affairs Fertility at the pharmaceutical company Merck-marketing authorisation holder of the Progesterone vaginal gel (Crinone®)-and has remained a part-time professor at KU Leuven (Belgium) and adjunct professor at Yale University (New Haven, CT, USA). T.B.M.: at the initiation and completion of this study, employee of Actavis Group PTC ehf. I.K.: consultant to Actavis, later TEVA and received consulting fees for work performed. S.H.: at the initiation and completion of this study, employee of Actavis Group PTC ehf.Trial Registration Number: EudraCT number 2013-001105-81.Trial Registration Date: 2 July 2013.Date Of First Patient’s Enrolment: 9 October 2013. [ABSTRACT FROM AUTHOR]

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries.Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group.Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China.Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol. [ABSTRACT FROM AUTHOR]

Aims: Implanters of cardiac implantable electronic devices cannot easily choose devices by longevity as usually current models only have projected longevity data since those with known performance are obsolete. This study examines how projected device longevities are derived, the influencing factors, and their roles in guiding model choice.Methods and Results: Ninety-eight implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) models released in Europe in 2007-17 were analysed for reported battery capacities, projected longevities for standardized settings stipulated by the French Haute Autorité de Santé (HAS) and manufacturer-chosen settings. Battery capacities and HAS projected longevities increased during the study period. Based on current drain estimation, therapy functions consumed only a small portion (2-7%) of the battery energy for single- and dual-chamber ICDs, but up to 50% (from biventricular pacing) for CRT-Ds. Large differences exist between manufacturers and models both in terms of battery capacity and energy consumption.Conclusion: Battery capacity is not the sole driver of longevity for electronic implantable cardiac devices and, particularly for ICDs, the core function consume a large part of the battery energy even in the absence of therapy. Providing standardized current drain consumption in addition to battery capacity may provide more meaningful longevity information among implantable electronic cardiac devices. [ABSTRACT FROM AUTHOR]

APOE is a well-studied gene with multiple effects on aging and longevity. The gene has three alleles: e2, e3, and e4, whose frequencies vary by ethnicity. While the e2 is associated with healthy cognitive aging, the e4 allele is associated with Alzheimer's disease and early mortality and therefore its prevalence among people with extreme longevity (EL) is low. Using the PopCluster algorithm, we identified several ethnically different clusters in which the effect of the e2 and e4 alleles on EL changed substantially. For example, PopCluster discovered a large group of 1,309 subjects enriched of Southern Italian genetic ancestry with weaker protective effect of e2 (odds ratio [OR] = 1.27, p = .14) and weaker damaging effect of e4 (OR = 0.82, p = .31) on the phenotype of EL compared to other European ethnicities. Further analysis of this cluster suggests that the odds for EL in carriers of the e4 allele with Southern Italian genetic ancestry differ depending on whether they live in the United States (OR = 0.29, p = .009) or Italy (OR = 1.21, p = .38). PopCluster also found clusters enriched of subjects with Danish ancestry with varying effect of e2 on EL. The country of residence (Denmark or United States) appears to change the odds for EL in the e2 carriers. [ABSTRACT FROM AUTHOR]

Background To compare patterns of alcohol consumption and alcohol-related harm from a survey of university students sampled from universities in Denmark, England, Germany, Italy, Portugal and Switzerland. Methods A total of 2191 university students (70% female, 90% white ethnic group, age range 18–25) completed the survey. Participants completed measures of demographic variables (age, age of onset, ethnic group and sex) and the Alcohol Use Disorders Identification Test (AUDIT), which was the primary outcome. Results Sixty-three percent of the sample scored negative for harmful drinking on the AUDIT (<8), with 30% categorized as hazardous drinkers, 4% harmful drinkers and 3% with probable dependence. Analysis of variance, including demographic factors as covariates, identified a main effect of country on AUDIT scores F (5, 2086) = 70.97, P < 0.001, partial eta square = 0.15. AUDIT scores were highest in England (M = 9.99; SD = 6.17) and Denmark (M = 9.52; SD = 4.86) and lowest in Portugal (M = 4.90; ° = 4.60). Post hoc tests indicated large effect size differences between scores in Denmark and England and scores in all other countries (0.79 < d < 0.94; all P 's < 0.001). Conclusions European university students in our sample mainly reported low risk patterns of alcohol consumption and alcohol-related harm. However, students from Northern European countries had significantly higher AUDIT scores compared with students from Central and Southern European countries. Research is needed to replicate the present study using nationally representative samples to estimate the prevalence of alcohol use disorders among university students in different European countries. [ABSTRACT FROM AUTHOR]

Aims: The present study sought to determine predictors for success and outcomes of patients who underwent cardiac implantable electronic devices (CIED) extraction indicated for systemic or local CIED related infection in particular where complete lead removal could not be achieved.Methods and Results: ESC-EORP ELECTRa (European Lead Extraction ConTRolled Registry) is a European prospective lead extraction registry. Out of the total cohort, 1865/3510 (52.5%) patients underwent removal due to CIED related infection. Predictors and outcomes of failure were analysed. Complete removal was achieved in 1743 (93.5%) patients, partial (<4 cm of lead left) in 88 (4.7%), and failed (>4 cm of lead left) in 32 (1.8%) patients. Removal success was unrelated to type of CIED infection (pocket or systemic). Predictors for failure were older leads and older patients [odds ratio (OR) 1.14 (1.08-1.19), P < 0.0001 and OR 2.68 (1.22-5.91), P = 0.0146, respectively]. In analysis by lead, predictors for failure were: pacemaker vs. defibrillator removal and failure to engage the locking stylet all the way to the tip [OR 0.20 (0.04-0.95), P = 0.03 and OR 0.32 (0.13-0.74), P = 0.008, respectively]. Significantly higher complication rates were noted in the failure group (40.6% vs. 15.9 for partial and 8.7% for success groups, P < 0.0001). Failure to remove a lead was a strong predictor for in hospital mortality [hazard ratio of 2.05 (1.01-4.16), P = 0.046].Conclusion: A total of 6.5% of infected CIED patients failed attempted extraction. Only were >4 cm of lead remained resulted in higher procedural complications and mortality rates. [ABSTRACT FROM AUTHOR]

Aims: Female sex is considered an independent risk factor of transvenous leads extraction (TLE) procedure. The aim of the study was to evaluate the effectiveness of TLE in women compared with men.Methods and Results: A post hoc analysis of risk factors and effectiveness of TLE in women and men included in the ESC-EHRA EORP ELECTRa registry was conducted. The rate of major complications was 1.96% in women vs. 0.71% in men; P = 0.0025. The number of leads was higher in men (mean 1.89 vs. 1.71; P < 0.0001) with higher number of abandoned leads in women (46.04% vs. 34.82%; P < 0.0001). Risk factors of TLE differed between the sexes, of which the major were: signs and symptoms of venous occlusion [odds ratio (OR) 3.730, confidence interval (CI) 1.401-9.934; P = 0.0084], cumulative leads dwell time (OR 1.044, CI 1.024-1.065; P < 0.001), number of generator replacements (OR 1.029, CI 1.005-1.054; P = 0.0184) in females and the number of leads (OR 6.053, CI 2.422-15.129; P = 0.0001), use of powered sheaths (OR 2.742, CI 1.404-5.355; P = 0.0031), and white blood cell count (OR 1.138, CI 1.069-1.212; P < 0.001) in males. Individual radiological and clinical success of TLE was 96.29% and 98.14% in women compared with 98.03% and 99.21% in men (P = 0.0046 and 0.0098).Conclusion: The efficacy of TLE was lower in females than males, with a higher rate of periprocedural major complications. The reasons for this difference are probably related to disparities in risk factors in women, including more pronounced leads adherence to the walls of the veins and myocardium. Lead management may be key to the effectiveness of TLE in females. [ABSTRACT FROM AUTHOR]

We compute and compare risk-adjusted CEO pay in the United States and United Kingdom, where the risk adjustment is based on estimated risk premiums stemming from the equity incentives borne by CEOs. Controlling for firm and industry characteristics, we find that U.S. CEOs have higher pay, but also bear much higher stock and option incentives than U.K. CEOs. Using reasonable estimates of risk premiums, we find that risk-adjusted U.S. CEO pay does not appear to be large compared to that of U.K. CEOs. We also examine differences in pay and equity incentives between a sample of non-U.K. European CEOs and a matched sample of U.S. CEOs, and find that risk-adjusting pay may explain about half of the apparent higher pay for U.S. CEOs. [ABSTRACT FROM PUBLISHER]

Background Cross-national comparison studies on gender differences have mainly focussed on life expectancy, while less research has examined differences in health across countries. We aimed to investigate gender differences in cognitive function and grip strength over age and time across European regions. Methods We performed a cross-sectional study including 51 292 men and 62 007 women aged 50 + participating in the Survey of Health, Ageing and Retirement in Europe between 2004–05 and 2015. Linear regression models were used to examine associations. Results In general, women had better cognitive function than men, whereas men had higher grip strength measures. Sex differences were consistent over time, but decreased with age. Compared with men, women had higher cognitive scores at ages 50–59, corresponding to 0.17 SD (95% CI 0.14, 0.20) but slightly lower scores at ages 80–89 (0.08 SD, 95% CI 0.14, 0.00). For grip strength, the sex difference decreased from 18.8 kg (95% CI 18.5, 19.1) at ages 50–59 to 8.5 kg (95% CI 7.1, 9.9) at age 90 +. Northern Europeans had higher cognitive scores (19.6%) and grip strength measures (13.8%) than Southern Europeans. Gender differences in grip strength were similar across regions, whereas for cognitive function they varied considerably, with Southern Europe having a male advantage from ages 60–89. Conclusion Our results illustrate that gender differences in health depend on the selected health dimension and the age group studied, and emphasize the importance of considering regional differences in research on cognitive gender differences. [ABSTRACT FROM AUTHOR]

Background: Globally, access to healthcare and diagnostic technologies are known to substantially impact the reported birth prevalence of congenital heart disease (CHD). Previous studies have shown marked heterogeneity between different regions, with a suggestion that CHD prevalence is rising globally, but the degree to which this reflects differences due to environmental or genetic risk factors, as opposed to improved detection, is uncertain. We performed an updated systematic review to address these issues.Methods: Studies reporting the birth prevalence of CHD between the years 1970-2017 were identified from searches of PubMed, EMBASE, Web of Science and Google Scholar. Data on the prevalence of total CHD and 27 anatomical subtypes of CHD were collected. Data were combined using random-effect models. Subgroup and meta-regression analyses were conducted, focused on geographical regions and levels of national income.Results: Two hundred and sixty studies met the inclusion criteria, encompassing 130 758 851 live births. The birth prevalence of CHD from 1970-2017 progressively increased to a maximum in the period 2010-17 of 9.410/1000 [95% CI (confidence interval) 8.602-10.253]. This represented a significant increase over the fifteen prior years (P = 0.031). The change in prevalence of mild CHD lesions (ventricular septal defect, atrial septal defect and patent ductus arteriosus) together explained 93.4% of the increased overall prevalence, consistent with a major role of improved postnatal detection of less severe lesions. In contrast the prevalence of lesions grouped together as left ventricular outflow tract obstruction (which includes hypoplastic left heart syndrome) decreased from 0.689/1000 (95% CI 0.607-0.776) in 1995-99, to 0.475/1000 (95% CI 0.392-0.565; P = 0.004) in 2010-17, which would be consistent with improved prenatal detection and consequent termination of pregnancy when these very severe lesions are discovered. There was marked heterogeneity among geographical regions, with Africa reporting the lowest prevalence [2.315/1000 (95% CI 0.429-5.696)] and Asia the highest [9.342/1000 (95% CI 8.072-10.704)].Conclusions: The reported prevalence of CHD globally continues to increase, with evidence of severe unmet diagnostic need in Africa. The recent prevalence of CHD in Asia for the first time appears higher than in Europe and America, where disease ascertainment is likely to be near-complete, suggesting higher genetic or environmental susceptibility to CHD among Asian people. [ABSTRACT FROM AUTHOR]

Background: Although the effects of individual-level factors on wellbeing change following work exit have been identified, the role of welfare-state variables at the country level has yet to be investigated.Methods: Data on 8037 respondents aged 50 years and over in 16 European countries were drawn from the Survey of Health, Ageing and Retirement in Europe (SHARE) and the English Longitudinal Study of Ageing (ELSA). We employed multilevel models to assess determinants of change in wellbeing following work exit, using CASP-12 change scores. After adjusting for institutionally defined route and timing of work exit, in addition to other individual-level variables, we tested country-level variables including welfare-state regime and measures of disaggregated welfare spending to determine their associations with wellbeing change and the proportion of between-country variance explained.Results: Individuals whose exit from paid work was involuntary or diverged from the typical retirement age experienced declines in wellbeing. Country effects accounted for 7% of overall variance in wellbeing change. Individuals residing in countries with a Mediterranean welfare regime experienced more negative changes in wellbeing, with a difference of -2.15 (-3.23, -1.06) CASP-12 points compared with those in Bismarckian welfare states. Welfare regime explained 62% of between-country variance. National per-capita expenditure on non-healthcare in-kind benefits (services) was associated with more positive wellbeing outcomes.Conclusions: National expenditure on in-kind benefits, particularly non-healthcare services, is associated with more favourable wellbeing change outcomes following work exit in early old age. Welfare-state effects explain the majority of between-country differences in change in wellbeing. [ABSTRACT FROM AUTHOR]

The objective of this article is to contribute to the emerging attempts to foster empirical, quantitative approaches to Responsible Research and Innovation (RRI), and to provide a low-resolution map of the European RRI landscape, which can serve as a vehicle for international learning. The article presents indicators of RRI aimed at characterising countries. It examines the empirical structure of the data collected in the 'Monitoring the evolution and benefits of Responsible Research and Innovation' (MoRRI) project and reports patterns across Europe. Factor analysis is applied to identify 11 empirically-anchored dimensions of RRI. Based on indices for these dimensions, cluster analysis reveals four distinct clusters of countries. These results point to diversity regarding the empirically-manifest components of RRI as well as diversity in the RRI profiles of the 28 European Union Member States. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe.Methods: A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM).Results: Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models.Conclusions: Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions. [ABSTRACT FROM AUTHOR]

Objectives: The activity of ceftazidime/avibactam was assessed against 24 750 isolates of Enterobacteriaceae collected from 96 medical centres in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2012 to 2015. Activity was analysed against subsets of isolates based on resistant phenotypes and β-lactamase content.Methods: Antimicrobial susceptibility testing was performed using broth microdilution and the presence of β-lactamase genes in isolates of interest was determined using PCR and sequencing.Results: Ceftazidime/avibactam was the most active agent, compared with all other tested comparator agents, against the overall collection of Enterobacteriaceae isolates (99.4% susceptible) and against subsets of ceftazidime-non-susceptible (97.7% susceptible), colistin-resistant (98.2% susceptible), MDR (96.7% susceptible) and meropenem-non-susceptible, MBL-negative (98.5% susceptible) isolates. At the country level, susceptibility to ceftazidime/avibactam ranged from 96.3% to 100% among Enterobacteriaceae isolates, with decreased susceptibilities only observed in countries where MBLs were more frequently encountered (e.g. Greece and Romania). Ceftazidime/avibactam was active against 99.7% of Enterobacteriaceae isolates that carried serine β-lactamases, including ESBLs, AmpC cephalosporinases and carbapenemases (KPC, GES and OXA-48-like) in all combinations. As expected, ceftazidime/avibactam was not active against isolates carrying MBLs.Conclusions: The data show that ceftazidime/avibactam is highly potent in vitro against clinical isolates of Enterobacteriaceae collected in European countries, including isolates that exhibit resistance to ceftazidime, meropenem and colistin and combined resistance to agents from multiple drug classes. [ABSTRACT FROM AUTHOR]

Objectives: The activity of ceftazidime/avibactam was assessed against 5716 Pseudomonas aeruginosa isolates collected from 96 medical centres in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2012 to 2015. Activity was analysed against subsets of isolates based on resistance phenotypes and β-lactamase content.Methods: Antimicrobial susceptibility testing was performed by broth microdilution and β-lactamase genes were detected by PCR screening and sequencing.Results: Ceftazidime/avibactam was highly active in vitro against the overall collection of P. aeruginosa isolates and colistin-resistant isolates (92.4% and 92.9% susceptible, respectively). Although activity was slightly reduced against MBL-negative subsets of ceftazidime-non-susceptible (79.6% susceptible), meropenem-non-susceptible (85.1% susceptible) and MDR (81.6% susceptible) P. aeruginosa, ceftazidime/avibactam remained the second most active entity, after colistin, compared with all other comparator agents tested. At the country level, susceptibility to ceftazidime/avibactam ranged from 74.6% to 99.6%, with decreased susceptibilities only observed in countries where MBLs are more frequently encountered, such as the Czech Republic, Greece, Romania and Russia. Ceftazidime/avibactam was also active in vitro against 87.6% of meropenem-non-susceptible isolates in which no acquired β-lactamases were detected by molecular methods; these isolates were assumed to hyperproduce the chromosomally encoded AmpC in combination with alterations in OprD or drug efflux. As expected, ceftazidime/avibactam was not active against isolates carrying MBLs.Conclusions: The data show that ceftazidime/avibactam is highly potent in vitro against clinical isolates of P. aeruginosa collected in European countries, including isolates that exhibit resistance to ceftazidime, meropenem and colistin and combined resistance to agents from multiple drug classes. [ABSTRACT FROM AUTHOR]

Objectives: We present the results of two European external quality assessments (EQAs) conducted in 2014 and 2016 under the auspices of the Study Group on Staphylococci and Staphylococcal Infections of ESCMID. The objective was to assess the performance of participating centres in characterizing Staphylococcus aureus using their standard in-house phenotypic and genotypic protocols.Methods: A total of 11 well-characterized blindly coded S. aureus (n = 9), Staphylococcus argenteus (n = 1) and Staphylococcus capitis (n = 1) strains were distributed to participants for analysis. Species identification, MIC determination, antimicrobial susceptibility testing, antimicrobial resistance and toxin gene detection and molecular typing including spa typing, SCCmec typing and MLST were performed.Results: Thirteen laboratories from 12 European countries participated in one EQA or both EQAs. Despite considerable diversity in the methods employed, good concordance (90%-100%) with expected results was obtained. Discrepancies were observed for: (i) identification of the S. argenteus strain; (ii) phenotypic detection of low-level resistance to oxacillin in the mecC-positive strain; (iii) phenotypic detection of the inducible MLSB strain; and (iv) WGS-based detection of some resistance and toxin genes.Conclusions: Overall, good concordance (90%-100%) with expected results was observed. In some instances, the accurate detection of resistance and toxin genes from WGS data proved problematic, highlighting the need for validated and internationally agreed-on bioinformatics pipelines before such techniques are implemented routinely by microbiology laboratories. We strongly recommend all national reference laboratories and laboratories acting as referral centres to participate in such EQA initiatives. [ABSTRACT FROM AUTHOR]

Abstract: Background: Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients. Subjects, Materials, and Methods: National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001–2006 and 2007–2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame. Results: Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II–IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54–0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69–0.96) compared with Belgium. Conclusion: There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed. Implications for Practice: With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality. [ABSTRACT FROM AUTHOR]

Objectives: Relebactam is an inhibitor of class A β-lactamases, including KPC β-lactamases, and class C β-lactamases, and is currently under clinical development in combination with imipenem. The objective of the current study was to evaluate the in vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) submitted by clinical laboratories in 17 European countries to the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance programme in 2015.Methods: MICs were determined using the CLSI standard broth microdilution method and interpreted using EUCAST clinical breakpoints. Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of imipenem. Imipenem/relebactam MICs were interpreted using breakpoints for imipenem.Results: Rates of susceptibility to imipenem and imipenem/relebactam for isolates of P. aeruginosa (n = 1705), K. pneumoniae (n = 1591) and Enterobacter spp. (n = 772) were 72.0/94.7%, 88.7/94.8% and 95.6/96.8%, respectively. Relebactam restored imipenem susceptibility to 81.1%, 54.2% and 26.5% of imipenem-non-susceptible isolates of P. aeruginosa (n = 477), K. pneumoniae (n = 179) and Enterobacter spp. (n = 34). Most imipenem/relebactam-non-susceptible isolates carried MBLs, OXA-48 or GES carbapenemases. Relebactam did not increase the number of isolates of A. baumannii (n = 486) susceptible to imipenem.Conclusions: Relebactam restored susceptibility to imipenem for the majority of imipenem-non-susceptible isolates of P. aeruginosa and K. pneumoniae tested as well as some isolates of imipenem-non-susceptible Enterobacter spp. Based on our results, imipenem/relebactam appears to be a promising therapeutic option for treating patients with infections caused by antimicrobial-resistant Gram-negative bacilli. [ABSTRACT FROM AUTHOR]

Unintended pregnancy is a public health concern throughout Europe. There is no common definition and no standard way to measure unintended pregnancy. Identifying unintended births is difficult and prevalence estimates vary depending on how and when the question is asked. Abortion rates are not a proxy and are themselves notoriously inaccurate. An estimated 34% (in Western Europe) to 54% (in Eastern Europe) of pregnancies are unintended. The determinants of unintended pregnancy are the length of the reproductive span and exposure to the risk of conception; the desired number of children and contraceptive use and effectiveness. The age of sexual debut fell during the 20th century in Europe to between 15 and 18 years of age. Mean age at first birth for women is now over 30 years in most European countries and most couples want no more than two children. Thus most couples must use contraception perfectly for many years in order to avoid unintended pregnancy. Use of effective contraception is high throughout most of Europe but there is scope, through better provision of sexual health services, better formal sex education and better training of providers, to increase the uptake of the most effective contraceptives and improve use of all methods. For individual women unintended pregnancy can be a disaster and recourse to induced abortion should be freely available. [ABSTRACT FROM AUTHOR]

Background: Comparisons of outcomes of health care in different systems can be used to inform health policy. The EuroHOPE (European Healthcare Outcomes, Performance and Efficiency) project investigated the feasibility of comparing routine data on selected conditions including breast cancer across participating European countries. Methods: Routine data on incidence, treatment and mortality by age and clinical characteristics for breast cancer in women over 24years of age were obtained (for a calendar year) from linked hospital discharge records, cancer and death registers from Finland, the Turin metropolitan area, Scotland and Sweden (all 2005), Hungary (2006) and Norway (2009). Age-adjusted breast cancer incidence and 1-year survival were estimated for each country/region. Results: In total, 24576 invasive breast cancer cases were identified from cancer registries from over 13 million women. Age-adjusted incidence ranged from 151.1 (95%CI 147.2-155.0) in Hungary to 234.7 (95%CI 227.4-242.0)/100 000 in Scotland. One-year survival ranged from 94.1% (95%CI 93.5-94.7%) in Scotland to 97.1% (95%CI 96.298.1%) in Italy. Scotland had the highest proportions of poor prognostic factors in terms of tumour size, nodal status and metastases. Significant variations in data completeness for prognostic factors prevented adjustment for case mix. Conclusion: Incidence of and survival from breast cancer showed large differences between countries. Substantial improvements in the use of internationally recognised common terminology, standardised data coding and data completeness for prognostic indicators are required before international comparisons of routine data can be used to inform health policy. [ABSTRACT FROM AUTHOR]

Background: In order to provide effective primary care for refugees and to develop interventions tailored to them, we must know their needs. Little is known of the health needs and experiences of recently arrived refugees and other migrants throughout their journey through Europe. We aimed to gain insight into their health needs, barriers in access and wishes regarding primary health care. Methods: In the spring of 2016, we conducted a qualitative, comparative case study in seven EU countries in a centre of first arrival, two transit centres, two intermediate-stay centres and two longer-stay centres using a Participatory Learning and Action research methodology. A total of 98 refugees and 25 healthcare workers participated in 43 sessions. Transcripts and sessions reports were coded and thematically analyzed by local researchers using the same format at all sites; data were synthesized and further analyzed by two other researchers independently. Results: The main health problems of the participants related to war and to their harsh journey like common infections and psychological distress. They encountered important barriers in accessing healthcare: time pressure, linguistic and cultural differences and lack of continuity of care. They wish for compassionate, culturally sensitive healthcare workers and for more information on procedures and health promotion. Conclusion: Health of refugees on the move in Europe is jeopardized by their bad living circumstances and barriers in access to healthcare. To address their needs, healthcare workers have to be trained in providing integrated, compassionate and cultural competent healthcare. [ABSTRACT FROM AUTHOR]

Background: The aim was to compare alcohol drinking patterns in economically active people aged 50-64 years before the last economic crisis (2006) and during the crisis (2013). Methods: Cross-sectional study with data from 25 479 economically active people aged 50-64 years resident in 11 European countries who participated in wave 2 or wave 5 of the SHARE project (2006 and 2013). The outcome variables were hazardous drinking, abstention in previous 3 months and the weekly average number of drinks per drinker. The prevalence ratios of hazardous drinking and abstention, comparing the prevalence in 2013 vs. 2006, were estimated with Poisson regression models with robust variance, and the changes in the number of drinks per week with Poisson regression models. Results: The prevalence of hazardous drinking decreased among both men (PR = 0.75; 95%CI = 0.63-0.92) and women (PR = 0.91; 95%CI = 0.72-1.15), although the latter decrease was smaller and not statistically significant. The proportion of abstainers increased among both men (PR = 1.11; 95%CI = 0.99-1.29) and women (PR = 1.18; 95%CI = 1.07-1.30), although the former increase was smaller and not statistically significant. The weekly average number of drinks per drinker decreased in men and women. The decreases in consumption were larger in Italy and Spain. Conclusion: From 2006 to 2013, the amount of alcohol consumed by late working age drinkers decreased in Europe, with more pronounced declines in the countries hardest hit by the economic crisis. [ABSTRACT FROM AUTHOR]