Search

Objective: This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health‐related quality of life, health status, work productivity, and healthcare resource utilization. Methods: This cross‐sectional study utilized SF‐12, EQ‐5D‐5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self‐reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx‐treated or Rx‐untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. Results: Of 2086 respondents with CLBP, 683 had mild pain (276 Rx‐untreated, 407 Rx‐treated) and 1403 had moderate/severe pain (781 Rx‐untreated, 622 Rx‐treated). Respondents with moderate/severe pain had significantly worse health‐related quality of life (SF‐12v2 physical component summary), health status (EQ‐5D‐5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx‐untreated (moderate/severe pain Rx‐untreated vs. mild pain Rx‐untreated, p ≤ 0.05) and Rx‐treated (moderate/severe pain Rx‐treated vs. mild pain Rx‐treated, p ≤ 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx‐treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx‐untreated (8.72 vs. 7.61, p = 0.072) groups. Health‐related quality of life (SF‐12v2 physical component summary) and health status (EQ‐5D‐5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx‐treated group compared with all other groups (all p ≤ 0.05). Conclusion: Greater severity of CLBP was associated with worse health‐related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users. [ABSTRACT FROM AUTHOR]

The cohabitation of Drosophila melanogaster with humans is nearly ubiquitous. Though it has been well established that this fly species originated in sub-Saharan Africa, and only recently has spread globally, many details of its swift expansion remain unclear. Elucidating the demographic history of D. melanogaster provides a unique opportunity to investigate how human movement might have impacted patterns of genetic diversity in a commensal species, as well as providing neutral null models for studies aimed at identifying genomic signatures of local adaptation. Here, we use whole-genome data from five populations (Africa, North America, Europe, Central Asia, and the South Pacific) to carry out demographic inferences, with particular attention to the inclusion of migration and admixture. We demonstrate the importance of these parameters for model fitting and show that how previous estimates of divergence times are likely to be significantly underestimated as a result of not including them. Finally, we discuss how human movement along early shipping routes might have shaped the present-day population structure of D. melanogaster. [ABSTRACT FROM AUTHOR]

Previous research documents a correlation between education and political ideology, usually indicating a positive relationship between education and left-wing political views. In this paper, I examine to what extent this association is causal. I merge political ideology data from 25 waves of Eurobarometer surveys with information on 18 educational reforms in 11 European countries. I then instrument for educational attainment with a regression discontinuity design that estimates the increase in education due to compulsory educational reforms. Notably, it appears that omitted variables bias is important here. I find a significant causal effect of education moving individuals to the right when properly addressing the endogeneity whereas there is a significant association between education and left-wing political ideology when treating education as exogenous. I find that on average, among the individuals compelled into additional education from these specific reforms, an additional year of education moves individuals to the right of the political continuum by about 5–6%. However, I also find no evidence of a causal effect on political ideology for a subgroup of countries. [ABSTRACT FROM AUTHOR]

Interstitial lung disease in children (chILD) is rare, and most centres will only see a few cases/year. There are numerous possible underlying diagnoses, with specific and non-specific treatment possibilities. The chILD-EU collaboration has brought together centres from across Europe to advance understanding of these considerations, and as part of this process, has created standard operating procedures and protocols for the investigation of chILD. Where established consensus documents exist already, for example, for the performance of bronchoalveolar lavage and processing of lung biopsies, these have been adopted. This manuscript reports our proposals for a staged investigation of chILD, starting from when the condition is suspected to defining the diagnosis, using pathways dependent on the clinical condition and the degree of illness of the child. These include the performance of genetic testing, echocardiography, high-resolution CT, bronchoscopy when appropriate and the definitive investigation of lung biopsy, in order to establish a precise diagnosis. Since no randomised controlled trials of treatment have ever been performed, we also report a Delphi consensus process to try to harmonise treatment protocols such as the use of intravenous and oral corticosteroids, and add-on therapies such as hydroxychloroquine and azithromycin. The aim is not to dictate to clinicians when a therapeutic trial should be performed, but to offer the possibility to collaborators of having a unified approach when a decision to treat has been made. [ABSTRACT FROM AUTHOR]

Background: Vulvovaginal atrophy (VVA) is a condition associated with decreased estrogenization of the vaginal tissue, which can result in vaginal dryness, irritation, and dyspareunia. This study quantified the burden associated with VVA symptoms across the United States and Europe and compared this burden with other chronic conditions. Methods: Data were analyzed from the International Women's Health Study, a cross-sectional Internet survey of women aged 40-75 years in the United States and Europe. All postmenopausal women aged 40-75 years were included in the analyses (Germany n=970, Spain n=294, France n=1054, Italy n=387, United Kingdom n=1096, United States n=3267). VVA symptom severity (none, mild, moderate, severe) was assessed using the Menopause Rating Scale and included in general linear models to predict EuroQol-5D (EQ-5D) quality of life scores. Results: The prevalence of VVA symptoms varied between 40.00% (Germany) and 54.42% (Spain), with half of women reporting their symptoms as either moderate or severe. Pooling data from all countries together, each incremental level of severity (none through severe) was associated with a significant decrement in EQ-5D scores (none=0.84 vs. mild=0.81 vs. moderate=0.79 vs. severe=0.74; p<0.05). The decrements in EQ-5D scores associated with moderate to severe VVA symptoms were comparable to those observed in other serious conditions including arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome. Conclusions: VVA symptoms are associated with clinically meaningful decrements in quality of life that may be comparable to serious conditions such as arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome. Improved management of VVA symptoms may be required to alleviate the impact of VVA on the quality of life of affected women. [ABSTRACT FROM AUTHOR]

The article discusses Australian foreign affairs in the years leading up to World War II, focusing on the influence of Australian historian Stephen H. Roberts on Australia's foreign policy. Other topics include a discussion of Roberts' contributions on international affairs to the periodical "Sydney Mail," Australian ideas about Nazism and fascism, and Roberts' ideas about the potential for war, prior to the outbreak of World War II.

Background: Dense consensus genetic maps based on high-throughput genotyping platforms are valuable for making genetic gains in Brassica napus through quantitative trait locus identification, efficient predictive molecular breeding, and map-based gene cloning. This report describes the construction of the first B. napus consensus map consisting of a 1,359 anchored array based genotyping platform; Diversity Arrays Technology (DArT), and non-DArT markers from six populations originating from Australia, Canada, China and Europe. We aligned the B. napus DArT sequences with genomic scaffolds from Brassica rapa and Brassica oleracea, and identified DArT loci that showed linkage with qualitative and quantitative loci associated with agronomic traits. Results: The integrated consensus map covered a total of 1,987.2 cM and represented all 19 chromosomes of the A and C genomes, with an average map density of one marker per 1.46 cM, corresponding to approximately 0.88 Mbp of the haploid genome. Through in silico physical mapping 2,457 out of 3,072 (80%) DArT clones were assigned to the genomic scaffolds of B. rapa (A genome) and B. oleracea (C genome). These were used to orientate the genetic consensus map with the chromosomal sequences. The DArT markers showed linkage with previously identified non-DArT markers associated with qualitative and quantitative trait loci for plant architecture, phenological components, seed and oil quality attributes, boron efficiency, sucrose transport, male sterility, and race-specific resistance to blackleg disease. Conclusions: The DArT markers provide increased marker density across the B. napus genome. Most of the DArT markers represented on the current array were sequenced and aligned with the B. rapa and B. oleracea genomes, providing insight into the Brassica A and C genomes. This information can be utilised for comparative genomics and genomic evolution studies. In summary, this consensus map can be used to (i) integrate new generation markers such as SNP arrays and next generation sequencing data; (ii) anchor physical maps to facilitate assembly of B. napus genome sequences; and (iii) identify candidate genes underlying natural genetic variation for traits of interest. [ABSTRACT FROM AUTHOR]

China's rapid social transformation recapitulates processes that occurred in an earlier era in Europe and North America, and which gave birth to the discipline of sociology. Research on contemporary China therefore provides a rare opportunity to revisit and rethink the founding ideas of the discipline and its radical, liberal, and conservative traditions. [ABSTRACT FROM AUTHOR]

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2-4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence. [ABSTRACT FROM AUTHOR]

This article presents a new dataset of transitional justice mechanisms utilized worldwide from 1970--2007. These data complement the growing body of quantitative and comparative analyses of transitional justice. This article summarizes three important contributions made by the dataset. First, it includes five transitional justice mechanisms (trials, truth commissions, amnesties, reparations, and lustration policies), allowing scholars to avoid many of the methodological errors committed by performing single-mechanism studies. Second, it provides an expanded sample, both temporally and geographically, to facilitate greater comparative and policy impact. Third, the dataset enables scholars to analyze transitional justice across a variety of political contexts, including democratic transitions and civil wars. These data illuminate a new set of general trends and patterns in the implementation of transitional justice worldwide. The findings show that countries adopt amnesties more often than other mechanisms. They predominantly grant them in the context of civil war and to opponents of the state, rather than state agents. Courts rarely prosecute those currently in power for human rights violations. In civil war settings, rebels, rather than state actors, face trials. In post-authoritarian settings, courts try former authoritarian actors, but do not address crimes committed by the opposition to authoritarian rule. The dataset also reveals regional patterns of mechanism usage. Trials, lustration policies, and reparations occur most often in Europe. Non-European countries more frequently adopt truth commissions and amnesties than do their European counterparts, with a particularly high number of amnesties granted in Latin America. [ABSTRACT FROM PUBLISHER]

A novel shrew was discovered recently in Alaska and described based on morphological characters as Sorex yukonicus. This species is closely allied to Sorex minutissimus, a widespread shrew ranging through Eurasia. Together their distribution spans Beringia, a large Pleistocene nonglaciated area that connected Asia and North America. Beringia was repeatedly divided due to raised sea levels during Pleistocene interglacials and subsequently reconnected during glacials. We tested predictions related to the influence of large-scale geologic events on genetic variability through a phylogeographic analysis of both species of shrew using evidence from 3 independent genetic loci. We found low genetic divergence between S. minutissimus and S. yukonicus across continents. However, major phylogeographic breaks were found for Eurasian and Maritime Northeast Asia populations. Neither species is reciprocally monophyletic for any of the loci examined. Coalescence times for all pairwise population comparisons within both species fall within the Wisconsinan--Weichselian glacial (<130 thousand years ago), and significant population expansion estimates date to the Holocene suggesting that divergence between these taxa is minimal and may not warrant recognition of 2 distinct species. Phylogeographic relationships and sequence divergence estimates place populations of North American S. yukonicus and Siberian S. minutissimus as most closely related, and together they are sister to European S. minutissimus. We conclude that populations east and west of the Bering Strait represent a single Holarctic species, S. minutissimus. Temporal changes in range based on ecological niche predictions and a comparative assessment of other codistributed taxa provide a preliminary view of potential Last Glacial Maximum refugia in northern Asia. [ABSTRACT FROM AUTHOR]

Standard approaches to estimating population-attributable risk (PAR) include modelling estimates of exposure prevalence and relative risk. Here, we examine the associations between body mass index (BMI) and cancer risk and how effect modifications of these associations impact on PAR estimates. In 2008, sex- and population-specific risk estimates were determined for associations with BMI in a standardised meta-analysis for 20 cancer types. Since then, refinements of these estimates have emerged: (i) absence of menopausal hormonal therapy (MHT) is associated with elevated BMI associations in post-menopausal breast, endometrial and ovarian cancers; (ii) current smoking attenuates the BMI associations in oesophageal squamous cell carcinoma, lung and pancreatic cancers; (iii) prostate screening attenuates BMI associations when all prostate cancers are considered together; and (iv) BMI is differentially associated with different histological subtypes within the same cancer group. Using secondary analyses of the aforementioned meta-analysis, we show 2–3-fold shifts in PAR estimations for breast and endometrial cancers depending on the MHT usage in European countries. We also critically examine how to best handle exposures (in this example, BMI distributions) and relative risk estimates in PAR models, and argue in favour of a counterfactual approach based around BMI means. From these observations, we develop a research framework in which to optimally evaluate future trends in numbers of new cancers attributable to excess BMI. Overall, this framework gives conservative estimates for PAR – nonetheless, the numbers of avoidable cancers across Europe through avoidance of excess weight are substantial. [Copyright &y& Elsevier]

The relative contributions to modern European populations of Paleolithic hunter-gatherers and Neolithic farmers from the Near East have been intensely debated. Haplogroup R1b1b2 (R-M269) is the commonest European Y-chromosomal lineage, increasing in frequency from east to west, and carried by 110 million European men. Previous studies suggested a Paleolithic origin, but here we show that the geographical distribution of its microsatellite diversity is best explained by spread from a single source in the Near East via Anatolia during the Neolithic. Taken with evidence on the origins of other haplogroups, this indicates that most European Y chromosomes originate in the Neolithic expansion. This reinterpretation makes Europe a prime example of how technological and cultural change is linked with the expansion of a Y-chromosomal lineage, and the contrast of this pattern with that shown by maternally inherited mitochondrial DNA suggests a unique role for males in the transition. [ABSTRACT FROM AUTHOR]

The European Recommendation on Integrated Coastal Zone Management has six core principles. These form two groups, one concerned with strategic goals and one that has a local focus. The principles are presented as a menu of free-standing options, with no prioritization either within or between groups. In the case of coastal erosion management these characteristics result in irreconcilable conflicts, and actively hinder sustainable management of eroding coasts. The principles require clarification, and recognition that they are an indivisible integrated set which should not be used to select principles to advance a particular agenda. It is essential that the strategic principles are given priority, because only they can underpin a sustainable approach to the issue of coastal erosion. [ABSTRACT FROM AUTHOR]

Quantifying the number of deleterious mutations per diploid human genome is of crucial concern to both evolutionary and medical geneticists. Here we combine genome-wide polymorphism data from PCR-based exon resequencing, comparative genomic data across mammalian species, and protein structure predictions to estimate the number of functionally consequential single-nucleotide polymorphisms (SNPs) carried by each of 15 African American (AA) and 20 European American (EA) individuals. We find that AAs show significantly higher levels of nucleotide heterozygosity than do EAs for all categories of functional SNPs considered, including synonymous, non-synonymous, predicted ‘benign’, predicted ‘possibly damaging’ and predicted ‘probably damaging’ SNPs. This result is wholly consistent with previous work showing higher overall levels of nucleotide variation in African populations than in Europeans. EA individuals, in contrast, have significantly more genotypes homozygous for the derived allele at synonymous and non-synonymous SNPs and for the damaging allele at ‘probably damaging’ SNPs than AAs do. For SNPs segregating only in one population or the other, the proportion of non-synonymous SNPs is significantly higher in the EA sample (55.4%) than in the AA sample (47.0%; P < 2.3 × 10-37). We observe a similar proportional excess of SNPs that are inferred to be ‘probably damaging’ (15.9% in EA; 12.1% in AA; P < 3.3 × 10-11). Using extensive simulations, we show that this excess proportion of segregating damaging alleles in Europeans is probably a consequence of a bottleneck that Europeans experienced at about the time of the migration out of Africa. [ABSTRACT FROM AUTHOR]

To lock in progress over the last three years, Southeast Europe needs to take steps now to develop effective cross-border cooperation at both the practical and political levels. It also needs to demonstrate that it can speak out on major issues of concern with a single, coordinated voice. Not only does meaningful regional cooperation build local confidence and reflect full regional buy-in on tough, challenging economic and political issues, it also helps form crucial regional networks in political, diplomatic and specialist areas. This in turn leads crucially to standard setting at the regional level, which can significantly enhance the durability of national commitments. The Southeast European Cooperation Process (SEECP) is starting to take on this role in important areas. It has progressively become more focused in its goals and objectives. It now needs to begin to exert the leadership necessary to craft workable solutions to persistent regional challenges. This means developing an indigenous capacity to follow through on and implement commitments made by the region's political leadership at summits and ministerial meetings. [ABSTRACT FROM AUTHOR]

Discusses the modelling of the volatility of money market interest rates and the transmission of volatility along the money market yield curve in four European countries. Measurement of shortest-maturity overnight interest rate volatilities; Conditional variance of overnight interest rates; Potential spillovers of volatility from overnight onto longer-maturity interest rates.

The understanding of risk factors underpinning the aetiology of many common cancers is well established, yet the conversion of this knowledge into prevention lags considerably behind. The title of this Special Issue - Implementing cancer prevention in Europe - captures the central theme within; namely, the translation of cancer epidemiology into public health policy. The Special Issue is supported by focused evidence-based case studies of how these processes might be best taken forward. [Copyright &y& Elsevier]

Background Individual country- and cancer site-specific studies suggest that the age-adjusted incidence of many common cancers has increased in European populations over the past two decades. To quantify the extent of these trends and the recent burden of cancer, here we present a comprehensive overview of trends in population-based incidence of the five common cancers across Europe derived from a new web-based portal of the European cancer registries. Methods Data on incidence for cancers of the colon and rectum, prostate, breast, corpus uteri and stomach diagnosed from 1988 to 2008 were obtained from the European Cancer Observatory for cancer registries from 26 countries. Annual age-standardised incidence rates and average annual percentage changes were calculated. Results Incidence of four common cancers in eastern and central European countries (prostate, postmenopausal breast, corpus uteri and colorectum) started to approach levels in northern and western Europe, where rates were already high in the past but levelled off in some countries in recent years. Decreases in stomach cancer incidence were seen in all countries. Discussion Increasing trends in incidence of the most common cancers, except stomach cancer, are bad news to public health but can largely be explained by well-known changes in society in the past decades. Thus, current and future efforts in primary cancer prevention should not only remain focussed on the further reduction of smoking but engage in the long-term efforts to retain healthy lifestyles, especially avoiding excess weight through balanced diets and regular physical exercise. [ABSTRACT FROM AUTHOR]

Background: Across Europe, there are over 300,000 new cases of colorectal cancer annually. Major risk factors include excess body weight (usually expressed by a high body mass index, BMI) and physical inactivity (PA). In this study we modelled the potential long-term effects on colon cancer incidence of changes in prevalence of excess body weight and physical inactivity in seven European countries across Europe with adequate data. Methods: We addressed the impact of interventions aimed at preventing weight gain and increasing physical activity on colon cancer incidence using the Prevent model as refined in the FP-6 Eurocadet project. Relative risk (RR) estimates were derived from meta-analyses; sex- and country-specific prevalences of BMI and PA were determined from survey data. Models were made for Czech Republic, Denmark, France, Latvia, the Netherlands, Spain and the United Kingdom. Results: In a hypothetical scenario in which a whole population had obtained an ideal weight distribution in the year 2009, up to 11 new cases per 100,000 person-years would be avoided by 2040. The population attributable fractions (PAF) for excess weight were much higher for males (between 13.5% and 18.2%) than for females (2.3–4.6%). In contrast, using the optimum scenario where everybody in Europe would adhere to the recommended guideline of at least 30min of moderate PA 5d per week, the PAFs for PA in various countries were substantially greater in women (4.4–21.2%) than in men (3.2–11.6%). Sensitivity analyses were performed assuming underreporting of BMI by using self-reports (difference of 5 and 0.8 percent-points in males and females, respectively), using different risk estimates (between 5.8 and 11.5 percent-points difference for BMI for men and women, respectively, and up to 11.6 percent-points difference for PA for women). Interpretation: Changes in lifestyle can indeed result in large health benefits, including for colon cancer. Two interesting patterns emerged: for colon cancer, achieving optimum BMI levels in the population appears to offer the greatest health benefits in population attributable fractions in males, while increased physical activity might offer the greatest fraction of avoidable cancers in females. These observations suggest a sex-specific strategy to colon cancer prevention. [Copyright &y& Elsevier]

We characterized Apis mellifera in both native and introduced ranges using 1136 single-nucleotide polymorphisms genotyped in 341 individuals. Our results indicate that A. mellifera originated in Africa and expanded into Eurasia at least twice, resulting in populations in eastern and western Europe that are geographically close but genetically distant. A third expansion in the New World has involved the near-replacement of previously introduced "European" honey bees by descendants of more recently introduced A. m. scutellata ("African" or "kilter" bees). Our analyses of spatial transects and temporal series in the New World revealed differential replacement of alleles derived from eastern versus western Europe, with admixture evident in all individuals. [ABSTRACT FROM AUTHOR]

Investigates the molecular basis and clinical features of patients with variegate porphyria (VP) in Europe. Characteristics of VP; Influence of deficiency of protoporphyrinogen oxidase encoded by the PPOX gene on VP; Demonstration of allelic heterogeneity.

Introduction: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed., Methods: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed., Results: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work., Conclusions: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA., Competing Interests: Competing interests: TPMVV was the Vice president EULAR health professionals 2020–2022 and is part of the EULAR Advocacy Committee 2020–present. MG holds a leadership position in OpenReuma/Spanish Association of Health Professionals in Rheumatology (unpaid). CDM received Grants from Versus Arthritis, MRC, NIHR (paid to Keele University) and is the director of the NIHR School for Primary Care Research. SL received payment as scientific consultant from Arthro Therapeutics AB and received payment from AstraZeneca as a member of DSMB. DC received grants from Fundação para a Ciência e Tecnologia SFRH/BD/148420/2019 and Pfizer (ID 64165707). GZ received payment for expert testimony from Casa di Cura San Francesco, Verona and Support for attending meetings and/or travel from Orthotech and Jtech, payment for participation on a Data Safety Monitoring Board or Advisory Board from VIVENKO for Gruenenthal and Ethos for Angelini and holds other financial interests related to clinical practice as an orthopedic surgeon (performing total joint replacement, arthroscopies and other types of surgeries), either directly from private patients or indirectly from the health system or insurances acting as a private consultant. JEV has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Lilly Netherlands BV. TG has received paid honoraria for lectures by Abbvie, Novartis, Boehringer Ingelheim, UCB, Berlin-Chemie/A. Menarini Bulgaria, Sandoz and received support for attending meetings by Abbvie, Pfizer and UCB. DW is an International Advisory Board Member of DRFZ (Germany) 2019–current and was the EULAR PARE Chair 2015–2017and an EULAR Vice President representing PARE 2017–2021., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. Objectives: To identify and validate molecular determinants of IPF survival. Methods: A staged genome-wide association study was performed using paired genomic and survival data. Stage I cases were drawn from centers across the United States and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplantation-free survival (TFS). Stage I variants with nominal significance ( P  < 5 × 10 -5 ) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance ( P  < 5 × 10 -8 ). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance. Measurements and Main Results: After quality controls, 1,481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of PCSK6 (proprotein convertase subtilisin/kexin type 6) reaching genome-wide significance (hazard ratio, 4.11 [95% confidence interval, 2.54-6.67]; P  = 9.45 × 10 -9 ). PCSK6 protein was highly expressed in IPF lung parenchyma. PCSK6 lung staining intensity, peripheral blood gene expression, and plasma concentration were associated with reduced TFS. Conclusions: We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein plays a potentially important role in IPF progression.

Arab populations are largely understudied, notably their genetic structure and history. Here we present an in-depth analysis of 6,218 whole genomes from Qatar, revealing extensive diversity as well as genetic ancestries representing the main founding Arab genealogical lineages of Qahtanite (Peninsular Arabs) and Adnanite (General Arabs and West Eurasian Arabs). We find that Peninsular Arabs are the closest relatives of ancient hunter-gatherers and Neolithic farmers from the Levant, and that founder Arab populations experienced multiple splitting events 12-20 kya, consistent with the aridification of Arabia and farming in the Levant, giving rise to settler and nomadic communities. In terms of recent genetic flow, we show that these ancestries contributed significantly to European, South Asian as well as South American populations, likely as a result of Islamic expansion over the past 1400 years. Notably, we characterize a large cohort of men with the ChrY J1a2b haplogroup (n = 1,491), identifying 29 unique sub-haplogroups. Finally, we leverage genotype novelty to build a reference panel of 12,432 haplotypes, demonstrating improved genotype imputation for both rare and common alleles in Arabs and the wider Middle East., (© 2021. The Author(s).)

Objectives: Although the osteoarthritis (OA) burden is well-recognised, the benefit of currently available OA pharmacological therapy is not clear. This study aimed to assess whether the impact of OA pain on health-related quality of life (HRQoL), work, and healthcare resource utilisation (HRU) differed by both pain severity and prescription medication status., Methods: This cross-sectional study used pooled data from the 2016/2017 European National Health and Wellness Survey. Respondents with self-reported physician-diagnosed OA and pain were included. Outcomes examined included HRQoL, health utility, health status, work productivity and activity impairment, and HRU. Groups derived from self-reported pain severity and prescription medication use were compared using chi-square tests, analysis of variance, and generalised linear models controlling for socio-demographics, health behaviours, and health status., Results: Respondents with OA (n=2417) reported mild (40.4%, of which 44.9% prescription-treated) and moderate to severe pain (59.6%, of which 54.0% prescription-treated). HRQoL, health utility, health status, and work and activity impairment were substantially worse among the moderate/severe pain prescription-treated group compared to the rest (e.g. SF-12v2 physical component score [PCS] for moderate/severe pain prescription-treated=34.5 versus mild pain prescription-treated =39.3, moderate/severe pain prescription-untreated=40.6, and mild pain prescription-untreated=45.6; p<0.01). HRU such as the mean number of emergency room visits for >6 months was higher in the prescription-treated groups (0.51-0.52, 95% CI 0.437-0.71) than the prescription-untreated groups (0.30-0.34, 95% CI 0.21-0.46; p<0.05)., Conclusions: Persons with moderate to severe OA pain treated with available prescription medications have poor health status and HRQoL and increased HRU compared to those not receiving prescription medications.

Introduction: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is required to determine the eligibility for pembrolizumab monotherapy in advanced NSCLC worldwide and for several other indications depending on the country. Four assays have been approved/ Communauté Européene-In vitro Diagnostic (CV-IVD)-marked, but PD-L1 IHC seems diversely implemented across regions and laboratories with the application of laboratory-developed tests (LDTs)., Method: To assess the practice of PD-L1 IHC and identify issues and disparities, the International Association for the Study of Lung Cancer Pathology Committee conducted a global survey for pathologists from January to May 2019, comprising multiple questions on preanalytical, analytical, and postanalytical conditions., Result: A total of 344 pathologists from 64 countries participated with 41% from Europe, 24% from North America, and 18% from Asia. Besides biopsies and resections, cellblocks were used by 75% of the participants and smears by 11%. The clone 22C3 was most often used (69%) followed by SP263 (51%). They were applied as an LDT by 40% and 30% of the users, respectively, and 76% of the participants developed at least one LDT. Half of the participants reported a turnaround time of less than or equal to 2 days, whereas 13% reported that of greater than or equal to 5 days. In addition, quality assurance (QA), formal training for scoring, and standardized reporting were not implemented by 18%, 16%, and 14% of the participants, respectively., Conclusions: Heterogeneity in PD-L1 testing is marked across regions and laboratories in terms of antibody clones, IHC assays, samples, turnaround times, and QA measures. The lack of QA, formal training, and standardized reporting stated by a considerable minority identifies a need for additional QA measures and training opportunities., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

National strategies to prevent sports injuries can potentially improve health outcomes at a population level and reduce medical costs. To date, a compilation of the strategies that countries have attempted, and their effectiveness, does not exist. This scoping review sets out to: identify nationwide attempts at implementing sports injury prevention strategies; examine the impact of these strategies; and map them onto the Translating Research into Injury Prevention Practice (TRIPP) framework. Using Levac's scoping review method, we: (a) identified the research questions, (b) identified relevant studies, (c) identified the study selection criteria, (d) charted the data, and (e) reported the results. A search of MEDLINE, Scopus, SPORTDiscus, CINAHL, and Web of Science databases for articles published pre-June 2019 was conducted. We identified 1794 studies and included 33 studies (of 24 strategies). The USA (n = 7), New Zealand (n = 4), Canada (n = 3), the Netherlands (n = 3), Switzerland (n = 2), Belgium (n = 1), France (n = 1), Ireland (n = 1), South Africa (n = 1), and Sweden (n = 1) have implemented nationwide sports injury prevention strategies with 29 (88%) of the included studies demonstrating positive results. Mapping the strategies onto the TRIPP framework highlighted that only four (17%) of the 24 included strategies reported on the implementation context (TRIPP Stage 5), suggesting an important reporting gap. Nationwide sports injury prevention efforts are complex, requiring a multidimensional approach. Future research should report intervention implementation data; examine the implementation context early in the research process to increase the likelihood of real-world implementation success; and could benefit from incorporating qualitative or mixed research methods., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Malnutrition is highly prevalent in patients with foregut tumors comprising head and neck (HNC) and esophageal (EC) cancers, negatively impacting outcomes. International evidence-based guidelines (EBGs) for nutrition care exist; however, translation of research evidence into practice commonly presents considerable challenges and consequently lags. This study aimed to describe and evaluate current international nutrition care practices compared with the best-available evidence for patients with foregut tumors who are at high risk of malnutrition. A multi-centre prospective cohort study enrolled 170 patients commencing treatment of curative intent for HNC ( n = 119) or EC ( n = 51) in 11 cancer care settings in North America, Europe and Australia between 2016 and 2018. Adherence criteria were derived from relevant EBG recommendations with pooled results for participating centres reported according to the Nutrition Care Model at either system or patient levels. Adherence to EBG recommendations was: good (≥80%) for performing baseline nutrition screening and assessment, perioperative nutrition assessment and nutrition prescription for energy and protein targets; moderate (≥60 to 80%) for utilizing validated screening and assessment tools and pre-radiotherapy dietitian consultation; and poor (60%) for initiating post-operative nutrition support within 24 h and also dietetic consultation weekly during radiotherapy and fortnightly for 6 weeks post-radiotherapy. In conclusion, gaps in evidence-based cancer nutrition care remain; however, this may be improved by filling known evidence gaps through high-quality research with a concurrent evolution of EBGs to also encompass practical implementation guidance. These should aim to support multidisciplinary cancer clinicians to close evidence-practice gaps throughout the patient care trajectory with clearly defined roles and responsibilities that also address patient-reported concerns.

Objectives: The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee-Thymic Domain conducted a web-based cross-sectional survey to assess the acceptance of the TNM thymic staging system in the thoracic community., Methods: A 50-item, web-based questionnaire was circulated among the members of the major thymic organizations worldwide from September to December 2018. The survey consisted of six sections (general information; overall perception of the TNM system; pretreatment staging; T category; N category; and perioperative treatments)., Results: In total, 217 responses were collected from 37 countries in four continents. The TNM classification was considered useful by 78% of the responders (N = 169); the Masaoka-Koga staging system was being used by 87% of the responders (N = 189). With regard to the T category, most responders (mostly surgeons) felt that the capsular and mediastinal pleural involvements should be considered separate T categories. As for the N category, 48% of the responders (N = 105) used the International Thymic Malignancies Interest Group/International Association for the Study of Lung Cancer thymic nodal map, and lymph node dissection (N1/N2) was performed for 50%/21% thymomas and 66%/41% thymic carcinomas. While analyzing the results by the three continents (Europe, Asia, and Americas), responders in Asia were found to report the largest use of the TNM system, the greatest attention to the N category, and the best participation in international thymic databases., Conclusions: The survey indicates that the Union for International Cancer Control/American Joint Committee on Cancer TNM stage classification of thymic tumors is gaining acceptance among the scientific community. The present results will guide the work of the Staging and Prognostic Factors Committee-Thymic Domain for the revision of the ninth edition of the TNM stage classification of thymic tumors., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

We performed a prospective, observational, cohort study of children newly diagnosed with children's interstitial lung disease (ChILD), with structured follow-up at 4, 8, 12 weeks and 6 and 12 months. 127 children, median age 0.9 (IQR 0.3-7.9) years had dyspnoea (68%, 69/102), tachypnoea (75%, 77/103) and low oxygen saturation (SpO 2 ) median 92% (IQR 88-96). Death (n=20, 16%) was the most common in those <6 months of age with SpO 2 <94% and developmental/surfactant disorders. We report for the first time that ChILD survivors improved multiple clinical parameters within 8-12 weeks of diagnosis. These data can inform family discussions and support clinical trial measurements., Competing Interests: Competing interests: SC and VS report other from Boehringer Ingelheim, outside the submitted work; MG reports other from Vertex and Boehringer Ingelheim, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Coexistence between great tits Parus major and blue tits Cyanistes caeruleus, but also other hole-nesting taxa, constitutes a classic example of species co-occurrence resulting in potential interference and exploitation competition for food and for breeding and roosting sites. However, the spatial and temporal variations in coexistence and its consequences for competition remain poorly understood. We used an extensive database on reproduction in nest boxes by great and blue tits based on 87 study plots across Europe and Northern Africa during 1957-2012 for a total of 19,075 great tit and 16,729 blue tit clutches to assess correlative evidence for a relationship between laying date and clutch size, respectively, and density consistent with effects of intraspecific and interspecific competition. In an initial set of analyses, we statistically controlled for a suite of site-specific variables. We found evidence for an effect of intraspecific competition on blue tit laying date (later laying at higher density) and clutch size (smaller clutch size at higher density), but no evidence of significant effects of intraspecific competition in great tits, nor effects of interspecific competition for either species. To further control for site-specific variation caused by a range of potentially confounding variables, we compared means and variances in laying date and clutch size of great and blue tits among three categories of difference in density between the two species. We exploited the fact that means and variances are generally positively correlated. If interspecific competition occurs, we predicted a reduction in mean and an increase in variance in clutch size in great tit and blue tit when density of heterospecifics is higher than the density of conspecifics, and for intraspecific competition, this reduction would occur when density of conspecifics is higher than the density of heterospecifics. Such comparisons of temporal patterns of means and variances revealed evidence, for both species, consistent with intraspecific competition and to a smaller extent with interspecific competition. These findings suggest that competition associated with reproductive behaviour between blue and great tits is widespread, but also varies across large spatial and temporal scales., (© 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.)

Background: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society., Methods: The evidence syntheses were discussed and recommendations formulated by a multidisciplinary committee of IPF experts. The evidence was appraised and recommendations were formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach., Results: The guideline panel updated the diagnostic criteria for IPF. Previously defined patterns of usual interstitial pneumonia (UIP) were refined to patterns of UIP, probable UIP, indeterminate, and alternate diagnosis. For patients with newly detected interstitial lung disease (ILD) who have a high-resolution computed tomography scan pattern of probable UIP, indeterminate, or an alternative diagnosis, conditional recommendations were made for performing BAL and surgical lung biopsy; because of lack of evidence, no recommendation was made for or against performing transbronchial lung biopsy or lung cryobiopsy. In contrast, for patients with newly detected ILD who have a high-resolution computed tomography scan pattern of UIP, strong recommendations were made against performing surgical lung biopsy, transbronchial lung biopsy, and lung cryobiopsy, and a conditional recommendation was made against performing BAL. Additional recommendations included a conditional recommendation for multidisciplinary discussion and a strong recommendation against measurement of serum biomarkers for the sole purpose of distinguishing IPF from other ILDs., Conclusions: The guideline panel provided recommendations related to the diagnosis of IPF.

Background: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection., Methods: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided., Results: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients., Conclusions: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Paediatric interstitial lung disease (ILD) is rare and diverse, meaning no single centre will see sufficient children to perform the studies needed to make progress. This EU FP-7 grant will standardise the evaluation of these rare conditions by establishing pan-European multidisciplinary expert panels and establish consensus on treatment protocols and standard operating procedures across Europe. We will work with patient groups to determine optimal treatment end-points and biomarkers. A biobank will be established as a Europe-wide resource for mechanistic studies. Ultimately we aim to do the first randomised controlled trial of a pharmacological treatment in paediatric ILD.

Background: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs., Purpose: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs., Methods: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011., Results: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment., Conclusions: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

Objective: Despite large waves of westward migration, little is known about how to adapt services to assist Russian-speaking immigrants. In an attempt to bridge the scientist-practitioner gap, the current review synthesizes diverse literatures regarding what is known about immigrants from the Former Soviet Union., Method: Relevant empirical studies and reviews from cross-cultural and cultural psychology, sociology, psychiatric epidemiology, mental health, management, linguistics, history, and anthropology literature were synthesized into three broad topics: culture of origin issues, common psychosocial challenges, and clinical recommendations., Results: Russian speakers probably differ in their form of collectivism, gender relations, emotion norms, social support, and parenting styles from what many clinicians are familiar with and exhibit an apparent paradoxical mix of modern and traditional values. While some immigrant groups from the Former Soviet Union are adjusting well, others have shown elevated levels of depression, somatization, and alcoholism, which can inform cultural adaptations., Conclusions: Testable assessment and therapy adaptations for Russians were outlined based on integrating clinical and cultural psychology perspectives., (© 2013 Wiley Periodicals, Inc.)

Background: Hepatic steatosis, a common condition associated with insulin resistance and excess body weight, is reported to be associated with an increased risk for perioperative mortality in patients undergoing resection of colorectal liver metastases (CLM), but its impact upon longterm survival is less well documented., Methods: The effects of background liver pathology, categorized as 'normal', 'with steatosis' and 'other', on perioperative mortality, overall survival (OS) and cancer-specific survival (CSS) were assessed in patients undergoing resection for CLM according to data maintained in the LiverMetSurvey database. As preoperative chemotherapy may confound the effects of steatosis, patients who had been given preoperative chemotherapy were excluded. Survival analyses included log-rank tests for comparisons, and multivariate Cox models, including well-established prognosticators., Results: Of 5853 patients who underwent first-time liver resection without preoperative chemotherapy, 1793 (30.6%) had background steatosis. Rates of 90-day perioperative mortality in patients with normal, steatosis and other pathologies were 2.8%, 2.1% and 4.9%, respectively. Steatosis was associated with improved 5-year OS (47.4% versus 43.0%; log rank, P = 0.0017) and CSS (56.1% versus 50.3%; P = 0.002) compared with normal background liver. After adjustments, the survival advantage associated with steatosis remained (hazard ratio = 0.806, 95% confidence interval 0.717-0.905 for CSS)., Discussion: The paradoxical survival advantage observed in patients with steatosis undergoing liver resection for CLM generates a hypothesis that peri-diagnosis of excess body adiposity has a survival protective effect that warrants further research., (© 2012 International Hepato-Pancreato-Biliary Association.)

This document is an international evidence-based guideline on the diagnosis and management of idiopathic pulmonary fibrosis, and is a collaborative effort of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. It represents the current state of knowledge regarding idiopathic pulmonary fibrosis (IPF), and contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For the diagnosis and treatment sections, pragmatic GRADE evidence-based methodology was applied in a question-based format. For each diagnosis and treatment question, the committee graded the quality of the evidence available (high, moderate, low, or very low), and made a recommendation (yes or no, strong or weak). Recommendations were based on majority vote. It is emphasized that clinicians must spend adequate time with patients to discuss patients' values and preferences and decide on the appropriate course of action.

Introduction: Due to resource limitations, few critical care interventions have been rigorously evaluated with adequately powered randomized clinical trials (RCTs). There is a need to improve the efficiency of RCTs in critical care so that more definitive high quality RCTs can be completed with the available resources. The objective of this study was to validate and demonstrate the utility of a novel composite outcome measure, persistent organ dysfunction (POD) plus death, for clinical trials of critically ill patients., Methods: We performed a secondary analysis of a dataset from a prospective randomized trial involving 38 intensive care units (ICUs) in Canada, Europe, and the United States. We define POD as the persistence of organ dysfunction requiring supportive technologies during the convalescent phase of critical illness and it is present when a patient has an ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points. In 600 patients enrolled in a randomized trial of nutrition therapy and followed prospectively for six months, we evaluated the prevalence of POD and its association with outcome., Results: At 28 days, 2.3% of patients had circulatory failure, 13.7% had renal failure, 8.7% had respiratory failure, and 27.2% had died, for an overall prevalence of POD + death = 46.0%. Of survivors at Day 28, those with POD, compared to those without POD, had a higher mortality rate in the six-month follow-up period, had longer ICU and hospital stays, and a reduced quality of life at three months. Given these rates of POD + death and using a two-sided Chi-squared test at alpha = 0.05, we would require 616 patients per arm to detect a 25% relative risk reduction (RRR) in mortality, but only 286 per arm to detect the same RRR in POD + mortality., Conclusions: POD + death may be a valid composite outcome measure and compared to mortality endpoints, may reduce the sample size requirements of clinical trials of critically ill patients. Further validation in larger clinical trials is required.

Objective: To determine how patient-rated osteoarthritis (OA) severity correlates with other patient-reported and clinical outcomes in the European clinical setting., Methods: We used the Adelphi Arthritis VII (2008) Disease Specific Program (DSP). OA severity was patient-rated using the question 'How bad would you say your arthritis is now?' with responses of 'mild,' 'moderate,' and 'severe.' Patient-reported outcomes included a 0-100 mm pain visual analogue scale (VAS); questions on daily functioning; Work Productivity and Activity Impairment (WPAI) scale; and EuroQoL (EQ-5D). Regression models and chi-square analyses evaluated relationships between self-rated OA severity and other outcomes., Results: Patient-reported data were available from 1739 individuals (63.1% female, mean age 64.4 [standard deviation 11.9] years) from France, Germany, Italy, Spain, and the UK. With increasing OA severity; mild (24.5%), moderate (56.3%), severe (19.2%), statistically significant differences (p<0.05) were observed with higher pain VAS scores (28.3, 49.9, 69.2, respectively), reduced function, and greater overall work impairment due to OA (24.3%, 38.5%, 68.6%, respectively). Significant associations of patient-reported OA severity with function and health status were indicated, including the EQ-5D health state index; 0.77 (mild), 0.62 (moderate), 0.30 (severe) (p<0.0001). Physicians tended to overestimate patients who rated their OA as mild, and underrate patients who rated their OA as severe., Conclusions: In five European countries, patient-rated OA severity was associated with other patient-reported outcomes, and may be of benefit in the clinical setting when choosing treatment options aimed at improving pain, function and productivity, providing an accurate and tangible assessment of patient's perceptions of their disease.

Excess adiposity is associated with increased risks of developing adult malignancies. To inform public health policy and guide further research, the incident cancer burden attributable to excess body mass index (BMI >or= 25 kg/m(2)) across 30 European countries were estimated. Population attributable risks (PARs) were calculated using European- and gender-specific risk estimates from a published meta-analysis and gender-specific mean BMI estimates from a World Health Organization Global Infobase. Country-specific numbers of new cancers were derived from Globocan2002. A ten-year lag-period between risk exposure and cancer incidence was assumed and 95% confidence intervals (CI) were estimated in Monte Carlo simulations. In 2002, there were 2,171,351 new all cancer diagnoses in the 30 countries of Europe. Estimated PARs were 2.5% (95% CI 1.5-3.6%) in men and 4.1% (2.3-5.9%) in women. These collectively corresponded to 70,288 (95% CI 40,069-100,668) new cases. Sensitivity analyses revealed estimates were most influenced by the assumed shape of the BMI distribution in the population and cancer-specific risk estimates. In a scenario analysis of a plausible contemporary (2008) population, the estimated PARs increased to 3.2% (2.1-4.3%) and 8.6% (5.6-11.5%), respectively, in men and women. Endometrial, post-menopausal breast and colorectal cancers accounted for 65% of these cancers. This analysis quantifies the burden of incident cancers attributable to excess BMI in Europe. The estimates reported here provide a baseline for future modelling, and underline the need for research into interventions to control weight in the context of endometrial, breast and colorectal cancer.

This paper presents the work of an expert group established by the International Life Sciences Institute - European branch (ILSI Europe) to follow up the recommendations of an international conference on "Risk Assessment of Compounds that are both Genotoxic and Carcinogenic: New Approaches". Twelve genotoxic and carcinogenic chemicals that can be present in food were selected for calculation of a Margin of Exposure (MOE) between a point of departure on the dose-response for oral carcinogenicity in animal studies and estimates of human dietary exposure. The MOE can be used to support prioritisation of risk management action and, if the MOE is very large, on communication of a low level of human health concern. Depending on the approaches taken in determining the point of departure and the estimation of exposure, it is possible to derive very different values for the MOE. It is therefore essential that the selection of the cancer endpoint and mathematical treatment of the data are clearly described and justified if the results of the MOE approach are to be trusted and of value to risk managers. An outline framework for calculating an MOE is proposed in order to help to ensure transparency in the results., (Copyright 2009 ILSI Europe. Published by Elsevier Ltd.. All rights reserved.)

Background: The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set., Methods: We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients., Results: In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower., Conclusion: This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.