Editor's Choice-2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)

Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS) Authors/Task Force Members (a), Victor Aboyans (*), Jean- Baptiste Ricco (*), Marie- Louise E. L. Bartelink, Martin Bjorck, Marianne Brodmann, Tina Cohnert, Jean-Philippe Collet, Martin Czerny, Marco De Carlo, Sebastian Debus, Christine Espinola-Klein, Thomas Kahan, Serge Kownator, Lucia Mazzolai, A. Ross Naylor, Marco Roffi, Joachim Rother, Muriel Sprynger, Michal Tendera, Gunnar Tepe, Maarit Venermo, Charalambos Vlachopoulos, Ileana Desormais Document Reviewers (b), Petr Widimsky, Philippe Kolh, Stefan Agewall, Hector Bueno, Antonio Coca, Gert J. De Borst, Victoria Delgado, Florian Dick, Cetin Erol, Marc Ferrini, Stavros Kakkos, Hugo A. Katus, Juhani Knuuti, Jes Lindholt, Heinrich Mattle, Piotr Pieniazek, Massimo Francesco Piepoli, Dierk Scheinert, Horst Sievert, Iain Simpson, Jakub Sulzenko, Juan Tamargo, Lale Tokgozoglu, Adam Torbicki, Nikolaos Tsakountakis, Jose Tunon, Melina Vega de Ceniga, Stephan Windecker, Jose Luis ZamoranoPeer reviewe

Τα επιδημιολογικά δεδομένα του καρκίνου του μαστού στη Κρήτη και η συσχέτιση τους με προγνωστικούςπαράγοντες

Background Several researchers have claimed that classification of tumours on the basis of HER-2/neu overexpression or amplification may define a subset of breast cancer in which the net effect of a risk factor could be rather more obvious and its impact on breast cancer development more clear. We decided to investigate, in a group of patients from a geographical area with a low incidence of breast cancer, whether HER-2/neu positive tumours are correlated with established or suspected risk factors for breast cancer and thus to identify distinct subgroups of high risk women. We also examine the differences on breast cancer risk profile between younger and older Cretan women and between women living in the rural and urban areas of the island. Methods This study analysed data from patients who attended the Breast Unit at the University Hospital of Heraklion, Crete, Greece between 1990 and 2002. 509 Cretan women with incident, histological confirmed breast cancer, compared with 566 Cretan women referred to the unit for screening or minor breast problems and they never developed breast neoplasm until data were analyzed. The overexpression of the HER-2/neu protein was further detected in a sample of 384 women with breast cancer. Risk factor data were obtained from each subject by personal interviews using a structured questionnaire. The detection and scoring of the HER-2/neu protein, estrogen and progesterone receptor expression were performed using immunochemistry. Odds ratios and 95% confidence intervals were determined by chi-square test and logistic regression analysis. Case-case odds ratios were calculated in order to reveal the risk heterogeneity between HER-2/neu+ and HER-2/neu-tumours and case-control analyses to measure the magnitude of the correlation. Separate analyses were performed for premenopausal and postmenopausal women and according to age and estrogen receptor status. Results In multivariate analysis without HER-2/neu stratification, an increased breast cancer risk was associated with only four of the factors examined: use of oral contraceptives (OR=4.40, 95%C.I: 1.46-13.28), use of HRT (OR=7.34, 95%C.I: 2.03-26.53), an age at first full pregnancy more than 23 years (OR=1.91, 95%C.I: 1.29-2.83) and body mass index more than 29 kg/m2 (OR=3.13, 95%C.I: 2.02-4.84). Additionally, a history of abortion or miscarriage (OR=0.56, 95%C.I: 0.38-0.82) was correlated with a decreased risk of breast cancer. In the case to case comparison only BMI >29 kg/m2 revealed a relative connection that was stronger with positive than with negative HER-2/neu tumours (ratio of ORs=2.23, 95%C.I: 1.20-4.15, p=0.011). This may indicate evidence of heterogeneity of a rather significant degree for this factor. In the ER negative group an age at first full pregnancy >23 years and a BMI >29 kg/m2 were associated with an increased risk in both HER-2/neu groups, but the association was significantly stronger for the latter factor in the positive HER-2/neu tumours (ratio of ORs =2.46, 95%CI: 0.97-6.21). Additionally, women living in the rural areas were less nulliparous (p=0.019), gave births at an earlier age (p=0.010), had less abortions, (p 23 έτη (OR=1.91, 95% C.Ι:1.29-2.83) και ΒΜΙ> 29 kg/m2 (OR=3.13, 95%C.Ι: 2.02-4.84). Επιπλέον, ιστορικό προηγούμενων αμβλώσεων ή αποβολών(OR=0.56, 95%C. Ι: 0.38-0.82) συσχετίστηκε με μειωμένο κίνδυνο καρκίνου του μαστού. Στην σύγκριση HER-2/neu θετικών και αρνητικών όγκων μόνο ο BMI >29 kg/m2 αποκάλυψε μια στατιστικά σημαντική σχέση που ήταν ισχυρότερη με τους θετικούς απ' ό,τι με τους αρνητικούς όγκους για HER-2/neu (ratio of ORs=2.23, 95%C.I: 1.20-4.15, p=0.011). Αυτό δείχνει ένα σημαντικό βαθμό ετερογένειας για αυτόν τον παράγοντα σε σχέση με την ανάπτυξη HER-2/neu θετικών όγκων . Στην ομάδα με τους όγκους που δεν εκφράζανε οιστρογονικούς υποδοχείς, η ηλικία στην πρώτη πλήρη εγκυμοσύνη >23 έτη και ο BMI >29 kg/m2 συνδέθηκε με έναν αυξανόμενο κίνδυνο και στις δύο ομάδες, αλλά πάλι η συσχέτιση ήταν σημαντικά ισχυρότερη για τον τελευταίο παράγοντα στους HER-2/neu θετικούς όγκους (ratio of ORs = 2,46, 95%CI: 0.97-6.21). Επιπλέον, λιγότερες γυναίκες που ζούσαν στις αγροτικές περιοχές ήταν άτεκνες (p=0.019), είχαν γέννησαν σε πιο νεαρή ηλικία (p=0.010), είχαν κάνει λιγότερες αμβλώσεις(p<0.001), είχαν θηλάσει περισσότερο(p=0.038), κατανάλωναν συχνότερα κόκκινο κρέας (p<0.001) αλλά δεν ήταν πιο παχύσαρκες από τις γυναίκες που ζούσαν στις πόλεις. Επιπλέον, οι γυναίκες από τις αστικές περιοχές είχαν χρησιμοποιήσει τις ορμόνες για να καταστείλουν τη γαλακτοπαραγωγή (p=0.001) και τα από του στόματος αντισυλληπτικά (p=0.001), συχνότερα από τις γυναίκες των αγροτικών περιοχών. Συμπεράσματα Η παχυσαρκία και η όψιμη ηλικία πρώτης τελειόμηνης κύησης φαίνονται να είναι οι σημαντικότεροι παράγοντες κινδύνου για καρκίνο του μαστού στις γυναίκες της Κρήτης. Αντίθετα οι αποβολές ή και εκτρώσεις φαίνεται να μειώνουν τον κίνδυνο. Η μελέτη δεν επιβεβαίωσε ότι οι γνωστοί ορμονοεξαρτώμενοι παράγοντες κινδύνου εμφάνισης καρκίνου του μαστού διαφέρουν σε σχέση με την ανάπτυξη HER-2/neu θετικών ή HER-2/neu αρνητικών καρκίνων στο μαστό. Μοναδική εξαίρεση αποτέλεσε η παχυσαρκία όπως αυτή μετρήθηκε με το Δείκτη Μάζας Σώματος. Απαιτούνται περαιτέρω μελέτες με μεγαλύτερα μεγέθη δειγμάτων για να εξετάσουν πώς αυτοί οι ενδεχομένως τροποποιήσιμοι παράγοντες κινδύνου για καρκίνο του μαστού αλληλεπιδρούν με μοριακούς βιολογικούς δείκτες όπως το ογκογονίδιο HER-2/neu και οδηγούν στην καρκινογένεση. Παράλληλα, υπήρξαν μερικές διαφορές στο προφίλ των παραγόντων κινδύνου μεταξύ των γυναικών από τις αστικές και αγροτικές περιοχές που μπορούν να απεικονίσουν τις αλλαγές στις συνήθειες τρόπου ζωής λόγω στην κοινωνικοοικονομική πρόοδο. Εάν αυτές οι αλλαγές θα αυξήσουν την εμφάνιση καρκίνου του μαστού στο νησί πρέπει να δειχτεί σε μια μελλοντική μελέτη

Τα επιδημιολογικά δεδομένα του καρκίνου του μαστού στη Κρήτη και η συσχέτιση τους με προγνωστικούςπαράγοντες

Background Several researchers have claimed that classification of tumours on the basis of HER-2/neu overexpression or amplification may define a subset of breast cancer in which the net effect of a risk factor could be rather more obvious and its impact on breast cancer development more clear. We decided to investigate, in a group of patients from a geographical area with a low incidence of breast cancer, whether HER-2/neu positive tumours are correlated with established or suspected risk factors for breast cancer and thus to identify distinct subgroups of high risk women. We also examine the differences on breast cancer risk profile between younger and older Cretan women and between women living in the rural and urban areas of the island. Methods This study analysed data from patients who attended the Breast Unit at the University Hospital of Heraklion, Crete, Greece between 1990 and 2002. 509 Cretan women with incident, histological confirmed breast cancer, compared with 566 Cretan women referred to the unit for screening or minor breast problems and they never developed breast neoplasm until data were analyzed. The overexpression of the HER-2/neu protein was further detected in a sample of 384 women with breast cancer. Risk factor data were obtained from each subject by personal interviews using a structured questionnaire. The detection and scoring of the HER-2/neu protein, estrogen and progesterone receptor expression were performed using immunochemistry. Odds ratios and 95% confidence intervals were determined by chi-square test and logistic regression analysis. Case-case odds ratios were calculated in order to reveal the risk heterogeneity between HER-2/neu+ and HER-2/neu-tumours and case-control analyses to measure the magnitude of the correlation. Separate analyses were performed for premenopausal and postmenopausal women and according to age and estrogen receptor status. Results In multivariate analysis without HER-2/neu stratification, an increased breast cancer risk was associated with only four of the factors examined: use of oral contraceptives (OR=4.40, 95%C.I: 1.46-13.28), use of HRT (OR=7.34, 95%C.I: 2.03-26.53), an age at first full pregnancy more than 23 years (OR=1.91, 95%C.I: 1.29-2.83) and body mass index more than 29 kg/m2 (OR=3.13, 95%C.I: 2.02-4.84). Additionally, a history of abortion or miscarriage (OR=0.56, 95%C.I: 0.38-0.82) was correlated with a decreased risk of breast cancer. In the case to case comparison only BMI >29 kg/m2 revealed a relative connection that was stronger with positive than with negative HER-2/neu tumours (ratio of ORs=2.23, 95%C.I: 1.20-4.15, p=0.011). This may indicate evidence of heterogeneity of a rather significant degree for this factor. In the ER negative group an age at first full pregnancy >23 years and a BMI >29 kg/m2 were associated with an increased risk in both HER-2/neu groups, but the association was significantly stronger for the latter factor in the positive HER-2/neu tumours (ratio of ORs =2.46, 95%CI: 0.97-6.21). Additionally, women living in the rural areas were less nulliparous (p=0.019), gave births at an earlier age (p=0.010), had less abortions, (p 23 έτη (OR=1.91, 95% C.Ι:1.29-2.83) και ΒΜΙ> 29 kg/m2 (OR=3.13, 95%C.Ι: 2.02-4.84). Επιπλέον, ιστορικό προηγούμενων αμβλώσεων ή αποβολών(OR=0.56, 95%C. Ι: 0.38-0.82) συσχετίστηκε με μειωμένο κίνδυνο καρκίνου του μαστού. Στην σύγκριση HER-2/neu θετικών και αρνητικών όγκων μόνο ο BMI >29 kg/m2 αποκάλυψε μια στατιστικά σημαντική σχέση που ήταν ισχυρότερη με τους θετικούς απ' ό,τι με τους αρνητικούς όγκους για HER-2/neu (ratio of ORs=2.23, 95%C.I: 1.20-4.15, p=0.011). Αυτό δείχνει ένα σημαντικό βαθμό ετερογένειας για αυτόν τον παράγοντα σε σχέση με την ανάπτυξη HER-2/neu θετικών όγκων . Στην ομάδα με τους όγκους που δεν εκφράζανε οιστρογονικούς υποδοχείς, η ηλικία στην πρώτη πλήρη εγκυμοσύνη >23 έτη και ο BMI >29 kg/m2 συνδέθηκε με έναν αυξανόμενο κίνδυνο και στις δύο ομάδες, αλλά πάλι η συσχέτιση ήταν σημαντικά ισχυρότερη για τον τελευταίο παράγοντα στους HER-2/neu θετικούς όγκους (ratio of ORs = 2,46, 95%CI: 0.97-6.21). Επιπλέον, λιγότερες γυναίκες που ζούσαν στις αγροτικές περιοχές ήταν άτεκνες (p=0.019), είχαν γέννησαν σε πιο νεαρή ηλικία (p=0.010), είχαν κάνει λιγότερες αμβλώσεις(p<0.001), είχαν θηλάσει περισσότερο(p=0.038), κατανάλωναν συχνότερα κόκκινο κρέας (p<0.001) αλλά δεν ήταν πιο παχύσαρκες από τις γυναίκες που ζούσαν στις πόλεις. Επιπλέον, οι γυναίκες από τις αστικές περιοχές είχαν χρησιμοποιήσει τις ορμόνες για να καταστείλουν τη γαλακτοπαραγωγή (p=0.001) και τα από του στόματος αντισυλληπτικά (p=0.001), συχνότερα από τις γυναίκες των αγροτικών περιοχών. Συμπεράσματα Η παχυσαρκία και η όψιμη ηλικία πρώτης τελειόμηνης κύησης φαίνονται να είναι οι σημαντικότεροι παράγοντες κινδύνου για καρκίνο του μαστού στις γυναίκες της Κρήτης. Αντίθετα οι αποβολές ή και εκτρώσεις φαίνεται να μειώνουν τον κίνδυνο. Η μελέτη δεν επιβεβαίωσε ότι οι γνωστοί ορμονοεξαρτώμενοι παράγοντες κινδύνου εμφάνισης καρκίνου του μαστού διαφέρουν σε σχέση με την ανάπτυξη HER-2/neu θετικών ή HER-2/neu αρνητικών καρκίνων στο μαστό. Μοναδική εξαίρεση αποτέλεσε η παχυσαρκία όπως αυτή μετρήθηκε με το Δείκτη Μάζας Σώματος. Απαιτούνται περαιτέρω μελέτες με μεγαλύτερα μεγέθη δειγμάτων για να εξετάσουν πώς αυτοί οι ενδεχομένως τροποποιήσιμοι παράγοντες κινδύνου για καρκίνο του μαστού αλληλεπιδρούν με μοριακούς βιολογικούς δείκτες όπως το ογκογονίδιο HER-2/neu και οδηγούν στην καρκινογένεση. Παράλληλα, υπήρξαν μερικές διαφορές στο προφίλ των παραγόντων κινδύνου μεταξύ των γυναικών από τις αστικές και αγροτικές περιοχές που μπορούν να απεικονίσουν τις αλλαγές στις συνήθειες τρόπου ζωής λόγω στην κοινωνικοοικονομική πρόοδο. Εάν αυτές οι αλλαγές θα αυξήσουν την εμφάνιση καρκίνου του μαστού στο νησί πρέπει να δειχτεί σε μια μελλοντική μελέτη

Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC 4 E Trial

Background and Objective Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone. Methods Resource use data were extracted from participants’ daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed. Results Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: €17 [0–95% Crl: 16–19] vs. €24 [5–100% Crl: 18–29]; healthcare provider: €37 [28–67] vs. €44 [25–55]; healthcare payers: €54 [45–85] vs. €68 [45–81]; and society: €423 [399–478] vs. €451 [390–478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences. Conclusion The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant

Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness : economic evaluation alongside the randomised controlled ALIC(4)E trial in 15 European countries

Backgroun: oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries.Methods: direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed.Results: the healthcare payers' expected ICERs of oseltamivir were €22,459 per QALY gained in adults/adolescents and €13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is €8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged €1-€35 per patient).Conclusion: adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained &gt; €22,459) and cost-saving in adults/adolescents from a societal perspective.</p

Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC4E trial in 15 European countries

Backgroun: oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries.Methods: direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed.Results: the healthcare payers' expected ICERs of oseltamivir were €22,459 per QALY gained in adults/adolescents and €13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is €8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged €1-€35 per patient).Conclusion: adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained &gt; €22,459) and cost-saving in adults/adolescents from a societal perspective.</p

2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)

International audienc

2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)

International audienc