Search

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased mortality and significant personal, psychological and socioeconomic consequences. An agreed definition of remission is needed and lacking. We sought to visualize ‘remission in SLE’ in European patients considered by their physicians to be ‘in remission’ by comparing the reported symptom burden as reported by treating physicians for patients considered to be ‘in remission’ and those not considered to be ‘in remission’. Data for 1227 patients drawn from a multinational, real-world survey of patients with SLE consulting practising rheumatologists and nephrologists in France, Germany, Italy, Spain, and the UK show that physicians classed their patients as ‘in remission’ despite a considerable ongoing symptom burden and intensive immunosuppressive medication. Patients considered to be ‘in remission’ still had a mean of 2.68 current symptoms vs 5.48 for those considered to be not ‘in remission’ (p < 0.0001). The most common symptoms among those seen to be ‘in remission’ were joint symptoms, fatigue, pain, mucocutaneous involvement, haematological manifestations and kidney abnormalities. The current analysis highlights important ongoing disease activity, symptom burden and immunosuppressive medication in European patients with SLE considered by their treating physician to be ‘in remission’. For a further improvement of outcome, there is an urgent need for an international consensus on the definitions for remission among patients with SLE. [ABSTRACT FROM AUTHOR]

The seasonal cycle accounts for a dominant mode of total column CO2 (XCO2) annual variability and is connected to CO2 uptake and release; it thus represents an important quantity to test the accuracy of the measurements from space. We quantitatively evaluate the XCO2 seasonal cycle of the Greenhouse Gases Observing Satellite (GOSAT) observations from the Atmospheric CO2 Observations from Space (ACOS) retrieval system and compare average regional seasonal cycle features to those directly measured by the Total Carbon Column Observing Network (TCCON). We analyse the mean seasonal cycle amplitude, dates of maximum and minimum XCO2, as well as the regional growth rates in XCO2 through the fitted trend over several years. We find that GOSAT/ACOS captures the seasonal cycle amplitude within 1.0 ppm accuracy compared to TCCON, except in Europe, where the difference exceeds 1.0 ppm at two sites, and the amplitude captured by GOSAT/ACOS is generally shallower compared to TCCON. This bias over Europe is not as large for the other GOSAT retrieval algorithms (NIES v02.21, RemoTeC v2.35, UoL v5.1, and NIES PPDF-S v.02.11), although they have significant biases at other sites. We find that the ACOS bias correction partially explains the shallow amplitude over Europe. The impact of the co-location method and aerosol changes in the ACOS algorithm were also tested and found to be few tenths of a ppm and mostly non-systematic. We find generally good agreement in the date of minimum XCO2 between ACOS and TCCON, but ACOS generally infers a date of maximum XCO2 2-3 weeks later than TCCON. We further analyse the latitudinal dependence of the seasonal cycle amplitude throughout the Northern Hemisphere and compare the dependence to that predicted by current optimized models that assimilate in situ measurements of CO2. In the zonal averages, models are consistent with the GOSAT amplitude to within 1.4 ppm, depending on the model and latitude. We also show that the seasonal cycle of XCO2 depends on longitude especially at the mid-latitudes: the amplitude of GOSAT XCO2 doubles from western USA to East Asia at 45-50° N, which is only partially shown by the models. In general, we find that model-tomodel differences can be larger than GOSAT-to-model differences. These results suggest that GOSAT/ACOS retrievals of the XCO2 seasonal cycle may be sufficiently accurate to evaluate land surface models in regions with significant discrepancies between the models. [ABSTRACT FROM AUTHOR]

Within the European project UFTIR (Time series of Upper Free Troposphere observations from an European ground-based FTIR network), six ground-based stations in Western Europe, from 79° N to 28° N, all equipped with Fourier Transform infrared (FTIR) instruments and part of the Network for the Detection of Atmospheric Composition Change (NDACC), have joined their efforts to evaluate the trends of several direct and indirect greenhouse gases over the period 1995-2004. The retrievals of CO, CH4, C2H6, N2O, CHClF2, and O3 have been optimized. Using the optimal estimation method, some vertical information can be obtained in addition to total column amounts. A bootstrap resampling method has been implemented to determine annual partial and total column trends for the target gases. The present work focuses on the ozone results. The retrieved time series of partial and total ozone columns are validated with ground-based correlative data (Brewer, Dobson, UV-Vis, ozonesondes, and Lidar). The observed total column ozone trends are in agreement with previous studies: 1) no total column ozone trend is seen at the lowest latitude station Izaña (28° N); 2) slightly positive total column trends are seen at the two mid-latitude stations Zugspitze and Jungfraujoch (47° N), only one of them being significant; 3) the highest latitude stations Harestua (60° N), Kiruna (68° N) and Ny-Ålesund (79° N) show significant positive total column trends. Following the vertical information contained in the ozone FTIR retrievals, we provide partial columns trends for the layers: ground-10 km, 10-18 km, 18-27 km, and 27-42 km, which helps to distinguish the contributions from dynamical and chemical changes on the total column ozone trends. We obtain no statistically significant trends in the ground-10 km layer for five out of the six ground-based stations. We find significant positive trends for the lowermost stratosphere at the two mid-latitude stations, and at Ny- Ålesund. We find smaller, but significant trends for the 18- 27 km layer at Kiruna, Harestua, Jungfraujoch, and Izaña. The results for the upper layer are quite contrasted: we find significant positive trends at Kiruna, Harestua, and Jungfraujoch, and significant negative trends at Zugspitze and Izaña. These ozone partial columns trends are discussed and compared with previous studies. [ABSTRACT FROM AUTHOR]

Objective To compare early and late responses to highly active antiretroviral therapy (HAART) in European and non-European HIV-1 infected patients in a Dutch cohort. Methods We retrospectively analysed the response to HAART of 216 previously treatment-naive HIV-1-infected patients using the University Medical Centre Utrecht HIV database. African ( n=51), Asian ( n=7), and Central/South American ( n=6) patients were classified as non-European, and others as European ( n=152). Early failure was defined as a viral load that remained above 400 HIV-1 RNA copies/mL after 6 months of treatment with HAART. Late-phase failure was determined in patients who were successfully treated in the early phase and was defined as two consecutive viral load measurements above 400 copies/mL, a new AIDS-defining event or death. Results In the early phase, four of 152 (2.6%) European and eight of 64 (12.5%) non-European patients failed HAART. A significant increased risk of virological failure in the early phase of treatment was observed for non-Europeans as compared to Europeans (odds ratio 4.6; 95% confidence interval 1.1–20.2). Low serum drug levels in the absence of resistant virus were often seen at the time of early failure. No difference in late-phase failure was observed between the two groups (adjusted hazard ratio 0.6; 95% confidence interval 0.3–1.2). Conclusions Non-European patients had a 4.6 times higher risk of virological failure than their European counterparts in the first 6 months of treatment with HAART. This failure seemed to be associated with low serum drug levels at the time of failure. However, if HAART was successful in the early phase, response rates in the late phase were similar for Europeans and non-Europeans. [ABSTRACT FROM AUTHOR]

Anaemia is a serious and frequent complication of cancer and its treatment. ECAS was conducted in 24 European countries. 15,367 patients were enrolled and followed-up to 6 months in 2001. 1,335 patients affected by solid tumours or haematological diseases were enrolled in France. Disease status at enrollment was newly diagnosed with or without treatment, some patients had persistent/recurrent disease and some were in remission. Cancer treatments were chemotherapy, radiotherapy, radiochemotherapy or no treatment at all. At enrollment, 49.4 % of the French patients were anaemic (hb < 12 g/dL). Anaemia was noted in all cancer types, being solid tumours or haematological diseases, and whatever the disease status or the treatment. Low Hb rate correlated significantly with poor performance status during the entire survey. 75% of the French population were anaemic at some points during the 6 month study. Of patients who were not anaemic at enrollment, 58% became anaemic during chemotherapy. Only 40% of anaemic patients received anaemia treatment during the survey. This high frequency of anaemia in cancer patients was observed in all European countries. Anaemia remains a complication that is too rarely treated in cancer patients in Europe. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To analyse the differences in disease expression of European SLE patients based on gender, age at diagnosis, and ethnicity. Methods: A two-year, retrospective, multicentre, observational study was carried out in five countries (France, Germany, Italy, Spain and the UK). Patients' clinical manifestations including disease activity, organ involvement, organ damage and flares were analysed. Results: Thirty-one centres enrolled 412 consecutive eligible patients (90.5% of women), with active disease, stratified by disease severity (half severe and half non-severe). Baseline characteristics included; mean (SD) age: 43.3 (13.6) years, SLE duration: 10.7 (8.0) years and age at disease diagnosis: 32.6 (13.0) years old. The mean (SD) SELENA-SLEDAI and SLICC/ACR scores were: 8.1 (6.7) and 0.82 (1.36), respectively. Over half of patients experienced flares (54.9%). The average number of annual flares was 1.01 (0.71) flares/year. In males compared to females, the renal system was more frequently active (53.8% vs 30.0%, p=0.002), the mean SLICC/ACR score was higher (1.15 vs 0.79, p=0.039) and the pulmonary system was more likely to be damaged (12.8% vs 3.8%, p=0.010). Furthermore, patients diagnosed at younger age displayed more renal system activity (young: 56.3% vs adult: 33.4% vs elder: 8.9%, p<0.001) and renal damage (25.0% vs 6.9% vs 2.2%, p=0.018) compared to the others. The annual number of flares (1.13 vs 1.05 vs 0.81 flares/year, p<0.0001), including the occurrence of severe flares (0.58 vs 0.51 vs 0.20, p<0.0001), was also higher in these patients. Conversely, greater organ damage was observed in patients diagnosed at an older age compared to the others. The mean SLICC/ACR score was higher (1.31 vs young: 0.88 and adult: 0.78, p<0.001) in patients diagnosed in the older age groups. The pulmonary (13.3% vs younger: 0% vs adult: 3.7%, p=0.030) and cardiovascular (17.8% vs younger: 0% vs adult: 2.9%, p<0.001) systems were more frequently damaged in these patients. Black African descents showed greater disease activity compared to Caucasian patients. They flared more often (77.1% vs 48.6%, p=0.001) and experienced a greater number of annual flares (1.57 vs 0.89 flares/year, p<0.0001), mainly more severe flares (0.89 vs 0.38/year, p<0.0001). They also were more likely to experience renal system damage. Conclusion: The study showed clearly two patient subsets. The disease was the most active in Black African descents, and this phenomenon has never been described before in continental Europe. The disease was also more active in patients diagnosed at a younger or adult. Greater disease damage was observed in males and in patients diagnosed at an older age. [Copyright &y& Elsevier]

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients.It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

Pasture-based and small-scale livestock farming systems are the main source of livelihood in the mountain primary sector, ensuring socioeconomic sustainability and biodiversity in rural communities throughout Europe and beyond. Mountain livestock farming (MLF) has attracted substantial research efforts from a wide variety of scientific communities worldwide. In this study, the use of text mining and topic modelling analysis drew a detailed picture of the main research topics dealing with MLF and their trends over the last four decades. The final data corpus used for the analysis counted 2 679 documents, of which 92% were peer-reviewed scientific publications. The number of scientific outputs in MLF doubled every 10 years since 1980. Text mining found that milk, goat and sheep were the terms with the highest weighed frequency in the data corpus. Ten meaningful topics were identified by topic analysis: T1-Livestock management and vegetation dynamics; T2-Animal health and epidemiology; T3-Methodological studies on cattle; T4-Production system and sustainability; T5-Methodological studies; T6-Wildlife and conservation studies; T7-Reproduction and performance; T8-Dairy/meat production and quality; T9-Land use and its change and T10-Genetic/genomic studies. A hierarchical clustering analysis was performed to explore the interrelationships among topics, and three main clusters were identified: the first focused on sustainability, conservation and socioeconomic aspects (T4; T6 and T9), the second was related to food production and quality (T7 and T8) and the last one considered methodological studies on mountain flora and fauna (T1; T2; T3; T5 and T10). The 10 topics identified represent a useful and a starting source of information for further and more detailed analysis (e.g. systematic review) of specific research or geographical areas. A truly holistic and interdisciplinary research approach is needed to identify drivers of change and to understand current and future challenges faced by livestock farming in mountain areas., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Timely identification of COVID-19 patients at high risk of mortality can significantly improve patient management and resource allocation within hospitals. This study seeks to develop and validate a data-driven personalized mortality risk calculator for hospitalized COVID-19 patients. De-identified data was obtained for 3,927 COVID-19 positive patients from six independent centers, comprising 33 different hospitals. Demographic, clinical, and laboratory variables were collected at hospital admission. The COVID-19 Mortality Risk (CMR) tool was developed using the XGBoost algorithm to predict mortality. Its discrimination performance was subsequently evaluated on three validation cohorts. The derivation cohort of 3,062 patients has an observed mortality rate of 26.84%. Increased age, decreased oxygen saturation (≤ 93%), elevated levels of C-reactive protein (≥ 130 mg/L), blood urea nitrogen (≥ 18 mg/dL), and blood creatinine (≥ 1.2 mg/dL) were identified as primary risk factors, validating clinical findings. The model obtains out-of-sample AUCs of 0.90 (95% CI, 0.87-0.94) on the derivation cohort. In the validation cohorts, the model obtains AUCs of 0.92 (95% CI, 0.88-0.95) on Seville patients, 0.87 (95% CI, 0.84-0.91) on Hellenic COVID-19 Study Group patients, and 0.81 (95% CI, 0.76-0.85) on Hartford Hospital patients. The CMR tool is available as an online application at covidanalytics.io/mortality&#95;calculator and is currently in clinical use. The CMR model leverages machine learning to generate accurate mortality predictions using commonly available clinical features. This is the first risk score trained and validated on a cohort of COVID-19 patients from Europe and the United States., Competing Interests: KN, MS, BS are employed by Hartford HealthCare. ON is employed by Benefits Science Technologies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Broomcorn millet (Panicum miliaceum L.) is not one of the founder crops domesticated in Southwest Asia in the early Holocene, but was domesticated in northeast China by 6000 BC. In Europe, millet was reported in Early Neolithic contexts formed by 6000 BC, but recent radiocarbon dating of a dozen 'early' grains cast doubt on these claims. Archaeobotanical evidence reveals that millet was common in Europe from the 2nd millennium BC, when major societal and economic transformations took place in the Bronze Age. We conducted an extensive programme of AMS-dating of charred broomcorn millet grains from 75 prehistoric sites in Europe. Our Bayesian model reveals that millet cultivation began in Europe at the earliest during the sixteenth century BC, and spread rapidly during the fifteenth/fourteenth centuries BC. Broomcorn millet succeeds in exceptionally wide range of growing conditions and completes its lifecycle in less than three summer months. Offering an additional harvest and thus surplus food/fodder, it likely was a transformative innovation in European prehistoric agriculture previously based mainly on (winter) cropping of wheat and barley. We provide a new, high-resolution chronological framework for this key agricultural development that likely contributed to far-reaching changes in lifestyle in late 2nd millennium BC Europe.

Introduction: The European Reference Network (ERN) ReCONNET is the ERN aimed at improving the management of rare and complex connective tissue and musculoskeletal diseases (rCTDs) across the European Union (EU). In the mission of ERN ReCONNET, clinical practice guidelines (CPGs) play a crucial role, representing a valid tool towards the harmonisation of the management of rCTDs while improving effectiveness and quality of care delivered to patients., Methods: ERN ReCONNET developed two surveys to map the adherence to rCTDs CPGs among healthcare providers and to assess the knowledge and awareness of CPGs for their diseases among patients, family members and caregivers., Results: The results of the surveys highlighted that healthcare professionals find it useful to apply CPGs in clinical practice (93%), while 62% of them experience difficulties and barriers in the application in their centres. Healthcare professionals also highlighted the need to develop CPGs for all rCTDs and to implement the use of the existing CPGs in clinical practice. On the other hand, patients, families and caregivers are relatively aware of the purpose of CPGs (51%) and 62% of them were aware of the existence of CPGs for their disease. Patient-friendly versions of CPGs and patients' lifestyle guidelines should be systematically developed contributing to the empowerment of patients in the disease management., Conclusion: ERN ReCONNET is addressing the main issues identified in the results of the survey, promoting practical actions for the local adaptation of CPGs across Europe, improving their routine clinical use and increasing the awareness on CPGs among rCTDs patients, family members and caregivers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN)., Methods: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements., Results: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease., Conclusions: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care., Competing Interests: Competing interests: AF reports personal fees from GSK, Abbvie, Amgen, Enorasis, Roche and Genesis Pharma, outside the submitted work. HJA reports personal fees from GSK, Astra Zeneca and Janssen, during the conduct of the study; personal fees from Secarna, Inositec, Previpharma and Noxxon, outside the submitted work. MA reports honoraria fees from GSK and Roche, outside the submitted work; FH reports honoraria fees from GSL, outside the submitted work. MP reports personal fees from Otsuka, grants and personal fees from Alexion, personal fees from Retrophin, outside the submitted work. YKOT reports grants from GSK, personal fees from Aurinia Pharmaceuticals, personal fees from Novartis, during the conduct of the study. MT reports grants from Abbvie, BMS, Novartis, Pfize and Roche and honoraria fees from Novartis, outside the submitted work. DJ reports personal fees from Astra-Zeneca, Aurinia, Boehringer-Ingelheim, grants and personal fees from Chemocentryx, GSK, Roche/Genentech, and Sanofi-Genzyme, personal fees and other from Vifor, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Research primarily conducted in Europe find high neighborhood ethnic density (i.e., proportion of own ethnic group) lessens risk of psychotic symptoms among racial and ethnic minorities; however, most studies measure ethnic density through crude demarcations in geographic data only at illness onset which may miss meaningful variation from the perspective of residents. The present study is the first in the U.S. to examine whether changes in perceived ethnic density from childhood are associated with psychotic-like experiences (PLE)., Methods: A Northeastern U.S. urban undergraduate sample of 1330 racial and ethnic minorities completed a self-report inventory of PLE, the Prodromal Questionnaire, and indicated their racial and ethnic neighborhood composition before and after age 12. One way analyses of covariance (ANCOVA) adjusted for age, family poverty, racial and ethnic group, immigrant status, and lifetime cannabis use, compared PLE across ethnic density categories and change., Results: Racial and ethnic minorities who grew up in a neighborhood (before age 12) predominantly inhabited by a different group of color (e.g., being Black in a predominantly Asian neighborhood) endorsed significantly more PLE than those who grew up in racially concordant, mixed, or predominantly White neighborhoods. In addition, those reporting a change in perceived neighborhood ethnic density after age 12 endorsed significantly more PLE than those reporting no change., Conclusion: Racial dynamics among people of color in urban neighborhood U.S. contexts may create psychological challenges in the social environment. The developmental timing of demographic changes in neighborhoods may influence stress processes that enhance risk for PLE., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The European Union member states received about 385,000 asylum applications from children and adolescents below 18 years in 2015, and 398,000 in 2016. The latest political crises and war have led to an upsurge in refugee movements into European countries, giving rise to a re-evaluation of the epidemiology of psychiatric disorders and mental health problems among young refugees and asylum seekers. We systematically searched five electronic databases and reference lists of pertinent review articles. We then screened the results of forward citation tracking of key articles for relevant studies in the field for the period from January 1990 to October 2017. We dually reviewed citations and assessed risk of bias. We reported the results narratively, as meta-analyses were impeded due to high heterogeneity. We included 47 studies covered in 53 articles. Overall, the point prevalence of the investigated psychiatric disorders and mental health problems varied widely among studies (presenting interquartile ranges): for posttraumatic stress disorder between 19.0 and 52.7%, for depression between 10.3 and 32.8%, for anxiety disorders between 8.7 and 31.6%, and for emotional and behavioural problems between 19.8 and 35.0%. The highly heterogeneous evidence base could be improved by international, methodologically comparable studies with sufficiently large sample sizes drawn randomly among specific refugee populations. The prevalence estimates suggest, nevertheless, that specialized mental health care services for the most vulnerable refugee and asylum-seeking populations are needed. REGISTRATION: The systematic review protocol was registered in PROSPERO on October 19th, 2017 with the number: CRD42017080039 and is available from: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=80039.

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR)., Methods: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects., Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria., Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research., (© 2019, American College of Rheumatology.)

Polymyalgia rheumatica (PMR) occurs almost exclusively in persons aged 50 years or older and it is the second most common inflammatory rheumatic disease in older people after rheumatoid arthritis. Since there are no specific tests for PMR, the exclusion of clinically similar differential diagnoses is essential to ascertain the diagnosis. These recommendations for the management of PMR assume an already established diagnosis of PMR. It is recommended to initiate treatment with glucocorticoids immediately after diagnosis and to provide appropriate patient information and education about the impact of the disease and its treatment. Methotrexate should be considered in patients at high risk for relapse and/or glucocorticoid-related adverse events. These guidelines have been elaborated because there is significant heterogeneity in the management of PMR in clinical practice in Germany (but also Europe and worldwide), despite the large number of patients with this disease. These guidelines are primarily based on the 2015 EULAR-ACR recommendations for the management of PMR, which were updated by the guideline committee and adapted to the German speaking countries.

The treatment of rheumatic diseases with bioloics has significantly improved the prognosis of patients. Currently, there are 13 preparations available in Germany for the treatment of patients with inflammatory rheumatic diseases. These original preparations generally have-depending on the individual country-15 years of patent protection. As soon as the patent has expired, approved biosimilars can be brought into use. For the approval of a biosimilar, authorities such as the European Medical Agency or the American Food and Drug Administration require proof of the best possible comparability with respect to efficacy and safety in comparison to the original or reference product. Since 2015, biosimilars of inifliximab, adalimumab, etanercept and rituximab have been granted approval in the European Union, the USA, Japan and in other countries. Further biosimilar products for these reference products are in development for treatment in rheumatology. From a societal and medical point of view, this opens up the possibility to increase the availability of biopharmaceutical products for patients through lower prices. In Germany, this possibility has already occurred-statutory health insurance physicians have introduced quotas for biosimilars, which will ultimately decrease spending and healthcare costs. This can lead to price reductions of the original products, which has already happened in Germany. Biosimilars can be prescribed for new patients or as a change from the original to the generic drug. When switching, a distinction is made between individual switching (interchangeability), which is made in individual consultation between the physician and the patient, and nonmedical switching (substitution) made at the societal or governmental level, which is made in the context of health care cost containment, and then, for example, implemented at the pharmacy level. Preliminary data from Norway and Denmark are available for substitution on the basis of results from large studies or registries in which systematic changes were made. The previous conclusion was that this does not lead to new problems for the patients. The German Society for Rheumatology recognizes the advantages of introducing biosimilars in Germany, but recommends that their use be based primarily on a joint decision by the treating physician and patient.

Objectives: The aim was to evaluate the cross-cultural validity of the Lupus Impact Tracker (LIT) in five European countries and to assess its acceptability and feasibility from the patient and physician perspectives., Methods: A prospective, observational, cross-sectional and multicentre validation study was conducted in clinical settings. Before the visit, patients completed LIT, Short Form 36 (SF-36) and care satisfaction questionnaires. During the visit, physicians assessed disease activity [Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI], organ damage [SLICC/ACR damage index (SDI)] and flare occurrence. Cross-cultural validity was assessed using the Differential Item Functioning method., Results: Five hundred and sixty-nine SLE patients were included by 25 specialists; 91.7% were outpatients and 89.9% female, with mean age 43.5 (13.0) years. Disease profile was as follows: 18.3% experienced flares; mean SELENA-SLEDAI score 3.4 (4.5); mean SDI score 0.8 (1.4); and SF-36 mean physical and mental component summary scores: physical component summary 42.8 (10.8) and mental component summary 43.0 (12.3). Mean LIT score was 34.2 (22.3) (median: 32.5), indicating that lupus moderately impacted patients' daily life. A cultural Differential Item Functioning of negligible magnitude was detected across countries (pseudo- R 2 difference of 0.01-0.04). Differences were observed between LIT scores and Physician Global Assessment, SELENA-SLEDAI, SDI scores = 0 (P < 0.035) and absence of flares (P = 0.004). The LIT showed a strong association with SF-36 physical and social role functioning, vitality, bodily pain and mental health (P < 0.001). The LIT was well accepted by patients and physicians. It was reliable, with Cronbach α coefficients ranging from 0.89 to 0.92 among countries., Conclusion: The LIT is validated in the five participating European countries. The results show its reliability and cultural invariability across countries. They suggest that LIT can be used in routine clinical practice to evaluate and follow patient-reported outcomes in order to improve patient-physician interaction., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Introduction: Microvascular surgery following tumour resection has become an important field of oral maxillofacial surgery (OMFS). This paper aims to evaluate current microsurgical practice in Europe., Methods: The questionnaire of the DOESAK collaborative group for Microsurgical Reconstruction was translated into English, transformed into an online based survey and distributed to 200 OMFS units with the aid of the European Association for Cranio-Maxillo-Facial Surgery (EACMFS)., Results: 65 complete and 72 incomplete questionnaires were returned. Hospitals from the United Kingdom, France, Italy, the Netherlands, Spain, Belgium, Greece, Slovenia and Lithuania participated. 71% of contributing centres were university hospitals, 87% out of these perform microvascular tumour surgery at least on a two-weekly base. Overall complication rate was at around five percent. Most frequently used transplants were the radial forearm flap and the fibular flap. The perioperative management varied widely. Success factors for flap survival, however, were uniformly rated, with the surgical skill being the most important factor, followed by the quality of postoperative management. Medication seems to play a less important role., Conclusion: Within Europe microvascular surgery is a common and safe procedure for maxillofacial reconstructive surgery in the field of OMFS. While there is a major accordance for the surgical procedure itself and the most frequently used flaps, perioperative management shows a wide variety of protocols with low presumed impact on surgical outcome., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The Central European Watershed divides the Rhine-Main catchment and the Danube catchment. In the Early Medieval period, when ships were important means of transportation, Charlemagne decided to link both catchments by the construction of a canal connecting the Schwabian Rezat and the Altmühl rivers. The artificial waterway would provide a continuous inland navigation route from the North Sea to the Black Sea. The shortcut is known as Fossa Carolina and represents one of the most important Early Medieval engineering achievements in Europe. Despite the important geostrategic relevance of the construction it is not clarified whether the canal was actually used as a navigation waterway. We present new geophysical data and in situ findings from the trench fills that prove for the first time a total length of the constructed Carolingian canal of at least 2300 metres. We have evidence for a conceptual width of the artificial water course between 5 and 6 metres and a water depth of at least 60 to 80 cm. This allows a crossing way passage of Carolingian cargo scows with a payload of several tons. There is strong evidence for clayey to silty layers in the trench fills which reveal suspension load limited stillwater deposition and, therefore, the evidence of former Carolingian and post-Carolingian ponds. These findings are strongly supported by numerous sapropel layers within the trench fills. Our results presented in this study indicate an extraordinarily advanced construction level of the known course of the canal. Here, the excavated levels of Carolingian trench bottoms were generally sufficient for the efficient construction of stepped ponds and prove a final concept for a summit canal. We have evidence for the artificial Carolingian dislocation of the watershed and assume a sophisticated Early Medieval hydrological engineering concept for supplying the summit of the canal with adequate water.

Objective: The objective of this study was to explore the burden of SLE and its effect on patients' lives., Methods: The Lupus European Online (LEO) survey included patient-designed questions on demographics, SLE diagnosis, and the impact of SLE on careers. Three SLE-specific patient-reported outcome (PRO) questionnaires were also completed: the Lupus Quality of Life (LupusQoL), the Fatigue Severity Scale (FSS), and the Work Productivity and Activity Impairment (WPAI)-Lupus v2.0. The survey was available online in five languages from May through August 2010. All self-identified SLE participants were eligible to respond. Survey results were analysed using descriptive statistics. Multivariate linear regression explored factors contributing to impaired productivity., Results: Of the 2070 European SLE patients completing the survey, 93.1% were women, 86.7% were aged <50 years and 71.8% had a college or university education. More than two-thirds of respondents (69.5%) reported that SLE affected their careers; 27.7% changed careers within a year of diagnosis. All LupusQoL domains (score range 0-100) were impaired, with fatigue (median domain score 43.8) being the most affected and intimate relationships (median domain score 75.0) the least. Most patients (82.5%) reported fatigue (FSS score ≥4). Productivity was impaired across all WPAI domains, both at work and in general activities. Fatigue, an inability to plan and reduced physical health were significantly associated with impaired productivity. Patients whose careers were affected by SLE had worse health-related quality of life, more fatigue and worse productivity than patients whose careers were not affected., Conclusion: LEO survey respondents reported that SLE negatively affects their daily lives, productivity and career choices.

Aims: Duty-cycled radiofrequency ablation (RFA) has been used for atrial fibrillation (AF) for around 5 years, but large-scale data are scarce. The purpose of this survey was to report the outcome of the technique., Methods and Results: A survey was conducted among 20 centres from seven European countries including 2748 patients (2128 with paroxysmal and 620 with persistent AF). In paroxysmal AF an overall success rate of 82% [median 80%, interquartile range (IQR) 74-90%], a first procedure success rate of 72% [median 74% (IQR 59-83%)], and a success of antiarrhythmic medication of 59% [median 60% (IQR 39-72%)] was reported. In persistent AF, success rates were significantly lower with 70% [median 74% (IQR 60-92%)]; P = 0.05) as well as the first procedure success rate of 58% [median 55% (IQR 47-81%)]; P = 0.001). The overall success rate was similar among higher and lower volume centres and were not dependent on the duration of experience with duty-cycled RFA (r = -0.08, P = 0.72). Complications were observed in 108 (3.9%) patients, including 31 (1.1%) with symptomatic transient ischaemic attack or stroke, which had the same incidence in paroxysmal and persistent AF (1.1 vs. 1.1%) and was unrelated to the case load (r = 0.24, P = 0.15), bridging anticoagulation to low molecular heparin, routine administration of heparin over the long sheath, whether a transoesophageal echocardiogram was performed in every patient or not and average procedure times., Conclusion: Duty-cycled RFA has a self-reported success and complication rate similar to conventional RFA. After technical modifications a prospective registry with controlled data monitoring should be conducted to assess outcome.

A set of 13 dinucleotide STR loci (G1A, G10B, G1D, G10L, MU05, MU09, MU10, MU15, MU23, MU26, MU50, MU51, MU59) were selected as candidate markers for a DNA forensic profiling system for Northern European brown bear (Ursus arctos). We present results from validation of the markers with respect to their sensitivity, species specificity and performance (precision, heterozygote balance and stutter ratios). All STRs were amplified with 0.6ng template input, and there were no false bear genotypes in the cross-species amplification tests. The validation experiments showed that stutter ratios and heterozygote balance was more pronounced than in the tetranucleotide loci used in human forensics. The elevated ratios of stutter and heterozygote balance at the loci validated indicate that these dinucleotide STRs are not well suited for interpretation of individual genotypes in mixtures. Based on the results from the experimental validations we discuss the challenges related to genotyping dinucleotide STRs in single source samples. Sequence studies of common alleles showed that, in general, the size variation of alleles corresponded with the variation in number of repeats. The samples characterized by sequence analysis may serve as standard DNA samples for inter laboratory calibration. A total of 479 individuals from eight Northern European brown bear populations were analyzed in the 13 candidate STRs. Locus MU26 was excluded as a putative forensic marker after revealing large deviations from expected heterozygosity likely to be caused by null-alleles at this locus. The remaining STRs did not reveal significant deviations from Hardy-Weinberg equilibrium expectations except for loci G10B and MU10 that showed significant deviations in one population each, respectively. There were 9 pairwise locus comparisons that showed significant deviation from linkage equilibrium in one or two out of the eight populations. Substantial genetic differentiation was detected in some of the pairwise population comparisons and the average estimate of population substructure (F(ST)) was 0.09. The average estimate of inbreeding (F(IS)) was 0.005. Accounting for population substructure and inbreeding the total average probability of identity in each of the eight populations was lower than 1.1×10(-9) and the total average probability of sibling identity was lower than 1.3×10(-4). The magnitude of these measurements indicates that if applying these twelve STRs in a DNA profiling system this would provide individual specific evidence., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud's phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI >or=1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.

Current therapeutic and diagnostic resources have turned systemic lupus erythematosus (SLE) into a chronic disease by reducing mortality rates. The exact contribution of disease activity and disease related damage to mortality is not well studied. The aim of this study was to describe the current causes of death (COD) in a multinational European cohort of patients with SLE in relation to quantified measures of disease activity and damage. Prospective five-year observational study of case fatalities in SLE patients at 12 European centres was performed. Demographics, disease manifestations, interventions and quantified disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death were related to the various COD. Ninety-one case fatalities (89% females) occurred after median disease duration of 10.2 years (range 0.2-40) corresponding to a annual case fatality of one for each of the participating cohorts. Cumulative mortality correlated linearly with disease duration with nearly 10% of fatalities occurring in the first year and 40% after more than 10 years of disease. Death occurred during SLE remission in one third of cases. In the remaining cases a mixture of disease activity (median ECLAM 5.5, median SLEDAI 15) and accrued damage (median SLICC-DI 5.0) with opposing relationships to disease duration contributed to death. Infections and cardiovascular events were the most frequent COD in both early and late fatalities with no gender differences for type of COD, disease activity, damage or comorbidity. In Europe, case fatalities have become uncommon events in dedicated SLE cohorts. The bimodal mortality curve has flattened out and deaths now occur evenly throughout the disease course with infectious and cardiovascular complications as the main direct COD in both early and late fatalities. Accrued damage supplants disease activity over time as the main SLE specific contributor to death over time.

Background: At least in Germany, it is widely assumed that healthcare-related labour costs weaken the competitiveness of national industries. However, there is a lack of knowledge about the amount of employers' financial burden in Germany and in other competing countries, as well as the impact on market prices of German goods., Objective: To quantify the health-related labour costs for employers in seven countries and different industries, and identify the effects of current reforms in Germany on the financial burden of employers., Methods: We calculated the spending on health in Germany and the burden on German employers (by branch of production). We then compared the total burden with that of six other countries. A univariate analysis was then conducted to examine the connection between health-related labour costs and employment., Results: In 2000, employers paid 41.2% of the total of 283.3 billion spent on health matters in Germany. These total costs account for 3.2% of the gross output (UK: 1.8%, Switzerland: 1.9%, Poland: 2.1%, US: 3.2%, France: 3.6%, The Netherlands: 3.7%). Health-related labour costs account for 10.6% of the total labour costs. The health-related labour costs per employee are on average 3013 (from 2752 to 4793 in healthcare and the chemical industry, respectively). In the UK and the US there are corresponding labour costs of 1836 and 4256 per employee, respectively. The current health reform (2003) would reduce the labour costs by only 0.7% after 4 years (based on 2000, with all factors remaining constant). Employment increased by 3.7% from 1995 to 2000 (textile industry: -26.8%, vehicle manufacture: +18.3%). There is no empirical connection between employment and health-related labour costs. Labour costs increased by a higher amount than the health-related labour costs., Conclusions: The burden on German employers is moderate when compared internationally. The current reform of the German health system is not expected to improve companies' financial situation or German competitiveness. Restrictions on the range of medical services would provide a relatively small amount of relief for employers.

Objectives: To develop a hitherto unavailable risk factor model for accurately predicting anemia development in cancer patients before chemotherapy (CT) administration., Methods: 2,070 nonanemic patients from the European Cancer Anaemia Survey (ECAS) with hemoglobin (Hb) > or =12 g/dl at enrollment who received their first CT during ECAS and underwent at least two CT cycles were divided randomly into split half (SH) 1 and SH2 (n = 1,035 each). The model was developed on SH1 using logistic regression to simultaneously evaluate predictive factors, and was validated using SH2 and an additional similar subpopulation of 5,901 ECAS patients. Anemia risk values were assigned to the predictive factors and the sum of the predictive factors gave the total anemia risk score; lower-, higher-, and highest-risk cutoff points of the total anemia risk score were determined., Results: Variables ultimately identified as significant predictive factors for anemia were: lower initial Hb (< or =12.9 g/dl in females, and < or =13.4 g/dl in males); having lung or gynecologic cancer versus gastrointestinal (GI)/colorectal cancer; cancer at any other site versus GI/colorectal cancer; treatment with platinum CT, and female gender., Conclusion: Using this evidence-based risk model, nonanemic patients who are at the highest risk of developing anemia prior to receiving CT can be identified clinically, allowing appropriate anemia management to be planned., (Copyright 2006 S. Karger AG, Basel.)

The European Cancer Anaemia Survey (ECAS) was conducted to prospectively evaluate the prevalence, incidence and treatment of anaemia (haemoglobin <12.0 g/dL) in European cancer patients, including the relationship of mild, moderate and severe anaemia to performance status. Patients were evaluated for up to 6 months. Data (N=15367) included demographics, tumour type, performance status, haemoglobin levels, cancer treatments and anaemia treatments. Prevalence of anaemia at enrollment was 39.3% (haemoglobin <10.0 g/dL, 10%), and 67.0% during the survey (haemoglobin <10.0 g/dL, 39.3%). Low haemoglobin levels correlated significantly with poor performance status. Incidence of anaemia was 53.7% (haemoglobin <10.0 g/dL, 15.2%). Anaemia was treated in 38.9% of patients (epoetin, 17.4%; transfusion, 14.9%; and iron, 6.5%). Mean haemoglobin to initiate anaemia treatment was 9.7 g/dL. Anaemia prevalence and incidence in cancer patients are high. Anaemia significantly correlates with poor performance status and many anaemic patients are not treated.

Purpose: We examined the interaction of various established risk factors for acute mountain sickness (AMS) in a setting relevant for mountaineering and trekking., Methods: Questionnaires were obtained from 827 mountaineers on the day of arrival at the Capanna Margherita (4559 m) and on the next morning. Susceptibility to AMS was assessed by type and frequency of symptoms during previous exposures. AMS was defined as an AMS-C score >/= 0.7 (environmental symptom questionnaire) on the morning after arrival at 4559 m. Preexposure was defined as having spent more than 4 d above 3000 m during the 2 months preceding the climb to the Capanna Margherita. Slow ascent was defined as ascending in more than 3 d. A risk model was developed by multiple logistic regression and prospectively validated on independent data., Results: In susceptible individuals, the prevalence of AMS was 58% with rapid ascent and no preexposure, 29% with preexposure only, 33% with slow ascent only, and 7% with both preexposure and slow ascent. The corresponding values for nonsusceptible individuals were 31%, 16%, 11%, and 4%. The overall odds ratio for developing AMS in susceptible versus nonsusceptible individuals was 2.9 (95% confidence interval, 2.1-4.1). Age, gender, training, body mass index, alcohol intake, and cigarette smoking had no significant effect in bivariate analyses or in multivariate logistic regressions., Conclusion: Individual susceptibility, rate of ascent, and preexposure are the major, independent determinants for prevalence of AMS.

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.

During the last two decades, the countries of Central and Eastern Europe have been transforming their health systems and built an intermediate model between market and socialised economies. At the same time, they have been trying to establish a system of observed in public health between the countries of the European Union and those of Central and Eastern Europe widened in the last decade. In view of accessing the European Union, this article develops the different points in a context where public health represents a topic of extreme importance for the European Commission.

A total of 582 individuals (1,164 chromosomes) from two African, eight African-derived South American, five South American Amerindian, and three Brazilian urban populations were studied at four variable number of tandem repeat (VNTR) and two short tandem repeat (STR) hypervariable loci. These two sets of loci did not show distinct allele profiles, which might be expected if different processes promoted their molecular differentiation. The two African groups showed little difference between them, and their intrapopulational variation was similar to those obtained in the African-derived South American communities. The latter showed different degrees of interpopulation variability, despite the fact that they presented almost identical average degrees of non-African admixture. The F(ST) single locus estimates differed in the five sets of populations, probably due to genetic drift, indicating the need to consider population structure in the evaluation of their total variability. A high interpopulational diversity was found among Amerindian populations in relation to Brazilian African-derived isolated communities. This is probably a consequence of the differences in the patterns of gene flow and genetic drift that each of these semi-isolated groups experienced., (Copyright 1999 Wiley-Liss, Inc.)

A clinical trial was conducted to assess the feasibility, safety, and efficacy of the atrial septal defect (ASD) occlusion system for transcatheter closure of secundum ASD and patent foramen ovale (PFO) after episodes of cerebral embolism. Occlusion was attempted in 200 patients aged 1 to 74 years (mean 32). The procedure failed in 26 patients (13%); the device was retrieved through a catheter in 20 and through surgery in 6 patients. Procedure-related complications necessitating surgical removal of the device included device embolization in 2, device entrapment within the Chiari network in 1, frame fracture in 1, and perforation of atrial wall in 2. All 6 patients experienced an uneventful postoperative course. An additional 11 patients (6%) underwent surgical removal of the device during follow-up. There were 163 patients (81%) with an implanted ASD occlusion system at follow-up of from 6 to 36 months (mean 17). Thrombus formation around the device was detected by transesophageal echocardiography in 9 patients 1 to 4 weeks after implantation. One of these patients (who had a coagulation factor XII deficiency) suffered a cerebral thromboembolism. Late atrial wall perforation (5, 6, and 8 months after implantation) occurred in 3 adult patients. Infectious endocarditis developed in 2 adult patients (1%). No late device embolization and no atrioventricular valve injury occurred. An asymptomatic device frame fracture was found in 14% and frame deformity in 4% of all patients during the follow-up period of >230 patient-years. Immediately after closure, a moderate/large residual shunt remained in 8% and a small shunt in 29% of patients. After 1 year, a moderate/large shunt was present in 2% and a small one in 26% of patients. During a total follow-up of 49 patient-years, only 1 of 46 patients with PFO had a transient neurologic event after the closure. The study indicates that patients with centrally situated secundum ASD and those with PFO after cerebral embolism can be treated with this system with a high success rate and an acceptable morbidity.

Since 1989, a Certification in Medical Oncology is offered to ESMO members on the basis of their professional curriculum vitae and of their scores in a multiple choice examination. The first session took place in London, U.K., in September 1989, during ECCO 5. One hundred and twenty-five ESMO members were evaluated by means of 60 multiple choice questions covering various aspects of medical oncology, such as tumor diagnosis, prognosis and treatment, drug pharmacology and toxicity, histology and cytology, epidemiology, carcinogenesis and tumor biology. The mean percent of correct answers was 77.4. The best results were obtained with questions dealing with chemotherapy. Scores of 40% or less were obtained in 8 questions, including 2 questions on AIDS related tumors. A similar examination is available in 1990 and will be prepared yearly in the future. It is hoped that this European ESMO Certification will contribute to lessen the professional discrepancies between oncologists of European countries and improve the level of oncological training in Europe.