Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration.

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.

Epidemiological, clinical and economic burden of alopecia areata in Spain: a real-world retrospective study. The PETALO study.

Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring hair loss. Data are lacking on the epidemiology and clinical and economic burden of AA in Spain. To estimate the prevalence and incidence of AA in Spain and describe sociodemographic and clinical characteristics, treatment patterns, healthcare resource utilization (HCRU) and associated costs. This was an observational, retrospective, descriptive study based on the Health Improvement Network (THIN®) database (Cegedim Health Data, Spain). Patients with ICD9-Code 704.01 for AA, registered between 2014 and 2021, were identified. Prevalence (%) and incidence rates per 1,000 patient-years (IR) of AA were calculated and clinical characteristics, treatment characteristics and HCRU/costs were assessed. A total of 5,488 patients with AA were identified. The point prevalence of AA in 2021 was 0.44 (95% confidence interval [CI]: 0.43-0.45) overall, 0.48 (0.47-0.49) in adults, and 0.23 (0.21-0.26) in children ≤12 years. The 2021 IR for AA in adults was 0.55 (0.51-0.60). Of 3,351 adults with AA, 53.4% were female, mean (standard deviation [SD]) age was 43.1 (14.7) years, and 41.6% experienced comorbidities. Among adults, 2.7% used systemic treatment (0.5% immunosuppressants, 2.5% oral corticosteroids, 0.3% both). Laboratory tests and health care professional visits were the principal drivers of cost, which was €821.2 (1065.6)/patient in the first year after diagnosis. The epidemiology of AA in Spain is comparable with that reported for other countries, being more prevalent among adults. There is a significant burden of comorbidities and cost for patients, with limited use of systemic treatments, suggesting an unmet treatment need in this population.

[Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain]. / Coste-efectividad de drotrecogina alfa (activada) en el tratamiento de la sepsis grave en España.

INTRODUCTION: The PROWESS clinical trial has shown that treatment with drotrecogin alpha (activated) in patients with severe sepsis is associated with a reduction in the absolute risk of death compared with standard treatment. The aim of the present study was to assess the cost-effectiveness of drotrecogin alpha (activated) versus that of standard care in the treatment of severe sepsis in Spain. PATIENTS AND METHODS: A decision analysis model was drawn up to compare costs to hospital discharge and the long-term efficacy of drotrecogin alpha (activated) versus those of standard care in the treatment of severe sepsis in Spain from the perspective of the health care payer. Most of the information for creating the model was obtained from the PROWESS clinical trial. A two-fold baseline analysis was performed: a) for all patients included in the PROWESS clinical trial and b) for the patients with two or more organ failures. The major variables for clinical assessment were the reduction in mortality and years of life gained (YLG). Cost-effectiveness was expressed as cost per YLG. A sensitivity analysis was applied using 3% and 5% discount rates for YLG and by modifying the patterns of health care, intensive care unit costs, and life expectancy by initial co-morbidity and therapeutic efficacy of drotrecogin alpha (activated). RESULTS: Treatment with drotrecogin alfa (activated) was associated with a 6.0% drop in the absolute risk of death (p = 0.005) when all of the patients from the PROWESS trial were included and with a 7.3% reduction (p = 0.005) when the analysis was restricted to patients with two or more organ failures. The cost-effectiveness of drotrecogin alfa (activated) was 13,550 euros per YLG with respect to standard care after analysing all of the patients and 9,800 euros per YLG in the group of patients with two or more organ failures. In the sensitivity analysis, the results ranged from 7,322 to 16,493 euros per YLG. The factors with the greatest impact on the results were the change in the efficacy of drotrecogin alfa (activated), adjustment of survival by initial co-morbidity and the application of discount rates to YLG. CONCLUSIONS: Treatment with drotrecogin alfa (activated) presents a favorable cost-effectiveness ratio compared with other health care interventions commonly used in Spain.

Coste-efectividad de drotrecogina alfa (activada) en el tratamiento de la sepsis grave en España / Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain

Introducción: El ensayo clínico PROWESS ha demostrado que el tratamiento con drotrecogina alfa (activada) en pacientes con sepsis grave se asocia a una reducción del riesgo absoluto de muerte en comparación con el tratamiento estándar. El objetivo del estudio fue evaluar el coste-efectividad de drotrecogina alfa (activada), frente a tratamiento estándar, en el tratamiento de la sepsis grave en España. Pacientes y métodos: Se elaboró un modelo de análisis de decisión en el que se compararon los costes hasta el alta hospitalaria y la eficacia a largo plazo de drotrecogina alfa (activada) frente a tratamiento estándar de pacientes con sepsis grave en España, desde la perspectiva del financiador de los servicios sanitarios. La mayoría de la información para realizar el modelo se obtuvo del ensayo clínico PROWESS. El análisis basal fue doble: a) para todos los pacientes incluidos en el ensayo clínico PROWESS, y b) para los pacientes con 2 o más fallos orgánicos. Las variables principales de valoración clínica fueron la reducción de la mortalidad hospitalaria y los años de vida ganados (AVG). El coste-efectividad se expresó como coste por AVG. Se realizó un análisis de sensibilidad utilizando tasas de descuento del 3 y el 5 por ciento para los AVG y modificando los patrones de atención sanitaria, los costes de la unidad de cuidados intensivos, la esperanza de vida según la comorbilidad inicial y la eficacia terapéutica de drotrecogina alfa (activada).Resultados: El tratamiento con drotrecogina alfa (activada) se asoció a un descenso del riesgo absoluto de mortalidad hospitalaria del 6,0 por ciento (p = 0,005) cuando se incluyeron todos los pacientes del estudio PROWESS, y una reducción del 7,3 por ciento (p = 0,005) cuando sólo se incluyeron los pacientes con 2 o más fracasos orgánicos. El coste-efectividad de drotrecogina alfa (activada) fue de 13.550 euros por AVG respecto a placebo cuando se analizó el total de pacientes, y de 9.800 euros por AVG en el grupo de pacientes con 2 o más fallos orgánicos. En el análisis de sensibilidad, los resultados oscilaron desde 7.322 a 16.493 euros por AVG. Los factores que más influyeron en los resultados fueron la modificación de la eficacia de drotrecogina alfa (activada), el ajuste de la supervivencia según la comorbilidad inicial y la aplicación de descuento a los AVG. Conclusiones: El tratamiento con drotrecogina alfa (activada) presenta una relación coste-efectividad favorable en comparación con otras intervenciones sanitarias comúnmente utilizadas en España (AU)