Transforming the treatment for hemophilia B patients: update on the clinical development of recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP)

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Liberalne podstawy polityki konkurencji UE a rynek gazu

The TFEU is not defining competition. The definition we propose is: A policy bound to: detect and deter cartels; avoid mergers leading to abuse of dominant position, control and prohibit State aid, promote liberalisations. This definitions contains the mail elements of the liberal theory of competition. The paper explores them: entry freedom, competition order, state aids and cartels. Liberalizations are strictly linked to Einaudi’s concept of “juridical possibility of having competition”. The third Gas Directive represents an example of this “juridical possibility”. Progresses in its application have been small. Furthermore the crisis has produced a sort of euro-sclerosis of the liberalization process. The revitalization of liberalisations is essential to regain growth in Europe.Traktat o funkcjonowaniu Unii Europejskiej nie zawiera definicji konkurencji. Zaproponowana w pracy definicja mówi, że jest to polityka zmierzająca do wykrywania i zapobiegania powstawaniu karteli, unikania fuzji, które mogą prowadzić do nadużywania pozycji dominującej, kontroli i ograniczania pomocy publicznej i promowania liberalizacji. W dalszej części pracy poszczególne elementy tej definicji są poddane szerszej analizie: swoboda wchodzenia na rynek, zasady konkurencji, pomoc państwowa oraz kartele. Liberalizacja jest ściśle powiązana z koncepcją Finaudiego dotyczącą możliwości zapewnienia konkurencji na rynku. Trzecia Dyrektywa Gazowa jest przykładem takiego podejścia. Jednak postępy w jej implementacji są niewielkie. Co więcej, kryzys spowodował pojawienie się swoistej eurosklerozy w procesie liberalizacji. Dynamizacja tego procesu jest niezbędna do odbudowania wzrostu gospodarczego w Europie

Analisi costo/efficacia di sevelamer nel trattamento dell'iperfosforemia del paziente in dialisi

Dialysis-associated hyperphosphatemia has been treated with chelating calcium salts, in particular with calcium carbonate. A new option for the management of this problem is represented by sevelamer, a chelating agent which contains no calcium and no metals. Sevelamer and calcium carbonate are more or less equally effective and tolerated. The prolonged use of sevelamer instead of calcium carbonate, nevertheless, reduces calcemia and C-reactive protein levels, with a consequent reduction in myocardial infarction, angina pectoris and other peripheral vasculopathies. The limit to the wide-spread use of sevelamer is in its very high acquisition cost, as compared to the alternative. In this article, a semi-markovian pharmacoeconomical model for the comparison of clinical and economical outcomes of sevelamer and calcium carbonate is presented. The analysis is conducted in the perspective of the Italian health system (SSN). Clinical data are derived from published studies and integrated with expert panel estimates, cost data are relative to the Italian setting. The incremental cost-effectiveness analysis indicated that sevelamer is more costly, but also more costeffective: a one month gain in survival costs the SSN additional 2710 Euro, a value inferior to the conventionally accepted willingness-to-pay of industrialised countries. The majority of this excess cost is derived from the gain in survival, and consequent increase in dialysis costs. Thus, the choice of using sevelamer instead of calcium carbonate is even more justified from an ethical point of view. Sensibility analyses confirmed the robustness of the basic scenario results

Recombinant FVIIIFc Versus BAY 94-9027 for Treatment of Patients with Haemophilia A:Comparative Efficacy Using a Matching Adjusted Indirect Comparison

INTRODUCTION: Prophylaxis with recombinant factor VIII (rFVIII) is the current standard of care for haemophilia A. Several approaches have been used to extend the half-life of rFVIII to improve prophylaxis outcomes. An indirect comparison of pivotal clinical trial data was performed to evaluate the relative efficacy of two extended half-life therapies approved for the prophylactic treatment of haemophilia A: recombinant FVIII-IgG1 Fc domain fusion protein (rFVIIIFc) and pegylated rFVIII (BAY 94-9027). METHODS: Matching-adjusted indirect comparison (MAIC) was conducted to compare the rFVIIIFc individualised prophylaxis arm of the A-LONG phase III clinical trial (n = 117) and the BAY 94-9027 approved dosing regimens of the PROTECT VIII phase II/III study (n = 110). Following matching for baseline characteristics, mean annualised bleeding rate (ABR) and the proportion of patients with zero bleeds were compared for rFVIIIFc and BAY 94-9027. Additional supportive analyses comparing rFVIIIFc individualised prophylaxis and the individual prophylaxis regimens included in the PROTECT VIII group (twice weekly, and every 5 and 7 days [Q5D and Q7D]) were conducted. RESULTS: Mean ABR was lower in the rFVIIIFc individualised prophylaxis group versus the BAY 94-9027 pooled prophylaxis population (3.0 versus 4.9), providing a clinically relevant and statistically significant difference (mean difference [MD] - 1.9; 95% confidence interval [CI] - 3.5 to - 0.4). A statistically significant difference in ABR was also observed for rFVIIIFc compared with BAY 94-9027 Q7D (3.2 versus 6.4; MD - 3.3; 95% CI - 6.4 to - 0.2). The difference in the proportion of patients with zero bleeds between rFVIIIFc (46.5%) and BAY 94-9027 pooled prophylaxis population (38.2%) was not statistically significant (odds ratio 1.4; 95% CI 0.8 to 2.5). CONCLUSIONS: This indirect treatment comparison indicates a statistically significant and clinically relevant difference in ABR favouring individualised prophylaxis with rFVIIIFc versus BAY 94-9027 prophylaxis. The proportion of patients with zero bleeds was numerically greater with rFVIIIFc treatment but did not achieve statistical significance

Iatrogenic Left Internal Mammary Artery Perforation Treated With a Covered Stent Via Transradial Approach

Abstract Inadvertent perforation of the left internal mammary artery during a blind approach to the subclavian vein for pacemaker or central venous catheter insertion is an emergency that requires immediate treatment. Covered stent deployment is a quick and effective treatment, especially in patients with hemodynamic instability. The procedure may be safely performed by using the radial approach. (Level of Difficulty: Intermediate.

Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution

A comparative analysis of two primate and two rodent genomes suggests that telomerase was utilized, in some instances, for the repair of DNA double-strand breaks during mammalian evolution

Simplifying surgery in haemophilia B: Low factor IX consumption and infrequent infusions in surgical procedures with rIX-FP.

Abstract Introduction Long-acting recombinant factor IX (FIX) products may simplify the surgical treatment of haemophilia B patients. The impact of rIX-FP, a recombinant FIX fused to recombinant albumin, on FIX consumption and surgical management was assessed in patients with haemophilia B. Materials and methods Male patients, ≤65 years old with severe haemophilia B (FIX activity ≤2%) requiring non-emergency surgery were enrolled in the surgical substudy of PROLONG-9FP. Dosing was based on World Federation of Hemophilia guidelines and patients' pharmacokinetics. Haemostatic efficacy was assessed on a 4-point scale. rIX-FP consumption and safety were monitored throughout the perioperative period. Results This updated dataset reports on thirty (8 minor and 22 major) surgeries conducted in 21 patients. A single preoperative bolus was used in 96.7% (n = 29) of surgeries. After minor surgery, patients received a median (range) of 0 (0–3) infusions with a median (range) consumption of 0 (0–178.89) IU/kg in the 14-day postoperative period. In patients who underwent major surgery (including 15 patients undergoing joint replacement surgery), the median (range) number of infusions in the 14-day postoperative period was 5 (0−11) and median consumption was 221.7 (0–444.07) IU/kg. Haemostatic efficacy was rated as excellent or good in 87.5% (7/8) of minor surgeries and 95.5% (21/22) of major surgeries. Conclusion Surgical procedures can be performed using a single preoperative bolus of rIX-FP in nearly all patients. During postoperative care, use of rIX-FP necessitated infrequent infusions and low FIX consumption. Overall, data suggest rIX-FP simplifies perioperative care in patients with haemophilia B

International workshop on immune tolerance induction: consensus recommendations 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73382/1/j.1365-2516.2007.01497.x.pd