Cost-effectiveness analysis of dupilumab versus omalizumab, mepolizumab, and benralizumab added to the standard of care in adults with severe asthma in Colombia.

BACKGROUND: Cost-effectiveness studies evaluate health technologies and help choose treatments. The current study compared dupilumab to omalizumab, mepolizumab, and benralizumab in Colombian adults with severe uncontrolled type 2 asthma. METHODS: Over a 5-year period, a Markov model was utilized to assess the costs of biological treatments and management of exacerbations, comparing various doses of exacerbations, comparing various doses of dupilumab, omalizumab, mepolizumab, and benralizumab as add-on treatments. It included a 5% annual discount rate per local HTA, and set willingness-to-pay at three times GDP per capita per quality-adjusted life year (QALY) in Colombia. RESULTS: Dupilumab (200 mg) exhibited greater QALYs and reduced overall costs compared to mepolizumab (100 mg), benralizumab (30 mg), and omalizumab (450 mg and 600 mg), with the incremental cost-effectiveness ratio (ICER) per QALYgained being -$5.429, -$6.269, -$196.567 and -$991.007, respectively. Dupilumab had greater QALYs and costs versus omalizumab 300 mg (ICERof $200.653 per QALY, above the willingness-to-pay threshold of 3 × GDP per capita). Sensitivity analyses were consistent with base case results. CONCLUSIONS: Dupilumab 200 mg was strongly dominant versus omalizumab 450 mg and 600 mg, mepolizumab 100 mg, and benralizumab 30 mg; however, cost-effectiveness was not demonstrated versus omalizumab 300 mg. These results could assist healthcare professionals in choosing an appropriate biologic for treating severe type 2 asthma.

Signal transduction of the insulin secretion induced by the chalcone analogue, (E)-3-(phenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, and its role in glucose and lipid metabolism.

A chalcone analogue, (E)-3-(phenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (DMU 101), was synthesized using classic base catalysis and Claisen-Schmidt condensation, and then screened for its antidiabetic properties. The compound's effects on glucose and lipid metabolism were assayed in rats that were treated acutely and for a short time to elucidate its mechanism of action, evaluating glucose tolerance and lactate dehydrogenase activity in response to chalcone analogue administration. The chalcone's in vitro and ex vivo effects on glycogen, glucose, lipid and lipolysis were also investigated, as well as the mechanism by which it induces 45Ca2+ influx-mediated insulin secretion. The analogue (10 mg/kg) diminished glycemia, without inducing acute cell damage, increased glycogen content in the skeletal muscle and reduced serum triacylglycerol and total cholesterol, but did not alter high-density lipoprotein or low-density lipoprotein. Chalcone (10 µM) stimulated glucose uptake in the soleus muscle and did not modulate in vitro or ex vivo lipolysis. This analogue also increased insulin secretion by triggering calcium influx and blocking ATP-sensitive K+ channels and voltage-dependent calcium channels. However, it also modulated stored calcium via sarco/endoplasmic reticulum calcium ATPase (SERCA) and ryanodine receptor (RYR) activity. These findings indicate that this chalcone may induce cellular repolarization via a mechanism mediated by calcium-dependent potassium channels.

Extract of Calyces from Physalis peruviana Reduces Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Diabetes mellitus is a metabolic disorder mainly characterized by obesity, hyperglycemia, altered lipid profile, oxidative stress, and vascular compromise. Physalis peruviana is a plant used in traditional Colombian medicine for its known activities of glucose regulation. This study aimed to evaluate the anti-diabetic activity of the butanol fraction from an extract of Physalis peruviana calyces in two doses (50 mg/kg and 100 mg/kg) in induced type 2 diabetic mice. Blood glucose levels were evaluated once a week, demonstrating that a dose of 100 mg/kg resulted in greater regulation of blood glucose levels in mice throughout the experiment. The same overall result was found for the oral glucose tolerance test (OGTT) and the homeostatic model assessment for insulin resistance (HOMA- IR). The lipid profile exhibited improvement compared to the non-treated group, a dose of 100 mg/kg having greater protection against oxidative stress (catalase, superoxide dismutase, and malondialdehyde levels). Histopathological findings in several tissues showed structure preservation in most of the animals treated. The butanol fraction from Physalis peruviana at 100 mg/kg showed beneficial results in improving hyperglycemia, lipidemia, and oxidative stress status, and can therefore be considered a beneficial coadjuvant in the therapy of diabetes mellitus.

A first-in-class, first-in-human, phase I trial of CIGB-552, a synthetic peptide targeting COMMD1 to inhibit the oncogenic activity of NF-κB in patients with advanced solid tumors.

CIGB-552 is a synthetic peptide that interacts with COMMD1 and upregulates its protein levels. The objectives of this phase I study were safety, pharmacokinetic profile, evaluation of the lymphocytes CD4+ and CD8+ and preliminary activity in patients with advanced tumors. A 3 + 3 dose-escalation design with seven dose levels was implemented. Patients were included until a grade 3 related adverse event occurred and the maximum tolerated dose was reached. The patients received subcutaneous administration of CIGB-552 three times per week for 2 weeks. Single-dose plasma pharmacokinetics was characterized at two dose levels, and tumor responses were classified by RECIST 1.1. Twenty-four patients received CIGB-552. Dose-limiting toxicity was associated with a transient grade 3 pruritic maculopapular rash at a dose of 7.0 mg. The maximum tolerated dose was defined as 4.7 mg. Ten patients were assessable for immunological status. Seven patients had significant changes in the ratio CD4/CD8 in response to CIGB-552 treatment; three patients did not modify the immunological status. Stable disease was observed in five patients, including two metastatic soft sarcomas. We conclude that CIGB-552 at dose 4.7 mg was well tolerated with no significant adverse events and appeared to provide some clinical benefits.

Filhos de dependentes químicos, suas percepções sobre as relações intrafamiliares / Children of drug addicts: their perceptions on intra-family relationships

Descrever a percepção de crianças, filhos de pais dependentes químicos, acerca do funcionamento familiar e as relações de apego construídas com seus pais. Trata-se de um estudo qualitativo realizado com quatro crianças, filhos de dependentes químicos. A coleta dos dados foi realizada através do genograma familiar e entrevista semiestruturada. Os depoimentos foram submetidos à análise de conteúdo. Os funcionamentos familiares foram classificados como desligado, emaranhado em fortalecimento de fronteiras ou não classificado. Os tipos de apego foram seguro e evitativo. O funcionamento familiar está relacionado com as formas de interação entre os membros e não ao uso de substâncias psicoativas. A dependência não é o fator desencadeante da rigidez do sistema, mas uma consequência do estilo de vinculação predominante no mesmo. Dificultam-se as interações positivas e a busca por padrões alternativos de funcionamento, sendo um importante fator de risco para o desenvolvimento saudável dos seus membros

The perception of children of drug-dependent parents on family functioning and affectionate relationships with their parents is described. Current qualitative study has been conducted with four children, children of drug addicts. Data were collected through family genogram and semi-structured interview. The statements were submitted to content analysis. Family functioning was classified as careless, entangled in border strengthening, or non- classified. Attachment types were safe and preventive. Family functioning is related to the forms of interaction between members and not to the use of psychoactive substances. Dependency is not the triggering factor of the system´s rigidity, but a consequence of the predominant style of attachment. It hinders positive interactions and the search for alternative patterns of functioning, being an important risk factor for healthy development of its members.

Cellular target of isoquercetin from Passiflora ligularis Juss for glucose uptake in rat soleus muscle.

Quercetin 3-O-beta-d-glucopyranoside (isoquercetin) is one of the most frequent metabolites of the Passiflora ligularis Juss. The purpose of this study was to investigate the effect of the aqueous extract and ethanol fraction from P. ligularis Juss leaves on glycaemia and the mechanism of action of isoquercetin on glucose uptake. In the glucose tolerance test, the aqueous extract and ethanol fraction from P. ligularis Juss (125 mg/kg to 500 mg/kg o. g.) reduced glycaemia and increased the hepatic and muscular glycogen content. Phytochemical analysis evidenced the dominant presence of isoquercetin in the extract and fraction from leaves of P. ligularis Juss. Isoquercetin mediates the stimulatory effect on glucose uptake independent of insulin receptor activation but, involve PI3K, MAPK, MEK/ERK pathways and de novo protein synthesis to GLUT-4 translocation. Overall findings revealed that isoquercetin and aqueous extract and ethanol fraction of P. ligularis Juss leaves might be a promising functional food or medicine for the treatment or prevention of diabetes.

Astragalin augments basal calcium influx and insulin secretion in rat pancreatic islets.

Astragalin is a flavonol glycoside with several biological activities, including antidiabetic properties. The objective of this study was to investigate the effects of astragalin on glycaemia and insulin secretion, in vivo, and on calcium influx and insulin secretion in isolated rat pancreatic islets, ex vivo. Astragalin (1 and 10 mg / kg) was administered by oral gavage to fasted Wistar rats and serum glucose and plasma insulin were measured. Isolated pancreatic islets were used to measure basal insulin secretion and calcium influx. Astragalin (10 mg/ kg) decreased glycaemia and increased insulin secretion significantly at 15-180 min, respectively, in the glucose tolerance test. In isolated pancreatic cells, astragalin (100 µM) stimulated calcium influx through a mechanism involving ATP-dependent potassium channels, L-type voltage-dependent calcium channels, the sarcoendoplasmic reticulum calcium transport ATPase (SERCA), PKC and PKA. These findings highlight the dietary coadjuvant, astragalin, as a potential insulin secretagogue that may contribute to glucose homeostasis.

Intimal sarcoma of the pulmonary artery presenting as pulmonary embolism / Sarcoma de la íntima de la arteria pulmonar que se presentó como embolismo pulmonar / O sarcoma da íntima da artéria pulmonar, que se apresentou como um quadro de embolia pulmonar

SUMMARY Pulmonary artery sarcomas are extremely rare; due to their insidious growth, diagnosis occurs late and prognosis is poor. We present the case of a 33-year-old woman with a history of dyspnea, chest pain and syncope. An obstructing mass on the right ventricle, main pulmonary artery and right branch were interpreted as a possible pulmonary embolism.

RESUMEN Los sarcomas de la arteria pulmonar son extremadamente raros; debido a su crecimiento lento y silencioso, el diagnóstico suele ser tardío y son de mal pronóstico. Presentamos el caso de una mujer de 33 años de edad con historia de disnea, dolor torácico y síncope. Una masa que obstruía el ventrículo derecho, el tronco pulmonar y la arteria pulmonar derecha llevó a la sospecha de embolismo pulmonar.

RESUMO Os sarcomas da artéria pulmonar são extremamente raros devido ao seu crescimento lento e silencioso, o diagnóstico normalmente é tardio e são de mal prognóstico. Apresentamos um caso de uma mulher de 33 anos de idade com história de dispneia dor torácica e desmaios. Uma massa que obstruía o ventrículo direito, tronco pulmonar e artéria pulmonar direita levou à suspeita de embolia pulmonar

Validación de la escala europea de autocuidado en la falla cardiaca / Validation of the European Heart Failure Self-care Behaviour Scale

Resumen Introducción: La falla cardiaca es una enfermedad frecuente, con exacerbaciones relacionadas con la capacidad para seguir las indicaciones médicas Objetivo: Se pretende determinar la confiabilidad y la validez interna de una escala de autocuidado en la ciudad de Bogotá, Colombia. Materiales y métodos: Estudio transversal, en el que se exportaron los registros de los pacientes del programa de falla cardiaca, se identificaron las características generales de los ítems de la escala, fueron transformados a valores de 0 - 100 y se estimó la confiabilidad por el coeficiente Alfa de Cronbach (> 0,7) así como la validez interna por coeficiente de correlación intraclase para las medidas únicas y el promedio (p < 0,05). Resultados : Se revisaron 144 registros, el sexo femenino aportó el 30,6%; la hipertensión arterial el 54,9%, la fibrilación auricular el 35% y las alteraciones del funcionamiento tiroideo el 31%, fueron las comorbilidades más frecuentes; solo el 9,2% se encontraba con clase funcional baja; la escala mostró apropiados valores de confiabilidad y validez interna, el puntaje total de autocuidado se encontró en 48,30; los ítems con puntaje más alto fueron ''me vacuno contra la gripe todos los años'' (61,19 puntos) y ''me peso cada día'' (60,04 puntos); los ítems con puntaje más bajo fueron ''tomo toda la medicación como me han indicado'' (29,66 puntos), y ''realizo dieta baja en sal'' (38,59 puntos). Conclusiones : La escala de autocuidado demostró apropiadas la confiabilidad y la validez para la determinación del autocuidado en los pacientes con falla cardiaca en la ciudad de Bogotá, Colombia; se requieren estudios adicionales que permitan determinar la validez concurrente con otros instrumentos y diseños prospectivos.

Abstract Introduction: Heart failure is a frequent condition, with exacerbations related to the ability to follow medical indications. Objetive: The goal is to determine the reliability and internal validity of a self-care scale in the Colombian city of Bogotá. Material and methods: Cross-sectional study. Te registers of the heart failure program were exported, general characteristics of the scale items were identified, they were transformed into 0-100 values and Cronbach's alpha coefficient (>0.7) was estimated, as well as the internal validity by intraclass correlation coefficient for unique measurements and the average (p < 0.05). Results: 144 registers were reviewed, 30.6% of whom were female; most common comorbidities were arterial hypertension with 54.9%, atrial fibrillation with 35% and alterations of the thyroid function with 31%; only 9.2% presented low functional class. The scale showed appropriate confidence and internal validity values, the total self-care score was 48.30. Items with the highest score were ''I get a flu shot every year'' (61.19 points) and ''I weigh myself every day'' (60.04 points); items with the lowest score were ''I take all medication as instructed'' (29.66 points) and ''I follow a low-salt diet'' (38.59 points). Conclusions: The self-care scale revealed appropriate confidence and internal validity for determining self-care in patients with heart failure in the city of Bogotá, Colombia. Further research is required to determine the concurrent validity with other instruments and prospective designs.

Inhibitory effects of an extract of fruits of Physalis peruviana on some intestinal carbohydrases / Evaluación in vitro del efecto de un extracto de frutos de Physalis peruviana sobre algunas carbohidrasas intestinales

Physalis peruviana is an Andean specie whose fruits are eaten as food and also has been reported in Colombian folk medicine for diabetes mellitus treatment. In addition, previous pharmacological studies on diabetic Wistar rats, an extract of P. peruviana fruits has been showed antidiabetic activity. In order to deepen in P. peruviana action mode as antidiabetic, in this investigation were determinate the Inhibitory Concentrations 50 (IC50) of P. peruviana fruits crude extract on alpha glucosidase from S. cerevisiae and from intestinal rat powder, on maltase and alpha amylase enzymes. The kinetic behavior of the extract on each enzyme was also investigated, and the enzyme constant (Km) and maximum rate (Vmax) were determined. Extract of fruits of P. peruviana showed different IC50 for alpha glucosidase from S. cerevisiae and intestinal rat powder, suggesting greater affinity for the enzyme of mammalian source (4114.7 and 3552.7 µg/mL, respectively). For maltase, the IC50 was close to that obtained for alpha glucosidase (4191.0 µg/mL) while for alpha amylase, the extract exhibited the highest inhibition (IC50: 619.9 g/mL). Regarding kinetic behavior, the extract showed competitive inhibition on alpha-glucosidase and maltase, and on the non-competitive type of alpha amylase. These suggest that inhibition of intestinal carbohydrases is one of the modes of action for the antidiabetic activity of fruits of P. peruviana.

Physalis peruviana es una especie andina, cuyos frutos además de ser usados como alimento, son empleados en la medicina tradicional para el tratamiento de la diabetes mellitus. Además, estudios farmacológicos previos en ratas Wistar han demostrado actividad antidiabética de extractos de frutos de P. peruviana. Con el fin de profundizar en el modo de acción de la actividad antidiabética de los frutos de P. peruviana, en la presente investigación se determinó la concentración inhibitoria 50 (CI50) del extracto crudo de frutos de P. peruviana, sobre las enzimas alfa glucosidasa obtenida de S. cerevisiae y de polvo intestinal de rata, maltasa y alfa amilasa. El comportamiento cinético del extracto sobre cada una de las enzimas también fue investigado y la constante enzimática (Km) y la velocidad máxima (Vmax) fueron determinadas. El extracto de frutos de P. peruviana, mostró diferentes valores de CI50 para alfa glucosidasa obtenida de S. cerevisiae y para la obtenida de polvo intestinal de rata, sugiriendo una mayor afinidad por la enzima de origen mamífero (4114,7 and 3552,7 µg/mL, respectivamente). Para maltasa la CI50 fue cercana a la obtenida para alfa glucosidasa (4191,0 µg/mL), mientras para alfa amilasa, el extracto presentó la mayor inhibición (CI50: 619,9 g/mL). Respecto al comportamiento cinético, el extracto mostró inhibición de tipo competitiva sobre alfa glucosidasa y maltasa y no competitiva sobre alfa amilasa. Los resultados sugieren que la inhibición de carbohidrasas intestinales es uno de los modos de acción de los frutos de P. peruviana como agente antidiabético.