Italian Law 326/2003 for The Reimbursement of Orphan and Life Saving Drugs Awaiting Market Entry: Approvals, Rejections And Methods In Aifa's Evaluation Process Between January 2013 And May 2015

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'Word from the street' : when non-electoral representative claims meet electoral representation in the United Kingdom

Taking the specific case of street protests in the UK – the ‘word from the street’– this article examines recent (re)conceptualizations of political representation, most particularly Saward’s notion of ‘representative claim’. The specific example of nonelectoral claims articulated by protestors and demonstrators in the UK is used to illustrate: the processes of making, constituting, evaluating and accepting claims for and by constituencies and audiences; and the continuing distinctiveness of claims based upon electoral representation. Two basic questions structure the analysis: first, why would the political representative claims of elected representatives trump the nonelectoral claims of mass demonstrators and, second, in what ways does the ‘perceived legitimacy’ of the former differ from the latter

The New Italian Health Care Reform: Introducing New Measures to Speed Up Market Access

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Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export

Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export

Is swimming safe in heart failure? : a systematic review

It is not clear whether swimming is safe in patients with chronic heart failure. Ten studies examining the hemodynamic effects of acute water immersion (WI) (155 patients; average age 60 years; 86% male; mean left ventricular ejection fraction (LVEF) 29%) and 6 randomized controlled trials of rehabilitation comparing swimming with either medical treatment only (n = 3) or cycling (n = 1) or aerobic exercise (n = 2), (136 patients, average age 59 years; 84% male, mean LVEF 31%) were considered. In 7 studies of warm WI (30–35°C): heart rate (HR) fell (2% to −15%), and both cardiac output (CO) (7–37%) and stroke volume (SV) increased (13–41%). In 1 study of hot WI (41°C), systemic vascular resistance (SVR) fell (41%) and HR increased (33%). In 2 studies of cold WI (12–22°C), there were no consistent effects on HR and CO. Compared with medical management, swimming led to a greater increase in peak Vo₂ (7–14%) and 6 minute walk test (6MWT) (7–13%). Compared with cycle training, combined swimming and cycle training led to a greater reduction in resting HR (16%), a greater increase in resting SV (23%) and SVR (15%), but no changes in resting CO and a lesser increase in peak Vo₂ (6%). Compared with aerobic training, combined swimming and aerobic training lead to a reduction in resting HR (19%) and SVR (54%) and a greater increase in SV (34%), resting CO (28%), LVEF (9%), and 6MWT (70%). Although swimming appears to be safe, the studies conducted have been small, very heterogeneous, and inconclusive

Cutting edge: extracellular high mobility group box-1 protein is a proangiogenic cytokine.

The chromosomal high mobility group box-1 (HMGB1) protein acts as a proinflammatory cytokine when released in the extracellular environment by necrotic and inflammatory cells. In the present study, we show that HMGB1 exerts proangiogenic effects by inducing MAPK ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells of different origin. Accordingly, HMGB1 stimulates membrane ruffling and repair of a mechanically wounded endothelial cell monolayer and causes endothelial cell sprouting in a three-dimensional fibrin gel. In keeping with its in vitro properties, HMGB1 stimulates neovascularization when applied in vivo on the top of the chicken embryo chorioallantoic membrane whose blood vessels express the HMGB1 receptor for advanced glycation end products (RAGE). Accordingly, RAGE blockade by neutralizing Abs inhibits HMGB1-induced neovascularization in vivo and endothelial cell proliferation and membrane ruffling in vitro. Taken together, the data identify HMGB1/RAGE interaction as a potent proangiogenic stimulus

Cost-effectiveness analysis of Vaborem in Carbapenem-resistant Enterobacterales (CRE) -Klebsiella pneumoniae infections in Italy

Background: Vaborem is a fixed dose combination of vaborbactam and meropenem with potent activity against target Carbapenem-resistant Enterobacterales (CRE) pathogens, optimally developed for Klebsiella pneumoniae carbapenemase (KPC). The study aims to evaluate the cost-effectiveness of Vaborem versus best available therapy (BAT) for the treatment of patients with CRE-KPC associated infections in the Italian setting. Methods: A cost-effectiveness analysis was conducted based on a decision tree model that simulates the clinical pathway followed by physicians treating patients with a confirmed CRE-KPC infection in a 5-year time horizon. The Italian National Health System perspective was adopted with a 3% discount rate. The clinical inputs were mostly sourced from the phase 3, randomised, clinical trial (TANGO II). Unit costs were retrieved from the Italian official drug pricing list and legislation, while patient resource use was validated by a national expert. Model outcomes included life years (LYs) and quality adjusted life years (QALYs) gained, incremental costs, incremental cost- effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Deterministic and probabilistic sensitivity analyses were also performed. Results: Vaborem is expected to decrease the burden associated with treatment failure and reduce the need for chronic renal replacement therapy while costs related to drug acquisition and long-term care (due to higher survival) may increase. Treatment with Vaborem versus BAT leads to a gain of 0.475 LYs, 0.384 QALYs, and incremental costs of €3549, resulting in an ICER and ICUR of €7473/LY and €9246/QALY, respectively. Sensitivity analyses proved the robustness of the model and also revealed that the probability of Vaborem being cost-effective reaches 90% when willingness to pay is €15,850/QALY. Conclusions: In the Italian setting, the introduction of Vaborem will lead to a substantial increase in the quality of life together with a minimal cost impact, therefore Vaborem is expected to be a cost-effective strategy compared to BAT

Avaliação dos efeitos da adição de sal e da densidade no transporte de tambaqui.

Os objetivos deste trabalho foram testar a eficiência do sal como redutor de estresse e verificar a melhor densidade de transporte de juvenis de tambaqui em caixas de plástico adaptadas