Search

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

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]

This paper investigates different uses of the Journal Impact Factor (JIF) in national journal rankings and discusses the merits of supplementing metrics with expert assessment. Our focus is national journal rankings used as evidence to support decisions about the distribution of institutional funding or career advancement. The seven countries under comparison are China, Denmark, Finland, Italy, Norway, Poland, and Turkey—and the region of Flanders in Belgium. With the exception of Italy, top‐tier journals used in national rankings include those classified at the highest level, or according to tier, or points implemented. A total of 3,565 (75.8%) out of 4,701 unique top‐tier journals were identified as having a JIF, with 55.7% belonging to the first Journal Impact Factor quartile. Journal rankings in China, Flanders, Poland, and Turkey classify journals with a JIF as being top‐tier, but only when they are in the first quartile of the Average Journal Impact Factor Percentile. Journal rankings that result from expert assessment in Denmark, Finland, and Norway regularly classify journals as top‐tier outside the first quartile, particularly in the social sciences and humanities. We conclude that experts, when tasked with metric‐informed journal rankings, take into account quality dimensions that are not covered by JIFs. [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: 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 paper presents the first ethnobotanical application of Ellenberg indicator values, which are widely used in European plant ecology. The aim of the study was to find out if Ellenberg values (indicating habitat preferences) differ for wild food and medicinal plants used in north-eastern Istria (Croatia). We used Ellenberg-Pignatti values (the version of Ellenberg values used in this part of Europe). Methods: Fifty semi-structured interviews were carried out among local key informants, asking which wild food and medicinal plants they used. Results: The mean number of food and medicinal plants mentioned per interview was 30. Altogether, 121 species were recorded as food or medicine used or previously used in the study area. Thirty-one species are used exclusively as food or everyday drink, 50 species are used exclusively as medicine and 40 species are used for both food and medicine. There were no significant differences between Ellenberg values for food and medicinal plants, apart from the Nitrogen indicator value - the plants used exclusively as food had a significantly higher index than those used in medicine. This probably stems from the fact that plants with soft fleshy shoots are attractive as food and they are more likely to come from nitrogen-rich ruderal habitats. Conclusions: Food plants and medicinal plants are collected from a variety of habitats and no clear difference between the two categories of plants was detected, however further testing of Ellenberg values in ethnobotanical studies could be interesting. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance This paper has two overarching aims: (1) presenting the results of studying the Albacete tariff of medicines of 1526 and (2) broadly analyzing the origin and influences of medicinal traditional knowledge in the region of Albacete, Spain. We use historical and modern literature that may have influenced this knowledge. Our primary goal was to determine the ingredients used in the pharmacy in the 16th century CE in Albacete through the analysis of the tariff, and our secondary goal was to investigate until when ingredients and uses present in pharmacy and herbals persisted in later periods. Methods The identity of medicines and ingredients was determined by analyzing contemporary pharmacopoeias and classical pharmaceutical references. We analyzed further 21 sources (manuscripts, herbals, and books of medicines, pharmacopoeias, pharmacy inventories, and modern ethnobotanical records) for the presence/absence of ingredients and complex formulations of the tariff. Using factorial and cluster analysis and Bayesian inference applied to evolution models (reversible-jump Markov chain Monte Carlo), we compared textual sources. Finally, we analyzed the medicinal uses of the top 10 species in terms of frequency of citation to assess the dependence of modern ethnobotanical records on Renaissance pharmacy and herbals, and, ultimately, on Dioscorides. Results In Albacete 1526, we determined 101 medicines (29 simple drugs and 72 compound medicines) comprising 187 ingredients (85% botanical, 7.5% mineral, and 7.5% zoological substances). All composed medicines appear standardized in the pharmacopoeias, notably in the pharmacopoeia of Florence from 1498. However, most were no longer in use by 1750 in the pharmacy, and were completely absent in popular herbal medicine in Albacete 1995 as well as in Alta Valle del Reno (Italy) in 2014. Among the ingredients present in different formulation are the flowers of Rosa gallica , honey ( Apis mellifera ), the roots of Nardostachys jatamansi , and Convolvulus scammonia , pistils of Crocus sativus , grapes and raisins ( Vitis vinifera ), rhizomes of Zingiber officinale , bark of Cinnamomum verum , leaves and fruits of Olea europaea , mastic generally of Pistacia lentiscus , and wood of Santalum album . The statistical analysis of sources produces four well-separated clusters (Renaissance Herbals and Pharmacopoeias, Ethnobotany and Folk Medicine, Old phytotherapy, and Modern phytotherapy including Naturopathy) confirming our a priori classification. The clade of Renaissance Herbals and Pharmacopoeias appears separated from the rest in 97% of bootstrapped trees. Bayesian inference produces a tree determined by an initial set of two well-distinct core groups of ingredients: 64, locally used in Mediterranean Europe during centuries; and 45, imported, used in pharmacy during centuries. Complexity reached its maximum in Albacete 1526 and contemporary pharmacopoeias, gradually decreasing over time. The analysis of medicinal uses of the top 10 ingredients showed low coincidence between Dioscorides and different Renaissance herbals or medical treatises and of all of them with ethnobotany in Albacete. Conclusions Regarding our question: is there something new under the sun? In some aspects, the answer is “No”. The contrast between expensive drugs, highly valued medicines, and unappreciated local wild medicinal plants persists since the Salerno's school of medicine. Old medicine in Mediterranean Europe, as reflected by Albacete 1526 tariff of medicines, involved strict formulations and preferences for certain ingredients despite other ingredients locally available but underappreciated. This confirms the fact that any system of medicine does not get to use all available resources. Ethnobiological records of materia medica, in rural areas of Albacete, describe systems with a high degree of stability and resilience, where the use of local resources, largely wild but also cultivated, is predominant in contrast with the weight of imported exotic products in pharmacy. [ABSTRACT FROM AUTHOR]

In what social contexts are rich people more likely to support government redistribution of income? Motivated by the literature on inequality aversion and the literature on the relationship between ethnic fractionalization and redistribution, the paper examines whether the relationship between own income and redistributive preferences depends on the regional level of poverty and the ethnic composition of the poor. Using data from the European Social Survey, the paper demonstrates that support for redistribution among the rich is lower when the proportion of ethnic minorities among the poor is high. Several possible mechanisms to account for this relationship are examined. The paper finds no support for explanations based on more animosity towards the poor or towards ethnic minorities and no support for explanations based on lower social trust or social capital: instead, rich people are less concerned with downward income mobility when the proportion of minorities among the poor is high. [ABSTRACT FROM PUBLISHER]

Purpose: The European 'Healthy Lifestyle in Europe by Nutrition in Adolescence' (HELENA) project evaluated two different approaches to harmonize the matching procedures between 24-h recall data and food composition databases. In the first approach, the 24-h recall data were linked to the local/national food composition databases using standardized procedures, while in the second approach, the 24-h recall data were linked to the German BLS database which includes a larger food list. The aim of this paper was to compare the intakes of energy and eight nutrient components calculated via both approaches. Methods: Two non-consecutive 24-h recalls were performed in 1268 adolescents. Energy, carbohydrates, proteins, fat, fiber, water, alcohol, calcium and vitamin C were calculated via the two approaches at individual level. Paired samples t test and Pearson's correlations were used to compare the mean intakes of energy and the eight mentioned nutrients and to investigate the possible associations between the two approaches. Results: Small but significant differences were found between the intakes of energy and the eight food components when comparing both approaches. Very strong and strong correlations (0.70-0.95) were found between both methods for all nutrients. Conclusion: The dietary intakes obtained via the two different linking procedures are highly correlated for energy and the eight nutrients under study. [ABSTRACT FROM AUTHOR]

This paper provides an empirical study of the between-individual and between-country differences in the popular legitimacy of European healthcare systems. In order to explain two dimensions of popular legitimacy (satisfaction and support for state responsibility), we assess the impact of self-interest motives (income and personal health), ideology (egalitarianism) and institutional arrangements (level of service provision, and private and government health expenditure). For this purpose, data from the European Social Survey Round 4 (ESS-4, 2008–2009) are analysed by means of multilevel models. Universal high support for state responsibility is found, while satisfaction varies considerably, with particularly low levels found in Eastern European and former Soviet Union countries. It appears that individuals are not guided by self-interest motives and ideology alone. In addition to these factors interacting, the results suggest that state-provided healthcare might be in everyone’s interest. Introducing a patient perspective could advance our understanding of healthcare legitimacy. [ABSTRACT FROM PUBLISHER]

Introduction: The aim of this paper was to investigate the association between health, social position, social participation and the welfare state. Extending recent research on the social consequences of poor health, we asked whether and how welfare generosity is related to the risk of social exclusion associated with combinations of poor health, low education and economic inactivity. Methods: Our analyses are based on data from the European Social Survey, round 3 (2006/7), comprising between 21,205 and 21,397 individuals, aged 25--59 years, within 21 European welfare states. The analyses were conducted by means of multilevel logistic regression analysis in STATA 12. Results: The results demonstrated that the risk of non-participation in social networks decreased as welfare generosity increased. The risk of social exclusion, i.e. non-participation in social networks among disadvantaged groups, seldom differed from the overall association, and in absolute terms it was invariably smaller in more generous welfare state contexts. Conclusions: The results showed that there were no indications of higher levels of non-participation among disadvantaged groups in more generous welfare states. On the contrary, resources made available by the welfare state seemed to matter to all individuals in terms of overall lower levels of non-participation. As such, these results demonstrate the importance of linking health related social exclusion to the social policy context. [ABSTRACT FROM AUTHOR]

Objectives:Despite many years of research, there is currently no treatment available that results in major neurological or functional recovery after traumatic spinal cord injury (tSCI). In particular, no conclusive data related to the role of the timing of decompressive surgery, and the impact of injury severity on its benefit, have been published to date. This paper presents a protocol that was designed to examine the hypothesized association between the timing of surgical decompression and the extent of neurological recovery in tSCI patients.Study design:The SCI-POEM study is a Prospective, Observational European Multicenter comparative cohort study. This study compares acute (<12 h) versus non-acute (>12 h, <2 weeks) decompressive surgery in patients with a traumatic spinal column injury and concomitant spinal cord injury. The sample size calculation was based on a representative European patient cohort of 492 tSCI patients. During a 4-year period, 300 patients will need to be enrolled from 10 trauma centers across Europe. The primary endpoint is lower-extremity motor score as assessed according to the 'International standards for neurological classification of SCI' at 12 months after injury. Secondary endpoints include motor, sensory, imaging and functional outcomes at 3, 6 and 12 months after injury.Conclusion:In order to minimize bias and reduce the impact of confounders, special attention is paid to key methodological principles in this study protocol. A significant difference in safety and/or efficacy endpoints will provide meaningful information to clinicians, as this would confirm the hypothesis that rapid referral to and treatment in specialized centers result in important improvements in tSCI patients. [ABSTRACT FROM AUTHOR]