Toward international peace and security: Addressing the challenge of nuclear proliferation in a globalized world. ACES Working Papers, August 2010

With a growing number of threats to governance in the international system that result from globalization and technological innovation, it is no surprise that states have come to rely more heavily on each other and the global community for support. While the EU is partially constrained by the ultimate outcome of its own integration process, limited knowledge on this issue, and the national interests of its Member States, other governments are also experiencing difficulty in domestic implementation of international resolutions. To better understand the impact of the most recent sanctioning efforts, this paper will explore the development of the non-proliferation regime, examine implementation mechanisms of non-proliferation agreements, and analyze the impact of increased cooperation among states to thwart the spread of WMD technology and material. Case studies of unilateral measures undertaken by the US and EU against Iran will provide insight into the political and economic implications of economic sanctions from individual governments. New and emerging methods for limiting rogue states and non-state actors from acquiring the means to develop WMD will also be discussed in an effort to further discussion for future policy debates on this critical topic

Next-generation drug-eluting stents in coronary artery disease: focus on everolimus-eluting stent (Xience V®)

Percutaneous coronary revascularization has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stents and, more recently, first-generation drug-eluting stents (DES), such as sirolimus-eluting (Cypher®) and paclitaxel-eluting stents (Taxus®), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. There is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. There are well known caveats on the performance of their respective metallic stent platforms, delivery, and dilation systems, and polymer coatings. Second-generation DES, such as zotarolimus-eluting (Endeavor®) and everolimus-eluting stents (Xience V®), have recently become available in the USA and/or Europe. The Xience V stent holds the promise of superior anti-restenotic efficacy as well as long-term safety. In addition, this stent is based on the Multi-link platform and delivery system. Recently available data already suggest the superiority of the Xience V stent in comparison to the Taxus stent in terms of prevention of restenosis, without significant untoward events. Nonetheless, the number of patients studied and the follow-up duration are still too limited to enable definitive conclusions. Only indirect meta-analyses can be used to date to compare the Xience V with the Cypher. This systematic review tries to provide a concise and critical appraisal of the data in support of the Xience V everolimus-eluting stent

A novel closed-chest porcine model of chronic ischemic heart failure suitable for experimental research in cardiovascular disease

Cardiac pathologies are among the leading causes of mortality and morbidity in industrialized countries, with myocardial infarction (MI) representing one of the major conditions leading to heart failure (HF). Hitherto, the development of consistent, stable, and reproducible models of closed-chest MI in large animals, meeting the clinical realism of a patient with HF subsequent to chronic ischemic necrosis, has not been successful. We hereby report the design and ensuing application of a novel porcine experimental model of closed-chest chronic ischemia suitable for biomedical research, mimicking post-MI HF. We also emphasize the key procedural steps involved in replicating this unprecedented model, from femoral artery and vein catheterization to MI induction by permanent occlusion of the left anterior descending coronary artery through superselective deployment of platinum-nylon coils, as well as endomyocardial biopsy sampling for histologic analysis and cell harvesting. Our model could indeed represent a valuable contribution and tool for translational research, providing precious insights to understand and overcome the many hurdles concerning, and currently quenching, the preclinical steps mandatory for the clinical translation of new cardiovascular technologies for personalized HF treatments

Right versus left radial artery access for coronary procedures: an international collaborative systematic review and meta-analysis including 5 randomized trials and 3210 patients

BACKGROUND: Radial artery access is a mainstay in the diagnosis and treatment of coronary artery disease. However, there is uncertainty on the comparison of right versus left radial access for coronary procedures. We thus undertook a systematic review and meta-analysis comparing right versus left radial access for coronary diagnostic and interventional procedures. METHODS: Pertinent studies were searched in CENTRAL, Google Scholar, MEDLINE/PubMed, and Scopus, together with international conference proceedings. Randomized trials comparing right versus left radial (or ulnar) access for coronary diagnostic or interventional procedures were included. Risk ratios (RR) and weighted mean differences (WMD) were computed to generate point estimates (95% confidence intervals). RESULTS: A total of 5 trials (3210 patients) were included. No overall significant differences were found comparing right versus left radial access in terms of procedural time (WMD=0.99 [-0.53; 2.51]min, p=0.20), contrast use (WMD=1.71 [-1.32; 4.74]mL, p=0.27), fluoroscopy time (WMD=-35.79 [-3.54; 75.12]s, p=0.07) or any major complication (RR=2.00 [0.75; 5.31], p=0.49). However, right radial access was fraught with a significantly higher risk of failure leading to cross-over to femoral access (RR=1.65 [1.18; 2.30], p=0.003) in comparison to left radial access. CONCLUSIONS: Right and left radial accesses appear largely similar in their overall procedural and clinical performance during transradial diagnostic or interventional procedures. Nonetheless, left radial access can be recommended especially during the learning curve phase to reduce femoral cross-overs

Colchicine for children with pericarditis: systematic review of clinical studies

OBJECTIVE: To review the evidence for the efficacy and safety of colchicine in children with pericarditis. DESIGN: Systematic review. SEARCH STRATEGY: The following databases were searched for studies about colchicine in children with pericarditis (June 2015): Cochrane Central, Medline, EMBASE and LILACS. ELIGIBILITY CRITERIA: All observational and experimental studies on humans with any length of follow-up and no limitations on language or publication status were included. The outcomes studied were recurrences of pericarditis and adverse events. DATA EXTRACTION: Two authors extracted data and assessed quality of included studies using the Cochrane risk of bias tool for non-randomised trials. RESULTS: Two case series and nine case reports reported the use of colchicine in a total of 86 children with pericarditis. Five articles including 74 paediatric patients were in favour of colchicine in preventing further pericarditis recurrences. Six studies including 12 patients showed that colchicine did not prevent recurrences of pericarditis. LIMITATIONS: No randomised controlled trials (RCTs) were found. CONCLUSIONS: Although colchicine is an established treatment for pericarditis in adults, it is not routinely used in children. There is not enough evidence to support or discourage the use of colchicine in children with pericarditis. Further research in the form of large double-blind RCTs is needed to establish the efficacy of colchicine in children with pericarditis

GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin

Background: There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world. Methods: We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression. Results: There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17). Conclusions: In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did. © Schiariti et al