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Introduction: Fractional fl ow reserve (FFR) implies the ratio of the maximal hyperemic myocardial blood fl ow in the case of a pathologically changed coronary artery to the maximal hyperemic myocardial blood fl ow in the case of a healthy coronary artery. Aims: The aim of the current study is to perform an economic evaluation and budget impact analysis of measuring FFR as a medical activity in Bulgaria. Material and Methods: For the purpose of the current analysis, two models using Microsoft Excel and TreeAge Pro were developed to evaluate the cost-effectiveness of the FFR-guided percutaneous coronary intervention (PCI) compared to the classic angiography-guided PCI in patients with ischemic heart disease (IHD) with one-vessel coronary artery disease (CAD) or multivessel CAD. The analysis will focus on the health perspective and the payer perspective - National Health Insurance Fund (NHIF). Results: The medico-diagnostic activity related to measuring FFR in patients with multi-vessel coronary artery disease is shown to be a cost-effective therapeutic approach in Bulgaria compared to the angiography-guided PCI (ICER = 50 456 BGN/QALY) with a cost-effectiveness threshold of 51 510 BGN/QALY. FFR- guided PCI strategy in one-vessel coronary artery disease patients is a cost-saving approach (-853 BGN) when compared to the angiography-guided PCI (4 150 BGN). Conclusion: Budget impact analysis revealed that the FFR-guided PCI strategy is a cost-saving alternative approach to the angiographyguided PCI. The savings of the NHIF during the fi rst year of reimbursement of FFR would be -1,1 million BGN and could reach -1,6 million BGN in the third year.

The ascertainment of rules of customary international law has been typically inserted in the methodological dualism between induction and deduction. By induction, lawyers find existing legal rules on the basis of the empirical material – state practice and opinio juris. By deduction, instead, lawyers find legal rules by deducing them from existing principles and rules of international law. Notably, while induction is portrayed as empirically grounded – therefore objective – deduction is presented as a logical exercise, thus disguising the margin of manoeuvre that interpreters enjoy in ascertaining rules of customary international law. The determination of rules of customary international law has been typically inserted in the methodological dualism between induction and deduction. By induction, interpreters find existing legal rules on the basis of the empirical material – state practice and opinio juris. By deduction, interpreters find legal rules by deducing them from existing principles and rules of international law. Notably, while induction is portrayed as empirically-grounded – therefore arguably objective – deduction is presented as a logical exercise, thus disguising the margin of manoeuvre that interpreters enjoy in ascertaining rules of customary international law. The chapter contends that the methodological dualism informing the discourse on the determination of rules of customary international law shall be revisited to reflect the argumentative nature of such a determination. This twist is conducive to unveil the role that discretion plays in the ascertainment of rules of customary international law, instead of embracing the methodological lens which rather mystifies it. Accordingly, interpreters operate within an argumentative framework in that they necessarily select and appreciate evidence of practice and opinio juris, which is far from being incontrovertible, let alone fully representative of the majority of states.

Percutaneous coronary interventions (PCI) in calcified coronary artery lesions are associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using calcium modifying techniques such as Rotational Atherectomy (RA) or Intravascular Lithotripsy (IVL) has been advocated. Studies comparing these technologies are lacking. We aimed to compare in-stent pressure gradients, evaluated by vessel fractional flow reserve (vFFR), in calcific lesions treated using either RA or IVL.Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post-PCI in-stent pressure gradients calculated by vFFR (vFFRgrad). Secondary outcomes included the proportion of patients with complete functional revascularization defined as distal vFFR post-PCI (vFFRpost) ≥ 0.90.From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0.65 ± 0.13 RA and 0.67 ± 0.11 IVL). After PCI, in-stent pressure gradients were significantly lower in the IVL group (0.032 ± 0.026 vs 0.043 ± 0.026 in the RA group, p = 0.024). The proportions of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p = 0.669).Calcific lesions preparation with IVL is effective and resulted in lower in-stent pressure gradients compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL.

While the law on state responsibility is a well-developed field in international law, the potential for responsibility on the part of the state as a result of events taking place during peacekeeping missions is a fairly novel phenomenon. Internationally, claims in this field have been brought before the European Court of Human Rights and the International Court of Justice. National courts, on the other hand, have heard a total of six cases on the matter, in Belgium, the UK, and the Netherlands, all eventually apportioning responsibility to the state. This paper explores the effect that the potential for responsibility, as manifested in the outcomes of these recent cases, may have on state behaviour with respect to its future contributions to peacekeeping. The paper combines an exploration of the relevant adjudged cases with views collected from experts and academia in order to formulate three hypotheses on the effect of the potential for responsibility on future state behaviour. These hypotheses are then applied to the example of the Netherlands in the aftermath of a series of decisions finding it responsible for events taking place during its involvement in peacekeeping in Bosnia and Herzegovina in the 1990s. Due to the recent timing of the cases, the paper concludes with preliminary findings on each of the hypotheses, thereby opening the door to future research on the topic.

Coronary artery disease (CAD) continues to be the leading cause of mortality and morbidity in developed countries. Assessment of pre-test probability (PTP) based on patient's characteristics, gender and symptoms, help to identify more accurate patient's clinical likelihood of coronary artery disease. Consequently, non-invasive imaging tests are performed more appropriately to rule in or rule out CAD rather than invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) is the first-line non-invasive imaging technique in patients with suspected CAD and could be used to plan and guide coronary intervention. Invasive coronary angiography remains the gold-standard method for the identification and characterization of coronary artery stenosis. However, it is recommended in patients where the imaging tests are non-conclusive, and the clinical likelihood is very high, remembering that in clinical practice, approximately 30 to 70% of patients with symptoms and/or signs of ischemia, referred to coronary angiography, have non obstructive coronary artery disease (INOCA). In this contest, physiology and imaging-guided revascularization represent the cornerstone of contemporary management of chronic coronary syndromes (CCS) patients allowing us to focus specifically on ischemia-inducing stenoses. Finally, we also discuss contemporary medical therapeutic approach for secondary prevention. The aim of this review is to provide an updated diagnostic and therapeutic approach for the management of patients with stable coronary artery disease.

Background The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents. Methods In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels. Results The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275–0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status. Conclusions Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease. Trial Registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT 05261867.

Aims: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users). Methods: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization. Results: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33–0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21–0.98; p = 0.041). Conclusions: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI. Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867.

Il volume affronta una dimensione cruciale di offerta formativa, ossia l’efficacia della spesa per tecnologie didattiche dei 27 Ministeri dell'Istruzione dell'Unione Europea e dei Ministeri della Pubblica Istruzione e l'istruzione superiore in tutto il mondo, per i diversi livelli di scolarizzazione. Se non può essere dimostrato che c'è un impatto della tecnologia sulla formazione e se non può essere dimostrato che vi sono effetti positivi questa spesa è senza giustificazione. Il libro ha un approccio diverso da altri studi di settore, in quanto si concentra sull'impatto della tecnologia sulla formazione nell'educazione degli adulti, nel lifelong learning e nell’istruzione a distanza e non sui livelli di scolarizzazione inferiori. This book addresses a crucial dimension of educational provision: the expenditure on educational technology of the 27 Ministries of Education in the European Union and of Ministries of Education and Higher Education throughout the world, for their schools, colleges and universities. If it cannot be proved that there is an impact of technology on learning and if it cannon be proved that this impact is beneficial then this expenditure is without justification. The book takes a different approach to other studies in the field in that it concentrates on the impact of technology on learning in adult education, lifelong learning and distance education. In this context it has a special focus on distance education. Much previous work in the field has focused on the impact of technology on learning by children in schools.

This is a European Commission Leonardo da Vinci Reference Material project on the impact of new technology on distance learning students. It is known that all the Ministries of Education of the 27 European Union countries pay millions of Euros annually in the provision of educational technology for their schools, colleges and universities. A review of the literature of the impact of technology, however, showed that the research in this field was unacceptably fragile. What research there was focused on the impact of technology on children in American schools. The project set out, therefore, to measure the impact of technology on adult education, lifelong learning and distance education, with a particular focus on adult distance learning.