Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia.

INTRODUCTION: Timely diagnosis of invasive candidiasis (IC) remains difficult as the clinical presentation is not specific and blood cultures lack sensitivity and need a long incubation time. Thus, non-culture-based methods for diagnosing IC have been developed. Mannan antigen (Mn) and anti-mannan antibodies (A-Mn) are present in patients with IC. On behalf of the Third European Conference on Infections in Leukemia, the performance of these tests was analysed and reviewed. METHODS: The literature was searched for studies using the commercially available sandwich enzyme-linked immunosorbent assays (Platelia™, Bio-Rad Laboratories, Marnes-la-Coquette, France) for detecting Mn and A-Mn in serum. The target condition of this review was IC defined according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity, specificity and diagnostic odds ratios (DOR) were calculated for Mn, A-Mn and combined Mn/A-Mn testing. RESULTS: Overall, 14 studies that comprised 453 patients and 767 controls were reviewed. The patient populations included in the studies were mainly haematological and cancer cases in seven studies and mainly intensive care unit and surgery cases in the other seven studies. All studies but one were retrospective in design. Mn sensitivity was 58% (95% confidence interval [CI], 53-62); specificity, 93% (95% CI, 91-94) and DOR, 18 (95% CI 12-28). A-Mn sensitivity was 59% (95% CI, 54-65); specificity, 83% (95% CI, 79-97) and DOR, 12 (95% CI 7-21). Combined Mn/A-Mn sensitivity was 83% (95% CI, 79-87); specificity, 86% (95% CI, 82-90) and DOR, 58 (95% CI 27-122). Significant heterogeneity of the studies was detected. The sensitivity of both Mn and A-Mn varied for different Candida species, and it was the highest for C. albicans, followed by C. glabrata and C. tropicalis. In 73% of 45 patients with candidemia, at least one of the serological tests was positive before the culture results, with mean time advantage being 6 days for Mn and 7 days for A-Mn. In 21 patients with hepatosplenic IC, 18 (86%) had Mn or A-Mn positive test results at a median of 16 days before radiological detection of liver or spleen lesions. CONCLUSIONS: Mn and A-Mn are useful for diagnosis of IC. The performance of combined Mn/A-Mn testing is superior to either Mn or A-Mn testing.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases.

The process to develop a guideline in a European setting remains a challenge. The ESCMID Fungal Infection Study Group (EFISG) successfully achieved this endeavour. After two face-to-face meetings, numerous telephone conferences, and email correspondence, an ESCMID task force (basically composed of members of the Society's Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic and management/therapeutic guideline for Candida diseases. By appreciating various patient populations at risk for Candida diseases, four subgroups were predefined, mainly ICU patients, paediatric, HIV/AIDS and patients with malignancies including haematopoietic stem cell transplantation. Besides treatment recommendations, the ESCMID guidelines provide guidance for diagnostic procedures. For the guidelines, questions were formulated to phrase the intention of a given recommendation, for example, outcome. The recommendation was the clinical intervention, which was graded by a score of A-D for the 'Strength of a recommendation'. The 'level of evidence' received a score of I-III. The author panel was approved by ESCMID, European Organisation for Research and Treatment of Cancer, European Group for Blood and Marrow Transplantation, European Society of Intensive Care Medicine and the European Confederation of Medical Mycology. The guidelines followed the framework of GRADE and Appraisal of Guidelines, Research, and Evaluation. The drafted guideline was presented at ECCMID 2011 and points of discussion occurring during that meeting were incorporated into the manuscripts. These ESCMID guidelines for the diagnosis and management of Candida diseases provide guidance for clinicians in their daily decision-making process.

Diagnostic yield of short-term video-EEG monitoring for epilepsy and PNESs: a European assessment.

INTRODUCTION: Although long-term video-EEG monitoring (LVEM) is routinely used to investigate paroxysmal events, short-term video-EEG monitoring (SVEM) lasting <24 h is increasingly recognized as a cost-effective tool. Since, however, relatively few studies addressed the yield of SVEM among different diagnostic groups, we undertook the present study to investigate this aspect. METHODS: We retrospectively analyzed 226 consecutive SVEM recordings over 6 years. All patients were referred because routine EEGs were inconclusive. Patients were classified into 3 suspected diagnostic groups: (1) group with epileptic seizures, (2) group with psychogenic nonepileptic seizures (PNESs), and (3) group with other or undetermined diagnoses. We assessed recording lengths, interictal epileptiform discharges, epileptic seizures, PNESs, and the definitive diagnoses obtained after SVEM. RESULTS: The mean age was 34 (±18.7) years, and the median recording length was 18.6 h. Among the 226 patients, 127 referred for suspected epilepsy - 73 had a diagnosis of epilepsy, none had a diagnosis of PNESs, and 54 had other or undetermined diagnoses post-SVEM. Of the 24 patients with pre-SVEM suspected PNESs, 1 had epilepsy, 12 had PNESs, and 11 had other or undetermined diagnoses. Of the 75 patients with other diagnoses pre-SVEM, 17 had epilepsy, 11 had PNESs, and 47 had other or undetermined diagnoses. After SVEM, 15 patients had definite diagnoses other than epilepsy or PNESs, while in 96 patients, diagnosis remained unclear. Overall, a definitive diagnosis could be reached in 129/226 (57%) patients. CONCLUSIONS: This study demonstrates that in nearly 3/5 patients without a definitive diagnosis after routine EEG, SVEM allowed us to reach a diagnosis. This procedure should be encouraged in this setting, given its time-effectiveness compared with LVEM.

Lowering blood alcohol content levels to save lives: The european experience

Road safety has become an increasing concern in developed countries due to the significant amount of mortal victims and the economic losses derived. Only in 2005 these losses rose to 200.000 million euros, a significant amount - approximately the 2% of its GDP- that easily justifies any public intervention. One tool used by governments to face this challenge is the enactment of stricter policies and regulations. Since drunk driving is one of the most important concerns of public authorities on this field, several European countries decided to lower their illegal Blood Alcohol Content levels to 0.5 mg/ml during the last decade. This study evaluates for the first time the effectiveness of this transition using European panel-based data (CARE) for the period 1991-2003 using the Differences-in-Differences method in a fixed effects estimation that allows for any pattern of correlation (Cluster-Robust). My results show the existence of positive impacts on certain groups of road users and for the whole population when the policy is accompanied by some enforcement interventions. Moreover, a time lag of more than two years is found in that effectiveness. Finally, I also assert the importance of controlling for serial correlation in the evaluation of this kind of policies.

Calculation of the variance in surveys of the economic climate

Public opinion surveys have become progressively incorporated into systems of official statistics. Surveys of the economic climate are usually qualitative because they collect opinions of businesspeople and/or experts about the long-term indicators described by a number of variables. In such cases the responses are expressed in ordinal numbers, that is, the respondents verbally report, for example, whether during a given trimester the sales or the new orders have increased, decreased or remained the same as in the previous trimester. These data allow to calculate the percent of respondents in the total population (results are extrapolated), who select every one of the three options. Data are often presented in the form of an index calculated as the difference between the percent of those who claim that a given variable has improved in value and of those who claim that it has deteriorated. As in any survey conducted on a sample the question of the measurement of the sample error of the results has to be addressed, since the error influences both the reliability of the results and the calculation of the sample size adequate for a desired confidence interval. The results presented here are based on data from the Survey of the Business Climate (Encuesta de Clima Empresarial) developed through the collaboration of the Statistical Institute of Catalonia (Institut d’Estadística de Catalunya) with the Chambers of Commerce (Cámaras de Comercio) of Sabadell and Terrassa.

Why the EU does not Have an Independent Competition Agency: French Interests and Transaction Costs in Early European Integration

A major achievement of new institutionalism in economics and political science is the formalisation of the idea that certain policies are more efficient when administered by a politically independent organisation. Based on this insight, several policy actors and scholars criticise the European Community for relying too much on a multi-task, collegial, and politicised organisation, the European Commission. This raises important questions, some constitutional (who should be able to change the corresponding procedural rules?) and some political-economic (is Europe truly committed to free and competitive markets?). Though acknowledging the relevance of legal and normative arguments, this paper contributes to the debate with a positive political-scientific perspective. Based on the view that institutional equilibria raise the question of equilibrium institutions, it shows that collegiality was (a) an equilibrium institution during the Paris negotiations of 1950-51; and (b) an institutional equilibrium for the following 50 years. The conclusion points to some recent changes in the way that European competition policy is implemented, and discusses how these affect the “constitutional” principle of collegial European governance.

Trends in lung cancer among young European women: the rising epidemic in France and Spain.

Lung cancer mortality in young women in the European Union (EU) has steadily increased until the mid 1990 s and has levelled off thereafter, but trends have been heterogeneous in various countries. We analyzed therefore age-standardized trends in lung cancer mortality in young women (20-44) for the 6 major European countries, using joinpoint regression. In the early 1970s the highest lung cancer mortality in young women was in the UK (2.1/100,000). UK rates, however, steadily declined and in 2000-2004 they were the lowest of all 6 major EU countries (1.2/100,000). The second lowest rate in 2000-2002 was in Italy, whose rates remained around 1.1/100,000 between 1970 and 1994, and increased to 1.4 thereafter. In Germany and Poland, lung cancer rates in young women rose from 0.8-1.0/100,000 in the early 1970s to 1.7-1.9 in the mid 1990 s and levelled off during the last decade. Major rises over recent years were observed in France (from 0.8/100,000 in 1985-1989 to 2.2 in 2000-2003) and in Spain (from 0.8 in the 1985-1989 to 1.7 in 2000-2004). Thus, France showed both the highest rate observed over the last 3 decades and the largest rise over the last 2 decades. Since recent trends in the young give relevant information to the likely future trends in middle age, the female lung cancer epidemic is likely to expand in southern Europe from the current rates of 5.0/100,000 in Spain and 7.7 in France to approach 20/100,000 within the next 2-3 decades. Urgent interventions for smoking cessation in women are therefore required.

Common and Idiosyncratic Factors of the Exchange Risk Premium in Emerging European Markets

Existing empirical evidence suggests that the Uncovered Interest Rate Parity (UIRP) condition may not hold due to an exchange risk premium. For a panel data set of eleven emerging European economies we decompose this exchange risk premium into an idiosyncratic (country-specific) elements and a common factor using a principal components approach. We present evidence of a stationary idiosyncratic component and nonstationary common factor. This result leads to the conclusion of a nonstationary risk premium for these countries and a violation of the UIRP in the long-run, which is in contrast to previous studies often documenting a stationary premium in developed countries. Furthermore, we report that the variation in the premium is largely attributable to a common factor influenced by economic developments in the United States.

Contextual determinants of alcohol consumption changes and preventive alcohol policies: a 12-country European study in progress.

Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and 2008 are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes.

Optimal Climate Change Policies When Governments Cannot Commit

This paper examines the optimal design of climate change policies in the context where governments want to encourage the private sector to undertake significant immediate investment in developing cleaner technologies, but the carbon taxes and other environmental policies that could in principle stimulate such investment will be imposed over a very long future. The conventional claim by environmental economists is that environmental policies alone are sufficient to induce firms to undertake optimal investment. However this argument requires governments to be able to commit to these future taxes, and it is far from clear that governments have this degree of commitment. We assume instead that governments cannot commit, and so both they and the private sector have to contemplate the possibility of there being governments in power in the future that give different (relative) weights to the environment. We show that this lack of commitment has a significant asymmetric effect. Compared to the situation where governments can commit it increases the incentive of the current government to have the investment undertaken, but reduces the incentive of the private sector to invest. Consequently governments may need to use additional policy instruments – such as R&D subsidies – to stimulate the required investment.

Colonialism, European Descendants and Democracy

This paper advances that the share of European descendants in the population is a major determinant of democracy in former colonial countries. We test this hypothesis using cross-section and panel regressions with 60 developing and developed countries that were once colonies. We find that the share of European descendants can explain more than half of the difference in measures of democracy between the least and the most democratic countries in our sample. We control for other potential determinants of democracy and test for endogeneity bias using instrumental variables.

Phylogeographical footprints of the Strait of Gibraltar and Quaternary climatic fluctuations in the western Mediterranean: a case study with the greater white-toothed shrew, Crocidura russula (Mammalia: Soricidae).

We used mitochondrial cyt b sequences to investigate the phylogenetic relationships of Crocidura russula (sensu lato) populations across the Strait of Gibraltar, western Europe, Maghreb, and the Mediterranean and Atlantic islands. This revealed very low genetic divergence between European and Moroccan populations. The application of a molecular clock previously calibrated for shrews suggested that the separation of European from Moroccan lineages occurred less than 60 000 bp, which is at least 5 million years (Myr) after the reopening of the Strait of Gibraltar. This means that an overwater dispersal event was responsible for the observed phylogeographical structure. In contrast, genetic analyses revealed that Moroccan populations were highly distinct from Tunisian ones. According to the molecular clock, these populations separated about 2.2 million years ago (Ma), a time marked by sharp alternations of dry and humid climates in the Maghreb. The populations of the Mediterranean islands Ibiza, Pantelleria, and Sardinia were founded from Tunisian populations by overwater dispersal. In conclusion, overwater dispersal across the Strait of Gibraltar, probably assisted by humans, is possible for small terrestrial vertebrates. Moreover, as in Europe, Quaternary climatic fluctuations had a major effect on the phylogeographical structure of the Maghreb biota.