Activism on rifapentine pricing: removing cost barriers to improve the uptake of tuberculosis research innovations.

As recent advances have been made in developing tools to fight tuberculosis (TB), there is also a trend towards increasing advocacy by the civil society for TB research and access. One recent successful effort to increase access to treatment options for TB involved a collaborative effort to identify the need for and barriers to the use of rifapentine (RPT) use in the United States. Survey responses confirmed the under-utilization of RPT: 82% of survey respondents selected cost as a significant or potential barrier to use. Survey results provided data to support a year-long advocacy campaign urging the drug company Sanofi to lower the price of RPT. This campaign was based on a common evidence base built in part by the stakeholders themselves. After multiple engagements with communities and providers, Sanofi US announced on 12 December 2013 that they would drop the price of RPT to US$32 per blister pack of 32 tablets for US public health programs. While further work remains to secure access to RPT in the United States and worldwide, the lowering of the price of RPT reflects the positive impact that collaborative advocacy can accomplish, and sets an example for other drug companies to follow.

Comme de récents progrès ont été réalisés dans l'élaboration d'outils de lutte contre la tuberculose (TB), on note également une tendance de la société civile à s'impliquer davantage dans la recherche et l'accès au traitement. Une activité récente couronnée de succès, visant à accroitre l'accès aux différentes options thérapeutiques de la TB, a impliqué un effort d'identification des besoins de rifapentine (RPT) aux Etats-Unis et des obstacles à son utilisation. Les réponses à l'enquête ont confirmé la sous-utilisation de la RPT : 82% des répondants ont estimé que son coût était un obstacle significatif ou potentiel à son utilisation. Ces résultats ont constitué des données permettant de soutenir une campagne de plaidoyer d'une année exhortant le fabricant, Sanofi, à réduire le prix de la RPT. Cette campagne a été basée sur un ensemble de preuves rassemblées en partie par les partenaires eux-mêmes. Après de multiples consultations avec les communautés et les fournisseurs, le 12 décembre 2013, Sanofi Etats-Unis a annoncé qu'ils allaient diminuer le prix de la RPT à US$32 par blister de 32 comprimés destinés aux programmes de santé publique américains. Même s'il reste du travail à faire pour sécuriser l'accès à la RPT aux Etats-Unis et dans le monde, la réduction du prix de la RPT témoigne de l'impact positif que le plaidoyer collaboratif peut avoir et constitue un exemple que les autres sociétés fabricant des médicaments devraient suivre.

Con el progreso reciente de los recursos destinados a combatir la tuberculosis (TB), se observa además una evolución en favor de la promoción de la causa de la investigación en TB y del acceso a sus resultados por parte de la sociedad civil. Una intervención reciente eficaz, encaminada a aumentar el acceso a las opciones de tratamiento antituberculoso, comportó un esfuerzo conjunto encaminado a reconocer la necesidad del uso de la rifapentina (RPT) en los Estados Unidos y los factores que obstaculizan su utilización. Las respuestas a una encuesta confirmaron la subutilización de la RPT; el 82% de quienes respondieron refirió el costo como un obstáculo importante o posible a su uso. Los datos de la encuesta respaldaron la utilidad de una campaña de promoción de la causa de un año de duración que instaba a la empresa Sanofi a disminuir el precio de la RPT. Esta campaña se basó en una serie de indicios aportados en parte por los mismos interesados directos. Después de celebrar múltiples compromisos con las comunidades y los profesionales de salud, Sanofi US anunció el 12 de diciembre del 2013 que disminuiría el precio de la RPT a US$32 por cada blíster de 32 comprimidos para los programas de salud pública en los Estados Unidos. Aunque todavía se precisan nuevas iniciativas que garanticen el acceso a la RPT en los Estados Unidos y en el mundo, la disminución del precio de este medicamento destaca el efecto positivo que puede lograr una promoción colectiva de la causa y constituye un ejemplo que deberían seguir otras empresas farmacéuticas.

Plasmin induces local thrombolysis without causing hemorrhage: a comparison with tissue plasminogen activator in the rabbit.

The direct fibrinolytic enzyme, plasmin, was compared with tissue plasminogen activator (TPA) in rabbit models of local thrombolysis and fibrinolytic hemorrhage. Plasmin was produced by solid-phase urokinase activation of plasminogen and purified on benzamidine Sepharose. Applied as an intra-arterial infusion into the thrombosed abdominal aorta under conditions of unimpeded blood flow, plasmin (4 mg/kg) and TPA (2 mg/kg) achieved equivalent clot dissolution and flow restoration. Using the model of restricted blood flow into the thrombosed aorta, which limits local plasminogen supply, plasmin was superior to TPA in clot lysis and vascular reperfusion. Using similar dosages of plasmin (2 or 4 mg/kg) and TPA (1 or 2 mg/kg) in the earpuncture rebleed model. TPA induced rebleeding in a dose-dependent manner from prior puncture sites in 9 of 10 animals, while none of the 10 animals exposed to plasmin rebled from these sites. These results suggest that plasmin is an effective, unique thrombolytic agent, distinguished from the plasminogen activators in current usage by its striking safety profile.

Automated latex agglutination and ELISA testing yield equivalent D-dimer results in patients with recent myocardial infarction. THROMBO Research Investigators.

Our previous prospective study of post-infarction patients described a strong and significant association of increased plasma D-dimer concentrations in those who experienced a subsequent coronary death or non-fatal myocardial infarction. In the present study, we compare results on stored plasma obtained two months after the index myocardial infarction from 1,038 patients of this trial, using a simple automated latex agglutination (LA) assay in parallel with the standard ELISA test. Results show a somewhat higher mean value for the LA assay (702+/-1092 vs. 638+/-986 ng/ml, p = 0.0002), a strong linear correlation of the two assays (r = 0.86) and 88% agreement for values below 500 ng/ml by the ELISA test. D-dimer concentrations determined by each assay were highly correlated in patients with subsequent coronary artery events (p = 0.93) and quartile values for both the LA and ELISA were equally predictive of such events (p = 0.003 and p = 0.001, respectively). This is the first demonstration that a latex agglutination assay for D-dimer can be used to assess the prognostic risk of recurrent coronary thrombotic disease after myocardial infarction

A soluble fibrin standard: comparable dose-response with immunologic and functional assays.

A soluble fibrin (SF) preparation has been developed as a potential standard by the Scientific and Standardization Committee for use in assays evaluating in vitro preparations and patient plasma samples. The SF standard was prepared by reaction of factor XIII-free fibrinogen with thrombin, followed by neutralization with hirudin and solubilization of the fibrin in acetic acid. As characterized by SDS-PAGE, the polypeptide chain structure shows the anticipated loss of fibrinopeptides and lack of gamma or alpha chain crosslinking. The standard was added to pooled normal plasma at concentrations from 12.5 microg/ml to 340 microg/ml and tested with four commercially available assays based on immunologic reactions using ELISA or latex agglutination or on t-PA cofactor activity for plasminogen to plasmin conversion. Absolute "soluble fibrin" concentrations were calculated using the manufacturers' calibrators and showed distinct dose-response relationships for each assay. Expression of the results following log-transformation produced a series of parallel lines, indicating that this SF preparation can serve as a standard, effectively normalizing the disparate proprietary internal calibrators currently used for each assay.