Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study.

BACKGROUND: Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis-ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab-and to identify clinical predictors that can influence the drug survival of these drugs. METHODS: This retrospective multicentric cohort study from 16 dermatology centers in Portugal, Spain, Italy, Switzerland, Czech Republic, Canada, and the United States included patients that started IL-12/23, IL-17 (IL-17A and IL-17R) and IL-23 inhibitors for the treatment of psoriasis between January 1, 2012 and December 31, 2019. Survival analysis was performed using a Kaplan-Meier estimator, to obtain descriptive survival curves, and proportional hazard Cox regression models. RESULTS: A total of 3312 treatment courses (total patients: 3145) were included in the study; 1118 (33.8%) with an IL-12/23 inhibitor (ustekinumab), 1678 (50.7%) with an IL-17 inhibitor [911 (27.5%) on secukinumab, 651 (19.7%) on ixekizumab, 116 (3.5%) on brodalumab], and 516 (15.5%) with an IL-23 inhibitor [398 (12.0%) on guselkumab, 118 (3.5%) on risankizumab]. At 18 months, the cumulative probability of survival was 96.4% for risankizumab, 91.1% for guselkumab, 86.3% for brodalumab, 86.1% for ustekinumab, 82.0% for ixekizumab, and 79.9% for secukinumab. Using ustekinumab as reference, drug survival of guselkumab was higher (HR 0.609; 95% CI 0.418-0.887) and that of secukinumab was lower (HR 1.490; 95% CI 1.257-1.766). In the final multivariable model, secukinumab, female sex, higher BMI, and prior exposure to biologic agents significantly increased the risk of drug discontinuation, whereas risankizumab was protective. CONCLUSION: In this multinational cohort with 8439 patient-years of follow-up, the cumulative probability of drug survival for all drugs was >79% at 18 months. Prescribed biologic, female sex, higher BMI, and previous exposure to biologic agents were predictors of drug discontinuation. Drug survival of guselkumab and risankizumab was higher than that of ustekinumab, and secukinumab was lower.

Enhancing community based health programs in Iran: a multi-objective location-allocation model.

Community Based Organizations (CBOs) are important health system stakeholders with the mission of addressing the social and economic needs of individuals and groups in a defined geographic area, usually no larger than a county. The access and success efforts of CBOs vary, depending on the integration between health care providers and CBOs but also in relation to the community participation level. To achieve widespread results, it is important to carefully design an efficient network which can serve as a bridge between the community and the health care system. This study addresses this challenge through a location-allocation model that deals with the hierarchical nature of the system explicitly. To reflect social welfare concerns of equity, local accessibility, and efficiency, we develop the model in a multi-objective framework, capturing the ambiguity in the decision makers' aspiration levels through a fuzzy goal programming approach. This study reports the findings for the real case of Shiraz city, Fars province, Iran, obtained by a thorough analysis of the results.

Gravitational collapse on the brane: a no-go theorem.

We investigate how braneworld gravity affects gravitational collapse and black hole formation by studying Oppenheimer-Snyder-like collapse on a Randall-Sundrum-type brane. Without making any assumptions about the bulk, we prove a no-go theorem: the exterior spacetime on the brane cannot be static, which is in stark contrast with general relativity. We also consider the role of Kaluza-Klein energy density in collapse, using a toy model.

Reacción reversal tardia en la enfermedad de Hansen / Late reversal reactions in Hansens disease

Las reacciones reversales tardías son episodios agudos producidos por un incremento de la inmunidad celular, en pacientes de lepra que ya han concluído su períodod de tratamiento. En estas circunstancias, su diagnóstico diferencial con la recidiva de la enfermedad, es a menudo dificultoso, e implica una conducta terapéutica diferentre que llevará a la reanudación de la poliquimioterapia en el último caso. Si bien existen algunos criterios que orientan la diferenciación entre ambas, debido a la importancia del compromiso neuronal que generalmente acompaña a las reacciones reversales, se preconiza el tratamiento precoz con esteroides, no sólo como prueba terapéutica sino como un método para prevenir importantes secuelas discapacitantes(AU)

Reacción reversal tardia en la enfermedad de Hansen / Late reversal reactions in Hansen's disease

Las reacciones reversales tardías son episodios agudos producidos por un incremento de la inmunidad celular, en pacientes de lepra que ya han concluído su períodod de tratamiento. En estas circunstancias, su diagnóstico diferencial con la recidiva de la enfermedad, es a menudo dificultoso, e implica una conducta terapéutica diferentre que llevará a la reanudación de la poliquimioterapia en el último caso. Si bien existen algunos criterios que orientan la diferenciación entre ambas, debido a la importancia del compromiso neuronal que generalmente acompaña a las reacciones reversales, se preconiza el tratamiento precoz con esteroides, no sólo como prueba terapéutica sino como un método para prevenir importantes secuelas discapacitantes

Evaluation of a bar-code system for nutrient analysis in dietary surveys.

OBJECTIVE: A novel system for nutrient analysis has been developed and tested over 5 years. Its key features are a nutrient database of 600 commonly eaten foods (95% of foods eaten in 7-day surveys); a booklet identifying each food with a bar code, bar codes for gram weight and for portion sizes (small, medium, large) and a bar-code reader with dietary analysis software for PCs. In the present study the bar-code system has been evaluated by comparison with a commonly used manual entry nutrient analysis software for dietitians' use. DESIGN: Cross-sectional. SETTING: Glasgow city district. SUBJECTS: One hundred and sixty adults aged 18-65 years old. RESULTS: Comparing mean intakes for macro- and micronutrients, using the Bland and Altman method, the bias between the two methods was small, ranging from 0.93 to 1.03. The bar-code system took significantly less professional time in data entry and nutrient analysis than the widely used manual system (29min per 7-day diary vs. 47 min per 7-day diary, P < 0.001). CONCLUSIONS: It is suggested that the bar-code system offers greater speed with a saving of professional time needed for nutrient analysis of dietary surveys. This system is commended for maintaining accuracy while promoting economy.

An alternative method of detecting dispersion staining colors for the determination of asbestos fibers in bulk materials.

Asbestiform mineral particles can be detected and identified by means of a polarized light microscope, making use of the dispersion staining technique. In order to obtain dispersion staining (central stop), che rays which pass undeviated through liquid and specimen must be stopped. A microscope objective can be fitted with a device which can insert a central stop on the objective back focal plane to prevent undeviated rays from reaching the objective. Alternatively, the sample can be observed in a conventional dark field set-up, that is, it can be illuminated by a hollow cone of light of greater aperture than the microscope objective so that only rays which are strongly deviated can enter the objective. The first method, proposed by McCrone and widely used in the USA, allows very bright and defined colors to be obtained but at the same time entails low resolution. The second method, recommended by italian regulations as a method that can be used in asbestos characterization, produces less defined and fainter colors. By suitably modifying the angular aperture of the illuminating cone and regulating the distance between condenser and specimen, good results were achieved: on the one hand a good image resolution were retained, on the other, the colors observed were bright and well defined. The detection of these colors can represent a fundamental step in the characterization of the specimen under analysis.