Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):: The Phase 2 SATURN Study.

PURPOSE: To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). DESIGN: Randomized, double-masked, placebo-controlled, phase 2 study. PARTICIPANTS: Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. METHODS: Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. RESULTS: At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 µm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 µm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] µm (P = 0.1317) in the subgroup of eyes with CST ≥300 µm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). CONCLUSIONS: Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

BACKGROUND: Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. METHODS: This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 108 vector genomes (vg); cohort 2, 2 × 109 vg; cohort 3, 6 × 109 vg; and cohort 4, 2 × 1010 vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 1010 vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. FINDINGS: 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 1010 vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 1010 vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight decrease to a mean of 53·2 ng/mL at week 52 (SD 17·1). At baseline, four of these five patients were negative for anti-AAV2 serum antibodies and the fifth had a very low titre (1:100) of anti-AAV2 antibodies, whereas four of the five non-expressers of sFLT01 had titres of 1:400 or greater. In 11 of 19 patients with intraretinal or subretinal fluid at baseline judged to be reversible, six showed substantial fluid reduction and improvement in vision, whereas five showed no fluid reduction. One patient in cohort 5 showed a large decrease in vision between weeks 26 and 52 that was not thought to be vector-related. INTERPRETATION: Intravitreous injection of AAV2-sFLT01 seemed to be safe and well tolerated at all doses. Additional studies are needed to identify sources of variability in expression and anti-permeability activity, including the potential effect of baseline anti-AAV2 serum antibodies. FUNDING: Sanofi Genzyme, Framingham, MA, USA.

Estrategia didáctica para gestionar información en el proceso de formación profesional / Didactic strategy for managing information in the process of professional formation

El trabajo aborda el rol que juega la gestión de información en relación con la infotecnología para los profesionales en formación, así como los elementos esenciales de una propuesta de estrategia didáctica que contribuye al desarrollo de la habilidad profesional gestionar información contentiva de las habilidades investigativas. Por su importancia y universalidad constituye una propuesta válida para la formación profesional en cualquiera de sus dimensiones, en el que se incluye, las Ciencias Médicas que bien pudiera ser aplicada como alternativa para favorecer y perfeccionar el aprendizaje de los futuros egresados.

This work deals with the relation between information management and infotechnology, and its influence on incoming professionals; as well as with the essential elements for a didactic strategy that could contribute to the development of a professional skill that is to manage contentious information of the researching skills. Due to its importance and universal values, it constitutes a valid proposal for the formation of professionals and its different venues in which could be included the Medical Sciences. This proposal could be used to favor and improve the learning process of the incoming graduates.

Algunas consideraciones teóricas acerca de la Enseñanza Problémica / Problem Solving teaching: some theoretical considerations

Se realizan algunas consideraciones, filosóficas, pedagógica, metodológicas sobre la Enseñanza Problémica la cual constituye una alternativa que pueden emplear los profesores para activar el proceso de enseñanza-aprendizaje, teniendo en cuenta las condiciones y características de los educandos. Se reflexiona sobre el origen de este tipo de enseñanza, su desarrollo histórico a partir de los autores más representativos que asumen esta forma de enseñar tanto en Cuba como de otras latitudes, así como los fundamentos teóricos, las categorías y, sus métodos. Además, se observan las ventajas y desventajas que a criterio de los autores tiene el referido tipo de enseñanza.

Some philosophical, pedagogic and methodological considerations on problem solving teaching are expressed, which constitutes an alternative that professors can use to activate the teaching-learning process, keeping in mind the conditions and characteristic of their students. It is meditated on the origin of this teaching type, its historical development starting from the most representative authors that assume this form of teaching in Cuba as in other latitudes, as well as its theoretical foundations, categories and methods. The advantages and disadvantages of this approach according to the authors are also mentioned.

Efectividad y Continuidad de la anticoncepción en el Municpio Diez de Octubre / Effectiveness and continuity of contraception at the municipality of diez de octubre

Una de las formas de valorar el uso adecuado de la anticoncepción y la eficacia de la planificación familiar es conociendo la efectividad y continuidad de los métodos anticonceptivos. El objetivos de este trabajo es mostrar las tasas de efectividad, abandono y fallo de la anticoncepción en mujeres del municipio Diez de Octubre. La información proviene de un proyecto financiado por el Programa de Reproducción Humana de la Organización Mundial de la Salud 'Contracepción y Factores Asociados'. Se utilizó la historia de uso de anticonceptivos de 876 mujeres. Mediante la tabla de vida se obtuvieron todos los indicadores. Las tasas de fallo encontradas van desde 12,67 por cien episodios para los métodos tradicionales, a 5,26 para los DIU tuvo una tasa de fallo de 18,01 por cien episodios. Se encontró diferencia significativa al 0,0001 (con la prueba de Lee-Disu) para el comportamiento del fallo y del abandono en relación con los antecedentes de hijos y abortos previos al inicio del uso. Se concluye que las tasas de fallo del DIU es una de las más altas en comparación con países con información y que tanto el fallo como el abandono de los DIU es elevado. Se recomienda que en el municipio se revisen las orientaciones del uso del DIU para beneficio de la salud reproductiva de las mujeres y aumento de la efectividad de los métodos