Real-life cost-effectiveness of benralizumab in patients with severe asthma.

BACKGROUND: Availability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma. METHODS: This was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs). RESULTS: After 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score. CONCLUSIONS: All the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.

Real-life experience with benralizumab during 6 months.

BACKGROUND: Benralizumab is a monoclonal antibody that binds to the human interleukin-5 (IL-5) receptor (IL-5R), thereby preventing IL-5 from binding to its receptor and inhibiting differentiation and maturation of eosinophils in the bone marrow. Because of its recent marketing approval, sufficient real-life evidence is lacking to confirm the efficacy and safety data from clinical trials. The purpose of this study was to evaluate the efficacy and safety of benralizumab for the treatment of severe refractory eosinophilic asthma in a real-world cohort of patients. METHODS: This was a cross-sectional multicentre study of consecutive patients with severe refractory eosinophilic asthma who received treatment with benralizumab during at least 6 months. Patient follow-up was performed in specialised severe asthma units. RESULTS: A total of 42 patients were enrolled and treated with benralizumab. Asthma control, as measured by the asthma control test (ACT), improved in all patients both at 3 months of treatment compared with baseline (13.9 ± 4 vs 20.1 ± 3.7, p < 0.001) and at 6 months of treatment compared with the results obtained at 3 months (20.1 ± 3.7 vs 21 ± 2.7, p = 0.037). Similarly, the number of emergency department visits decreased both at 3 months compared with baseline (1 [IR:0.7] vs 0 [IR:0.75], p < 0.001) and at 6 months compared with the results at 3 months (0 [IR:0.75] vs 0 [IR:0], p = 0.012). Reductions in the number of oral corticosteroid cycles, percentage of corticosteroid-dependent patients, and mean daily dose of oral or inhaled corticosteroid were also evidenced. Finally, mean lung function improvement was 291 mL (p < 0.001), and FEV1% improved both at 3 months compared with baseline (64.4 ± 9.3 vs 73.1 ± 9.1, p < 0.001) and at 6 months compared to 3 months (73.1 ± 9.1 vs 76.1 ± 12, p = 0.002). Side effects were mild and did not lead to treatment discontinuation. CONCLUSIONS: This study confirms the efficacy and safety of benralizumab in a real-life setting with improved asthma control and lung function, and a reduced oral and inhaled corticosteroid use as well as fewer emergency department visits. In addition to a rapid initial improvement, it appears that patients continue to improve during the first 6 months of treatment.

Structural diversity from the transannular cyclizations of natural germacrone and epoxy derivatives: a theoretical-experimental study.

Treatment of germacrone (1) with different electrophiles, and of its epoxy derivatives germacrone-4,5-epoxide (2), germacrone-1,10-epoxide (3) and isogermacrone-4,5-epoxide (4) with Brönsted/Lewis acids and Ti(III), gives rise to a great structural diversity. Thus, by using a maximum of two steps, the production of more than 40 compounds corresponding to 14 skeletons is described. Computational calculations rationalizing the structural divergence produced are also described. Finally, since some of the compounds generated are bioactive natural sesquiterpenes, the mechanisms of formation of these substances will provide new insights in their biosynthesis.

Functional characterization of an acidic SK(3) dehydrin isolated from an Opuntia streptacantha cDNA library.

Cactus pears are succulent plants of the Cactaceae family adapted to extremely arid, hot and cold environments, making them excellent models for the study of molecular mechanisms underlying abiotic stress tolerance. Herein, we report a directional cDNA library from 12-month-old cladodes of Opuntia streptacantha plants subjected to abiotic stresses. A total of 442 clones were sequenced, representing 329 cactus pear unigenes, classified into eleven functional categories. The most abundant EST (unigen 33) was characterized under abiotic stress. This cDNA of 905 bp encodes a SK(3)-type acidic dehydrin of 248 amino acids. The OpsDHN1 gene contains an intron inserted within the sequence encoding the S-motif. qRT-PCR analysis shows that the OpsDHN1 transcript is specifically accumulated in response to cold stress, and induced by abscisic acid. Over-expression of the OpsDHN1 gene in Arabidopsis thaliana leads to enhanced tolerance to freezing treatment, suggesting that OpsDHN1 participates in freezing stress responsiveness. Generation of the first EST collection for the characterization of cactus pear genes constitutes a useful platform for the understanding of molecular mechanisms of stress tolerance in Opuntia and other CAM plants.

Efficient synthesis of the anticancer ß-elemene and other bioactive elemanes from sustainable germacrone.

Highly efficient preparations of anticancer ß-elemene and other bioactive elemanes were carried out using the natural product germacrone as a renewable starting material. The syntheses were achieved in only 3-5 steps with excellent overall yields (43-54%). An enantioselective approach to these molecules is also described.

[Effectivity in the use of protein supplements in resistance training: systematic review]. / Efectividad del uso de suplementos de proteína en entrenamientos de fuerza: revisión sistemática.

To increase strength and lean body mass, protein has become one of the most popular supplements among athletes. The aim of this study was to analyze the effect of protein supplementation on body composition. A systematic review of the randomized controlled trials (RCT), published in MEDLINE/PubMed and SciELO up to April 10, 2009, was conducted. All RCT conducted in healthy subjects with interventions of six or more weeks were included. Nine studies fulfilled the inclusion criteria, and three of them had level 3 of evidence. Among these studies, the increase of lean mass ranged from 0.8 to 1.9 kg. However, the study with the longest term had duration of 12 weeks. Therefore, the evidence does not support the recommendation for the consumption of protein supplements among healthy individuals.

[Randomized controlled school based interventions to prevent childhood obesity: systematic review from 2006 to 2009]. / Intervenciones aleatorias controladas basadas en las escuelas para prevenir la obesidad infantil: revisión sistemática de 2006 a 2009.

The prevalence of overweight and obesity in children has increased to epidemic levels. Several authors have suggested that school is the best place for effective prevention programs. The purpose of this systematic review was to assess the evidence of randomized controlled trials concerning long-term (equal to or more than 9 months) observations at schools and published in the database of MEDLINE/Pubmed from January 1st of 2006 to February 28 of 2009. Ten studies were analyzed. Overall, regarding the design, the intervention components, target population age, intervention periods, educational techniques, cultural characteristics of the population, and outcome measures were heterogeneous. The results were modest. The outcomes showed a positive impact on lifestyle as intakes of fruits and vegetables increased, consumption of sugar-sweetened carbonated beverages decreased, and sedentary behaviors and adiposity were reduced. Generally, there were no significant reductions for BMI. These results warrant more strategies to achieve parental involvement, reduction of dropouts, and additional studies assessing different educational systems and cultural environments, including those in Latin America. Longer follow-up periods are also required.

[Pediatric obesity. An increasing epidemic]. / Obesidad infantil. Una epidemia en ascenso.

Throughout the world, the incidence of adults and children who are overweight or obese is increasing at a near epidemic rate. Childhood obesity bears implications on health over the short, medium and long term life of these children; therefore, the prevention of childhood obesity has become a world health necessity. Nonetheless, there are few existing studies which prove to be effective in the prevention and control of obesity over the long term. The objective of this first section is to review the effectiveness of programs for the prevention and control of childhood obesity by analysing research articles. A bibliography will be included in the second section.

[Childhood obesity. Are prevention and control programs efficient? A study based on original articles]. / Obesidad infantil. Son eficaces los programas de prevención y control? Un estudio según artículos originales.

Continuing with the importance given throughout the world to the prevalence of adults and children who are overweight or obese. The authors review the effectiveness of programs for the prevention and control of childhood obesity by analysing original articles in this second section of their article. A complete bibliography accompanies this article.

Hallazgo casual al realizar una broncoscopia: tuberculosis endobronquial / Casual findings after a bronchoscopy: endobronchial tuberculosis

La tuberculosis continúa siendo un problema de salud a nivel mundial. Existe una gran variabilidad clínica de esta entidad dependiendo, entre otros factores, del lugar del organismo donde se asiente el bacilo. Existe una entidad específica de tuberculosis, denominada Tuberculosis Endobronquial (EBTB), que se define como una infección tuberculosa del árbol traqeuobronquial con evidencia microbiológica y/o histopatológica. Ésta puede presentarse sola o junto con afectación parenquimatosa. Las manifestaciones clínicas de esta entidad son inespecíficas, lo cual dificulta el diagnóstico. Para este es fundamental la realización de una TC de tórax y una broncoscopia. Ésta última nos permitirá observar las características del árbol traqueobronquial y tomar muestras para poder hacer el diagnóstico de certeza. El tratamiento es similar al de la tuberculosis pulmonar y el objetivo fundamental de este es erradicar el bacilo y prevenir complicaciones, siendo la más frecuente la estenosis bronquial

Tuberculosis continues to be a health problem worldwide. There is a large degree of clinical variability for this disease which depends, among other factors, on the part of the organism where the bacillus settles. There is a specific type of tuberculosis, called endobronchial tuberculosis (EBTB), which is defined as a tuberculous infection of the tracheobronchial tree with microbiological and/or histopathological signs. It can present on its own or alongside parenchymal involvement. The clinical manifestations of this disease are non-specific, which makes diagnosis difficult. That is why performing a chest CT and bronchoscopy is essential. The latter will allow the characteristics of the tracheobronchial tree to be seen and samples to be taken in order to make an accurate diagnosis. Treatment is similar to that of pulmonary tuberculosis and the main objective is to eradicate the bacillus and prevent complications, the most frequent of which is bronchial stenosis

Childhood overweight and obesity prevention interventions among Hispanic children in the United States: systematic review.

The aim of this study was to conduct a systematic review of childhood obesity interventions among Hispanic children in the United States. An electronic search was conducted to identify articles published in the PubMED, CINAHL and EBSCO databases. Keyword that used included "Latino", "Hispanic", "childhood", "obesity", "interventions". The inclusion criteria were: published in English from January 2001 to January 2012, studies equal or longer than 6 months of follow-up, Hispanic children and obesity prevention studies (RCT or Quasi-experimental studies). We found 10 studies for inclusion in this review, seven RCT and three Quasi-experimental studies, published from 2005 to January 2012. Overall, improvements in BMI and z-BMI across studies were inconsistent. Only two studies had a follow-up of 3 years, and the most recent study showed an increase in the proportion of children classified as obese. The overall quality rate of evidence with respect to reducing BMI or the prevalence of childhood obesity was low.

Carcinomatosis meníngea: forma inusual de presentación del adenocarcinoma de pulmón / Meningeal carcinomatosis: unusual presentation of adenocarcinoma of the lung

Se presenta el caso de una paciente con antecedentes de ser fumadora de baja intensidad, con índice acumulado de tabaco menor de 5 paquetes/año y sin otros antecedentes personales de interés. Acudió en diversas ocasiones durante 2 meses a urgencias, refiriendo cefalea difusa, opresiva e intermitente y diplopía acompañada de visión borrosa ocasional, siendo diagnosticada de parálisis isquémica del IV par craneal del ojo izquierdo e iniciando tratamiento con antiagregante. A pesar del tratamiento, a la semana acudió de nuevo a urgencias, ya que progresivamente había ido presentado mareos, inestabilidad en la marcha, pérdida de visión con predominio en ojo izquierdo y mayor sensación de debilidad en miembros superiores, Finalmente, se decidió ingreso en Neurología ante la sospecha de meningoencefalitis subaguda tuberculosa, pero tras diversas pruebas diagnósticas se llegó a la conclusión de que se trataba de un adenocarcinoma pulmonar, que debutó en forma de carcinomatosis meníngea sin haber presentado sintomatología respiratoria asociada

A case is presented of a patient with a history of low-intensity smoking, with an accumulated tobacco index of less than 5 packs-year and without other personal history of interest. She went to the emergency room several times over 2 months, complaining of a diffuse, oppressive and intermittent headache and diplopia accompanied by occasional blurred vision, being diagnosed with ischemic paralysis of the fourth cranial nerve of the left eye and initiating treatment with antiplatelets. Despite treatment, she returned to the emergency room within a week, as she had been suffering from progressive dizziness, instability when walking, loss of vision mainly in the left eye and a greater feeling of weakness in the upper limbs. Finally, admission to Neurology was decided upon with the suspicion of subacute tuberculous meningoencephalitis. However, after various diagnostic tests, it was concluded that it was a pulmonary adenocarcinoma, which began as meningeal carcinomatosis without presenting associated respiratory symptoms

[Evidence of social support as therapy for weight loss: a systematic review]. / Evidencias del soporte social como terapia para la pérdida de peso: una revisión sistemática.

INTRODUCTION: Social Support (SS) therapy can be an effective method of weight loss compared with conventional treatment (CT). OBJECTIVE: To evaluate RCT's using SS therapy on weight in subjects with overweight or obesity. METHODOLOGY: We reviewed all original articles published in MEDLINE/PubMed, SciELO, EBSCO, Google Scholar, from 2000 to August 2011, and one referred in a previous metanalisis, of RCT's of the effect of SS therapy on weight loss, with at least five months of treatment, compared with another therapy or a CT. RESULTS: Eight articles were analyzed. It was observed heterogeneity in the design, differences in the components of the interventions, and cultural characteristics of the population. The difference between groups in weight loss in five out of seven studies, ranged from 2.3 kg (24 m) to 8.3 kg (12 m). However, the treatment in the control groups did not meet the accepted recommended guidelines. There was no allocation concealment in two studies, and no blindness in four. Most studies showed large dispersion in the results. Therefore, the quality of the evidence is low. CONCLUSIONS: These results warrant further and better design and longer term studies to generate higher quality evidence.

[Intervention programs to promote physical activity in school children: systematic review]. / Programas de intervención para la promoción de actividad física en niños escolares: revisión sistemática.

OBJECTIVE: The purpose of this systematic review was to assess physical activity promotion programs in school children from 6 to 12 years old. METHODS: Randomized and non-randomized controlled trials of physical activity studies with an intervention period equal to or more than 12 months, published in the databases of MEDLINE/PubMed, SciELO, EBSCO and SPORTDiscus through may 2010 were searched. RESULTS: Seven studies were analyzed. Overall, the study design, the follow-up periods, the ethnic characteristics of the population, and the instruments used to evaluate the interventions were heterogeneous. The outcomes showed moderate impact of intervention programs to increase the physical activity in children and adolescents. In two of the studies was observed an increase in the physical activity and in five of the studies no significant difference in the physical activity assessed with accelerometers and pedometers. CONCLUSION: In five out of seven studies it was not shown statistical differences in cpm, including the longest experimental study. These results suggest the need of designing studies including modifications in different environments.

The anorexigenic peptide cocaine-and-amphetamine-regulated transcript modulates rem-sleep in rats.

It is known that the sleep-waking cycle is modulated by several molecules that may also regulate food intake, among them several neuropeptides. The cocaine-and-amphetamine-regulated transcript has been studied in relation to food ingestion, but it seems to have several other functions that may include sleep regulation. In this context, we studied the effect of the intracerebroventricular administration of the cocaine-and-amphetamine-regulated transcript (0.15, 0.3, 0.6, 0.9nmol) on the sleep-waking cycle (12-h recordings), as well as its effect on food intake in rats. Additionally, we analyzed the neuronal activity as measured by c-Fos expression induced by the cocaine-and-amphetamine-regulated transcript in neurons of nuclei involved in the regulation of sleep and feeding behavior. Our main finding is that 0.3nmol of the cocaine-and-amphetamine-regulated transcript increases rapid-eye-movement sleep. In addition, our results further support that this neuropeptide triggers satiety; c-Fos expression suggested that the cocaine-and-amphetamine-regulated transcript activates specific hypothalamic nuclei without affecting other brain structures known to be involved in sleep regulation. These data further support the notion that a few neuropeptides are involved in the regulation of both the sleep-waking and the hunger-satiety cycles.

Intervenciones aleatorias controladas basadas en las escuelas para prevenir la obesidad infantil: revisión sistemática de 2006 a 2009 / Randomized controlled school based interventions to prevent childhood obesity: systematic review from 2006 to 2009

La prevalencia de sobrepeso y obesidad en niños ha incrementado a niveles epidémicos. Diferentes autores sugieren que la escuela puede ser el espacio más apropiado para realizar programas efectivos de prevención. El propósito de esta revisión sistemática fue valorar la evidencia de estudios aleatorios controlados con un periodo de intervención a largo plazo (igual o mayor a 9 meses) en escuelas y publicados en la base de datos de MEDLINE/PubMed del 1º de enero de 2006 hasta el 28 de febrero de 2009. Se analizaron en total 10 artículos. En general, se puede observar una heterogeneidad en el diseño y los componentes de la intervención, la edad del grupo objetivo, el tiempo de intervención, el sistema educativo, las características culturales de la población y los resultados. Estos últimos son modestos. Los resultados indican un cambio positivo en el estilo de vida, incremento en el consumo de frutas y verduras, menor consumo de bebidas carbonatadas y azucaradas, reducción del comportamiento sedentario y reducción en adiposidad. En general no hubo reducción significativa del IMC. Los resultados demandan estrategias para lograr mayor compromiso de los padres y adherencia a los programas, así como más estudios en diferentes sistemas educativos y ambientes culturales, incluyendo los de Latinoamérica. Además se requieren seguimientos a más largo plazo.

The prevalence of overweight and obesity in children has increased to epidemic levels. Several authors have suggested that school is the best place for effective prevention programs. The purpose of this systematic review was to assess the evidence of randomized controlled trials concerning long-term (equal to or more than 9 months) observations at schools and published in the database of MEDLINE/Pubmed from January 1st of 2006 to February 28 of 2009. Ten studies were analyzed. Overall, regarding the design, the intervention components, target population age, intervention periods, educational techniques, cultural characteristics of the population, and outcome measures were heterogeneous. The results were modest. The outcomes showed a positive impact on lifestyle as intakes of fruits and vegetables increased, consumption of sugar-sweetened carbonated beverages decreased, and sedentary behaviors and adiposity were reduced. Generally, there were no significant reductions for BMI. These results warrant more strategies to achieve parental involvement, reduction of dropouts, and additional studies assessing different educational systems and cultural environments, including those in Latin America. Longer follow-up periods are also required.

Obesidad infantil / Childhood obesity

En todo el mundo la prevalencia del sobrepeso y la obesidad en adultos y en niños aumenta de manera casi epidémica. La obesidad en niños tiene implicaciones sobre la salud a corto, mediano y largo plazo, por lo que su prevención se ha convertido en una necesidad sanitaria mundial. Sin embargo, existen pocos estudios que demuestren eficacia en la prevención y control de la obesidad a largo plazo. El objetivo de este artículo es revisar la eficacia de programas de prevención y control de la obesidad infantil, mediante el análisis de artículos de revisión (AU)

Obesidad infantil. ¿Son eficaces los programas de prevención y control? / Childhood obesity. Prevention and treatment

Continuando con la importancia que tiene en todo el mundo la prevalencia del sobrepeso y la obesidad en adultos y en niños, los autores revisan la eficacia de programas de prevención y control de la obesidad infantil, mediante el análisis de artículos originales (AU)