A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial.

BACKGROUND: Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.5% and 1% concentrations. OBJECTIVES: To assess the efficacy and safety of a novel, stabilized topical rapamycin cream formulation. METHODS: This multicentre double-blind randomized placebo-controlled dose-response phase II/III study with a parallel design included participants aged 6-65 years with FAs of mild or moderate severity according to the Investigator's Global Assessment (IGA) scale. Participants were randomized to one of three treatment arms: topical rapamycin 0.5%, topical rapamycin 1% or placebo. Treatment was applied once daily for 26 weeks. Safety and efficacy measures were assessed at days 14, 56, 98, 140 and 182. The primary endpoint was the percentage of participants achieving IGA scores of 'clear' or 'almost clear' after 26 weeks of treatment. Secondary measures included Facial Angiofibroma Severity Index (FASI) and participant- and clinician-reported percentage-based improvement. Safety measures included the incidence of treatment-emergent adverse events and blood rapamycin concentration changes over time. RESULTS: Participants (n = 107) were randomized to receive either rapamycin 1% (n = 33), rapamycin 0.5% (n = 36) or placebo (n = 38). All treated participants were included in the final analysis. The percentage of participants with a two-grade IGA improvement was greater in the rapamycin 0.5% treatment group (11%) and rapamycin 1% group (9%) than in the placebo group (5%). However, this was not statistically significant [rapamycin 0.5%: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.36-8.18 (P = 0.50); rapamycin 1%: OR 1.68, 95% CI 0.33-8.40 (P = 0.53)]. There was a statistically significant difference in the proportion of participants treated with rapamycin cream that achieved at least a one-grade improvement in IGA [rapamycin 0.5%: 56% (OR 4.73, 95% CI 1.59-14.10; P = 0.005); rapamycin 1%: 61% (OR 5.14, 95% CI 1.70-15.57; P = 0.004); placebo: 24%]. Skin adverse reactions were more common in patients following rapamycin application (64%) vs. placebo (29%). CONCLUSIONS: Both rapamycin cream formulations (0.5% and 1%) were well tolerated, and either strength could lead to clinical benefit in the treatment of FA.

Optimizing Management of Medically Responsive Epilepsy.

PURPOSE OF REVIEW: This article reviews the management of patients with medically responsive epilepsy, including discussion of factors that may lead to transient breakthrough seizures and patient and physician strategies to maintain freedom from seizures. RECENT FINDINGS: Imperfect adherence, unanticipated changes in ongoing medical therapy, inadvertent use of proconvulsants or concurrent medications that alter epilepsy medication kinetics, and a variety of seizure precipitants such as stress or sleep deprivation may alter long-term seizure control. SUMMARY: The majority of patients with epilepsy are medically responsive. Many potential factors may lead to breakthrough seizures in these patients. Identification of these factors, patient education, and use of self-management techniques including mindfulness therapy and cognitive-behavioral therapy may play a role in protecting patients with epilepsy against breakthrough seizures.

Mechanisms of traumatic brain injury.

The authors describe the mechanisms of traumatic brain injury (TBI), examining in depth the characteristics of closed head, penetrating, and blast-related TBI. Events on a structural as well as cellular level are reviewed. Blast-related brain injury, in particular, affects military service members preferentially, but is also relevant in cases of industrial accidents as well as terrorist events.

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Expanding sunshine laws affect public and private hospital boards.

Aumento de volumen de la glandula tiroides en mujeres embarazadas de la ciudad de La Paz: signo de deficiencia moderada de yodo / Increase thyroid volume in pregnact women in the city of La Paz: a sign of moderate iodine deficiency

Evaluar el aumento de volumen de la glándula tiroides durante el embarazo como signo de desorden de deficiencia de yodo (DDI) relacionada a una disminución del cntenido de yodo en la sal. Diseño y método. Se determinó el volumen tiroideo por ecografía utilizando la fórmula de Brunn en un grupo de mujeres embarazadas y un grupo control en el Hospital de la Mujer de la Ciudad de La Paz. Resultados. Se encontro un aumento significativo del volumen tiroideo en mueres embarazadas frente al grupo control (19.8+-12mL vs. 10+-5.3mL p=0.0048). Conclusión. El trabajo demuestra que existe incremento significativo del volumen tiroideo en mujeres embarazadas relacionado con un grado moderado de deficiencia de yodo.