Safety of drug-eluting stents

Drug-eluting stents (DESs) effectively reduce angiographic restenosis and the clinical need for repeat revascularization procedures as compared with bare-metal stents. Widely publicized concerns arose recently about the incidence of late and very late stent thrombosis with the use of first-generation DESs. Recent systematic reviews and large-scale registry studies demonstrated similar rates of overall mortality and myocardial infarction for patients treated with either DESs or bare-metal stents during long-term follow-up. Careful selection of stent type according to patient and lesion characteristics as well as monitoring of adherence to dual antiplatelet therapy could maximize the therapeutic potential of these devices. The purpose of the present Review is to provide the reader with an overview of the benefits and risks of first-generation DESs that could help physicians select the most appropriate stent type for each patient.

Development of a wireless platform to generate nitric oxide for implanted biomedical devices

The perturbation of homeostatic mechanisms caused by interactions between any indwelling biomedical device and the biological medium into which it is implanted initiates a dynamic wound healing response from the host which can be rigorous and ongoing. The typical result of this response is a severe degradation in the performance and safety of the device, often to the extent of precluding their clinical use. Nitric oxide (NO) is an endogenously produced biomolecule capable of mediating many of the cellular processes leveraged against implanted devices. The in vivo performance of indwelling devices prepared with NO release coatings has recently been evaluated with very encouraging results. This work developed a platform capable of both generating programmable fluxes of NO and directly evaluating the performance of indwelling probes under different profiles of NO generation. This platform can be used to improve the efficacy of NO release materials in mitigating the host response.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women at High Risk for Atherothrombosis: From the Women in Innovation and Drug-Eluting Stents Collaborative Patient-Level Pooled Analysis

BACKGROUND The safety and efficacy of new-generation drug-eluting stents (DES) in women with multiple atherothrombotic risk (ATR) factors is unclear. METHODS AND RESULTS We pooled patient-level data for women enrolled in 26 randomized trials. Study population was categorized based on the presence or absence of high ATR, which was defined as having history of diabetes mellitus, prior percutaneous or surgical coronary revascularization, or prior myocardial infarction. The primary end point was major adverse cardiovascular events defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Out of 10 449 women included in the pooled database, 5333 (51%) were at high ATR. Compared with women not at high ATR, those at high ATR had significantly higher risk of major adverse cardiovascular events (15.8% versus 10.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.34-1.75; P=0.006) and all-cause mortality. In high-ATR risk women, the use of new-generation DES was associated with significantly lower risk of 3-year major adverse cardiovascular events (adjusted hazard ratio: 0.69; 95% confidence interval: 0.52-0.92) compared with early-generation DES. The benefit of new-generation DES on major adverse cardiovascular events was uniform between high-ATR and non-high-ATR women, without evidence of interaction (Pinteraction=0.14). At landmark analysis, in high-ATR women, stent thrombosis rates were comparable between DES generations in the first year, whereas between 1 and 3 years, stent thrombosis risk was lower with new-generation devices. CONCLUSIONS Use of new-generation DES even in women at high ATR is associated with a benefit consistent over 3 years of follow-up and a substantial improvement in very-late thrombotic safety.

The association between maternal use of spermicides, condoms, intra-uterine devices or progesterone and major structural birth defects

Birth defects occur in 1 of every 33 babies born in the United States, and are the leading cause of infant death. Mothers using contraceptives that become pregnant may continue to use their contraceptives after their first missed menstrual period, thus exposing their baby in utero to the contraceptive product. Progesterone is also sometimes prescribed during the first trimester of pregnancy to mothers with a history of miscarriages or infertility problems. To ensure the safety of these products, it is important to investigate whether there is an increased occurrence of babies born with birth defects to mothers using various contraceptive methods or progesterone in early pregnancy. Using data from the National Birth Defects Prevention Study (NBDPS), an ongoing multi-state, population based case-control study, this study assessed maternal exposures to IUDs, spermicides, condoms and progesterone in early pregnancy. ^ Progesterone used for threatened miscarriage during the first three months of pregnancy was associated with an increased occurrence of hypoplastic left heart (adjusted odds ratios (OR) 2.24, 95% CI 1.13-4.21), perimembranous ventricular septal defects (OR 1.64, 95% CI 1.10-2.41), septal associations (OR 2.52, 95% CI 1.45-4.24), esophageal atresia (OR 1.82, 95% CI 1.04-3.08), and hypospadias (OR 2.12, 95% CI 1.41-3.18). Mothers using progesterone for injectable contraception had increased (OR > 2.5), but insignificant odds ratios for anencephaly, septal associations, small intestinal atresias and omphalocel. Progesterone used for fertility was not associated with an increased occurrence of any birth defects examined. ^ Mothers using progesterone for fertility assistance and threatened miscarriage were very similar with respect to their demographics and pregnancy history. They also both reported similar types of progesterone. Thus, if progesterone was a causal risk factor for birth defects we would have expected to observe similar increases in risk among mothers using progesterone for both indications. Because we predominantly observed increased associations among mothers using progesterone for threatened miscarriage but not fertility assistance, it is possible the increased associations we observed were confounded by indication (i.e. progesterone was administered for vaginal bleeding which occurred as a sequelae to the formation of a congenital anomaly. ^ No significant increased associations were observed between maternal spermicide use during pregnancy and 26 of 27 types of structural malformations. While multiple statistical tests were performed we observed first trimester maternal spermicide use to be associated with a significant increased occurrence of perimembranous ventricular septal defects (OR 2.21, 95% CI 1.16-4.21). A decreased occurrence (OR < 1.0) was observed for several categories of birth defects among mothers who conceived in the first cycle after discontinuing the use of spermicides (22 of 28) or male condoms (23 of 33). ^ Overall the percent of IUD use was similar between mothers of controls and mothers of all cases in aggregate (crude OR 1.05, 95% CI 0.61-1.84). Power was limited to detect significant associations between IUD use and birth defects, however mothers using an IUD in the month immediately prior to conception or during pregnancy were not associated with an increase of birth defects. Limb defects and amniotic band sequence previously reported to be associated with IUD use during pregnancy were not found to occur among any mothers reporting the use of an IUD during pregnancy.^

Safety, feasibility, and long-term results of percutaneous closure of atrial septal defects using the Amplatzer septal occluder without periprocedural echocardiography.

OBJECTIVES We sought to assess the safety and efficacy of percutaneous closure of atrial septal defects (ASDs) under fluoroscopic guidance only, without periprocedural echocardiographic guidance. BACKGROUND Percutaneous closure of ASDs is usually performed using simultaneous fluoroscopic and transthoracic, transesophageal (TEE), or intracardiac echocardiographic (ICE) guidance. However, TEE requires deep sedation or general anesthesia, which considerably lengthens the procedure. TEE and ICE increase costs. METHODS Between 1997 and 2008, a total of 217 consecutive patients (age, 38 ± 22 years; 155 females and 62 males), of whom 44 were children ≤16 years, underwent percutaneous ASD closure with an Amplatzer ASD occluder (AASDO). TEE guidance and general anesthesia were restricted to the children, while devices were implanted under fluoroscopic guidance only in the adults. For comparison of technical safety and feasibility of the procedure without echocardiographic guidance, the children served as a control group. RESULTS The implantation procedure was successful in all but 3 patients (1 child and 2 adults; 1.4%). Mean device size was 23 ± 8 mm (range, 4-40 mm). There was 1 postprocedural complication (0.5%; transient perimyocarditis in an adult patient). At last echocardiographic follow-up, 13 ± 23 months after the procedure, 90% of patients had no residual shunt, whereas a minimal, moderate, or large shunt persisted in 7%, 1%, and 2%, respectively. Four adult patients (2%) underwent implantation of a second device for a residual shunt. During a mean follow-up period of 3 ± 2 years, 2 deaths and 1 ischemic stroke occurred. CONCLUSION According to these results, percutaneous ASD closure using the AASDO without periprocedural echocardiographic guidance seems safe and feasible.

Application of gas-cooled Accelerator Driven System (ADS) transmutation devices to sustainable nuclear energy development

The conceptual design of a pebble bed gas-cooled transmutation device is shown with the aim to evaluate its potential for its deployment in the context of the sustainable nuclear energy development, which considers high temperature reactors for their operation in cogeneration mode, producing electricity, heat and Hydrogen. As differential characteristics our device operates in subcritical mode, driven by a neutron source activated by an accelerator that adds clear safety advantages and fuel flexibility opening the possibility to reduce the nuclear stockpile producing energy from actual LWR irradiated fuel with an efficiency of 45?46%, either in the form of Hydrogen, electricity, or both.

Innovative analytical strategies for the development of sensor devices and mass spectrometry methods

Il lavoro presentato in questa tesi di Dottorato è incentrato sullo sviluppo di strategie analitiche innovative basate sulla sensoristica e su tecniche di spettrometria di massa in ambito biologico e della sicurezza alimentare. Il primo capitolo tratta lo studio di aspetti metodologici ed applicativi di procedure sensoristiche per l’identificazione e la determinazione di biomarkers associati alla malattia celiaca. In tale ambito, sono stati sviluppati due immunosensori, uno a trasduzione piezoelettrica e uno a trasduzione amperometrica, per la rivelazione di anticorpi anti-transglutaminasi tissutale associati a questa malattia. L’innovazione di questi dispositivi riguarda l’immobilizzazione dell’enzima tTG nella conformazione aperta (Open-tTG), che è stato dimostrato essere quella principalmente coinvolta nella patogenesi. Sulla base dei risultati ottenuti, entrambi i sistemi sviluppati si sono dimostrati una valida alternativa ai test di screening attualmente in uso per la diagnosi della celiachia. Rimanendo sempre nel contesto della malattia celiaca, ulteriore ricerca oggetto di questa tesi di Dottorato, ha riguardato lo sviluppo di metodi affidabili per il controllo di prodotti “gluten-free”. Il secondo capitolo tratta lo sviluppo di un metodo di spettrometria di massa e di un immunosensore competitivo per la rivelazione di prolammine in alimenti “gluten-free”. E’ stato sviluppato un metodo LC-ESI-MS/MS basato su un’analisi target con modalità di acquisizione del segnale selected reaction monitoring per l’identificazione di glutine in diversi cereali potenzialmente tossici per i celiaci. Inoltre ci si è focalizzati su un immunosensore competitivo per la rivelazione di gliadina, come metodo di screening rapido di farine. Entrambi i sistemi sono stati ottimizzati impiegando miscele di farina di riso addizionata di gliadina, avenine, ordeine e secaline nel caso del sistema LC-MS/MS e con sola gliadina nel caso del sensore. Infine i sistemi analitici sono stati validati analizzando sia materie prime (farine) che alimenti (biscotti, pasta, pane, etc.). L’approccio sviluppato in spettrometria di massa apre la strada alla possibilità di sviluppare un test di screening multiplo per la valutazione della sicurezza di prodotti dichiarati “gluten-free”, mentre ulteriori studi dovranno essere svolti per ricercare condizioni di estrazione compatibili con l’immunosaggio competitivo, per ora applicabile solo all’analisi di farine estratte con etanolo. Terzo capitolo di questa tesi riguarda lo sviluppo di nuovi metodi per la rivelazione di HPV, Chlamydia e Gonorrhoeae in fluidi biologici. Si è scelto un substrato costituito da strips di carta in quanto possono costituire una valida piattaforma di rivelazione, offrendo vantaggi grazie al basso costo, alla possibilità di generare dispositivi portatili e di poter visualizzare il risultato visivamente senza la necessità di strumentazioni. La metodologia sviluppata è molto semplice, non prevede l’uso di strumentazione complessa e si basa sull’uso della isothermal rolling-circle amplification per l’amplificazione del target. Inoltre, di fondamentale importanza, è l’utilizzo di nanoparticelle colorate che, essendo state funzionalizzate con una sequenza di DNA complementare al target amplificato derivante dalla RCA, ne permettono la rivelazione a occhio nudo mediante l’uso di filtri di carta. Queste strips sono state testate su campioni reali permettendo una discriminazione tra campioni positivi e negativi in tempi rapidi (10-15 minuti), aprendo una nuova via verso nuovi test altamente competitivi con quelli attualmente sul mercato.

Development of new concepts in low tire pressure warning devices. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Pedestrian safety programs - a review of the literature and operational experience. Final report.

Federal Highway Administration, Office of Research, Washington, D.C.

Evaluation of retroreflective markings to increase rail car conspicuity -- safety of highway-railroad grade crossings.

Transportation Systems Center, Cambridge, Mass.

Development of criteria and test methods for eye and face protective devices /

Mode of access: Internet.

Cost evaluation for nine Federal Motor Vehicle Safety Standards. Volume II: FMVSS 108. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Cost evaluation for nine Federal Motor Vehicle Safety Standards. Volume VI: FMVSS 220, 221 and 222. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Urban intersection improvements for pedestrian safety. Volume II. Identification of safety and operational problems at intersections. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Splash and spray suppression: technological developments in the design and testing of spray reduction devices for heavy trucks. Report to Congress.

Mode of access: Internet.