Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options.

Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with a high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD is characterized by a wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms and interactions between genetics, immune system dysregulation and environmental factors. In this review, we describe the diverse cellular and molecular mechanisms involved in AD, including the critical role of T-cell-driven inflammation, primarily via T helper (Th) 2- and Th17-derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway. These local inflammatory processes interact with sensory neuronal pathways, contributing to the clinical manifestations of AD, including itch, pain and sleep disturbance. The recent elucidation of the molecular pathways involved in AD has allowed treatment strategies to evolve from broad-acting systemic immunosuppressive therapies to more targeted agents, including JAK inhibitors and cytokine-specific biologic agents. Evidence from the clinical development of these targeted therapies has reinforced and expanded our understanding of the pathophysiological mechanisms underlying AD and holds promise for individualized treatment strategies tailored to specific AD subtypes.

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial.

BACKGROUND: Baricitinib is an oral, selective, reversible Janus kinase 1/2 inhibitor approved in the European Union and Japan and under investigation in the United States for treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the impact of baricitinib plus background topical corticosteroids (TCS) on health-related quality of life (HRQoL), how AD symptoms impact work productivity and life functioning, and treatment benefit using patient-reported outcome (PRO) assessments in patients with moderate-to-severe AD previously experiencing inadequate response to TCS. METHODS: Adult patients with AD in BREEZE-AD7, a Phase 3, multicentre, double-blind trial, were randomised 1 : 1 : 1 to daily oral placebo (control) or baricitinib 4- or 2-mg plus TCS. PROs reported Week 1 through Week 16: Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-AD (WPAI-AD); Patient-Reported Outcomes Measurement Information System (PROMIS) Itch and Sleep measures, and Patient Benefit Index (PBI). Data were analysed using logistic regression (categorical) and mixed model repeated measures (continuous). PBI scores were analysed using analysis of variance. RESULTS: A total of 329 patients were randomised. Treatment with baricitinib 4-mg (N = 111) or 2 mg (N = 109) plus TCS led to rapid, statistically significant improvements [vs. TCS plus placebo (N = 109)] in DLQI ≥4-point improvement starting at Week 2 (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05), change from baseline in WPAI-AD presenteeism at Week 1 (4-mg plus TCS, P ≤ 0.01; 2-mg plus TCS P ≤ 0.05) and PROMIS itch interference at Week 2 (4-mg plus TCS P ≤ 0.01). Improvements were sustained through Week 16 for baricitinib 4-mg. Statistically significant improvements were observed at Week 16 for PBI global score (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05). CONCLUSIONS: Baricitinib plus TCS vs. placebo plus TCS showed significant improvements in treatment benefit at Week 16 and rapid significant improvements in HRQoL and impact of AD symptoms on work productivity and functioning through 16 weeks.

Factores asociados al abandono del tratamiento de la tuberculosis en la provincia de Granada / Factors associated to dropout of tuberculostatic treatment in the province of Granada

Objetivos. Los factores asociados al abandono del tratamiento de la tuberculosis (TBC) pueden ser muy específicos de la población y de la organización sanitaria locales. Hemos examinado los factores asociados al abandono del tratamiento de la TBC en la provincia de Granada. Sujetos y métodos. Cohorte retrospectiva de los casos registrados en Granada y notificados en el Sistema de Vigilancia Epidemiológica de Andalucía durante los años 2003-2010. Se calculó la incidencia en la población nacional y extranjera. Se realizó un análisis univariante para describir las características en ambos colectivos y se creó un modelo de regresión logística para identificar los factores asociados al abandono terapéutico. Resultados. Observamos una tendencia decreciente en la incidencia de TBC (20,47 casos en el año 2007 y 11,00 en el 2010 por 100.000 habitantes; tasa de descenso de 9,47 casos por 100.000 habitantes). La edad media de los pacientes extranjeros fue menor que la de los enfermos nacionales (30,8 años vs 46,0 años; p<0,001). Los primeros residían de forma predominante en el distrito Granada, mientras que los nacionales habitaban en el distrito Metropolitano. El porcentaje de pacientes que abandonaron el tratamiento antituberculoso fue del 12,2% y fue algo superior en los enfermos extranjeros que entre los nacionales (14 vs 10%; p=0,062). Ser varón (OR: 1,65; IC del 95%: 1,04-2,60; p=0,033), extranjero (OR: 1,72; IC del 95%: 1,04-2,83; p=0,032), residente en el distrito Nordeste (OR: 3,64; IC del 95%: 1,76-7,52; p=0,005) y/o padecer TBC extrapulmonar (OR: 1,78; IC del 95%: 1,06-3,00; p=0,029) se asociaron de forma significativa con el abandono terapéutico. Conclusiones. La incidencia de TBC en la provincia de Granada se ha reducido alrededor de 10 casos por 100.000 habitantes y año. El porcentaje de enfermos que abandonan el tratamiento TBC es considerable, siendo superior en los pacientes extranjeros que en los nacionales. El abandono del tratamiento TBC se asoció a ser varón, residir en el distrito Nordeste de Granada y padecer TBC extrapulmonar(AU)

Objectives. The factors associated to tuberculosis (TB) treatment drop-out can be very specific to the population and the local health care organization. We have studied the factors associated to TB treatment drop out in the province of Granada. Subjects and methods. A retrospective cohort study of TB cases registered in the province of Granada by the Epidemiological Surveillance System of Andalusia (SVEA) between 2003 and 2010 was carried out. Incidence was calculated in the native and foreign population. An univariate analysis was performed to describe the characteristics in both groups and a logistic regression model was used to identify factors associated to therapeutic abandonment. Results. A decreasing trend in the incidence of TB was observed, (20.47 in 2007 to 11 cases per 100,000 inhabitants in 2010, respectively. Mean age of foreign patients was lower than that of the natives (30.8 years vs. 46.0 years, P<.001). The former predominately lived in the Granada district, while the natives lived in the Metropolitan district. The percentage of patients who abandoned antituberculous treatment was 12.2%, this being somewhat higher in the foreign patients than the national ones (14% vs 10%; P=.062). Being male (OR: 1.65; 95% CI: 1.04-2.60; P=.033), foreigner (OR: 1.72; 95% CI: 1.04-2.83; P=.032), resident in the North-east district (OR: 3.64; 95% CI: 1.76-7.52; P=.005) and/or having extrapulmonary TB (OR: 1.78; 95% CI: 1.06-3.00; P=.029) were associated significantly to therapeutic abandonment. Conclusions. The incidence of TB in the province of Granada has decreased to about 10 cases per 100,000 inhabitants/year. The percentage of patients who abandon TB treatment is significant, it being higher in foreign patients than in the natives. TB treatment abandonment was associated to being a man, living in the North-east district of Granada and having extrapulmonary TB(AU)

[Factors associated to dropout of tuberculostatic treatment in the province of Granada]. / Factores asociados al abandono del tratamiento de la tuberculosis en la provincia de Granada.

OBJECTIVES: The factors associated to tuberculosis (TB) treatment drop-out can be very specific to the population and the local health care organization. We have studied the factors associated to TB treatment drop out in the province of Granada. SUBJECTS AND METHODS: A retrospective cohort study of TB cases registered in the province of Granada by the Epidemiological Surveillance System of Andalusia (SVEA) between 2003 and 2010 was carried out. Incidence was calculated in the native and foreign population. An univariate analysis was performed to describe the characteristics in both groups and a logistic regression model was used to identify factors associated to therapeutic abandonment. RESULTS: A decreasing trend in the incidence of TB was observed, (20.47 in 2007 to 11 cases per 100,000 inhabitants in 2010, respectively. Mean age of foreign patients was lower than that of the natives (30.8 years vs. 46.0 years, P<.001). The former predominately lived in the Granada district, while the natives lived in the Metropolitan district. The percentage of patients who abandoned antituberculous treatment was 12.2%, this being somewhat higher in the foreign patients than the national ones (14% vs 10%; P=.062). Being male (OR: 1.65; 95% CI: 1.04-2.60; P=.033), foreigner (OR: 1.72; 95% CI: 1.04-2.83; P=.032), resident in the North-east district (OR: 3.64; 95% CI: 1.76-7.52; P=.005) and/or having extrapulmonary TB (OR: 1.78; 95% CI: 1.06-3.00; P=.029) were associated significantly to therapeutic abandonment. CONCLUSIONS: The incidence of TB in the province of Granada has decreased to about 10 cases per 100,000 inhabitants/year. The percentage of patients who abandon TB treatment is significant, it being higher in foreign patients than in the natives. TB treatment abandonment was associated to being a man, living in the North-east district of Granada and having extrapulmonary TB.

Entrenamiento interválico en pacientes con cardiopatía isquémica: metodología y análisis de resultados ergoespirométricos / Interval training in patients with coronary artery disease: methodology and ergospirometric data analysis

Introducción. El ejercicio de tipo interválico es una modalidad de entrenamiento poco utilizada en pacientes con cardiopatía isquémica aunque sus beneficios fisiológicos han sido demostrados por distintos autores. Objetivo. Describir un método sencillo de entrenamiento interválico, así como evaluar los beneficios y la seguridad del mismo en pacientes con cardiopatía isquémica. Método. Se estudiaron 25 pacientes con cardiopatía isquémica estable que realizaron un entrenamiento interválico de alta intensidad en cicloergómetro. Para programar la intensidad del entrenamiento se realizó un Steep Ramp Test. El entrenamiento consistió en intervalos de 20 s al 50% de la carga máxima alcanzada en el Steep Ramp Test, seguido de intervalos de 40 s al 10% de la misma. Se realizó una ergoespirometría sobre cicloergómetro pre y posprograma para comparar resultados. Resultados. Tras 8 semanas de entrenamiento se produjeron incrementos significativos en el VO2pico (19,9 ± 5,3 vs. 23,8 ± 6ml/kg/min), en la carga máxima (103,5 ± 42,6 vs. 124,6 ± 53,4 vatios), en la frecuencia cardíaca (FC) máxima (117,6 ± 15,7 vs. 128 ± 16,5 lat./min) y en el índice de recuperación de la FC en el primer minuto (16,5 ± 9,2 vs. 21,3 ± 7,7 lat./min). No se registraron efectos adversos. Conclusión. El ejercicio interválico de alta intensidad es una modalidad de entrenamiento sencilla y segura que permite mejorar de forma significativa el VO2pico y la tolerancia al ejercicio en pacientes con cardiopatía isquémica (AU)

Background. Interval training is an exercise modality underused in patients with coronary artery disease even though different authors have shown its physiological benefits. Objective. To describe a simple method of interval training and to evaluate its benefits and safety in patients with coronary artery disease. Method. Twenty-five patients with stable coronary artery disease underwent high-intensity interval training on a cycle ergometer. To determine the training work rate, we performed a steep ramp test. The training consisted of intervals of 20seconds at 50% of the maximum load achieved in the steep ramp test, followed by intervals of 40seconds at 10%. A cycle ergospirometry was performed before and after the programme to compare data. Results. After 8 weeks of interval training, there were significant gains in V02 peak (19.9±5.3 vs. 23.8±6mL·kg-1·min−1), maximal work rate (103.5±42.6 vs.124.6±53.4 watts), maximal heart rate (117.6±15.7 vs. 128±16.5 bpm) and heart rate recovery index in the first minute (16.5±9.2 vs. 21.3±7.7 bpm). There were no adverse events. Conclusion. In patients with coronary artery disease, high-intensity interval training is an easy, safe exercise modality that produces improvement in VO2 peak and exercise tolerance (AU)

Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism.

The roles of androgen hypersecretion, in situ enzyme activity, and androgen receptors in androgenetic alopecia in women are still a matter of debate. We studied 187 women with alopecia, which we graded I, II, or III, according to Ludwig's classification, and 21 healthy control women. All participants were subjected to full basal and 1 h post-beta-1-24 corticotropin stimulation endocrine profiles. Abnormal hormone profiles were observed in 67% of the patients with alopecia alone (group A, n = 110) and in 84% of the patients with alopecia plus other symptoms of hyperandrogenism including acne, hirsutism, and menstrual cycle disturbances (group B, n = 77). Mean serum 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005). Mean serum sex hormone-binding globulin (SHBG) levels were inversely correlated with the grade of alopecia (I-III) and were significantly lower in all three patient groups (50.55+/-23.50, 40.00+/-17.65, and 38.80+/-14.10 nmol/l, respectively) than in the control group (61.15+/-17.65 nmol/l, P < 0.05). Mean serum levels of delta4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 3alpha-AdiolG were higher in group B than in group A, and higher in group A than in the control group. The significant correlations found between adrenal secretion - either positive (with 3alpha-AdiolG levels and the body mass index) or negative (with SHBG levels) - might reflect the important contribution of secretory and metabolic components in the development of alopecia, the severity of which has been shown to be very closely related to observed levels of two of these parameters (3alpha-AdiolG and SHBG).