Usabilidade de um aplicativo móvel de apoio aos profissionaisde saúde para cálculos de doses de vancomicina / Usability of a mobile application supporting healthprofessionals on vancomycin dosing calculation

O aplicativo móvel CalcVAN foi desenvolvido para auxiliar os profissionais de saúde para otimizar as doses de vancomicina em pacientes hospitalizados. Porém, é imprescindível avaliar a sua usabilidade antes de disponibilizá-lo para prática clínica. Assim, o objetivo do estudo é avaliar a usabilidade do aplicativo móvel na perspectiva dos profissionais de saúde. Trata-se de um estudo descritivo, de avaliação heurística da usabilidade de um aplicativo móvel. Foram convidados profissionais da área de saúde com expertise no tema de gerenciamento de antimicrobianos e vancomicina. O instrumento validado Smartphone Usability questionnaiRE (SURE) foi utilizado para mensuração da usabilidade por meio de um questionário on-line. Vinte e um especialistas participaram do estudo, com média de idade de 32,6 anos, sendo a maioria de mulheres (n = 14, 66,7%), profissionais farmacêuticos (n = 13, 61,9%), com pós-graduação lato sensu (n = 10, 47,6%), que trabalhavam em hospitais públicos ou privados (n = 15, 71,4%) e com média de experiência em 9,7 anos. Com base na interpretação dos resultados obtidos pelo instrumento SURE, a média de usabilidade geral do CalcVAN foi de 83 pontos, com escore menor de 78 e maior de 90 pontos. O teste de usabilidade foi enquadrado nos dois últimos níveis, 70 e 80, onde os profissionais de saúde passaram a concordar fortemente e totalmente, indicando que o aplicativo móvel apresenta uma usabilidade satisfatória. O CalcVAN atingiu uma usabilidade satisfatória e atende as necessidades e exigências dos profissionais de saúde, mostrando--se eficiente para realizar as funções propostas.

The CalcVAN app was developed to assist healthcare professionals in optimizing vancomycin doses for hospitalized patients. However, the usability test before making it available for clinical practice is essential. Therefore, the study aims to evaluate the usability of the app from the perspective of health professionals. A descriptive study, a heuristic evaluation of the usability of a mobile application was conducted. Healthcare professionals with expertise in antimicrobial management and vancomycin were invited to participate. The validated Smartphone Usability questionnaiRE (SURE) was used to measure usability through an online questionnaire. Twenty-one experts participated in the study, with a mean age of 32.6 years, mostly of them women (n = 14, 66.7%), pharmacists (n = 13, 61.9%), with postgraduate education (n = 10, 47.6%), working in private or public hospitals (n = 15, 71.4%), and a mean experience of 9.7 years. Overall usability score for CalcVAN was 83 points, ranging from a minimum of 78 to a maximum of 90 points. The usability test registered within the last two levels, 70 and 80, with users expressing strongly and fully agreed, indicating that the app demonstrates satisfactory usability. CalcVAN achieved satisfactory usability, fulfilling the needs and requirements of health professionals, proving to be efficient in performing the intended functions.

Effectiveness and safety of adalimumab biosimilar in patients with inflammatory bowel disease.

BACKGROUND: Adalimumab biosimilar MSB11022 (Idacio ®) has been approved for the same indications as its originator (Humira ®), based on findings from clinical trials in plaque psoriasis. Data on its efficacy and safety in inflammatory bowel disease, however, are scarce. METHODS: Retrospective, observational study of 44 patients with inflammatory bowel disease: 30 were treated with originator adalimumab, 5 were directly started on MSB11022, and 9 switched from originator to biosimilar adalimumab. To evaluate the effectiveness of the use of adalimumab in inflammatory bowel disease, both laboratory markers (fecal calprotectin and C-reactive protein) and scales that measure the activity of inflammatory bowel disease using specific scales (Harvey-Bradshaw Index (HBI) have been usEd.) for Crohn's disease and Mayo Score for Ulcerative Colitis. Efficacy was evaluated by recording the adverse effects that could occur with the administration of adalimumab (original or biosimilar). The success of the switch was determined by analyzing meaningful differences in effectiveness and safety criteria. Concomitant therapy and the need for dose intensification were also analyzed. Objective of this study was to assess the effectiveness and safety of biosimilar adalimumab in adalimumab-naïve patients and patients switched from originator adalimumab. RESULTS: No significant differences were observed in clinical disease activity (P=.317) or biochemical parameters [fecal calprotectin (P=.445) and C-reactive protein P=.661)] after the switch from the originator adalimumab to MSB11022. There was not a significant reduction in the concomitant use of corticosteroids and thiopurines (P=.157). No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects. CONCLUSIONS: Between originator adalimumab and biosimilar-start cohorts, no differences were observed, between originator adalimumab and switch cohorts, no significant differences were found either, and with the pre- and post-switch to biosimilar comparison, 2 of the 9 patients experienced AEs after the switch. The biosimilar showed a favorable safety profile (one patient with a serious adverse effect (rash) with biosimilar discontinued treatment) and no significant changes to clinical or biochemical parameters were observed after the switch.

Presence of metallic components in transdermal drug delivery systems and risk of skin burns. / [Artículo traducido] Presencia de partículas metálicas en parches transdérmicos de medicamentos y riesgo de quemaduras.

OBJECTIVE: Skin burns are associated with the presence of metallic components in transdermal drug delivery systems during Magnetic Resonance Imaging, cardioversion or defibrillation procedures. The aim of the study was to review the presence of metallic components in marketed products of transdermal drug delivery systems in Spain. METHOD: For each presentation, the summary of product characteristics was reviewed. If the information was not provided, manufacturers were contacted. RESULTS: We identified 59 marketed products of transdermal drug delivery systems of 12 different active substances. 59.3% of patches contained metallic components or their presence could not be ruled out. Information regarding the need to remove the patch was only included in 8 summaries of product characteristics (13.6%). A table was elaborated and included the following aspects: product, active substance, manufacturer, need to remove the patch before the exposure to magnetic or electric fields and references. CONCLUSION: More than a half of the patches at the time of the study contained metals or their absence could not be confirmed by the manufacturer. However, this information was only included in 13.6% of summaries of product characteristics.

Adherencia al tratamiento en paciente polimedicado con sistemas personalizados de dosificación (SPD) y su impacto en salud / Adherence to treatment in polymedicated patients using Monitored Dosage Systems (MDS) and their impact on health

Los Sistemas Personalizados de Dosificación (SPD) son una herramienta eficaz, segura y homologada para el reacondicionamiento de fármacos en farmacia comunitaria. Estos implican la revisión del uso del medicamento (RUM) y la colaboración con el médico de atención primaria (MAP). En el presente artículo se describe el caso de una paciente de 57 años intervenida de lumbociatalgia en 2021 y 2022, con dolor crónico mal controlado y aturdimiento derivado del olvido y/o duplicidad de las tomas. Durante la dispensación habitual se detectan estos problemas relacionados con el medicamento (PRM) y se deriva a la paciente al servicio SPD. Tras la implantación del mismo, la paciente mejora a nivel cognitivo, eliminando el aturdimiento y controlando el dolor, lo que supuso un aumento en su calidad de vida. En conclusión, se destaca la importancia de los diferentes servicios disponibles en la farmacia para mejorar la calidad de vida del paciente, la adherencia al tratamiento y la detección de PRM. (AU)

Monitored Dosage Systems (MDS) are an efficient, reliable and approved device for drug reconditioning in pharmacy. These systems imply a review on proper drug use and the collaboration between primary health care and pharmacists. The case study describes a female patient with a surgical intervention due to lumbosciatica in 2021 and 2022. Patient describes uncontrolled chronic pain and confusion related to improper drug use. During regular dispensing of her medication, these medicine-related problems (MRP) were detected and the patient was referred to the MDS service. After its implementation, the patient’s confusion was eliminated and pain management was achieved, increasing her quality of life. As a conclusion, the different health services provided by the pharmacy can improve a patient’s quality of life, treatment adherence and MRP detection. (AU)

Necrólisis epidérmica tóxica debido a un fármaco a base de caléndula más acetilcisteína: presentación de caso / Toxic Epidermal Necrolysis Induced by a Drug Combination of Calendula and Acetylcysteine: A Case Report / Necrólise epidermal tóxica por medicamento à base de calêndula mais acetilcisteína: relato de caso

Introducción: la hipersensibilidad por fármacos es inducida por una respuesta aberrante del sistema inmune; por lo general, impredecible, dosis independiente y amenazante para la vida del paciente. Las reacciones de hipersensibilidad por fármacos con compromiso mucocutáneo se dan en alrededor del 2 %-3 % de los pacientes hospitalizados. Objetivo: describir un caso de necrólisis tóxica epidérmica por un fármaco a base de caléndula y acetilcisteína como los presuntos desencadenantes. Presentación del caso: hombre de 39 años, quien asistió a emergencias, por malestar general, artralgias, mialgias, astenia y adinamia de un día de evolución. Tres días después refirió la aparición de lesiones purpúricas progre-sivas que se extendieron por cara, extremidades y glúteos; delimitadas; no dolorosas, y sin desaparecer a la digitopresión, asociado con disnea, inestabilidad hemodinámica y cardiovascular. Al sexto día de hos-pitalización, se interrogó al paciente, quien se había automedicado un fármaco de origen desconocido, presuntamente de extracto herbal a base de caléndula más acetilcisteína para artralgias, osteomialgias y disfagia. A la mañana siguiente, presentó lesiones purpúricas y ulcerativas extensas. Se observaron lesiones purpúricas progresivas y ulcerativas en cara extremidades y glúteos. Mediante la sospecha clínica y la evaluación histopatológica, se confirmó la necrólisis tóxica epidérmica. Conclusiones: las reacciones adversas medicamentosas severas que amenazan la vida del paciente son relativamente raras, pero representan un verdadero desafío diagnóstico y terapéutico. Es necesario profundizar en la investigación para esclarecer la causa de este tipo de reacción medicamentosa.

Introduction: Drug hypersensitivity is induced by an aberrant response from the immune system. It is usually unpredictable, dose-independent, and can be life-threatening to the patient. Drug-induced hypersensitivity reactions with mucocutaneous involvement occur in approximately 2­3% of hospitalized patients. However, Toxic Epidermal Necrolysis is a rare case. Aim: To describe a case of drug-induced toxic epidermal necrolysis triggered by Calendula officinalis and acetylcysteine. Case report: A 39-year-old male was pre-sented to the emergency room with malaise, arthralgia, myalgia, asthenia, and adynamia since day one. Three days later, he developed progressive purpuric lesions that spread to the face, extremities, and buttocks. These lesions were painless, not delineate, and did not blanch under pressure. They were asso-ciated with dyspnea and hemodynamic and cardiovascular instability. On the sixth day of hospitaliza-tion, the patient admitted to self-medicating with an unknown drug, presumably a herbal extract based on calendula and acetylcysteine, for arthralgia, myalgia, and dysphagia. The morning after the drug consumption, the patient developed extensive purpuric and ulcerative lesions. A diagnosis of toxic epi-dermal necrolysis was made based on clinical suspicion and histopathological confirmation. Conclusion:Severe adverse drug reactions that threaten a patient's life are relatively rare. However, they represent a real diagnostic and therapeutic challenge when they do occur

Introdução: a hipersensibilidade a drogas é induzida por uma resposta aberrante do sistema imunoló-gico; geralmente imprevisível, independente da dose e com risco de vida para o paciente. As reações de hipersensibilidade a drogas com comprometimento mucocutâneo estão em torno dos 2-3% dos pacien-tes hospitalizados. Objetivo: descrever um caso de necrólise epidérmica tóxica causada por uma droga à base de Calendula officinalis e acetilcisteína como os supostos desencadeantes. Apresentação do caso:homem, 39 anos, deu entrada no pronto-socorro manifestando mal-estar, artralgia, mialgia, astenia e adinamia há um dia. Posteriormente, três dias depois, relatou o aparecimento de lesões purpúricas pro-gressivas que se espalharam para a face, extremidades e nádegas; que são delimitadas, não dolorosas e não desaparecem com a acupressão associada a dispnéia, instabilidade hemodinâmica e cardiovascular. No sexto dia de internação, o paciente foi questionado, y disse que tinha se automedicado com uma droga de origem desconhecida, presumivelmente extrato de ervas à base de calêndula mais acetilcis-teína para artralgia, osteomialgia e disfagia. Na manhã seguinte, apresentou extensas lesões purpúricas e ulcerativas. Observam-se lesões purpúricas progressivas e ulcerativas que se estendem à face, extre-midades e nádegas. Pela suspeita clínica e confirmação histopatológica, confirma-se a necrólise epidér-mica tóxica. Conclusões: reações adversas graves a medicamentos que ameaçam a vida do paciente são relativamente raras, mas quando ocorrem representam um verdadeiro desafio a nível diagnóstico e terapêutico. São precisas mais pesquisas para esclarecer a causa desse tipo de reação medicamentosa.

Evaluación del perfil de seguridad del medicamento tocilizumab en pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug tocilizumab in patients suspected or confirmed by COVID-19

Introducción: La enfermedad de COVID-19, es una enfermedad emergente cuya patogénesis se relaciona con la tormenta de citocina, la interleucina 6 juega un papel importante en la tormenta de citocinas. El medicamento tocilizumab, es un anticuerpo monoclonal humanizado, el cual se une al receptor soluble IL-6. En pacientes con COVID-19 se ha observado que el uso de tocilizumab disminuye la inflamación exacerbada. Ante este nuevo uso del medicamento es relevante establecer el balance beneficio-riesgo en estos pacientes con COVID-19, identificando con ello las reacciones adversas a medicamentos que pueden estar relacionadas al uso de tocilizumab. Materiales y métodos: Estudio de farmacovigilancia descriptivo y transversal en una cohorte retrospectiva en pacientes sospechosos o confirmados por COVID-19 en el Instituto Nacional de Cardiología Ignacio Chávez de la Ciudad de México, México en el periodo 05 de mayo del 2020 al 20 de enero del 2021. Resultados: De los 36 pacientes participantes en este estudio, la edad promedio fue 53 años, de los cuales 30 fueron hombres y 6 fueron mujeres. Las comorbilidades identificadas en este estudio fue la hipertensión arterial sistémica, seguida de la diabetes mellitus tipo II. En la evaluación de los estudios de laboratorio se observó que 2 pacientes desarollaron neutropenia moderada, mientras que en 5 pacientes se identificó trombocitopenia leve y 2 pacientes desarrollaron trombocitopenia moderada. Las infecciones bacterianas identificadas en el estudio con el uso del medicamento fueron: 5 aislamientos de Klebsiella oxytoca, 4 a Escherichia coli y 4 a Pseudomonas aeruginosa... (AU)

Introduction: COVID-19 is a new emerging disease which pathogenesis is mediated by a cytokines storm, interleukin 6 plays an important part of this storm. Tocilizumab is a humanized monoclonal antibody that binds to the IL-6 receptor. In patient with COVID-19, exacerbated inflammation has been observed to decrease when given tocilizumab. Due to the new use of this drug is relevant to stablish the risk-benefit ratio in COVID-19 patients, by identifying the drug adverse reactions that may be related to the use of tocilizumab. Material and methods: Descriptive and cross-sectional pharmacovigilance study in a retrospective cohort in patients suspected or confirmed by COVID-19 in the National Institute of Cardiology in Mexico City, Mexico from May 5, 2020 to January 20, 2021. Outcomes: From 36 patients in this study, the average age was 53 years of which 30 were men and 6 were women. The comorbidities identified in this study were systemic arterial hypertension followed by type II diabetes mellitus. Evaluating the laboratory results we observed 2 patients developed moderate neutropenia, 5 patients presented mild thrombocytopenia and 2 patients moderate thrombocytopenia. The bacterial infections identified in the study with the use of the tocilizumab were: 5 isolates Klebsiella oxytoca, 4 isolates Escherichia coli and 4 Pseudomonas aeruginosa. Conclusion: Knowing the possible drug adverse reactions that occurred in patients with COVID-19 who were administered tocilizumab, allow us to the identify the risks associated with the drug, determining the safety profile and be alert of bacterial infections, neutropenia, and thrombocytopenia, throughout a pharmacotherapeutical follow up, thereby identifying possible associated alterations possibly restated with the use of tocilizumab. (AU)

Creation and content validity of 5r-medsafe: assessing adherence to the safe drug administration "five rights" / Elaboración y validez de contenido del instrumento 5r-medsafe: evaluación de la adhesión a los "cinco correctos" de la administración segura de medicamentos / Construção e validade de conteúdo do 5r-medsafe: avaliação da adesão aos cinco certos da administração segura de medicamentos

ABSTRACT Objective: to present the creation and content validity stages of a questionnaire to assess the determinants of adherence to the safe drug administration five "rights" "x", based on the Theory of Planned Behavior integrative model. Method: a methodological study to create and validate a self-reported measuring instrument for psychosocial variables. It took place in two public university teaching hospitals: one located in the South and the other in the Southeast of Brazil. Results: the results were organized according to each stage of the 5R-MEDSAFE content validation process. Conclusion: the results obtained in this creation and content validation study of the 5R-MEDSAFE indicated that the tool presented diverse content validity evidence. Its application can be useful in different contexts as a way of assessing adherence to these behaviors among Nursing workers. This will make it possible to identify which elements of the behaviors are amenable to intervention, as well as to implement the most appropriate intervention, according to the Theory of Planned Behavior constructs.

RESUMEN Objetivo: presentar las etapas de creación y validez de contenido correspondientes a un cuestionario para evaluar los determinantes del nivel de adhesión a los "Cinco correctos" de la administración segura de medicamentos - "5R-MEDSAFE", sobre la base del modelo integrador de la Teoría del Comportamiento Planificado. Método: estudio metodológico para crear y validar un instrumento de medición autoinformado de variables psicosociales. Se desarrolló en dos hospitales-escuela universitarios y públicos: uno situado en la región Sur y el otro en la región Sudeste de Brasil. Resultados: los resultados se organizaron conforme a cada etapa de la validación de contenido de 5R-MEDSAFE. Conclusión: los resultados obtenidos en este estudio de creación y validación del contenido del instrumento 5R-MEDSAFE indicaron que la herramienta presentó diversa evidencia de validez de contenido. Su aplicación puede resultar útil en diferentes contextos como una forma de evaluar el nivel de adhesión a estas conductas entre trabajadores de Enfermería. Eso permitirá identificar los elementos de los comportamiento que son pasibles de intervención, al igual que implementar la intervención más adecuada, conforme a los constructos de la Teoría del Comportamiento Planificado.

RESUMO Objetivo: apresentar as etapas de construção e validade de conteúdo de um questionário para avaliação dos determinantes da adesão aos cinco certos da administração segura de medicamentos - 5R-MEDSAFE, baseado no modelo integrador da Teoria do Comportamento Planejado. Método: estudo metodológico de construção e validação de instrumento de medida autorrelatada de variáveis psicossociais. Desenvolveu-se em dois hospitais-escola universitários, públicos, um localizado na região Sul e outro na região Sudeste do Brasil. Resultados: os resultados foram organizados conforme cada etapa da validação de conteúdo do 5R-MEDSAFE. Conclusão: os resultados obtidos neste estudo de construção e validação de conteúdo do instrumento 5R-MEDSAFE indicaram que o instrumento apresentou evidências de validade de conteúdo. Sua aplicação pode ser útil em contextos distintos como forma de avaliar a adesão a esse comportamento entre trabalhadores de enfermagem. Isso permitirá identificar qual elemento do comportamento é passível de intervenção, bem como implementar a intervenção mais adequada, conforme os construtos da Teoria do Comportamento Planejado.

Presence of metallic components in transdermal drug delivery systems and risk of skin burns.

OBJECTIVE: Skin burns are associated with the presence of metallic components in transdermal drug delivery systems during Magnetic Resonance Imaging, cardioversion, or defibrillation procedures. The aim of the study was to review the presence of metallic components in marketed products of transdermal drug delivery systems in Spain. METHOD: For each pharmaceutical form, the summary of product characteristics was reviewed. If the information was not provided, manufacturers were contacted. RESULTS: We identified 59 marketed products of transdermal drug delivery systems of 12 different active substances. 59.3% of patches contained metallic components or their presence could not be ruled out. Information regarding the need to remove the patch was only included in 8 summaries of product characteristics (13.6%) A table was elaborated and included the following aspects: product, active substance, manufacturer, need to remove the patch before the exposure to magnetic or electric fields, and references. CONCLUSION: More than a half of the patches at the time of the study contained metals or their absence could not be confirmed by the manufacturer. However, this information was only included in 13.6% of summaries of product characteristics.

Innovación tecnológica frente a la expiración de patentes farmacéuticas: el nacimiento de las terapias digitales / [Technological innovation in the face of the expiration of pharmaceutical patents: the birth of digital therapies]

La expiración de patentes farmacéuticas sobre medicamentos favorece la realización de prácticas comerciales dentro del sector que obstaculizan la entrada de los medicamentos genéricos. La creación de terapias digitales a través de la incorporación de componentes digitales en productos farmacéuticos tradicionales es una alternativa innovadora que combina la aportación de un valor añadido a un producto farmacéutico obsoleto a la vez que aborda problemas sanitarios serios de forma transformadora. Este tipo de prácticas podría ayudar a las empresas farmacéuticas a mantener su hueco de mercado tras la expiración de la patente de un medicamento superventas. (AU)

The expiry of pharmaceutical patents on medical products encourages commercial practices within the sector that hinder the entry of generic medicines. The creation of digital therapies through the incorporation of digital components into traditional pharmaceuticals is an innovative alternative that combines adding value to an obsolete pharmaceutical product while addressing serious health problems in a transformative way. Such practices could help pharmaceutical companies to maintain their market niche after the patent expiry of a blockbuster drug. (AU)

Experimental Medications for Using in Endodontics: Cytotoxicity, Genotoxicity and Mutagenesis Analysis / Medicamentos Experimentais para Uso em Endodontia: Análise de Citotoxicidade, Genotoxicidade E Mutagênese

The objective was to evaluate the cytotoxic, genotoxic and mutagenic properties of two experimental medication in Endodontics. For cytotoxic evaluation, fibroblast and osteoblast cells (1x104 cells/well) were plated and divided into groups conforming to the product added in culture medium: EM1 - 20 µL of experimental medication 1 (EM1); EM2 - 20 µL of experimental medication 2 (EM2); VE - 20 µL of vehicle used in medications; C - without product. The MTT assay was performed at 24, 48 e 72 hours for cytotoxic analysis. For genotoxic and mutagenic evaluation, 42 male rats were used. After 1 and 7 days of tubes containing EM1 or EM2, or empty (NC) were subcutaneously implanted, and after 1 day, a single dose of cyclophosphamide (CY) to be applied, the bone marrow was collected and submitted to comet and micronuclei assay. The significance level of 5% was considered for all statistical analysis. The viability of fibroblasts was <70% to both medications at 24h, and EM1 at 72h; at 72h, the proliferation cells was observed in EM2 (>100%). Both medications were non-cytotoxic to osteoblasts, and the EM2 stimulate the cell proliferation at 72h. The damage frequency of CY was statistically similar to EM1 and different to EM2 (p<0.05). The number of micronuclei was insignificant to EM1 and EM2 and no difference to group NC (p>0.05). Despite the absence of mutagenesis and non-cytotoxicity to osteoblasts, the EM1 was cytotoxic and genotoxic to fibroblasts. The EM2 was non-genotoxic, non-cytotoxic and nonmutagenic. (AU)

O objetivo foi avaliar as propriedades citotóxicas, genotóxicas e mutagênicas de dois medicamentos experimentais em Endodontia. Para avaliação citotóxica, células fibroblásticas e osteoblásticas (1x104 células/poço) foram plaqueadas e divididas em grupos de acordo com o produto adicionado no meio de cultura: EM1 - 20 µL da medicação experimental 1 (EM1); EM2 - 20 µL da medicação experimental 2 (EM2); VE - 20 µL de veículo utilizado em medicamentos; C ­ sem produto. O ensaio MTT foi realizado aos 24, 48 e 72 horas para análise citotóxica. Para avaliação genotóxica e mutagênica foram utilizados 42 ratos machos. Após 1 e 7 dias foram implantados por via subcutânea tubos contendo EM1 ou EM2, ou vazios (NC), e após 1 dia, foi aplicada dose única de ciclofosfamida (CY), a medula óssea foi coletada e submetida ao ensaio de cometa e micronúcleos. O nível de significância de 5% foi considerado para todas as análises estatísticas. A viabilidade dos fibroblastos foi <70% para ambas as medicações às 24h e ao EM1 às 72h; às 72h, a proliferação de células foi observada em EM2 (>100%). Ambas as medicações foram não citotóxicas para os osteoblastos, e o EM2 estimulou a proliferação celular às 72h. A frequência de dano do CY foi estatisticamente semelhante ao EM1 e diferente do EM2 (p<0,05). O número de micronúcleos foi insignificante para EM1 e EM2 e não houve diferença para o grupo NC (p>0,05). Apesar da ausência de mutagênese e não citotoxicidade para osteoblastos, o EM1 foi citotóxico e genotóxico para fibroblastos. O EM2 era não genotóxico, não citotóxico e não mutagênico. (AU)

Aspectos farmacológicos y adherencia al tratamiento antirretroviral en pacientes VIH

Introducción: La adherencia al tratamiento farmacológico favorece la supresión viral y reduce la resistencia a la terapia antirretroviral de gran actividad a largo plazo. Objetivo: Determinar la relación entre los aspectos farmacológicos y la adherencia al tratamiento antirretroviral de una IPS colombiana. Metodología: Estudio analítico transversal en pacientes con diagnóstico de VIH en tratamiento antirretroviral entre los años 2012 a 2020. Se utilizó un modelo de regresión logística binaria múltiple con fines explicativos. Resultados: Se analizaron 9835 pacientes donde la proporción de adherencia fue de 90 % y en el modelo ajustado se evaluó su relación con los antecedentes de no adherencia (ORa:0,52 IC95 °/o:0,40-0,66), grupo farmacológico (2 ITIAN + 1 IP u otro) (ORa:1,22 IC95 %:0,99-1,76), dos tomas al día (ORa:1,02 IC95 %:0,74-1,40), unidades al día (≥ 3) (ORa:0,69 IC95 %:0,47-1,02), reacciones adversas a medicamentos (ORa:0,56 IC95 °%:0,40-0,78), polimedicación (ORa:1,36 IC95 %:1,00-1,85), tiempo TAR (1 a 2 años) (ORa:1,63 IC95 %:1,27-2,09),tiempo TAR (6 a 12 meses) (ORa:1,66 IC95 %:1,27-2,18), tiempo TAR (<6 meses) (ORa:1,36 IC95 %:1,03-1,78), tasa de reclamación de los medicamentos (ORa:0,42 IC95 %:0,32-0,55) y antecedentes PRUM (ORa:0,11 IC95 %:0,09-0,14). Discusión: La proporción de adherencia obtenida es superior a lo descrito para otros países (entre 60-77 %); sin embargo se encuentra que los hallazgos correspondientes al efecto de las variables farmacológicas analizadas son acordes a lo descrito en estudios previos en el tema Conclusión: Los antecedentes de no adherencia, reacciones adversas, tasa de reclamación de los medicamentos y antecedentes de problemas relacionados con el uso de medicamentos son aspectos que reducen la probabilidad de adherencia; mientras que el mayor tiempo de uso del tratamiento aumenta la misma.

Introduction: Adherence to drug treatment promotes viral suppression and reduces long-term resistance to highly active antiretroviral therapy (HAART). Objective: To determine the relationship between the pharmacological aspects and adherence to antiretroviral treatment in a Colombian IPS. Methodology: Cross-sectional analytical study in patients with HIV on antiretroviral treatment between 2012 and 2020. A multiple binary logistic regression model was used for explanatory purposes. Results: A total of 9,835 patients were analyzed where the proportion of adherence was 90 % and in the adjusted model its relationship with history of non-adherence was assessed (ORa: 0,52 95 % CI: 0,40-0,66), pharmacological group (2 NRTI + 1 PI or other) (ORa: 1,22 95 % CI: 0,99-1,76), two doses per day (ORa: 1,02 95 % CI: 0,74-1,40), units per day (≥ 3 ) (ORa: 0,69 95 % CI: 0,47-1,02), adverse drug reactions (ORa: 0,56 95 % CI: 0,40-0,78), polypharmacy (ORa: 1,36 95 % CI : 1,00-1,85), ART time (1 to 2 years) (ORa: 1,63 95 % CI: 1,27-2,09), ART time (6 to 12 months) (ORa: 1,66 95 % CI: 1,27-2,18), ART time (<6 months) (ORa: 1,36 95 % CI: 1,03-1,78), inconsistency in the claim (ORa: 0,42 95 % CI: 0,32-0,55) and PRUM history (ORa: 0,11 95 % CI: 0,09-0,14). Discussion: The proportion of adherence obtained is higher than that described for other countries (between 60-77 %); however, the findings corresponding to the effect of the pharmacological variables analysed are in line with those described in previous studies on the subject. Conclusion: The history of non-adherence, adverse reactions, inconsistencies in the claim fill history and problems related to the use of medications are aspects that reduce the probability of adherence. While the longer time of use of the treatment increases adherence.

Atención farmacéutica en pacientes con inmunodeficiencia adquirida y/o tuberculosis en el área ambulatoria de un hospital pediátrico / Pharmacovigilance in patients with acquired immunodeficiency and/or tuberculosis in the outpatient area of a pediatric hospital

La Atención farmacéutica (AF) ayuda a los pacientes a alcanzar objetivos terapéuticos reduciendo los problemas relacionados al medicamento (PRM). Objetivos: analizar los PRM en la práctica de la AF a pacientes con inmunodeficiencia adquirida (IDA) y/o tuberculosis (TBC) y evaluar su impacto. Método: estudio, descriptivo, observacional, en el área ambulatoria de Farmacia. Se incluyeron pacientes con IDA y/o TBC con: inicio de tratamiento, polifarmacia, reinternaciones frecuentes, regular/mala adherencia, reacciones adversas a medicamentos (RAM) previas y/o comorbilidades. Se entrevistaron pacientes o cuidadores y se registraron PRM, errores, grados de adherencia y conocimiento farmacoterapéutico, retiro oportuno de medicamentos y parámetros clínicos. Se registró la intervención farmacéutica y entregó material educativo. Se repitieron las mediciones en una segunda entrevista. Resultados: Se estudiaron 54 pacientes (28 con IDA y 26 con TBC). Se realizaron 93 intervenciones (29.9% dirigidas al prescriptor, 27.8% a otros profesionales) y se detectaron 8 RAM y 53 errores (28 IDA y 25 TBC), el principal PRM fue la mala/regular adherencia con bajo porcentaje de conocimiento farmacoterapéutico completo. Después de la AF, en IDA el grado de adherencia tuvo una mejora estadísticamente significativa (p= 0.012), también fue significativa la mejora en el retiro oportuno de la medicación (28.6% a 71.4% p=0.005 IDA). Se obtuvieron resultados favorables de carga viral (CV) en 72% pacientes con IDA y aumento de peso en 92% pacientes con TBC, aunque no fueron estadísticamente significativos. Conclusiones: mediante AF se mejoró la adherencia y la comunicación en pacientes pediátricos con IDA y/o TBC (AU)

Pharmacovigilance (PV) helps patients achieve therapeutic goals by reducing drug-related problems (DRP). Objectives: to analyze DRPs in the practice of PV in patients with acquired immunodeficiency (AIDS) and/or tuberculosis (TB) and to evaluate its impact. Methods: A descriptive, observational study was conducted in the outpatient pharmacy area. Patients with AIDS and/or TB with: treatment initiation, polypharmacy, frequent readmissions, regular/poor adherence, previous adverse drug reactions (ADR) and/or comorbidities were included. Patients or caregivers were interviewed, and DRP, errors, adherence and pharmacotherapeutic knowledge, timely drug withdrawal, and clinical parameters were recorded. The pharmaceutical intervention was recorded and educational material was delivered. Measurements were repeated in a second interview. Results: We studied 54 patients (28 with AIDS and 26 with TB). Ninety-three interventions were performed (29.9% addressed to the drug prescriber, 27.8% to other professionals) and 8 ADRs and 53 errors were detected (28 AIDS and 25 TB). The main DRP was poor/regular adherence together with a low level of complete pharmacotherapeutic knowledge. After PV, in patients with AIDS the degree of adherence statistically significantly improved (p= 0.012). The improvement in timely medication withdrawal was also significant (28.6% vs. 71.4% p=0.005 AID). Favorable viral load results were obtained in 72% of patients with AIDS and weight gain in 92% of patients with TB, although they were not statistically significant. Conclusions: PV improved adherence and communication in pediatric patients with AIDS and/or TB (AU)

Consensus statement on the use of biosimilar drugs in immune-mediated diseases in Spain.

OBJECTIVE: To improve knowledge about biosimilar medicines and to generate a consensus framework on their use. METHODS: Qualitative study. A multidisciplinary group of experts in biosimilar medicines was established (1dermatologist, 1hospital pharmacist, 1rheumatologist, and 1gastroenterologist) who defined the sections and topics of the document. A narrative literature review was performed in Medline to identify articles on biosimilar medicines. Systematic reviews, controlled, pre-clinical, clinical, and real-life studies were selected. Based on the results of the review, several general principles and recommendations were generated. The level of agreement was tested in a Delphi that was extended to 66 health professionals who voted from 1 (totally disagree) to 10 (totally agree). Agreement was defined if at least 70% of the participants voted ≥7. RESULTS: The literature review included 555 articles. A total of 10 general principles and recommendations were voted upon. All reached the level of agreement established. The document includes data on the main characteristics of biosimilar medicines (definition, development, approval, indication extrapolation, interchangeability, financing, and traceability); published evidence (biosimilarity, efficacy, effectiveness, safety, immunogenicity, efficiency, switch); barriers and facilitators to its use; and data on information for patients. CONCLUSIONS: Authorized biosimilar medicines meet all the characteristics of quality, efficacy, and safety. They also significantly help improve patient access to biological therapies and contribute to health system sustainability.

Documento de consenso sobre los medicamentos biosimilares en enfermedades inmunomediadas en España / Consensus statement on the use of biosimilar drugs in immune-mediated diseases in Spain

Objetivo: Mejorar el nivel de conocimiento sobre los medicamentos biosimilares y generar un marco consensuado sobre su uso. Métodos: Estudio cualitativo. Se seleccionó un grupo multidisciplinar de expertos en medicamentos biosimilares (una dermatóloga, un farmacéutico de hospital, un reumatólogo y un gastroenterólogo) que definieron los apartados y los temas del documento. Se realizó una revisión narrativa de la literatura en Medline para identificar artículos sobre los medicamentos biosimilares. Se seleccionaron revisiones sistemáticas de la literatura, estudios controlados pre-clínicos, clínicos y en vida real. Con esta información se generaron varios principios generales y recomendaciones. El grado de acuerdo con los mismos se estableció mediante un Delphi que se extendió a 66 profesionales de la salud que votaron de 1 (totalmente en desacuerdo) a 10 (totalmente de acuerdo). Se definió acuerdo si al menos el 70% de los participantes votaron ≥7. Resultados: La revisión de la literatura incluyó 555 artículos. Se votaron un total de 10 principios generales y recomendaciones. Todos alcanzaron el nivel de acuerdo establecido en el Delphi. El documento incluye datos sobre las características principales de los medicamentos biosimilares (definición, desarrollo, aprobación, extrapolación de indicaciones, intercambiabilidad, financiación y trazabilidad); sobre la evidencia publicada (biosimilitud, eficacia, efectividad, seguridad, inmunogenicidad, eficiencia, switch); sobre barreras y facilitadores a su uso, y datos sobre la información para pacientes. Conclusiones: Los medicamentos biosimilares autorizados reúnen todas las características de calidad, eficacia y seguridad. Además, ayudan significativamente a mejorar el acceso de los pacientes a las terapias biológicas y contribuyen a la sostenibilidad de los sistemas sanitarios. (AU)

Objective: To improve knowledge about biosimilar medicines and to generate a consensus framework on their use. Methods: Qualitative study. A multidisciplinary group of experts in biosimilar medicines was established (1dermatologist, 1hospital pharmacist, 1rheumatologist, and 1gastroenterologist) who defined the sections and topics of the document. A narrative literature review was performed in Medline to identify articles on biosimilar medicines. Systematic reviews, controlled, pre-clinical, clinical, and real-life studies were selected. Based on the results of the review, several general principles and recommendations were generated. The level of agreement was tested in a Delphi that was extended to 66 health professionals who voted from 1 (totally disagree) to 10 (totally agree). Agreement was defined if at least 70% of the participants voted ≥7. Results: The literature review included 555 articles. A total of 10 general principles and recommendations were voted upon. All reached the level of agreement established. The document includes data on the main characteristics of biosimilar medicines (definition, development, approval, indication extrapolation, interchangeability, financing, and traceability); published evidence (biosimilarity, efficacy, effectiveness, safety, immunogenicity, efficiency, switch); barriers and facilitators to its use; and data on information for patients. Conclusions: Authorized biosimilar medicines meet all the characteristics of quality, efficacy, and safety. They also significantly help improve patient access to biological therapies and contribute to health system sustainability. (AU)

Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital. / [Artículo traducido] Farmacia hospitalaria ecológica: un enfoque sostenible del proceso de utilización de medicamentos en un hospital de tercer nivel.

BACKGROUND: Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. OBJECTIVE: To analyse the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. SECONDARY OBJECTIVES: To analyse the stage of the pharmacotherapeutic process and the number and type of drugs involved. METHODS: The study was carried out in a tertiary-level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (management, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analysed by the administration route: Into oral or parenteral. RESULTS: Twenty eight ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing, and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: Limiting the duration of treatments when possible, favouring the implementation of computer prescription order entry, favouring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. DISCUSION: In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process, and oral administration over intravenous should be prioritized in order to reduce environmental impact.

Farmacia hospitalaria ecológica: un enfoque sostenible del proceso de utilización de medicamentos en un hospital de tercer nivel / Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital

Background Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. Objective To analyze the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. Secondary objectives: to analyze the stage of the pharmacotherapeutic process and the number and type of drugs involved. Methods The study was carried out in a tertiary level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (procurement, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analyzed by the administration route: into oral or parenteral. Results 28 ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: limiting the duration of treatments when possible, favoring the implementation of computer prescription order entry, favoring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. Discussion In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process and oral administration over intravenous should be prioritized in order to reduce environmental impact. (AU)

Antecedentes La gestión sostenible de los residuos sanitarios tiene un impacto positivo en el medio ambiente mundial. Para reducirlo, es esencial la práctica sostenible del proceso farmacoterapéutico en todas sus etapas. Objetivo Analizar las estrategias de sostenibilidad propuestas por el servicio de farmacia para reducir los residuos de medicamentos derivados del proceso farmacoterapéutico. Objetivos secundarios: Analizar la etapa del proceso farmacoterapéutico y el número y tipo de medicamentos implicados. Métodos El estudio se realizó en un hospital de tercer nivel. Para coordinar las propuestas se seleccionó un farmacéutico referente de cada área del servicio de farmacia. Se evaluaron cuatro etapas del proceso (Adquisición, validación, dispensación y formulación), se clasificaron los pacientes afectados como ambulatorios u hospitalizados y se analizaron los fármacos potencialmente implicados según la vía de administración: oral o parenteral. Resultados Se propusieron 28 ideas, que podrían afectar a más de 1.200 medicamentos. El 39,3% afectarían al proceso de validación, el 17,9% a la gestión, el 17,9% a la dispensación y el 7,1% a la formulación. Se evaluó la viabilidad de la aplicación y la aceptabilidad de estas propuestas. Las de mayor potencial fueron: limitar la duración de los tratamientos cuando sea posible, favorecer la implantación de la entrada de órdenes de prescripción por ordenador, favorecer el uso de la vía oral frente a la parenteral e implantar ordenadores en las áreas de preparación para evitar el uso de guías en papel. Conclusiones En nuestro estudio, son muchas las ideas propuestas por los farmacéuticos de hospital para mejorar la sostenibilidad del proceso de utilización de medicamentos... (AU)

Caracterización de la oferta de medicamentos en la República Argentina / Characterization of the drug supply in Argentina

Resumen Introducción : Conocer las características del mercado farmacéutico permite obtener información sensible para entender la oferta, la demanda y el acceso de la pobla ción a los medicamentos. Con el objetivo de aportar da tos primarios respecto a la comercialización de fármacos en Argentina, se desarrolló la siguiente investigación. Métodos : Se trata de un estudio descriptivo cuanti tativo-cualitativo transversal del mercado farmacéutico argentino, tomando en cuenta 30 años de información oficial aportada por la Agencia Reguladora Nacional (ANMAT). Resultados : Se identificaron 216 laboratorios (182 nacionales) productores/importadores de medicamentos, 53 distribuidores y 479 droguerías (establecimientos de distribución de medicamentos al por mayor). Se detectó una alta concentración de la comercialización, agrupán dose el 90% de la misma, en solo 5 intermediarios. En el país existen actualmente 6670 productos/certificados, cantidad que fluctuó a lo largo de los últimos 30 años. Seis laboratorios son dueños de entre 116 y 208 certifica dos. El 84% de estos productos provienen de laboratorios nacionales, 5002 son monofármacos, mientras que el 83% se comercializa bajo un nombre de fantasía. Las tres principales indicaciones a las que se destina el registro de medicamentos en la Argentina son enfermedades del aparato digestivo, sistema nervioso, e infecciosas; el 58% es comercializado como formulaciones orales. Discusión : el presente trabajo muestra que el mer cado farmacéutico argentino tiene una participación mayoritaria de capitales nacionales, existiendo gran concentración en pocas empresas productoras y distri buidoras. Los productos son mayormente monodrogas comercializadas en forma oral y ofrecidas por su nombre de fantasía.

Abstract Introduction : Knowing the characteristics of the phar maceutical market allows obtaining sensitive informa tion to understand the supply, demand and access of the population to medicines. In order to provide primary data regarding the marketing of drugs in Argentina, the following research was performed. Method : This is a cross-sectional quantitative-quali tative descriptive study of the Argentine pharmaceutical market, taking into account 30 years of official information provided by the National Regulatory Agency (ANMAT). Results : Two hundred and sixteen laboratories (182 national) drug producers/importers, 53 distributors and 479 drugstores (wholesale drug distribution establishments) were identified. A high concentration of market ing was detected, grouping 90% in only 5 intermediaries. There are currently 6670 products/certificates in the country, an amount that fluctuated over the last 30 years. Six laboratories are owners of between 116 and 208 certificates; 84% of these products come from na tional laboratories, 5002 are mono-drugs, while 83% are marketed under a fancy name. The three main indica tions for which the registration of drugs in Argentina is intended are diseases of digestive system, nervous system and infectious diseases; 58% of the marketed products consist of oral formulations. Discussion : Based on data provided by this study, it is possible to assert that the Argentinian pharmaceutical market has a majority share of national capital, with a great concentration in a few pharmaceutical companies and distributors. The products are mostly available as non-combined drugs, in their oral form, and available by their brand names.

Hepatoxicity induced by clozapine: Case report and brief review.

INTRODUCTION: Antipsychotics are drugs that can produce transient elevations of hepatic enzymes. Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia and there is evidence that it can produce elevations of hepatic transaminases, expression of liver damage in a hepatocellular pattern. METHODS: Case report and non-systematic review of the relevant literature. CASE PRESENTATION: A 39-year-old woman with a diagnosis of paranoid schizophrenia attended the emergency department of a general hospital for nausea, vomiting and jaundice that appeared after the initiation of clozapine. There was no clinical improvement during hospitalisation, and death occurred after 44 days. LITERATURE REVIEW: Clozapine can increase the liver enzyme levels transiently and asymptomatically; however, there are clinical criteria that recommend the withdrawal of the antipsychotic. CONCLUSIONS: This is the third case reported in the literature of a fatal outcome of clozapine-induced hepatotoxicity.

Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital.

BACKGROUND: Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. OBJECTIVE: To analyze the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. SECONDARY OBJECTIVES: to analyze the stage of the pharmacotherapeutic process and the number and type of drugs involved. METHODS: The study was carried out in a tertiary level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (procurement, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analyzed by the administration route: into oral or parenteral. RESULTS: 28 ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: limiting the duration of treatments when possible, favoring the implementation of computer prescription order entry, favoring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. DISCUSSION: In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process and oral administration over intravenous should be prioritized in order to reduce environmental impact.

Government spending on antiretrovirals in Brazil and its main determinants / Gastos governamentais com antirretrovirais no Brasil e seus principais determinantes

The construction of public policies for the prevention and treatment of HIV/AIDS in Brazil is a history of struggle that unites sanitarians, researchers and activists since the 1980s. An important part of this path is linked to the production and distribution of antiretroviral drugs (ARV), initiatives to reduce the price of ARVs and civil society mobilizations for the guarantee of rights, which contributed to create one of the most successful programs to combat the disease in the country. world. Based on this history, this study aimed to analyze government spending on the acquisition of selected ARVs in the period between 2005 and 2020, making a comparison with international prices, in the light of determinants related to patent disputes, voluntary licensing, PDPs and ARV price reduction initiatives. Among other results, it was possible to observe that there was no immediate relationship between the end of the patent concession and the reduction of prices. Filings of other patent applications and the lack of nationally registered competitors, even after patent expiration, can be significant factors in maintaining high prices.

A construção de políticas públicas para a prevenção e tratamento do HIV/Aids no Brasil é uma história de luta que une sanitaristas, pesquisadores e ativistas desde os anos 1980. Parte importante desse caminho está ligado à produção e distribuição de medicamentos antirretrovirais (ARV), iniciativas de redução do preço dos ARV e mobilizações da sociedade civil pela garantia de direitos, que contribuíram para criar um dos programas mais bem-sucedidos de combate à doença no mundo. Com base nesse histórico, este trabalho teve por objetivo analisar os gastos governamentais na aquisição de ARV selecionados no período entre 2005 e 2020, fazendo uma comparação com preços internacionais, à luz dos determinantes relacionados às disputas patentárias, ao licenciamento voluntário, às PDPs e às iniciativas para redução de preços de ARVs. Entre outros resultados, foi possível observar que não houve uma relação imediata entre o fim da concessão patentária e a redução de preços. Depósitos de outros pedidos de patente e a inexistência de concorrentes registrados nacionalmente, mesmo após a expiração da patente, podem ser fatores significativos para a manutenção de altos preços.