78 research outputs found

    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

    Amitriptyline enhances the central component of physiological tremor

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    OBJECTIVES—Postural tremor is a regularly encountered side effect of amitriptyline which can be strong enough to cause discontinuation of therapy. The aim was to characterise amitriptyline induced tremor and to assess if the central or reflex component of physiological tremor was modulated by this drug.
METHODS—The postural hand tremor was measured in 15 patients on a clinical rating scale, by power spectral analysis of accelerometer, forearm flexor, and extensor EMG before and after the beginning of amitriptyline treatment for major depression or chronic pain syndrome. A coherence analysis between flexor and extensor muscles on the same side was performed.
RESULTS—There was a clinically visible increase in postural tremor in a third of these patients. The tremor amplitude measured by accelerometer total power increased in every patient under amitriptyline. The EMG synchronisation as reflected by significant peaks in the flexor or extensor spectrum generally occurring at higher frequencies (8-18 Hz) than the accelerometric tremor frequencies (6-11 Hz) did not change. The number of patients with a significant flexor-extensor coherence in the 7-15 Hz range increased significantly under amitriptyline, the frequency bands of significant coherence corresponded with the EMG frequencies, and both were independent of changes to the hand's resonant frequency by added inertia.
CONCLUSIONS—An enhancement of postural tremor under amitriptyline is a common phenomenon although not always clinically apparent. The increase in EMG-EMG coherence indicates an increased common central drive to the motor units as its frequency is not influenced by peripheral resonance or reflex mechanisms. This is the first account of a drug induced enhancement of the central component of physiological tremor.


    Una introducción a la derivada desde la variación y el cambio: resultados de una investigación con estudiantes de primer año de la universidad

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    El estudio del cálculo juega un rol importante cuando es necesario cuantificar o medir algún fenómeno. Sin embargo, en el sistema educativo se han priorizado, en general, procesos de construcción formales y aspectos algorítmicos. Buscando dar respuesta a esta problemática se inició una investigación, abordando el estudio de la derivada. El trabajo se enmarcó en la línea del Pensamiento y Lenguaje Variacional, que estudia la articulación entre la investigación y las prácticas sociales que dan vida a la matemática de la variación y el cambio en los sistemas didácticos. En el contexto de una ingeniería didáctica, se diseñó una secuencia que se llevó al aula con alumnos de Matemática II de la carrera Ingeniería Agronómica. Las actividades permitieron analizar diversos escenarios de variación (qué magnitudes cambian, cómo y cuánto cambian), caracterizar variaciones entre las magnitudes, a través del cálculo de razones de cambio, y explorar cómo la pendiente de una curva se relaciona con la razón de cambio. Su presentación, desde diferentes representaciones, favorece el desarrollo de uno de los procesos cognitivos implicados en el pensamiento matemático, el de visualización. En este artículo se describen brevemente los aspectos teóricos y metodológicos que fundamentan el diseño de la secuencia y se presentan algunos resultados obtenidos de su implementación a partir de la observación de las actividades desarrolladas por los alumnos. La propuesta logró motivar a los alumnos y movilizar sus concepciones. La discusión de los resultados obtenidos favorece la optimización de la secuencia
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