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.

Characterisation and optimisation of the new Prompt Gamma-ray Activation Analysis (PGAA) facility at FRM II

At the research reactor Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II) a new Prompt Gamma-ray Activation Analysis (PGAA) facility was installed. The instrument was originally built and operating at the spallation source at the Paul Scherrer Institute in Switzerland. After a careful re-design in 2004–2006, the new PGAA instrument was ready for operation at FRM II. In this paper the main characteristics and the current operation conditions of the facility are described. The neutron flux at the sample position can reach up 6.07×1010 [cm−2 s−1], thus the optimisation of some parameters, e.g. the beam background, was necessary in order to achieve a satisfactory analytical sensitivity for routine measurements. Once the optimal conditions were reached, detection limits and sensitivities for some elements, like for example H, B, C, Si, or Pb, were calculated and compared with other PGAA facilities. A standard reference material was also measured in order to show the reliability of the analysis under different conditions at this instrument.

Randomised trial of clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping (CONSCIOUS-2)

We report here results of a randomized, double-blind, placebo-controlled study ( http://www.ClinicalTrials.gov , NCT00558311) that investigated the effect of clazosentan (5 mg/h, n = 768) or placebo (n = 389) administered for up to 14 days in patients with aneurysmal subarachnoid hemorrhage (SAH) repaired by surgical clipping. The primary endpoint was a composite of all-cause mortality, new cerebral infarction or delayed ischemic neurological deficit due to vasospasm, and rescue therapy for vasospasm. The main secondary endpoint was the Glasgow Outcome Scale Extended (GOSE), which was dichotomized. Twenty-one percent of clazosentan- compared to 25% of placebo-treated patients met the primary endpoint (relative risk reduction [RRR] [95% CI]: 17% [-4% to 33%]; p = 0.10). Poor outcome (GOSE score ≤ 4) occurred in 29% of clazosentan- and 25% of placebo-treated patients (RRR: -18% [-45% to 4%]; p = 0.10). In prespecified subgroups, mortality/vasospasm-related morbidity was reduced in clazosentan-treated patients by 33% (8-51%) in poor WFNS (World Federation of Neurological Surgeons) grade (≥III) and 25% (5-41%) in patients with diffuse, thick SAH. Lung complications, anemia and hypotension occurred more frequently with clazosentan. Mortality (week 12) was 6% in both groups. The results showed that clazosentan nonsignificantly decreased mortality/vasospasm-related morbidity and nonsignificantly increased poor functional outcome in patients with aneurysmal SAH undergoing surgical clipping.

Increased sleep need and daytime sleepiness 6 months after traumatic brain injury: a prospective controlled clinical trial.

Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increased in patients as compared to controls (8.3 ± 1.1 h versus 7.1 ± 0.8 h, P < 0.0001). Objective daytime sleepiness was found in 57% of trauma patients and 19% of healthy subjects, and the average sleep latency in patients was reduced to 8.7 ± 4.6 min (12.1 ± 4.7 min in controls, P = 0.0009). Patients, but not controls, markedly underestimated both excessive sleep need and excessive daytime sleepiness when assessed only by subjective means, emphasizing the unreliability of self-assessment of increased sleep propensity in traumatic brain injury patients. At polysomnography, slow wave sleep after traumatic brain injury was more consolidated. The most important risk factor for developing increased sleep need after traumatic brain injury was the presence of an intracranial haemorrhage. In conclusion, we provide controlled and objective evidence for a direct relation between sleep-wake disturbances and traumatic brain injury, and for clinically significant underestimation of post-traumatic sleep-wake disturbances by trauma patients.

Depressive symptoms as a novel risk factor for recurrent venous thromboembolism: a longitudinal observational study in patients referred for thrombophilia investigation.

BACKGROUND Increasing evidence suggests that psychosocial factors, including depression predict incident venous thromboembolism (VTE) against a background of genetic and acquired risk factors. The role of psychosocial factors for the risk of recurrent VTE has not previously been examined. We hypothesized that depressive symptoms in patients with prior VTE are associated with an increased risk of recurrent VTE. METHODS In this longitudinal observational study, we investigated 271 consecutive patients, aged 18 years or older, referred for thrombophilia investigation with an objectively diagnosed episode of VTE. Patients completed the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). During the observation period, they were contacted by phone and information on recurrent VTE, anticoagulation therapy, and thromboprophylaxis in risk situations was collected. RESULTS Clinically relevant depressive symptoms (HADS-D score ≥ 8) were present in 10% of patients. During a median observation period of 13 months (range 5-48), 27 (10%) patients experienced recurrent VTE. After controlling for sociodemographic and clinical factors, a 3-point increase on the HADS-D score was associated with a 44% greater risk of recurrent VTE (OR 1.44, 95% CI 1.02, 2.06). Compared to patients with lower levels of depressive symptoms (HADS-D score: range 0-2), those with higher levels (HADS-D score: range 3-16) had a 4.1-times greater risk of recurrent VTE (OR 4.07, 95% CI 1.55, 10.66). CONCLUSIONS The findings suggest that depressive symptoms might contribute to an increased risk of recurrent VTE independent of other prognostic factors. An increased risk might already be present at subclinical levels of depressive symptoms.

¿Desarrollo local o enclave turístico? El caso paradigmático de Santa Ana, Misiones, Argentina. 16H298

a) Se ha relevando la oferta turística tradicional y nueva del municipio. b) Se han realizado encuestas a visitantes (encuesta personal y online) para analizar su opinión sobre el parque temático y propuestas de mejoras y cambios. c) Se hicieron encuestas a residentes de Santa Ana (encuesta personal) para analizar su opinión del parque temático y los posibles impactos positivos y negativos que el mismo podría producir en el municipio. d) Se han efectuado entrevistas a los funcionarios municipales y provinciales vinculados a la actividad turística del área en estudio. e) Se realizaron entrevistas a empresarios locales vinculados directa e indirectamente al turismo.

Estudio de las nuevas modalidades y tendencias de turismo en la provincia de Misiones. 16H250

Esta investigación se propone estudiar las nuevas modalidades de turismo y tendencias en la provincia de Misiones, a través del estudio de caso que será el “destino turístico Iguazú Argentina”. Se abordarán dos ejes de trabajo: por un lado el análisis de las nuevas modalidades de turismo haciendo énfasis en su análisis al Turismo de Naturaleza en Iguazú y por el otro la gestión empresaria hotelera y su adecuación a la demanda y por ende su competitividad. Para este estudio de dos años, se utilizarán fuentes secundarias, como las normativas y fuentes primarias mediante entrevistas a referentes locales, provinciales y expertos y encuestas a visitantes en temporada alta al destino. Se espera lograr un diagnostico en ambas áreas temáticas para luego desarrollar propuestas y estrategias de mejora de gestión y competitividad empresaria frente a las nuevas modalidades y tendencias turísticas. Este proyecto se articula con el PICTO 2006 ANPCyT UNaM Nº 37038 que analiza la calidad de servicios percibida y la imagen del destino internacional Iguazú incluyendo además de Iguazú a Foz y su Parque Nacional.

Estudio Integral del destino Iguazú-Cataratas. Controversias y desafíos para el desarrollo local II. 16H206

El estudio integral del destino IGUAZÚ-CATARATAS. Controversias y desafios para el desarrollo local II. para la presente etapa se propuso el objetivo general de “Contribuir al desarrollo del Destino Iguazú-Cataratas mediante la realización del estudio integral transfronterizo que permita la selección de las mejores alternativas de desarrollo local para la toma de decisiones en los respectivos municipiosciudades e instituciones públicas, privadas junto a la gestión de los Parques Nacionales”. Asimismo en el marco del objetivo general se desarrollaron los siguientes objetivos específicos:  Determinar y caracterizar en proceso continuo, las áreas de intervención y gestión municipal más urgentes en pos del ordenamiento territorial y ambiental de Puerto Iguazú, de elevada complejidad, apoyado en el programa político nacional y provincial, conjuntamente con las organizaciones sociales del municipio.  Indagar en la dinámica de desarrollo del Destino Iguazú – Cataratas los factores facilitadores e inhibidores de las variables económico-productivas, políticas y sociales (demográficas) en proceso; los flujos de la demanda y la evolución de la oferta que genera la actividad turística en dicho destino.  Estudiar comparativamente la sinergia generada a partir de los datos históricos y actuales de los visitantes en los Parques Nacionales de Argentina y Brasil, para identificar el rol promotor social, económico y turístico a fin de contrastarlo y lograr información que refleje la realidad de la actividad turística del Destino Iguazú-Cataratas.  Determinar y caracterizar el perfil socio laboral y trayectoria de vida de los residentes en las 2000 hectáreas, las formas de funcionamiento en redes de acciones de educación y trabajo cooperativo para construir escenarios alternativos en la expansión rururbana - periurbana en Puerto Iguazú.

¿Desarrollo local o enclave turístico? El caso paradigmático de Santa Ana, Misiones, Argentina. 16H298

Actividades desarrolladas durante el período: se han relevado y estudiado estadísticas sociales, económicas y turísticas del Municipio y su zona de influencia, desde los organismos oficiales de estadísticas (IPEC, INDEC, Programa Misiones Jesuíticas, Ministerio de Turismo de la Provincia de Misiones), además de analizar otros estudios inéditos de la Universidad vinculados al área de estudio. Además se relevaron las noticias vinculadas al tema de investigación en los diarios de circulación provincial; se realizó un relevamiento de la existencia y estado actual de la escasa oferta complementaria (alojamiento, alimentación, actividades conexas, servicio de agencias de turismo) del área de estudio;se han efectuado las primeras entrevistas a los funcionarios municipales y provinciales vinculados a la actividad económica y turística tradicional del área en estudio; se realizaron entrevistas a empresarios y responsables turísticos y productivos del área de estudio para conocer su opinión antes de la inauguración del parque temático y su posible impacto económico productivo y turístico en el municipio y zona de influencia, se efectuaron las primeras observaciones en el Parque Temático en relación a sus consideraciones ambientales y socio productivas, aspectos críticos y mejoras necesarias.

La Participación Juvenil en los Centros de Actividades Juveniles en las escuelas de Maipú 2013-2014

En Argentina, el modelo neoliberal instaurado por la dictadura militar a mediados de los años setenta, profundizado durante la década de los ochenta y consolidado en los noventa se caracterizó por la implementación de reformas estructurales tales como la privatización de las empresas estatales, la profundización de la apertura externa, la flexibilización laboral, la convertibilidad y la descentralización de la salud y la educación. La agudización de las contradicciones en el seno de la clase dominante ante el agotamiento del patrón de acumulación y de una gran conflictividad social pusieron fin al gobierno de la Alianza que culminó en la crisis política, social y económica del año 2001. La situación anteriormente descripta tuvo su impacto en el ámbito educativo teniendo como medida central, en las décadas de los ochenta y los noventa, la descentralización del sistema educativo y en menor medida la reducción del gasto público en la educación. Además se generaron políticas focalizadas y un acceso diferenciado a la educación según el nivel socio-económico de los estudiantes provocando el deterioro en la calidad de los servicios educativos.

Cenozoic radiolaria in the western North Atlantic

Eight Cenozoic radiolarian zones were recognized in samples from two holes at Site 603, drilled on the lower continental rise off North America during Leg 93 of the Deep Sea Drilling Project. Paleocene to early Eocene radiolarian zones (Bekoma bidartensis, Buryella clinata, and Phormocyrtis striata striata zones) and early to late Miocene radiolarian zones (Calocycletta costata, Dorcadospyris alata, Diartus petterssoni, and Didymocyrtis antepenultima zones) were recognized in sediments from Holes 603 and 603B. In addition, a new Paleocene Bekoma campechensis radiolarian Zone is defined by the interval between the first morphotypic appearance of B. campechensis and the B. campechensis-B. bidartensis evolutionary transition. This zone is immediately below the B. bidartensis Zone of Foreman (1973), and has previously been discussed as a Paleocene "unnamed zone" by other investigators. A hiatus between Neogene and Paleogene sequences was also recognized in the radiolarian faunas.