Background-Safe, effective therapy is needed for pediatric pulmonary arterial hypertension. Methods and Results-Children (nϭ235; weight Ն8 kg) were randomized to low-, medium-, or high-dose sildenafil or placebo orally 3 times daily for 16 weeks in the Sildenafil in Treatment-Naive Children, Aged 1-17 Years, With Pulmonary Arterial Hypertension (STARTS-1) study. The primary comparison was percent change from baseline in peak oxygen consumption (PV O 2 ) for the 3 sildenafil doses combined versus placebo. Exercise testing was performed in 115 children able to exercise reliably; the study was powered for this population. Secondary end points (assessed in all patients) included hemodynamics and functional class. The estimated meanϮSE percent change in PV O 2 for the 3 doses combined versus placebo was 7.7Ϯ4.0% (95% confidence interval, Ϫ0.2% to 15.6%; Pϭ0.056). PV O 2 , functional class, and hemodynamics improved with medium and high doses versus placebo; low-dose sildenafil was ineffective. Most adverse events were mild to moderate in severity. STARTS-1 completers could enter the STARTS-2 extension study; patients who received sildenafil in STARTS-1 continued the same dose, whereas placebo-treated patients were randomized to low-, medium-, or high-dose sildenafil. In STARTS-2 (ongoing), increased mortality was observed with higher doses. Conclusions-Sixteen-week sildenafil monotherapy is well tolerated in pediatric pulmonary arterial hypertension. Percent change in PV O 2 for the 3 sildenafil doses combined was only marginally significant; however, PV O 2 , functional class, and hemodynamic improvements with medium and high doses suggest efficacy with these doses. Combined with STARTS-2 data, the overall profile favors the medium dose. Further investigation is warranted to determine optimal dosing based on age and weight. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00159913. (Circulation. 2012;125:324-334.)
RESUMENModernamente, han surgido diversas elaboraciones teóricas en torno al concepto de «artefacto», desde diversas áreas y paradigmas de las ciencias sociales y las humanidades. Sin pretender agotar la revisión teórica multidisciplinar, el artículo describe algunos ejes de las discusiones conceptuales y criterios para posibles intervenciones didácticas dentro de las prácticas educativas. El concepto de «cultura letrada» ha sido puesto en valor por Roger Chartier y otros autores. La noción de «artefacto cultural» ha sido objeto de debate por autores como Holland y Cole. En este artículo se proponen varias aplicaciones de los citados conceptos a la realidad educativa,
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