Un análisis cualitativo de las políticas de preparación en salud en Chile

[RESUMEN]. Objetivo. Analizar las políticas de preparación en salud en Chile, e identificar sus fortalezas y debilidades. No hay hasta la fecha otros estudios que analicen las políticas de preparación en el país. Métodos. Se llevó a cabo una revisión documental y entrevistas semiestructuradas con expertos en prepara- ción y respuesta a emergencias para identificar el marco normativo, los actores principales, y las fortalezas y debilidades de las políticas de preparación en salud. Resultados. Se encontraron 103 normas y se entrevistó a 7 personas expertas en preparación. Las normas revisadas y las entrevistas demuestran que Chile se encuentra en un momento de transición entre el antiguo Sistema Nacional de Protección Civil y el nuevo Sistema Nacional de Prevención y Respuesta ante Desas- tres. Solo tres normas tenían relación directa con salud, pero la normativa de preparación prevé el abordaje de cualquier amenaza desde un conjunto de actores multidisciplinario. Los expertos valoraron de manera positiva el sistema chileno, si bien hubo consenso en algunas debilidades que deben corregirse. La principal fortaleza es la experiencia en respuesta a desastres, así como sus mecanismos de coordinación. Las princi- pales deficiencias se detectaron en la comunicación de riesgo, la mitigación, la preparación y evaluación, y los recursos humanos. Conclusiones. Chile cuenta con un marco normativo sólido con una perspectiva multiamenaza y un conjunto de instituciones multisectoral. El nuevo Sistema Nacional de Prevención y Respuesta ante Desastres debe apoyarse en sus fortalezas para corregir las debilidades que limitan su capacidad de preparación y respuesta ante emergencias.

[ABSTRACT]. Objective. Analyze health preparedness policies in Chile and identify their strengths and weaknesses. No other studies to date provide an analysis of the country's preparedness policies. Methods. A desk review and semi-structured interviews with experts in emergency preparedness and res- ponse were conducted to identify the regulatory framework, key actors, and the strengths and weaknesses of health preparedness policies. Results. The researchers identified 103 standards and interviewed seven preparedness experts. The reviewed standards and interviews show that Chile is in a transitional phase between the old National Civil Protection System and the new National Disaster Prevention and Response System. Only three standards were directly related to health, but the preparedness regulations provide for a multidisciplinary set of actors to address any threat. The experts gave a positive assessment of the Chilean system, although they agreed that certain weaknesses must be corrected. The country’s main strength is its disaster response experience, along with its coordination mechanisms. The main shortcomings include risk communication, mitigation, preparedness and assessment, and human resources. Conclusions. Chile has a solid regulatory framework with an all-hazards approach and a set of multisectoral institutions. The new National Disaster Prevention and Response System must build on its strengths to correct the weaknesses that limit its emergency preparedness and response capacity.

[RESUMO]. Objetivos. Analisar as políticas de preparação na área de saúde no Chile e identificar seus pontos fortes e fracos. Até o momento, não há outros estudos que analisem as políticas de preparação no país. Métodos. Foi realizada uma análise documental e entrevistas semiestruturadas com especialistas em prepa- ração e resposta a emergências para identificar a estrutura regulatória, os principais atores e os pontos fortes e fracos das políticas de preparação na área de saúde. Resultados. Foram encontradas 103 normas, e 7 especialistas em preparação foram entrevistados. As nor- mas analisadas e as entrevistas demostram que o Chile está em um momento de transição entre o antigo Sistema Nacional de Proteção Civil e o novo Sistema Nacional de Prevenção e Resposta a Desastres. Apenas três normas estavam diretamente relacionadas à saúde, mas a legislação de preparação prevê a abordagem de qualquer ameaça por um conjunto multidisciplinar de atores. Os especialistas fizeram uma avaliação positiva do sistema chileno, embora tenha havido consenso sobre alguns pontos fracos que precisam ser corrigidos. O principal ponto forte é a experiência na resposta a desastres, bem como seus mecanismos de coordenação. Os principais pontos fracos foram detectados na comunicação de riscos, na mitigação, na preparação e avaliação e nos recursos humanos. Conclusões. O Chile tem uma sólida estrutura regulatória, com uma perspectiva de múltiplas ameaças e um conjunto de instituições multissetoriais. O novo Sistema Nacional de Prevenção e Resposta a Desastres deve se basear em seus pontos fortes para corrigir as deficiências que limitam sua capacidade de preparação e resposta a emergências.

NMR analysis: potential and challenges as a homeopathic basic research tool

Homeopathic ultra-diluted solutions surpass the threshold of matter dispersion and, consequently, their chemical constitution is similar to inert solvent. Nevertheless, randomized clinical trials have shown that the clinical effects of these homeopathic medicines are superior to placebo1. Nuclear magnetic resonance (NMR) is one of the most promising techniques to detect physicochemical alterations induced by homeopathic procedures2,3. Aims: To investigate T2 NMR relaxation times of Zincum metallicumand lactose dynamized samples. Methodology: Zincum metallicumsamples were ground until 6dH using lactose as an excipient. Subsequently, these samples were dynamized with ultrapure water to produce 8dH, 9dH, 10dH,and 11dH. Lactose dynamized samples (6dH-11dH) were used as control. Aliquots of 540µl of each sample were diluted with 60µl of deuterated water (D2O) in 5mm tubes. The analyses were carried out in Bruker Ascend TM 500MHZ spectrometer at 288 K. Results and discussion: The Zincum metallicumand lactose T2 relaxation times were very similar, except for Zincum metallicum8dH, which presented a value of 1.226 in comparison to 1.036 of lactose 8dH. The following T2 values were registered: 1.287 -9dH; 1.413 -10dH; 1.467 -11dH, and 1.303 -9dH; 1.400 ­10dH; 1.350 -11dH, for Zincum metallicumand lactose, respectively. The differences detected in 8dH samples are probably due to the presence of lactose in the first dilution step, in which 1 part of the 6dH triturated mixture was diluted in 9 parts of water, to prepare 7dH. Following this homeopathic procedure, 8dH solutions remain around 1% of lactose which could be influenced by the T2 values registered.Conclusion: These preliminary results showed the possibility to apply the NMR technique to evaluate the influence of dynamization in the relaxation parameters. Further studies should be carried out with other potencies and/or other homeopathic substances, in addition to the evaluation of T1 and the T1/T2 parameters, as previously described by other groups.

Macrophage activity regulation by high dilution of aspirin and its possible mechanism

Under LPS-stimulus, platelets can activate macrophagesby a cell-to-cell contact or through cytokine degranulation. Rebound effects of anti-thrombotic agents, such as prostanoids and COX inhibitors can lead to thrombosis, infarct, and stroke. Aspirin has been prescribed for decades due to its powerful antiplatelet action, but it is also related to paradoxical effects such as withdrawal syndrome peaks, resistance, and thrombogenesis. Ultra-diluted aspirin can also produce the same effect in one hour, regardless of Cox-2, by still unknown pathways. Antithrombotic effects of aspirin are also reversed by its high dilutions.Aims: This study aims to characterize the effects of aspirin 15cH on macrophages challenged with LPS, a Cox-2 activator.Methodology: RAW 264.7 macrophages were sown in 24 wells plates using R10medium, boosted with 1µg/ml LPS,and treated with aspirin 15 cH and controls. The activity was evaluated after 24 hours. Supernatants were evaluated for cytokines, nitric oxide, and dielectric oscillations, through solvatochromic dyes (Cartwright's method).Results and discussion: macrophage spreading was increased by aspirin 15 cH, anLPS-like effect. Paradoxically, a significant reduction of this effect was noted when both, LPS and aspirin 15 cH, were added. Succussed water reversed the effect of LPS, leading to TNF (p<0.05) production close to baseline levels. Also, the single treatment with succussed water inhibited IL-10 production (p<0.05), but aspirin 200 µg/mL (positive control) highly increased it (p<0.0001), showing the validity of the model. Nitric oxide production was strengthened by LPS presence (p<0.0001), as expected, but partially downregulated after treatment with aspirin 200 µg/mL, water and succussed water. A pilot study with solvatochromic dyes showed no significant difference among treatments.Conclusion: The main data suggest that aspirin 15 cH increases macrophage activity but presents a paradoxal effect when mixed with LPS. On the other hand, succussed water itself has modulatory effects on macrophages.

High Dilutions of Drugs show Distinct Variation from each other in their Electronic Spectra

Drugs at high dilution (HD) produce therapeutic effect on man, animals and plants. Experimental evidence shows that free water molecules and hydrogen bond strength of OH groups constitute the physical basis of HDs which are otherwise devoid of original drug molecules. HDs are produced in aqueous EtOH by serial dilution of a substance with mechanical agitation or succussion in each step, and are called potencies. Three potencies 6 cH, 12 cH and 30 cH of two drugs Anacardium orientale and Natrum muriaticum(NaCl) and their mother tincture (MT) are used in this study. Electronic spectra of these MTs and potencies, all in 90% EtOH, were taken in the wavelength region of 190 nm ­350 nm. The objective is to find out any additional physical-chemical entities in potencies besides the aforesaid two factors. It was reported earlier that charge transfer (CT) interaction accompanies potentization of drugs. This study focused on the CT interaction. The results indicate that spectral pattern and absorbance intensities of the test samples vary from each other. Natm 6cH (absorbance 0.30 at 196.53nm), 12cH (abs. 0.06 at 196.53nm) and 30cH (abs. 1.32 at 196.5nm). Anac 6cH (abs. 0.33 at 203nm), 12cH (abs. 0.61 at 208nm) and 30cH (abs. 0.09 at 200.67nm). The spectrum of each potency shows two peaks. The 2nd peak at higher wave length belongs to CT interaction. Anac 6cH suc, 7cH unsuc. Insersections at 197.14nm with abs. 0.05, and 290nm with abs. 0.01. Anac 12cH suc, 13cH unsuc. Intersections at 196.93nm with abs. 0.06, and 273nm with abs. 0.00. Anac 30cH suc, 31cH unsuc. Intersections at 194.42nm with abs. -0.05, 238.03nm with abs. -0.01, 252.15nm with abs. -0.002, and 261nm with abs. 0.004. Natm 6cH suc, 7cH unsuc. Intersection at 199.44nm with Abs -0.11. Natm 12cH suc, 13cH unsuc. Instersection at 200.48nm with abs. -0.11. Natm 30cH suc, 31cH unsuc. Intersection at 204.24nm with abs. -0.08. Potentization involves CT interaction in consecutive potencies. Water and EtOH do not form a homogeneous mixture and have aggregates of EtOHand water molecules. CT interactions occur in these individual aggregates and are mostly inter molecular within EtOH or water. These aggregates vary from each other in the test samples. The spectra of test samples were analysed for margin of error (MOE). The MOE is very small (0.001-0.002%), and for this reason the difference between the spectra is significant. Besides that the intersection between consecutive spectra vary in number and position. It is concluded that water and EtOH aggregates and their relative distribution constitute additional physical-chemical basis of potencies.

Study of germination efficiency and temperature/drowning resistance in some ornamental plants treated with ultra high dilute compounds

The ultra-high dilutions (UHDs) can be used for decreasing stress conditions causing by climate variations. The present research investigated the effects of ultra-highdilutions (UHDs) on some ornamental plants, germination, and hormonal variations.Methods: In order to study the effect of UHDs (Calendula officinalisCalen. andArnica montanaArn.) on the physiological, primary metabolite, and hormonal variations of theOryza sativa L. (rice), 104 experiments were designed and statistically analyzed using the Design Expert 7.0.1 software over the general factorial design methodology. Two qualitative factors, including the UHDs/placebo usage and the type of plant usage, and two quantitative factors, including temperature and irrigation, were studied. The validated analysis was subjected to more extended studies on the variations in physiological growth, carbohydrate, protein content, and levels of plant hormones, including gibberellic acids, indole acetic acid, abscisic acid, and salicylic acid.Results: The statistical analysis resulted in a prediction model which was more than 75% correlates with experimental results. The results showed that the UHDs increased the carbohydrate and protein content of seedlings. Also, compared to placebo, the levels of hormones GA3 and IAA in all samples increase, and the amount of GA4 decreases. The amount of ABA and SA hormones inS. officinalisincreased under UHDs treatment while decreasing in the other two samples.Conclusion: The use of UHDs leads to an increase in the production of carbohydrate and protein content. Moreover, it causes significant variations in the growth-inducing hormone and increases the tolerance of seeds under higher/lower temperatures and draught/drowning. The results of this study open up a window to reduce germination survival and increase their resistance to sudden climate change.

Errores de enfermería en la preparación y administración de medicamentos / Nursing errors in drug preparation and administration

La preparación y administración de medicamentos, es parte importante en el proceso de recuperación de la salud, se destaca entre las funciones relevantes de los profesionales y auxiliares de enfermería, incluye etapas críticas que deben garantizar la correcta y segura administración de los mismos. Existe carencia de revisiones bibliográficas que aborden la problemática de los errores de enfermería, aunque, investigadores en todo el mundo, han estudiado el impacto que genera el error en la preparación de medicamentos, siendo este uno de los principales problemas en el campo de la enfermería. Objetivo: conocer la relación entre la calidad técnica en la preparación de medicamentos, identificando características y tipos, con la frecuencia en los errores de enfermería. Material y Métodos: se realizó revisión bibliográfica, identificando once artículos científicos en las bases de datos PubMed, Scopus y SciELO. Se incluyeron estudios originales y observacionales, excluyendo revisiones sistemáticas, estudios duplicados y sin acceso libre a la información. Conclusión: los factores predominantes en los errores de enfermería, se deben a la confusión al momento de elegir el fármaco, error en el cálculo de dosis, sobrecarga de trabajo y déficit de conocimiento...(AU)

Efeitos de Preparações Psicológicas Pré-Cirúrgicas sobre o Estresse e a Ansiedade de Meninos e Meninas / Efectos de la preparación psicológica prequirúrgica sobre el estrés y la ansiedad en niños y niñas / Effects of pre-surgical psychological preparations on stress and anxiety in boys and girls

Resumo A preparação infantil para a cirurgia é foco de atenção da equipe de saúde pelo potencial traumático dos procedimentos cirúrgicos e por ser fonte de estresse e ansiedade na infância. O impacto de três preparações psicológicas pré-cirúrgicas sobre o estresse e a ansiedade de crianças submetidas a cirurgias eletivas foi avaliado. A amostra foi composta por 80 crianças de um hospital infantil, a qual foi dividida em dois blocos de 40 sujeitos de acordo com o sexo e alocados aleatoriamente num dos quatro grupos: controle, preparação por informações verbais, preparação por jogo com kit de preparação ou preparação por vídeo informativo. O estresse e a ansiedade foram mensurados por meio da Escala de Stress Infantil (ESI) e do Inventário de Ansiedade Traço-Estado (Idate-c). A intervenção foi implementada em três etapas distintas: (a) aplicação da ESI e do Idate-c antes da preparação, no dia anterior a cirurgia; (b) a preparação propriamente dita nos grupos submetidos aos diferentes programas de preparação, também no dia anterior, e (C) a reaplicação da ESI e do Idate-c no dia da cirurgia. Os dados foram analisados por meio de equações de regressão simultâneas, e as estimativas são apresentadas em termos de diferença média padronizada e erro-padrão. Os resultados permitem inferir que a preparação com o vídeo reduziu o estresse (Tvídeo1= -38 ± .18) e a ansiedade (Tvídeo2 = - .54 ± .27), especialmente entre os meninos (TvídeoM1 = - .66 ± .25; TvídeoM2 = - .71 ± .38). Implicações práticas para a preparação psicológica das crianças em situação pré-cirúrgica e limitações da pesquisa são discutidas.

Resumen La preparación infantil para una cirugía es el centro de atención del equipo de salud debido al potencial traumático de los procedimientos quirúrgicos y debido a que es una fuente de estrés y ansiedad en la infancia. En la presente investigación se evaluó el impacto de tres formas de preparación psicológica prequirúrgica ante el estrés y la ansiedad de los niños sometidos a cirugía electiva. La muestra estuvo constituida por 80 niños de un hospital infantil, divididos en dos bloques de 40 sujetos según el sexo, y asignados al azar a uno de cuatro grupos: control, preparación a través de información verbal, preparación a través de juego con el kit de preparación, o preparación a través de video informativo. Se utilizó la Escala de Estrés Infantil (ESI) y el Inventario Ansiedad Estado-Rasgo para niños (STAIC) para medir el estrés y la ansiedad de los niños. La intervención se llevó a cabo en tres etapas distintas: (a) aplicación del ESI y el STAIC antes de la preparación, el día anterior a la cirugía; (b) preparación propiamente dicha en los grupos de los diferentes programas de preparación el día anterior; y (C) reaplicación del ESI-C y el STAIC el día de la cirugía. El análisis de los datos se hizo mediante ecuaciones de regresión simultáneas y las estimaciones se presentan por medio de la diferencia entre medias estandarizada y de la desviación estándar. Los resultados permiten inferir que la preparación con video redujo el estrés (Tvideo1 = -.38 ± .18) y la ansiedad (Tvideo2 = -.54 ± .27), especialmente en los niños (TvideoMl = -.66 ± .25; TvideoM2 = -.71 ± .38). Al final se discuten las implicaciones prácticas para la preparación psicológica de los niños en situación prequirúrgica y las limitaciones de la investigación.

Abstract Child preparation for surgery is a focus of attention of health teams due to the traumatic potential of surgical procedures and for being a source of stress and anxiety in childhood. The impact of three pre-surgical psychological preparations on stress and anxiety of children undergoing elective surgery were evaluated. The sample consisted of 80 children from a children's hospital, divided into two blocks of 40 subjects according to gender and randomly assigned to one of four groups: control, preparation by verbal information, preparation by game and preparation kit or preparation by informational video. Stress and anxiety were measured using the Escala de Stress Infantil (ESI) (Child Stress Scale) and the State-Trait Anxiety Inventory for Children (STAIC). The intervention was implemented in three distinct stages: a) application of ESI and STAIC before preparation, the day before surgery; b) actual preparation, in groups submitted to different preparation programs, also on the previous day; and c) reapplication of ESI and STAIC on the day of surgery. Data were analyzed using simultaneous regression equations, and estimates are presented in terms of standardized mean difference and standard error. Results allow to infer that preparation by video reduced stress (Tvideo1 = -0.38±0.18) and anxiety (Tvideo2 = -0.54±0.27), especially among boys (TvideoM1 = -0.66±0.25; TvideoM2 = -0.71±0.38). Practical implications for the psychological preparation of children in pre-surgical situations and the limitations of this study are discussed.

Técnicas para el monitoreo de los niveles de profundidad anestésica / Techniques to control the anesthetic depth levels

Se presentan aspectos esenciales del proceso de clasificación de los niveles de profundidad anestésica mediante señales electroencefalográficas. Se fundamenta el mencionado proceso desde un estudio exhaustivo que permitió precisar sus principales referentes. Finalmente, se realiza una caracterización de su estado actual, teniendo en cuenta los principales índices de profundidad anestésica y tipos de monitores comercializados(AU)

Essential aspects of the classification process of anesthetic depth levels are presented by means of electroencefalographic signs. The abovementioned process is supported from an exhaustive study that allowed to specify its main aspects. Finally, a characterization of its current state is carried out, taking into account the main indexes of anesthetic depth and types of marketed displays(AU)

Tecnologias da informação na gestão de recursos humanos: Aplicações informáticas para a elaboração de escalas / Information technology in human resource management: Computer applications for the preparation of scales

Os hospitais são organizações nas quais os recursos humanos são uma componente extremamente importante, não só por serem o seu ativo mais valioso mas também por consumirem a maior parcela dos seus recursos financeiros, o que obriga à implementação de medidas que contribuam para a eficiência. A obrigatoriedade de cumprir o previsto no artigo 14º do Decreto-Lei nº 259/98 de 18 de agosto, que na prática exigia o controlo biométrico da assiduidade, abriu uma janela de oportunidade para o desenvolvimento de aplicações informáticas que não se limitassem exclusivamente ao estabelecido na legislação, mas que apontassem para soluções integradas de gestão, incluindo módulos como o de elaboração de escalas, um real instrumento de trabalho facilitador para os gestores, nomeadamente do enfermeiro gestor operacional. Os resultados do estudo de natureza descritiva de abordagem quantitativa, permitiu identificar alguns aspetos e dimensões nas aplicações informáticas para a área da gestão de recursos humanos, respondendo assim às necessidades dos enfermeiros gestores operacionais. Foi aplicado um instrumento de colheita de dados aos enfermeiros gestores operacionais de uma instituição de saúde de grande dimensão e complexidade, gestores com experiências diferentes nos métodos utilizados para a elaboração de escalas, fator responsável por diferenças estatisticamente significativas encontradas em 18 dos 60 itens relativos a aspetos/dimensões que deveriam ser considerados na construção e desenvolvimento das aplicações informáticas. Os principais resultados obtidos levaram-nos a concluir que as aplicações informáticas devem ter um desenvolvimento progressivo e contínuo, incorporando novas funcionalidades que foram e virão a ser identificadas, contribuindo assim para a criação de soluções que integrem múltiplas dimensões da gestão de recursos humanos.

La escala cincuentamilesimal (LM) / The cincuentamilesimal scale (LM)

Después de 12 años de práctica exclusiva y literal con la técnica de la escala cincuentamilesimal (LM o Q) de potencias, descrita en la 6a edición del Organon, elautor analiza sus diferencias básicas con las directrices de la 5a edición de dicha obra. Describe la manera de administrar el medicamento, sus ventajas y desventajas, y enumera todas las conductas posibles durante el uso de esta técnica, la cual, concluye, es la que mejor se encamina para lograr una curación rápida y suave, ideal máximo de Samuel Hahnemann. (AU)

After 12 years of literal and exclusive practice with the 50 millesimal scale according to the 6th edition of the Organon, the autor analyses its basic differences with the guidelines of the 5th edition. He describes the posible procedures during the usage of this kind of medication; it´s advantages, disvantages and enumerates all the possible conducts of this technique, therefore concluding that this is the one that leads to a rapid and mild cure. Samuel Hahnemann´s maximum ideal (AU)

Revisión bibliográfica no sistemática sobre la escala cincuentamilesimal / Non-systematic bibliographic review on the fifty-thousand-scale scale

En cuanto a la preparación y la dosis del remedio homeopático Hahnemann hizo modificaciones en busca de una curación suave, pronta y duradera culminando con la propuesta de la escala cincuentamilesimal (LM), expuesta por primera vez en la VI edición del Órganon de la medicina; tuvo la oportunidad de experimentar y comprobar mucho más tiempo con la escala centesimal (C) y se calcula que manejó la escala LM en sus últimos cinco años de práctica médica, experiencia que quedó consignada en sus libros de Casos de París. Este fue uno de los últimos aportes de Hahnemann en la Homeopatía, con la intención que el medicamento fuera administrado según la individualidad del enfermo, buscando disminuir el tiempo de tratamiento y minimizar la agravación homeopática, alcanzando con esta técnica su método "casi ideal", volviéndose referencia puntual para que los médicos homeópatas pudieran usarla en forma más continua. Se realizó una revisión no sistemática de la literatura para la recolección de la información que existe actualmente relacionada con el tema de la escala LM con el fin de aportar a los estudiantes de homeopatía, así como a los médicos homeópatas ya formados, que sirva de base para proponer temas de estudio y futuras investigaciones a partir de la misma.

Preparation and scale up of extended-release tablets of bromopride

Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm) software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm) software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

A reprodutibilidade do processo de fabricação de comprimidos e o controle das suas propriedades farmacotécnicas depende da otimização dos aspectos de formulação e dos parâmetros de processo. O planejamento de experimentos como o Desenho de Experimentos (DOE) pode ser utilizado para acelerar a produção desta formulação, em particular, para a obtenção de comprimidos de liberação prolongada. Formulações de bromoprida são comercializadas sob a forma de péletes de liberação prolongada, o que torna o produto caro e de difícil fabricação. O objetivo deste estudo foi preparar novas formulações de bromoprida de liberação prolongada na forma de comprimidos e desenvolver modelos matemáticos visando ao escalonamento destas formulações, controlando o peso e a dureza dos comprimidos durante a fabricação, de acordo com a 34ª Edição da USP. Estudos de DOE foram realizados utilizando o software Minitab(tm). Diferentes combinações de excipientes foram avaliadas visando à obtenção dos comprimidos de liberação prolongada de bromoprida. No estudo de scale-up, coletaram-se e mediu-se a influência das variações nos parâmetros da máquina de compressão. Processaram-se os dados obtidos pelo software Minitab (tm), gerando equações matemáticas aptas para a previsão do comportamento de compactação do pó em escala industrial. Os comprimidos obtidos apresentavam características adequadas em termos de liberação sustentada, sendo a cinética de liberação estabelecida utilizando modelos matemáticos, indicando que esta formulação pode ser uma substituta aos péletes de bromoprida atualmente comercializados.

Validación de un método por cromatografía líquida de alta resolución (HPLC) para la determinación de ivabradina en comprimidos / Validation of a high resolution liquid chromatography method (HPLC) for the determination of ivabradine tablets

Se presentan los resultados obtenidos en la validación de un método analítico por cromatografía líquida de alta resolución, para la determinación de ivabradina en comprimidos, el cual se diseñó para identificar y cuantificar a dicho analito, con la utilización de una columna RP-18 (150 x 4,6 mm) 5 µm y un detector UV-Vis a una λ: 285 nm. Dicho método se empleará para el control de la calidad y estabilidad de ivabradina comprimidos. El método fue validado siguiendo una metodología de trabajo de acuerdo a los lineamientos de la Conferencia Internacional sobre Armonización de Requisitos Técnicos para el Registro de Medicamentos de uso humano, Validación de procedimientos analíticos (ICH Q2), obteniendo los siguientes resultados: linealidad (r2 = 0,999), precisión Desviación estándar relativa (DSR) = 0,67 % para comprimidos del lote piloto y DSR=0,31% para comprimidos del lote comercial) y exactitud recuperación media=100,2%, demostrando de esta manera que el método propuesto es aplicable a la dosificación de ivabradina en comprimidos, tanto en el análisis del producto terminado cómo en los estudios de estabilidad.

La calidad de los medicamentos fabricados industrialmente en España entre 1850 y 1950. Revisión de los requerimientos de calidad establecidos para los medicamentos en la legislación oficial durante este período / No disponible

Objetivo: Estudiar la evolución de los requerimientos de calidad establecidos en los expedientes de solicitud de autorización de los medicamentos fabricados industrialmente desde 1850 a 1950 y su relación con la calidad de los mismos, teniendo en cuenta la influencia del contexto político-social. Material y métodos: Análisis de la legislación publicada en España referente al Registro Farmacéutico desde 1850 hasta 1950, comparando las referencias a la calidad de cada documento con las de la legislación inmediatamente anterior destacando lo que representa un avance. Consulta de revistas y documentos no publicados. Discusión de la evolución de la calidad de los medicamentos relacionándola con el contexto político-social del país. Resultados y conclusiones: Hasta 1855 no se podía hablar de medicamentos sino de remedios secretos. La Ley de 28 de Noviembre de 1855 estableció la obligación de declarar los remedios a la Autoridad Sanitaria. Posteriormente el Real Decreto de 1919 estableció el Registro Farmacéutico y la asignación del nº de registro. El Real Decreto de 1924 lo actualizaba sin avanzar en la calidad. Siguió un estancamiento tanto en normativa como en calidad, debido a la guerra civil y al bloqueo internacional. La Ley de Bases de 1944 anunciaba una reforma que aún tardó en producirse. En resumen período largo y cambiante con bastantes avances en organización y pocos en exigencias de calidad. Los expedientes de registro son un elemento de referencia fundamental para conocer la calidad de un medicamento en un momento determinado(AU)

Objectives: The aim is to study the evolution of quality requirements in the application file for approval of drug products and their relationship with the quality of industrially manufactured drugs between 1850 and 1950, taking into account the influence of political and social context. Materials and methods: Analysis of the legislation published in Spain referring to pharmaceutical registration from 1850 to 1950, comparing the quality benchmarks to highlight the improvement. Search of information in journals and unpublished documents. Discussion on quality progress related to the socio-political context of the country. Results and conclusions: Until 1855 drugs did not exist as such, there were only secret remedies. The Law of November 28, 1855 established the obligation to declare the remedies to the Health Authority. Since then there was an evolution until the Royal Decree of 1919 established the official register of medicines and assigned a registration number to each medicine. The Royal Decree of 1924 updated the 1919 Decree but no advance was done referring to quality. Then a period of stagnation followed in both the rules of registration and the quality due to the civil war and the international blockade. A Law Reform was announced in 1944 but it took a long time to be done. Summarizing: It was a long period, with advances in organization and little progress in quality requirements in the pharmaceutical registration. When quality requirements increased, drug quality also did. Application files for registration are an essential reference to know the quality at some time(AU)

Sete semanas de treinamento melhoram a resistência aeróbia e a potência muscular de jogadores de futebol / Seven weeks of training improve the endurance and muscle power in soccer players

O futebol se caracteriza pela alternância de períodos de atividades de curta duração e alta intensidade intercalada por momentos de recuperação. Desta forma há uma exigência de desenvolvimento de diversas capacidades biomotoras ao longo de uma temporada. O objetivo desse estudo foi avaliar e discutir os efeitos de sete semanas de treinamento nas capacidades biomotoras. Participaram deste estudo 15 atletas profissionais de futebol com idade média de 25,3±3,8 anos, massa corporal de 76,6±7,5 Kg, estatura de 1,77±0,1 m e percentual de gordura de 11,7% que disputaram o Campeonato da terceira divisão nacional. Os conteúdos de treinamento foram divididos em funcional e neuromuscular. Todos os atletas foram submetidos a dois testes máximos: Yo-Yo Edurance Test Nível 1 e salto horizontal em dois momentos distintos (M1): início do programa de treinamento e (M2) após o término do período preparatório. Os dados coletados foram armazenados em banco computacional, produzindo-se informações no plano descritivo (medidas de centralidade e dispersão) e, no inferencial, após assumir a normalidade dos dados pelo teste de Shapiro-Wilk, utilizou-se o teste t de Student para amostras pareadas, a fim de se verificar as mudanças ocorridas nas capacidades entre os momentos avaliados. O principal resultado, quanto ao indicador funcional, apresentou melhora na distância percorrida no Yo-Yo Endurance Test Nível 1 de M1 (2376,0±202,4 m) para M2 (2581,3±173,1 m). O indicador neuromuscular apontou melhora no salto horizontal de M1 (2,44±0,1 m) para M2 (2,48±0,1 m). Assim, concluímos com os resultados encontrados que a metodologia utilizada no presente estudo foi considerada eficaz em causar alteração sobre o indicador funcional, bem como no neuromuscular durante o período estudado.

Soccer is characterized by alternating periods of activities of short duration and high intensity interspersed with moments of recovery. Thus there is a demand of development of various physical capacities. The aim of this study was to evaluate and discuss the effects of seven weeks of training on the physical capacities. 15 professionals soccer players with an average age of 25, 3±3,8, weigth of 76,6±7,5, height of 1,77±0,1 m and body fat of 11,7% were included in this study and who dispute the third division of national championship. The training program was divided into functional and neuromuscular. All the athletes were submitted to maximal tests: Yo-Yo Edurance Test Level 1 andStanding long jump test which were performed before the training program (M1) and after seven weeks (M2). The data collected were kept in a computer, producing the information in the plan descriptive (measures of centrality and dispersion) and, inferentially, after taking the data for normality by the Shapiro-Wilk, we used the Student t-test for paired samples, in order to verify the possible changes in the capacities between the both moments. The main results, as the functional indicator, showed improvement on the cover distance in the Yo-Yo Endurance Test Level 1 from M1 (2376,0±202,4 m) to M2 (2581,3±173,1 m). The neuromuscular indicator showed improvement in the Standing long jump test from M1 (2,44±0,1 m) to M2 (2,48±0,1 m). Thus, we conclude with the results found that the methodology used in this study was effective in causing change on the functional indicator, as well as in the neuromuscular indicator during the study period.

Pilotaje de un protocolo para la adecuación de la forma farmacéutica de la medicación oral al grado de disfagia, de los pacientes ingresados en un servicio de medicina interna / Monitoring of a protocol for the adequacy of the pharmaceutical form of the oral medication to the degree of dysphagia in patients hospitalized in an internal medicine service

Introducción: La vía oral es la forma de administrar medicación más cómoda, pero puede no ser segura. La disfagia es uno de los factores que dificulta la correcta alimentación y administración de la medicación. Objetivos: La mejora de la administración de la medicación oral en pacientes con disfagia, a través de la adecuación de la forma farmacéutica de los principios prescritos a las texturas toleradas. Métodos: Proyecto piloto de aplicación de un protocolo de disfagia, donde se incluyeron los pacientes ingresados en el Servicio de Medicina Interna-Los Montalvos durante 4 meses. Tras detectarse la sospecha de disfagia, se aplicaba un test de disfagia-viscosidad para conocer las texturas toleradas. Posteriormente se adecuaban las formas farmacéuticas y se indicaban las normas de manipulación de los fármacos para su correcta administración. Resultados: De los 627 pacientes ingresados se incluyeron 23 pacientes, con edad media de 85 años (σ ± 7,4). Las patologías implicadas en la disfagia fueron: demencia (65,2%); enfermedad cerebrovascular (30,4%) y enfermedad de Parkinson (4,4%). La textura óptima para la ingesta fue "pudin" en el 48,0%. Se revisaron 43 principios activos y se realizaron 134 intervenciones: En el 41% de ellas se facilitó la deglución mezclando el fármaco con los alimentos y en el 59% se utilizó la adición de agua y espesante. El 94% de las recomendaciones se consideraron adecuadas. Conclusión: La adecuación de las formas farmacéuticas al grado de disfagia repercute en la mejora de la calidad asistencial implementando la seguridad en los procesos de prescripción y administración de fármacos (AU)

Introduction: The oral route is the most convenient way of administering medication, although it may not be safe. Dysphagia is one of the factors rendering difficult a proper feeding and administration of medication. Objectives: to improve the administration of oral medication in patients with dysphagia by changing the pharmaceutical formulation of the principles prescribed to tolerable textures. Methods: Pilot project for the application of a dysphagia protocol that included the patients admitted to the Internal Medicine Unit at Los Montalvos Center for 4 months. After detecting the suspicion of dysphagia, a dysphagia-viscosity test was applied to know the tolerated textures. Then, the pharmaceutical formulations were adapted and the manipulation instructions for the drugs were indicated for their proper administration. Results: 23 out of 627 admitted patients were included, with a mean age of 85 years (σ ± 7.4). The pathologies implicated in dysphagia were: dementia (65.2%); cerebrovascular disease (30.4%), and Parkinson´s disease (4.4%). The best texture for drug intake was a "pudding" in 48.0%. 43 active ingredients were reviewed and 134 interventions were performed: in 41% of the cases, swallowing was made easier by mixing the drug with the food and in 59% water and a thickener were used. 94% of the recommendations were considered to be appropriate. Conclusion: the adaptation of the pharmaceutical formulations to the degree of dysphagia impacts on the improvement of healthcare quality by implementing safety in drug prescription and administration processes (AU)

Técnicas de remuestreo en la comparación de curvas de disolución de fármacos / Resampling techniques on the comparison of drug dissolution curves

De acuerdo con las directrices actuales (Guías EMEA y FDA/CDER) los ensayos de disolución son siempre necesarios y en consecuencia requeridos. Pueden servir para varios propósitos: (i) durante el desarrollo de un medicamento son utilizados como una herramienta para identificar los factores que influyen en la biodisponibilidad, (ii) en el control de calidad se utilizan para probar consistencia en la fabricación y para garantizar que los perfiles de disolución siguen siendo similares a los obtenidos con los lotes del ensayo clínico pivotal, además, (iii) en la inferencia de bioequivalencia subrogada el ensayo de disolución puede ser utilizado para demostrar similitud entre diferentes formulaciones de una sustancia activa y el producto de referencia. El interés de la normativa sobre la comparación de los perfiles está centrado en conocer cuál es el grado de similaridad de las curvas y disponer de una medida sensible a las diferencias grandes. Varios comités regulatorios han recomendado el factor de similaridad f2 como criterio para evaluar similaridad entre dos perfiles de disolución, por lo que su utilización está generalizada. El objetivo de este artículo fue desarrollar estudios teóricos y de simulación para evaluar por medio de intervalos de confianza bootstrap para f2, la similitud de los perfiles de disolución(AU)

According to the current Guidelines (EMEA and FDA/CDER) dissolution studies are always necessary and consequently required. Dissolution assays can serve several purposes: (i) during the development of a medicinal product a dissolution test is used as a tool to identify formulation factors that are influencing the bioavailability of the drug; (ii) in the quality control of scale-up and of production batches, a dissolution test is used to prove consistency in the manufacturing and to ensure that the dissolution profiles remain similar to those of pivotal clinical trial batches; furthermore, (iii) in bioequivalence surrogate inference a dissolution test can be used to demonstrate similarity between different formulations of an active substance and the reference medicinal product. Regulatory interest in dissolution profiles comparisons is in knowing how similar the curves are, and to have a measure sensitive to large differences at any particular time point. Similarity factor f2 is gaining popularity due to its recommendation by various regulatory committees as a criterion for the assessment of the similarity between two dissolution profiles. The aim of this study was to develop theoretical and simulation studies to assess by means of bootstrap confidence intervals for f2, the similarity of dissolution profiles(AU)

Development and in vitro evaluation of Letrozole loaded biodegradable nanoparticles for breast cancer therapy / Desenvolvimento e avaliação in vitro de Letrozole carregado nanopartículas biodegradáveis para o tratamento do câncer de mama

The objectives of our study were to prepare and evaluate a biodegradable nanoparticulate system of Letrozole (LTZ) intended for breast cancer therapy. LTZ loaded poly(lactide-co-glycolide) nanoparticles (LTZ-PLGA-NPs) were prepared by emulsion-solvent evaporation method using methylene chloride and polyvinyl alcohol. Percentage of drug (with respect to polymer) was selected as formulation variable. LTZ-PLGA-NPs were characterized by particle size, zeta potential, infrared spectra, drug entrapment efficiency and in vitro release. Sonication was done with an ultrasound pulse sonicator at 70 W, 30 kHz for 90 sec to produce stable NPs of mean size range from 64 nm to 255 nm with high entrapment efficiency (68 percent to 82 percent). Percentage of drug significantly influenced particle size, entrapment efficiency and release (p <0.05). The system sustained release of LTZ significantly and further investigation could exhibit its potential usefulness in breast cancer therapy.

Os objetivos de nosso estudo foram preparar e avaliar o sistema de nanopartícula biodegradável de letrozol na terapia de câncer mamário. Nanopartículas de poli(lactídeo-co-glicolídeo) carregadas com LTZ (LTZ-PLGA-NPs) foram preparadas pelo método de emulsão-evaporação de solvente, utilizando dicloro metano e álcool polivinílico. A porcentagem do fármaco (com relação ao polímero) foi selecionada como variável da formulação. LTZ-PLGA-NPs foram caracterizadas pelo tamanho da partícula, potencial zeta, espectros no infravermelho, eficiência de inclusão e liberação in vitro. A sonicação foi realizada com sonicador de ultrassom, de pulso a 70W e 30 kHz por 90 segundos para produzir NPs estáveis, de faixa de tamanho médio de 64 nm a 266 nm, com alta eficiência de inclusão (68 por cento a 82 por cento). A porcentagem do fármaco foi significativamente influenciada pelo tamanho da partícula, eficiência de inclusão e liberação (p<0,05). O sistema controlou significativamente a liberação de LTZ e estudos posteriores poderiam mostrar sua utilidade potencial na terapia de câncer de mama.

Fabricación de cápsulas de gelatina dura de yoduro potásico como agente preventivo frente a exposición a radiaciones ionizantes: aplicación de la tecnología de mezclado para la obtención de mezclas pulverulentas de yoduro potásico estables (AU) / Elaboration of strong jelly capsules of potassium iodine as preventive agent for exposure to ionizing radiations: mixing technology application to obtain stabile mixtures of powdered potassium iodine

Antecedentes y Objetivos: La administración de yoduro potásico en situaciones de emergencia nuclear previene la fijación de radioyoduro sobre la glándula tiroides. El anión yoduro es degradable por acción de la luz y humedad ambiental. El escaso número de proveedores de yoduro potásico estabilizado en el mercado internacional puede originar dificultades de abastecimiento. La obtención de mezclas estables de yoduro potásico permitirá atender las necesidades que se presenten y evitar este problema. Diseño: La operación de mezclado entre sólidos pulverulentos, mediante la formación de mezclas ordenadas, permite conseguir el recubrimiento de partículas de yoduro potásico con sustancias que disminuyan su contacto con la humedad ambiental. Se preparan y se encapsulan mezclas de yoduro potásico con estearato cálcico o magnésico, en una proporción definida, y celulosa microcristalina como excipiente diluyente; su solubilidad determina la aceptación o exclusión. Las formulaciones elegidas se someten a producción industrial y estudio de estabilidad según International Conference of Harmonization (ICH). Material Y Métodos: Equipos para producción industrial de cápsulas de gelatina dura y equipos para determinaciones analíticas, según métodos y especificaciones de Farmacopea Española y Americana. Resultados: La solubilidad de las mezclas obtenidas con estearato magnésico es superior a las realizadas con estearato cálcico. Los resultados de estudios de estabilidad prueban el buen comportamiento de las mezclas evaluadas durante los siguientes periodos: 6 meses en estudios acelerados y 12 meses en tiempo real. Conclusiones: La tecnología de mezclado se revela como eficaz medio para proporcionar protección al ión yoduro frente a los agentes que pueden provocar su degradación. Los resultados del estudio de estabilidad así parecen confirmarlo y permiten predecir el mantenimiento de la calidad durante un tiempo superior al evaluado; no obstante se continúan dichos estudios hasta completar el periodo fijado (AU)

Antecedents and objectives: Administration of potassium iodine in nuclear emergency situations prevents fixation of radioiodine to thyroid gland. Iodine anion is degraded by light action and environmental humidity. The brief number of suppliers for stabile potassium iodine at international markets may cause difficulties for acquiring. Stabilized mixtures of potassium iodine obtained allow the support of appeared necessities, avoiding this problem. The mixing operations between powdered solids, by ordered mixtures formations, let us to obtain the recovering of potassium iodine particles with substances able to diminish their contact with the environmental humidity. Mixtures of potassium iodine and calcium or magnesium stearate are prepared and encapsulated by a defined proportion, with microcrystalline as an excipient; its solubility determines acceptation or exclusion. Elected formulas are industrially produced, studying the stability according to the International Conference of Harmonization (ICH). Methods: Industrial equipments for production of strong jelly capsules and equipments for analysing determinations, adopting methods and specifications of the Spanish and American Pharmacology. Results: Solubility of the obtained mixtures with magnesium stearate is of higher quality than those with calcium stearate. The results of the stability studies prove the good response of the evaluated mixtures during the following periods: 6 months in quick studies and 12 months in real time. Conclusions: Mixture technology is revealed as an efficient method to obtain protection for iodine ion to the agents that can degrade it. The results of the stability studies seem to confirm so and let us to preview the quality maintaining along a greater period than evaluated; however, studies are continued to complete the fixed period (AU)

Desenvolvimento, validação e comparação de métodos analíticos para determinação de bloqueadores neuromusculares derivados de esteróides / Development, validation and comparison of analytical methods for determination of neuromuscular blocking derivatives of steroids

Os relaxantes neuromusculares não despolarizantes são fármacos indispensáveis nos procedimentos cirúrgicos que requerem entubação endotraqueal, visto que diminuem o tônus muscular. Quimicamente são divididos em derivados isoquinolinicos e derivados de esteróides, esses últimos com maior aplicação clinica e comercialização no Brasil. Assim sendo, é importante a validação de métodos analíticos para o controle de qualidade com alternativas confiáveis que garantam sua eficácia e segurança. Os brometos de vecurônio, de pancurônio e de rocurônio são fármacos relaxantes neuromusculares não despolarizantes derivados de esteróides. As propriedades farmacológicas destes fármacos são significativamente diferentes entre si, porém, as propriedades químicas são bastante similares. Na presente pesquisa foram desenvolvidos e validados métodos analíticos de separação (cromatografia líquida de alta eficiência e eletroforese capilar) para cada fármaco. Estes métodos foram aplicados a medicamentos comercializados no Brasil. Para todos os métodos cromatográficos foi utilizada uma coluna amino devido a seu caráter polar. Em função da baixa absorção dos três fármacos na região ultravioleta, os métodos eletroforéticos foram aplicados com detecções indiretas utilizando substâncias cromóforas. Comparando-se as técnicas utilizadas para determinação dos fármacos nos medicamentos isoladamente, não houve diferença significativa com nível de confiança de 95,0%. Nos testes de hipótese aplicados (F-Snedecor e t-Student), não foram observadas diferenças na precisão (variâncias) e no valor encontrado dos fármacos contidos nas amostras estudadas (comparação de duas médias).

The non-depolarizing neuromuscular relaxant drugs are essential in surgical procedures requiring endotracheal intubation, as they decrease muscle tonics. These drugs are chemically divided in isoquinolines derivatives and steroid derivatives, this latter group, with greater clinical application and commercialization in Brazil. Therefore, the study and validation of analytical methods are important for quality control with reliable alternatives to ensure their effectiveness and safety. The vecuronium, pancuronium and rocuronium bromides are steroid derivatives presenting non-depolarizing neuromuscular relaxant action. Pharmacological properties of these drugs differ significantly, however, its chemical properties are quite similar. In this research, analytical separation methods (high performance liquid chromatography and capillary electrophoresis), for each drug, were developed and fully validated. The methods were applied to pharmaceutical formulations commercialized in Brazil. For all chromatographic methods, an amino column was used, due to its polar characteristics. Due to the low absorption of the three drugs in the ultraviolet region, electrophoretic methods has been applied with indirect detection using chromophoric substances. When comparing both techniques used for quantitative determination of these drugs in pharmaceutical products, no significant difference was observed using a confidence level of 95.0%. By applying hypothesis tests (F-Snedecor and t-Student), it was not observed difference in precision (variance) and in the found amount of drugs contained in the selected samples (comparison of two means).