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Purpose: To study the trends of smoking-attributable mortality among the low and high educated in consecutive birth cohorts in 11 European countries. Methods: Register-based mortality data were collected among adults aged 30 to 79 years in 11 European countries between 1971 and 2012. Smoking-attributable deaths were estimated indirectly from lung cancer mortality rates using the Preston-Glei-Wilmoth method. Rate ratios and rate differences among the low and high-educated were estimated and used to estimate the contribution of inequality in smoking-attributable mortality to inequality in total mortality. Results: In most countries, smoking-attributable mortality decreased in consecutive birth cohorts born between 1906 and 1961 among low- and high-educated men and high-educated women, but not among low-educated women among whom it increased. Relative educational inequalities in smoking-attributable mortality increased among both men and women with no signs of turning points. Absolute inequalities were stable among men but slightly increased among women. The contribution of inequality in smoking-attributable mortality to inequality in total mortality decreased in consecutive generations among men but increased among women. Conclusions: Smoking might become less important as a driver of inequalities in total mortality among men in the future. However, among women, smoking threatens to further widen inequalities in total mortality. [ABSTRACT FROM AUTHOR]

Unfavorable health trends among the lowly educated have recently been reported from the United States. We analyzed health trends by education in European countries, paying particular attention to the possibility of recent trend interruptions, including interruptions related to the impact of the 2008 financial crisis. We collected and harmonized data on mortality from ca. 1980 to ca. 2014 for 17 countries covering 9.8 million deaths and data on selfreported morbidity from ca. 2002 to ca. 2014 for 27 countries covering 350,000 survey respondents. We used interrupted timeseries analyses to study changes over time and country-fixed effects analyses to study the impact of crisis-related economic conditions on health outcomes. Recent trends were more favorable than in previous decades, particularly in Eastern Europe, where mortality started to decline among lowly educated men and where the decline in less-than-good self-assessed health accelerated, resulting in some narrowing of health inequalities. In Western Europe, mortality has continued to decline among the lowly and highly educated, and although the decline of less-than-good selfassessed health slowed in countries severely hit by the financial crisis, this affected lowly and highly educated equally. Crisisrelated economic conditions were not associated with widening health inequalities. Our results show that the unfavorable trends observed in the United States are not found in Europe. There has also been no discernible short-term impact of the crisis on health inequalities at the population level. Both findings suggest that European countries have been successful in avoiding an aggravation of health inequalities. [ABSTRACT FROM AUTHOR]

Background: Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries.Objectives: The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test).Methods: Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression.Results: The mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female-male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients.Conclusions: Vasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men. [ABSTRACT FROM AUTHOR]

OBJECTIVE To update the recommendations for the structural characteristics of general thoracic surgery (GTS) in Europe in order to provide a document that can be used as a guide for harmonizing the general thoracic surgical practice in Europe. METHODS A task force was created to set the structural, procedural and qualification characteristics of a European GTS unit. These criteria were endorsed by the Executive Committee of the European Society of Thoracic Surgeons and by the Thoracic Domain of the European Association for Cardio-Thoracic Surgery and were validated by the European Board of Thoracic Surgery at European Union of Medical Specialists. RESULTS Criteria regarding definition and scope of GTS, structure and qualification of GTS unit, training and education and recommendations for subjects of particular interest (lung transplant, oesophageal surgery, minimally invasive thoracic surgery, quality surveillance) were developed. CONCLUSIONS This document will hopefully represent the first step of a process of revision of the modern thoracic surgeons' curricula, which need to be qualitatively rethought in the setting of the qualification process. The structural criteria highlighted in the present document are meant to help and tackle the challenge of cultural and language barriers as well as of widely varying national training programmes. [ABSTRACT FROM AUTHOR]

Five tyrosine kinase inhibitors (TKIs) are currently approved in the European Union for treatment of chronic myeloid leukemia (CML) and all have considerable overlap in their indications. While disease-specific factors such as CML phase, mutational status, and line of treatment are key to TKI selection, other important features must be considered, such as patient-specific comorbidities and TKI safety profiles. Ponatinib, the TKI most recently approved, has demonstrated efficacy in patients with refractory CML, but is associated with an increased risk of arterial hypertension, sometimes severe, and serious arterial occlusive and venous thromboembolic events. A panel of European experts convened to discuss their clinical experience in managing patients with CML. Based on the panel discussions, scenarios in which a CML patient may be an appropriate candidate for ponatinib therapy are described, including presence of the T315I mutation, resistance to other TKIs without the T315I mutation, and intolerance to other TKIs. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic inequalities in longevity have been found in all European countries. We aimed to assess which determinants make the largest contribution to these inequalities., Methods: We did an international comparative study of inequalities in risk factors for shorter life expectancy in Europe. We collected register-based mortality data and survey-based risk factor data from 15 European countries. We calculated partial life expectancies between the ages of 35 years and 80 years by education and gender and determined the effect on mortality of changing the prevalence of eight risk factors-father with a manual occupation, low income, few social contacts, smoking, high alcohol consumption, high bodyweight, low physical exercise, and low fruit and vegetable consumption-among people with a low level of education to that among people with a high level of education (upward levelling scenario), using population attributable fractions., Findings: In all countries, a substantial gap existed in partial life expectancy between people with low and high levels of education, of 2·3-8·2 years among men and 0·6-4·5 years among women. The risk factors contributing most to the gap in life expectancy were smoking (19·8% among men and 18·9% among women), low income (9·7% and 13·4%), and high bodyweight (7·7% and 11·7%), but large differences existed between countries in the contribution of risk factors. Sensitivity analyses using the prevalence of risk factors in the most favourable country (best practice scenario) showed that the potential for reducing the gap might be considerably smaller. The results were also sensitive to varying assumptions about the mortality risks associated with each risk factor., Interpretation: Smoking, low income, and high bodyweight are quantitatively important entry points for policies to reduce educational inequalities in life expectancy in most European countries, but priorities differ between countries. A substantial reduction of inequalities in life expectancy requires policy actions on a broad range of health determinants., Funding: European Commission and Network for Studies on Pensions, Aging, and Retirement., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess to what extent educational differences in total life expectancy (TLE) and disability-free life expectancy (DFLE) could be reduced by improving fruit and vegetable consumption in ten European countries., Methods: Data from national census or registries with mortality follow-up, EU-SILC, and ESS were used in two scenarios to calculate the impact: the upward levelling scenario (exposure in low educated equals exposure in high educated) and the elimination scenario (no exposure in both groups). Results are estimated for men and women between ages 35 and 79 years., Results: Varying by country, upward levelling reduced inequalities in DFLE by 0.1-1.1 years (1-10%) in males, and by 0.0-1.3 years (0-18%) in females. Eliminating exposure reduced inequalities in DFLE between 0.6 and 1.7 years for males (6-15%), and between 0.1 years and 1.8 years for females (3-20%)., Conclusions: Upward levelling of fruit and vegetable consumption would have a small, positive effect on both TLE and DFLE, and could potentially reduce inequalities in TLE and DFLE.

Objectives: A multicentre evaluation of the frequency and nature of major intraoperative complications during video-assisted thoracoscopic (VATS) anatomical resections., Methods: Six European centres submitted their series of consecutive anatomical lung resections with the intention to treat by VATS. Conversions to thoracotomy, vascular injuries and major intraoperative complications were studied in relation to surgeons' experience. Major complications included immediate life-threatening complications (i.e. blood loss of more than 2 l), injury to proximal airway or other organs or those leading to unplanned additional anatomical resections. All cases were discussed by a panel and recommendations were drafted., Results: A total of 3076 patients were registered. Most resections (90%, n = 2763) were performed for bronchial carcinoma. There were 3 intraoperative deaths, including 1 after conversion for technical reasons. In-hospital mortality was 1.4% (n = 43). Conversion to open thoracotomy was observed in 5.5% (n = 170), of whom 21.8% (n = 37) were for oncological reasons, 29.4% (n = 50) for technical reasons and 48.8% (n = 83) for complications. Vascular injuries were reported in 2.9% (n = 88) patients and led to conversion in 2.2% (n = 70). In 1.5% (n = 46), major intraoperative complications were identified. These consisted of erroneous transection of bronchovascular structures (n = 9); injuries to gastrointestinal organs (n = 5) or proximal airway (n = 6); complications requiring additional unplanned major surgery (n = 9) or immediate life-threatening complications (n = 17). Twenty-three percent of the in-hospital mortalities (n = 10/43) were related to major intraoperative complications. Eight pneumonectomies (five intraoperative and three postoperative at 0.3%) were a consequence of a major complication. Surgeon's experience was related to non-oncological conversions, but not to vascular injuries or major complications in a multivariable logistic regression analysis., Conclusion: Major intraoperative complications during VATS anatomical lung resections are infrequent, seem not to be related to surgical experience but have an important impact on patient outcome. Constant awareness and a structured plan of action are of paramount importance to prevent them., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome-positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph(+) CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.