Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Factors affecting germination in Justicia squarrosa Griseb, a native forage species of the Chaco region of Argentina

Justicia squarrosa es una especie forrajera presente en diferentes comunidades naturales del Chaco Árido argentino en donde constituye un importante componente en la dieta del ganado en épocas de escasez de agua. El objetivo del presente trabajo fue estudiar los factores que afectan la germinación de J. squarrosa. Se tuvieron en cuenta diferentes regímenes de temperatura, calidades de luz y potenciales hídricos; además, se evaluó la capacidad de germinación de sus semillas en el tiempo. La germinación de las semillas de J. squarrosa estuvo condicionada por factores como la temperatura y el estrés hídrico. Los mayores porcentajes de germinación se obtuvieron a 25/15 ºC tanto en luz como en oscuridad permanente. Por debajo de -0,2 MPa la germinación disminuyó significativamente. Las semillas de J. squarrosa fueron indiferentes a los tratamientos de luz. Luego de 48 meses se observó un alto porcentaje de germinación de las semillas de la especie. Los resultados obtenidos proporcionan información valiosa que ayudará a establecer estrategias de domesticación y propagación de la especie.usticia squarrosa is a forage species that lives in different natural communities in Chaco Arido, where it is an important component of cattle diet in unfavourable drought periods. The aim of this work was to study the factors affecting seed germination in J. squarrosa. Different temperature regimes, light quality and water potential were considered. Seed germination capacity along time was also evaluated. Justicia squarrosa seed germination was conditioned by factors such as temperature and water potential. The highest germination percent was found at 25/15 ºC, both in light and dark. Seed germination decreased significantly below -0.2 MPa. Justicia squarrosa seeds did not respond to light treatments. After 48 months the percentage of seed germination was high. The results found in this article provide valuable information that will help to establish proper strategies for the species domestication and propagation.Fil: Zalazar, M. I.. Provincia de La Rioja. Programa Social Agropecuario; ArgentinaFil: Funes, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Venier, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin

Implementation and uptake of the Conexiones y Opciones en la Argentina intervention: feasibility and acceptability

Challenging HIV-infected patients, those neither adherent nor actively engaged in care, represent an important opportunity for intervention if the HIV epidemic is to be contained. This pilot study assessed the feasibility and acceptability of an adapted patient adherence intervention and a motivational interviewing-based provider intervention in urban Buenos Aires, Argentina, in order to optimize health benefits in challenging HIV-infected patients. To maximize implementation and uptake of both strategies, interventions were adapted to the local setting. Qualitative data and a short quantitative assessment from patients, staff, fellows, residents and physicians (n = 84) were examined to establish the feasibility and acceptability of offering patient and provider evidence-based interventions in both public and private healthcare settings. Results identified key themes on provision of information, use of specialized communication techniques, and group support in the utilization of the interventions. Both providers (n = 12) and patients (n = 120) endorsed the acceptability and value of the interventions, and the feasibility of their delivery. Findings support the use of both intervention modalities with challenging patients in diverse urban healthcare settings