Preventing vasospasm improves outcome after aneurysmal subarachnoid hemorrhage: rationale and design of CONSCIOUS-2 and CONSCIOUS-3 trials

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a frequent but unpredictable complication associated with poor outcome. Current vasospasm therapies are suboptimal; new therapies are needed. Clazosentan, an endothelin receptor antagonist, has shown promise in phase 2 studies, and two randomized, double-blind, placebo-controlled phase 3 trials (CONSCIOUS-2 and CONSCIOUS-3) are underway to further investigate its impact on vasospasm-related outcome after aSAH. Here, we describe the design of these studies, which was challenging with respect to defining endpoints and standardizing endpoint interpretation and patient care. Main inclusion criteria are: age 18-75 years; SAH due to ruptured saccular aneurysm secured by surgical clipping (CONSCIOUS-2) or endovascular coiling (CONSCIOUS-3); substantial subarachnoid clot; and World Federation of Neurosurgical Societies grades I-IV prior to aneurysm-securing procedure. In CONSCIOUS-2, patients are randomized 2:1 to clazosentan (5 mg/h) or placebo. In CONSCIOUS-3, patients are randomized 1:1:1 to clazosentan 5, 15 mg/h, or placebo. Treatment is initiated within 56 h of aSAH and continued until 14 days after aSAH. Primary endpoint is a composite of mortality and vasospasm-related morbidity within 6 weeks of aSAH (all-cause mortality, vasospasm-related new cerebral infarction, vasospasm-related delayed ischemic neurological deficit, neurological signs or symptoms in the presence of angiographic vasospasm leading to rescue therapy initiation). Main secondary endpoint is extended Glasgow Outcome Scale at week 12. A critical events committee assesses all data centrally to ensure consistency in interpretation, and patient management guidelines are used to standardize care. Results are expected at the end of 2010 and 2011 for CONSCIOUS-2 and CONSCIOUS-3, respectively.

Truck escape ramp design methodology. Volume 2. Final report.

Federal Highway Administration, Washington, D.C.

O design de moda e a indústria

Dissertação para obtenção do grau de Mestre em Design de Moda, apresentada na Universidade de Lisboa - Faculdade de Arquitetura.

1.° Passio sancti Sixti et sociorum. — 2.° Passio sancti Laurentii. — 3.° Passio sancti Hippolyti. — 4.° Passio sanctorum Abdon et Sennes. — 5.° Passio sancti Symphoriani. — 6.° Passio sanctorum Timothei et Apollinaris. — 7.° Passio sanctae Susannae, Virginis. — 8.° Passio sancti Antonini. — 9.° Vita sancti Barsanorii, Abbatis. — 10.° Vita sancti Nicolai, Myrensis Episcopi. — 11.° Narratio de ejusdem translatione : authore Joanne, Archidiacono Barrensi. — 12.° Vita sancti Leonardi. — 13.° Vita sancti Odonis, Abbatis : authore Joanne, Monacho. — 14.° Vita beati Majoli : authore Odilone, Presbytero. — 15.° Vita beati Odilonis, Abbatis : authore Petro Damiano. — 16.° Vita sancti Tetbaldi, Confessoris. — 17.° Vita Euphimiani, servi Dei. — 18.° Passio S. Eustachii et uxoris ejus. — 19.° Vita sancti Romani, Rothomagensis Archiepiscopi. — 20.° Bedae, Presbyteri, tractatus in Proverbia Salomonis : initium tantùm superest.

Bigotianus

(Pre)textos perifèrics (2) : més Història de la Filosofia (Filosofia II). '(Pre)textos periféricos (2) : más Historia de la Filosofía (2)'.

Resumen tomado de la publicación