Prescription of off-label and unlicensed medication for newborns hospitalized in the Intensive Care Unit / Prescrição de medicamentos off-label e não licenciados para neonatos hospitalizados na Unidade de Terapia Intensiva

ABSTRACT Objective: To analyze the prevalence of off-label and unlicensed prescriptions for a population of neonates admitted to the Neonatal Intensive Care Unit in a hospital in southern Santa Catarina. Methods: Observational study with a cross-sectional design. All neonates admitted to the Intensive Care Unit during the period from March 2020 to March 2021 were included. Data collection was performed through a questionnaire made by the authors and the classification of drugs based on the Electronic Drug Description (Bulário Eletrônico) of the Brazilian Health Regulatory Agency and Drug Dex-Micromedex. Results: Data from 296 neonates were evaluated. The prevalence was 50,7% for prescribing off-label medications and 37,2% for unlicensed medications. The use of drugs was higher in preterm neonates, with low birth weight, 1st minute Apgar between 6-8, 5th minute Apgar between 7-8, and in need of invasive procedures. The most used off-label drugs were ampicillin, gentamicin and fentanyl (92.6, 92.0 and 26.6%, respectively), whereas the most used unlicensed drugs were caffeine, phenobarbital and bromopride (78.1, 16.3 and 10.9%, respectively). Conclusions: This study showed a large percentage of prescriptions made in the off-label (50.7%) and unlicensed (37.2%) form in the Neonatal Intensive Care Unit, corroborating the worrying world scenario. The most exposed neonates were precisely the most vulnerable ones and, among the most commonly prescribed medications, ampicillin and gentamicin stood out in off-label form and caffeine in unlicensed form.

RESUMO Objetivo: Analisar a prevalência de prescrições off-label e não licenciadas uma população de neonatos internados na Unidade de Terapia Intensiva Neonatal em um hospital ao sul de Santa Catarina. Métodos: Estudo observacional com delineamento transversal. Foram incluídos todos os neonatos admitidos na Unidade de Terapia Intensiva durante o período de março de 2020 a março de 2021. A coleta de dados foi realizada a partir de questionário elaborado pelos autores, e a classificação dos medicamentos, com base no Bulário Eletrônico da Agência Nacional de Vigilância Sanitária e no Drug Dex-Micromedex. Resultados: Foram avaliados dados de 296 neonatos. A prevalência foi de 50,7% para prescrição de medicações off-label e 37,2% para medicações não licenciadas. O uso dos fármacos foi maior em neonatos pré-termo, com baixo peso ao nascer, Apgar de 1o minuto entre 6-8, Apgar de 5o minuto entre 7-8, e com necessidade de procedimentos invasivos. Os fármacos off-label mais utilizados foram a ampicilina, gentamicina e fentanil (92,6, 92 e 26,6%, respectivamente), já os fármacos não licenciados mais utilizados foram a cafeína, fenobarbital e bromoprida (78,1, 16,3 e 10,9%, respectivamente). Conclusões: O estudo demonstrou grande porcentagem de prescrições realizadas de forma off-label (50,7%) e não licenciada (37,2%) na Unidade de Terapia Intensiva Neonatal de análise, corroborando o preocupante cenário mundial. Os neonatos mais expostos foram justamente aqueles mais vulneráveis e, entre as medicações mais utilizadas, destacam-se a ampicilina e a gentamicina de modo off-label e a cafeína de modo não licenciado.

Estado de las Políticas de regulación para el consumo de azúcar y para la comida chatarra en 3 países de América Latina

Introducción: El consumo de bebidas azucaradas y alimentos no saludables es un problema de Salud Pública y de las Políticas Públicas que buscan reducir el impacto de las Enfermedades No Trasmisibles (ENT) en América Latina. Objetivo: identificar las Políticas Públicas generadas en Colombia, Argentina y Chile para la regulación del consumo de azúcar y comida chatarra. Materiales y Métodos: Análisis exploratorio a través de una revisión de literatura y revisión de documentos normativos. Resultados: Colombia en el año 2021 sancionó la Ley 2120 denominada "Ley de Comida Chatarra", que promueve el acceso a información necesaria para fomentar entornos alimentarios saludables y prevenir las ENT, que incluye nuevas normas para el etiquetado de alimentos y describir sus características al consumidor y así limitar el consumo de alimentos procesados y ultraprocesados. Chile fue pionero en el desarrollo de los sellos de advertencia y desde el año 2014, aplica un impuesto adicional a las bebidas no alcohólicas. Argentina en 2021, sancionó la ley que obliga a la industria de alimentos a disponer de etiquetas en los envases que alerten al consumidor sobre los excesos de azúcares, grasas y sodio Conclusiones: Los tres países investigados cuentan con políticas de etiquetado de alimentos procesados, y en Chile existen impuestos a las bebidas azucaradas. Es importante estudiar el impacto de dichas políticas en la prevalencia y severidad de las ENT y de la caries.

Abstract: The consumption of sugar-sweetened beverages and unhealthy foods is a public health problem that has become a regulatory issue for the public policies aimed at reducing the impact of Non Communicable Diseases (NCDs) in Latin America. Objective: to identify the Public Policies in Colombia, Argentina and Chile for the regulation of the consumption of sugar and junk food. Materials and methods. Exploratory analysis through a literature and policy documents review. Results: In 2021, Colombia approved the Law 2120 called "Junk Food Law" promoting public access to information for a healthy food environment to prevent NCDs. It includes food labeling for overweight and obesity prevention and establishes a specific labeling regulation for processed and ultra-processed food and sweet drink products. Chile was pioneer in the development of warning stamps on food packages and since 2014 also taxes sweet non-alcoholic beverages. In 2021, Argentina approved a law to add labels on food packages to alert consumers about excess of sugars, fats and sodium. Conclusions: The three investigated countries have labeling policies for processed food, and Chile puts taxes on sugary drinks. It is important to study the impact of these policies on NCD prevalence, severity and on dental caries.

Effects of nutritional profile system and front labeling in food selection during purchases: a systematic review / Efecto de los sistemas de perfilado nutricional y etiquetado frontal en la selección de alimentos durante la compra: una revisión sistemática

Introduction. Nutritional profiling systems (NPS) are mainly used in front-end labeling policies in order to make the purchase and consumption choice conscious and healthy. Objetive. This study systematically reviewed evidence from interventions on the effect of NPS in the front-of- package on food purchases. Materials and methods. A bibliographic search was carried out in electronic sources from Medline, Elsevier, Scielo and Lilacs, of experimental studies and intervention between 2012 and 2022. A total of 14 articles were included in the review. They were analyzed according to the intervention modality used: 4 studies analyzed the effect of NPS in a real purchase situation and 10 evaluated purchase perception/intention. Results. According to the modality of intervention, the 6 studies that analyzed the NPS-warning system, all recorded healthier purchases compared to the control groups. While for the NPS-NutriScore, Health Star Rating and Multiple Traffic Lights were effective in the decision to purchase healthier foods, in 5 of 7 studies for the first NPS, in 4 of 7 for the second and in 4 of 8 for the third, compared with control groups. Conclusions. Findings of this study suggest that NPSs may be effective for healthy purchase choices, even so it is necessary to strengthen the system and policies with nutritional food education campaigns(AU)

Introducción. Los sistemas de perfilado nutricional (SPN) son utilizados principalmente en políticas de etiquetado frontal con la finalidad de que la elección de compra y consumo sea consciente y saludable. Objetivo. Este estudio revisó sistemáticamente la evidencia de las intervenciones sobre el efecto de SPN en el frente del paquete en las compras de alimentos. Materiales y métodos. Se realizó una búsqueda bibliográfica en fuentes electrónicas de Medline, Elsevier, Scielo y Lilacs, de estudios experimentales e intervenciones entre 2012 y 2022. Se incluyeron un total de 14 artículos en la revisión. Fueron analizados según la modalidad de intervención utilizada: 4 estudios analizaron el efecto de los SPN en una situación de compra real y 10 evaluaron percepción/intención de compra. Resultados. Según la modalidad de intervención, los 6 estudios que analizaron el SPN-sistema de advertencia, todos registraron compras más saludables en comparación con grupo controles. Mientras que para los SPN-NutriScore, Estrellas de Salud y Semáforo Tricolor Múltiple fueron efectivas en la decisión de compra de alimentos más saludables, en 5 de 7 estudios para el primer SPN, en 4 de 7 para el segundo y en 4 de 8 para el tercero, comparados con grupo controles. Conclusiones. Los hallazgos de este estudio sugieren que los SPN pueden ser efectivos para elecciones de compras saludables, aun así, es necesario reforzar el sistema y las políticas con campañas de educación alimentaria nutricional(AU)

Naltrexona em baixa dose (LDN): tendência de consumo nas capitais brasileiras e Distrito Federal, 2014-2020 / Low-dose naltrexone (LDN): consumption trend in Brazilian capitals and the Federal District, 2014-2020

Resumo Estudo ecológico com objetivo de determinar o consumo de naltrexona em baixa dose (LDN) nas 26 capitais brasileiras e Distrito Federal e acompanhar a tendência entre os anos de 2014 e 2020. A coleta de dados da dispensação de naltrexona manipulada, se deu por meio do Sistema Nacional de Gerenciamento de Produtos Controlados, publicizado em 2020, considerando-se baixa dose prescrições de até 5 mg. O cálculo dos coeficientes de dispensação utilizou as estimativas populacionais do Instituto Brasileiro de Pesquisa Geografia e Estatística. Utilizou-se análise estatística descritiva e de regressão generalizada de Prais-Winsten para a série temporal. As tendências observadas foram classificadas em crescentes, estáveis ou decrescentes, com intervalo de confiança de 95% e nível de significância de 5%. Os resultados demonstraram maiores coeficientes de consumo de LDN nas regiões Centro-Oeste, Sul e Sudeste e menores nas Norte e Nordeste. Observou-se dispensação de LDN crescente em 55,6% das capitais, estacionária em 44,4% e ausência de coeficientes decrescentes. Apesar das evidências limitadas quanto à farmacoterapia de LDN e da sua prescrição off-label, os dados demonstram que a prescrição, dispensação e consumo vem crescendo no Brasil, com ênfase nas regiões centro-sul do país.

Abstract The scope of this paper is an ecological study to determine the consumption of low-dose naltrexone (LDN) in the 26 Brazilian capitals and the Federal District and monitor the trend between the years 2014 to 2020. Data collection on the dispensation of manipulated naltrexone was done through the National Management System of Controlled Products, published in 2020, considering low-dose prescriptions of up to 5 mg. The calculation of the dispensation coefficients used the population estimates of the Brazilian Institute of Geography and Statistics. Descriptive statistical analysis and generalized Prais-Winsten regression analysis were used for the time series analysis. The trends observed were classified as increasing, stable, or decreasing, with a 95% confidence interval and 5% significance level. The results showed higher LDN consumption coefficients in the Mid-West, South and Southeast regions and lower coefficients in the North and Northeast. Increasing dispensation of LDN was observed in 55.6% of the capitals, being stationary in 44.4%, with no decreasing coefficients. Despite the limited evidence regarding LDN pharmacotherapy and its off-label prescription, the data show that prescription, dispensing, and consumption have been on the increase in Brazil, with emphasis on the central-south regions of the country.

Utilización de medicamentos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de alta complejidad español. Estudio descriptivo / Off-label and unlicensed drug use in a pediatric intensive care unit of a tertiary care Spanish hospital. A descriptive study

Introducción. En las unidades de cuidados intensivos pediátricos, se utiliza gran cantidad de medicamentos, muchos prescritos fuera de las condiciones establecidas en su ficha técnica (prescripciones off-label y unlicensed). El objetivo de este estudio fue describir el uso de medicamentos y estimar la prevalencia de fármacos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de tercer nivel español. Población y métodos. Estudio transversal, observacional, de una cohorte de niños ingresados en una unidad de cuidados intensivos pediátricos. El estudio se llevó a cabo en 2017. Se revisó cada fármaco prescrito, sus condiciones de uso y administración. Además, se analizaron las fichas técnicas de los fármacos implicados con la finalidad de identificar si el uso de los medicamentos se realizaba según sus condiciones de autorización, o bien se hacía fuera de prospecto (off-label) o como unlicensed. Resultados. La muestra fue de 97 pacientes. El 74,2 % (n = 72) de los pacientes recibieron algún fármaco off-label o unlicensed. El 23,8 % (n = 243) de las prescripciones fueron off-label y el 8,7 % (n = 89), unlicensed. El subanálisis realizado por grupos de edad mostró que el grupo de edad que recibió mayor número de prescripciones totales (n = 611) y el mayor porcentaje de fármacos prescritos en condiciones off-label y/o unlicensed (38,4 %) fue el de menores de 2 años. Conclusiones. La prescripción de fármacos off-label y/o unlicensed es una práctica habitual en la unidad de cuidados intensivos pediátricos. Este estudio permite documentar la complejidad de la terapéutica en niños.

Introduction. In pediatric intensive care units, a large number of drugs are used, many of which are prescribed for condition beyond those established in their summary of product characteristics (off-label and unlicensed drug prescriptions). The objective of this study was to describe drug use and estimate the prevalence of off-label and unlicensed drugs in a pediatric intensive care unit of a tertiary care Spanish hospital. Population and methods. Cross-sectional, observational study with a single cohort of children admitted to a pediatric intensive care unit. The study was conducted in 2017. Each drug prescription, its conditions of use and administration were reviewed. In addition, the summary of product characteristics of drugs used were analyzed in order to identify whether they were used according to their conditions of authorization, or whether they were used in an off-label or unlicensed manner. Results. The sample included 97 patients. At least one off-label or unlicensed drug was administered to 74.2% (n = 72) of patients; 23.8% (n = 243) corresponded to off-label prescriptions and 8.7% (n = 89), unlicensed prescriptions. A sub-analysis by age group showed that the age group that received a higher number of total prescriptions (n = 611) and a higher percentage of off-label and/or unlicensed drug prescriptions (38.4%) was under 2 years of age. Conclusions. Off-label and/or unlicensed drug prescription is a common practice in the pediatric intensive care unit. This study allowed us to document the complexity of therapeutics in children.

Effects of recombinant human erythropoietin on cerebral blood flow in preterm infants: arterial spin labeling magnetic resonance imaging evaluation / 中国新生儿科杂志

Objective:To study the effects of recombinant human erythropoietin (rhEPO) on cerebral blood flow (CBF) in preterm infants using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From September 2021 to June 2022, preterm infants (gestational age ≤32 weeks, birth weight ≤1 500 g) admitted to NICU of our hospital within 24 h after birth were randomly assigned into rhEPO group and control group for this prospective study. The rhEPO group was given rhEPO (500 IU/kg iv, once every other day for 2 weeks) within 72 h after birth plus symptomatic supportive treatment. The control group received same amount of normal saline injection. Both groups received brain MRI, diffusion-weighted imaging and ASL at adjusted gestational age of 35~37 weeks and CBF values of interested areas were measured.Results:A total of 85 infants were enrolled, including 40 in the rhEPO group and 45 in the control group. No significant differences existed in the incidences of periventricular-intraventricular hemorrhage, periventricular leukomalacia, focal white matter injury and extensive white matter injury between the two groups ( P>0.05). The CBF values [ml/(100 g·min)] of frontal cortex [left 15.1±3.9 vs. 17.9±3.1, right 15.9 (12.5, 17.8) vs. 18.1(16.1,20.2)], temporal cortex [left 15.8±4.3 vs. 18.6±3.8, right 16.3(13.2,19.4) vs. 18.1(15.7,19.7)], occipital cortex (left 15.8±6.1 vs. 18.8±3.3, right 16.8±5.5 vs. 19.3±4.8), basal ganglia (left 24.7±7.2 vs. 28.7±6.2, right 26.0±7.9 vs. 29.3±6.4) and thalamus (left 32.7±11.8 vs. 37.9±8.6, right 32.1±11.6 vs. 37.6±10.2) in the rhEPO group were significantly lower than the control group ( P<0.05). No significant differences existed of CBF value at the parietal cortex between the two groups ( P>0.05). Conclusions:Early application of rhEPO can reduce CBF in premature infants, which may be related to the neuro-protective effects of EPO.

The off-label use of antimicrobial medications in neonatal intensive care unit / 中华实用儿科临床杂志

Off-lable use of antimicrobial medications in neonatal intensive care unit (NICU) draws wide attention of medical professionals both abroad and inside China.The objective of this study is to give a commentary of off-label use of antimicrobial medications in NICU.There are 4 sections in this study: the causes, current status, management flow chart, and meditation of off-lable use of antimicrobial medications in NICU.

Current Status of Off-label Use of Denosumab in Bone Tumor and Bone Diseases / 肿瘤防治研究

Denosumab is a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) that significantly inhibits osteoclast activity and has been approved to treat osteoporosis, giant cell tumor of bone, and prophylactic as well as therapeutic entities for bone metastasis. However, the imbalance of RANKL/RANK/OPG has also been implicated in the pathogenesis of several other rare bone diseases and tumor-like disorders, including aneurysmal bone cyst, fibrous dysplasia of bone, and Langerhans cell histiocytosis. Nevertheless, there have been various clinical reports although these diseases have not been approved for indications. The review aims to summarize the available evidence for the off-label use of denosumab in metabolic bone diseases and tumor-like disorders and provide a reference for clinical diagnosis and treatment.

Qualidade nutricional de biscoitos disponíveis à venda em supermercados / Nutritional quality of biscuits available for sale in supermarkets

Introdução: Biscoitos são produtos de panificação feitos com farinha, gordura, açúcar e outros ingredientes, e podem ser alimentos processados ou ultraprocessados. Objetivo: O objetivo deste trabalho foi avaliar a qualidade nutricional de biscoitos comercializados em supermercados brasileiros. Materiais e Métodos: Após a autorização dos responsáveis, dois supermercados participaram do estudo. Foram coletados os dados de informação nutricional e a lista de ingredientes dos biscoitos a partir dos rótulos dos produtos, através de fotos e anotações. Os dados foram tabulados e analisados estatisticamente através de estatística descritiva e análise de variância (ANOVA) com nível de significância de p<0,05. Resultado: No total, foram incluídos 412 biscoitos diferentes, dos quais 73,5% eram doces e 26,5%, salgados. A média de ingredientes por produto foi de 14,80, e 84,7% dos biscoitos eram produzidos com 11 ou mais ingredientes; o número máximo de ingredientes encontrado foi de 29. A gordura vegetal foi encontrada em 79,6% dos produtos. Os biscoitos doces tiveram valores mais elevados de açúcares p<0,0001), gordura total (p=0,002) e gordura saturada (p<0,0001), e os biscoitos salgados tiveram valores mais altos de proteínas (p<0,0001), e sódio (p<0,0001). Quando comparados com biscoitos processados, os biscoitos ultraprocessados tiveram níveis mais elevados de carboidratos (p=0,001), açúcares (p<0,0001), gordura total (p<0,0001) e gordura saturada (p<0,0001). Conclusão: No presente estudo, biscoitos processados e salgados tiveram melhor qualidade nutricional que os biscoitos doces e ultraprocessados, e são considerados melhores opções para os consumidores em supermercados.

Introduction: Biscuits are small bakery products made with wheat flour, fat, sugar and other ingredients, and they can be processed or ultraprocessed food. This paper aimed to evaluate the nutritional quality of biscuits sold in Brazilian supermarkets. Materials and methods: After authorization from the managers, two supermarkets participated in the study. The data collected from labels was the nutritional information and the list of ingredients of cookoies, through photos and notes. Data were tabulated and statistically analyzed with analysis of variance (ANOVA) with a significant level of p<0,05. Results: A total of 412 different products were included, which 73,5% are sweet and 26,5% are salty biscuits. About processing, 98,05% are ultraprocessed and only 1,95% processed. The average of ingredients was 14,80 and 84,7% of biscuits were produced with 11 or more ingredients; the maxim number of ingredients was 29. Vegetal fat was found in 79,6% of products. Sweet biscuits have higher values of sugar (p<0,0001), total fat (p=0,002) and saturated fat (p<0,0001), and salty biscuits were higher in proteins (p<0,0001) and sodium (p<0,0001). When compared with processed biscuits, the ultraprocessed ones were higher in carbohydrates (p=0,001), sugar (p<0,0001), total fat (p<0,0001) and saturated fat (p<0,0001). Conclusion: In this study, processed and salty biscuits had better nutritional quality than sweet and ultraprocessed ones, and are considered better choice options for consumers in supermarkets.

Uso de antiepilépticos en niños hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell / Use of antiepileptic drugs in children hospitalized at the Pereira Rossell Pediatric Hospital / Uso de drogas antiepilépticas em crianças internadas no Hospital Pediátrico Pereira Rossell

Introducción: indicaciones off label, estrecho margen terapéutico, variabilidad farmacocinética, interacciones farmacológicas constituyen algunos de los problemas a abordar en el uso crónico de antiepilépticos (AE). Caracterizar su perfil de uso es necesario para promover su prescripción racional. Objetivo: Describir el perfil de uso de AE en menores de 15 años hospitalizados en el Centro Hospitalario Pereira Rossell entre 1/07/2020 y 31/12/2020. Material y método: estudio descriptivo, de menores de 15 años hospitalizados en cuidados moderados en tratamiento con AE. Variables: tipo y número de AE, motivo de la indicación, vía de administración, dosis, uso asociado con psicofármacos, adherencia. Resultados: recibían AE 113 pacientes, mediana edad 7 años, 50,4% sexo femenino. Motivo de la indicación: epilepsia (grupo A) 50,4% y otras patologías (grupo B) 49,6%. Mediana de edad: 2,7 años grupo A vs. 11,5 años grupo B. El AE más indicado fue levetiracetam en el grupo A (35%) y ácido valproico en el grupo B (35,7%). La asociación con psicofármacos se registró en 8,7% grupo A vs. 44,6% en el grupo B. Conclusiones: predominó el uso de levetiracetam en pacientes epilépticos. La mitad de los pacientes recibieron AE para patologías diferentes a la epilepsia, mayoritariamente psiquiátricas. En este grupo predominó el uso de ácido valproico. El análisis de esta serie permite una aproximación al conocimiento del perfil de uso de AE en los niños asistidos en este centro, y por tanto de los principales problemas a abordar. Futuros estudios multicéntricos con población ambulatoria son necesarios para mejorar el conocimiento y contribuir al uso racional de los mismos.

Introduction: off-label prescription, narrow therapeutic margin, pharmacokinetic variability, drug interaction, are some of the problems to consider in the chronic use of antiepileptic drugs (AEDs). It is necessary to characterize their utilization profile in order to promote rational prescription. Objective: to describe the utilization profile of AEDs in children under 15 years of age hospitalized at the Pereira Rossell Pediatric Hospital from 7/01/2020 to 12/31/2020. Material and Methods: descriptive study of children under 15 years of age hospitalized in moderate care units receiving treatment with AEDs. Variables: type and number of AEDs, reason for the prescription, dose, associated use of psychotropic drugs, compliance. Results: 113 patients received AEDs, median age 7 years, 50.4% females. Reason for prescription; epi- lepsy (group A) 50.4%, other pathologies (group B) 49.6%. Median age in group A 2.7 years, versus 1.1.5 years in group B. Most frequently prescribed AEDs was levetiracetam in group A (35%) and valproic acid in group B (37,7%). Association with psychotropic drugs was present in 8.7% of group A versus 44.6% of group B. Conclusions: levetiracem use was predominant in epileptic patients. Half of the patients received AEDs for pathologies other than epilepsy, mostly psychiatric. In this group the use of valproic acid was predominant. Analysis of this series enables an approximation to the understanding of the profile of AEDs use in children assisted at this Hospital, and there- fore an approximation to the problems to be considered. Future multicenter studies with an outpatient population are necessary to expand our knowledge and to contribute to a rational use of these drugs.

Introdução: indicações off-label, margem terapêutica estreita, variabilidade farmacocinética, interações farmacológicas são alguns dos problemas a serem abordados no uso crônico de drogas antiepilépticas (EA). Caracterizar seu perfil de uso é necessário para promover sua prescrição racional. Objetivo: descrever o perfil de utilização da AE em crianças menores de 15 anos internadas no Centro Hospitalar Pereira Rossell entre 01/07/2020 e 31/12/2020. Material e Métodos: estudo descritivo de crianças menores de 15 anos internadas em cuidados moderados em tratamento de EA. Variáveis: tipo e número de EAs, motivo da indicação, via de administração, dose, uso associado a psicotrópicos, adesão. Resultados: 113 pacientes receberam EA, com meia idade de 7 anos, 50,4% do sexo feminino. Motivo da indicação: epilepsia (grupo A) 50,4% e outras patologias (grupo B) 49,6%. Mediana de idade: 2,7 anos grupo A vs. 11,5 anos grupo B. O EA mais indicado foi Levetiracetam no grupo A (35%) e ácido valpróico no grupo B (35,7%). A associação com psicotrópicos foi registrada em 8,7% do grupo A vs. 44,6% no grupo B. Conclusões: o uso de Levetiracetam em pacientes epilépticos predominou. A metade dos pacientes recebeu AE por outras patologias que não foram a epilepsia, principalmente psiquiátricas. Nesse grupo, predominou o uso do ácido valpróico. A análise desta série permite aproximar o conhecimento do perfil de uso da AE nas crianças atendidas nesse centro e, portanto, a aproximação aos principais problemas a serem abordados. Futuros estudos multicêntricos com população ambulatorial são necessários para aprimorar o conhecimento e contribuir para sua utilização racional.

Los efectos negativos del uso de la etiqueta de superdotación: una revisión narrativa1 / The negative effects of using the giftedness label: a narrative review

RESUMEN La etiqueta de superdotado/a es un arma de doble filo, ya que implica simultáneamente privilegio y estigma: por un lado, se asocia con un mayor estatus, pero por otro, como cualquier otra etiqueta o categoría diferenciadora, tiene el riesgo de separar de la "normalidad" a los individuos, tanto física como psicológicamente. Con el objetivo de determinar los efectos del uso de la etiqueta de superdotación en los/as estudiantes, se trabajó con un método de revisión narrativa. A partir de los hallazgos, se plantea que la utilidad de la etiqueta de superdotación es marginal y, más bien, el proceso de etiquetamiento de la superdotación tiene efectos negativos en la identidad del individuo etiquetado, en sus formas de afrontamiento, en sus relaciones sociales e incluso, en su experiencia escolar, debido a que el uso de la etiqueta, los estereotipos y el estigma derivados de ellos, llevan a la sobreexigencia de su entorno y a la exclusión de los círculos naturales de pares cuando se imponen programas educacionales especializados.

ABSTRACT The gifted label of is a double-edged sword, as it simultaneously implies privilege and stigma: on the one hand, it is associated with higher status, but, on the other hand, like any other label or differentiating category, it takes the risk of separating individuals from "normality", both physically and psychologically. In order to determine the effects of using the giftedness label on students, a narrative review method was used. From the findings, it is proposed that the usefulness of the label of giftedness is marginal and, rather, the process of labeling giftedness has negative effects on the identity of the labeled individual, on his/her ways of coping, on his/her social relationships and even, on his/her school experience, because the use of the label, the stereotypes and the stigma derived from them, lead to an overly-demanding environment and exclusion from natural circles of peers when specialized educational programs are imposed.

Prevalência de aditivos alimentares em produtos industrializados e a tendência clean label / The impact of food additive intake on human health and the clean label trend

Introdução: A ingestão de aditivos por meio dos alimentos industrializados pode impactar a saúde humana. Diante disso, surge à tendência clean label visando produtos mais saudáveis e naturais. Objetivo: Analisar a proporção de produtos clean label e dos principais aditivos presentes em alimentos industrializados, comparando-os aos análogos clean label. Métodos: Estudo transversal, descritivo, onde compilou-se aditivos presentes nas listas de ingredientes de três categorias de alimentos (hambúrgueres de carne, iogurtes e pós para o preparo de gelatina). As informações foram extraídas de um banco de dados de 2021, por meio de coleta em supermercados de Belo Horizonte-Minas Gerais (MG). Resultados e Discussão: Atingiu-se um número final de 157 produtos: hambúrgueres de carne (n=14), pós para o preparo de gelatina (n=51) e iogurtes (n=92). Apenas 16 produtos (10,2%) foram considerados clean label ou similares. A categoria de pós para o preparo de gelatina apresentou maior média de aditivos (7,3). Os principais aditivos encontrados foram: Tripolifosfato de Sódio (100%; n=12) nos hambúrgueres de carne, Sorbato de Potássio (92%; n=77) nos iogurtes e Acessulfame de Potássio (89%; n=40) nos pós para o preparo de gelatina. Após levantamento dos aditivos mais frequentes, uma discussão sobre o impacto na saúde foi realizada. Conclusão: Os resultados indicaram que a maioria dos produtos avaliados possui 5 ou mais aditivos em sua composição e que os aditivos mais frequentes podem ter efeito negativo à saúde, logo a alternativa de alimentos clean label pode oferecer um mesmo aporte nutricional sem os riscos inerentes à ingestão de aditivos químicos. (AU)

Introduction: The ingestion of food additives in processed foods can impact human health. Considering this, the clean label trend arises with healthier and more natural ingredients. Objective: To analyze the proportion of clean label products and the main additives present in industrialized foods, comparing them to their clean label analogues. Methods: A cross-sectional, descriptive study, in which the additives present in the ingredients lists of three categories of industrialized foods (meat-based hamburgers, yogurts and powders for gelatin) were compiled. The information was extracted from a database built in 2021, through collection in supermarkets in Belo Horizonte-MG. Results and Discussion: A final number of 157 products was reached: meat-based hamburgers (n=14), powders for gelatin (n=51) and yogurts (n=92). Only 16 products (10.2%) were considered clean label or similar. The category of powders for gelatin had the highest average of additives per product (7.3). The main additives found were: Sodium Tripolyphosphate (100%; n=12) in meat-based hamburgers, Potassium Sorbate (92%; n=77) in yogurts and Acesulfame Potassium (89%; n=40) in powders for gelatin. After surveying the most frequent additives, a discussion about their impact on health was held. Conclusion: The results indicated that most of the evaluated products have 5 or more additives in their composition and that the most frequent additives can have a negative effect on health, so the clean label food alternative can offer the same nutritional contribution without the risks inherent to the ingestion of chemical additives. (AU)

Uso de antipsicóticos atípicos no tratamento da esquizofrenia no Sistema Único de Saúde do Brasil: estudo de coorte, 2008-2017 / Uso de antipsicóticos atípicos en el tratamiento de la esquizofrenia en el Sistema Único de Salud de Brasil: estudio de 2008 a 2017 / Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

Compounded medications for cardiovascular use in neonatology: an integrative review / Medicamentos manipulados de uso cardiovascular em neonatologia: uma revisão integrativa

ABSTRACT Objective: To analyze the profile of the compounded cardiovascular medicines prescribed in neonatology in Brazil. Data source: An integrative bibliographic review was carried out, including studies published in the last 20 years. The used descriptors were: Intensive Care Neonatal, Off-Label Use, Pharmaceutical Preparations, in the databases Virtual Health Library (VHL), PubMed, and Scientific Electronic Library Online (SciELO). Review articles and guidelines were excluded. The quality of the evidence was analyzed, and 10 articles were selected to integrate the study. Data synthesis: The profile of routine prescrption in the neonatal unit was evaluated. The main cardiovascular medications prescribed as compounding formulation were: Spironolactone, Captopril, Furosemide, Hydrochlorothiazide, Propranolol, Amiodarone, Nifedipine, Carvedilol, Digoxin, Enalapril, Epinephrine, and Hydralazine. The drugs were obtained from adaptations of dosage forms, through the transformation of capsules or tablets into liquid formulations, as a solution, suspension, or syrup, as well as in the form of solutions prepared from active pharmaceutical ingredients. The compounding of medications made drug therapy possible in neonatology, considering that such medications do not have registration of the oral liquid dosage form in the country, despite being part of the List of Essential Medicines for Children of the Word Health Organization. Conclusions: It was possible to analyze the profile of compounded cardiovascular medicines prescribed in neonatology in Brazil. The results showed the need for the development of medications suitable for the neonatal population, and the standardization of operational procedures for preparing extemporaneous formulations in neonatology to increase drug safety.

RESUMO Objetivo: Analisar o perfil dos medicamentos cardiovasculares manipulados prescritos em neonatologia no Brasil. Fontes de dados: Foi realizada uma revisão bibliográfica integrativa, incluindo estudos publicados nos últimos 20 anos. As palavras-chave utilizadas foram: intensive care neonatal, off-label use, pharmaceutical preparations, nos bancos de dados da Biblioteca Virtual em Saúde (BVS), PubMed e Biblioteca Eletrônica Científica Online (SciELO). Os artigos de revisão e diretrizes foram excluídos. A qualidade da evidência foi analisada, e foram selecionados 10 artigos para integrar o estudo. Síntese dos dados: Todos os estudos possibilitaram a avaliação do perfil de prescrição na rotina da unidade. Os principais fármacos cardiovasculares, prescritos em formulação extemporânea, foram espironolactona, captopril, furosemida, hidroclorotiazida, propranolol, amiodarona, nifedipina, carvedilol, digoxina, enalapril, epinefrina e hidralazina. Os medicamentos foram obtidos mediante adaptações de formas farmacêuticas, por meio da transformação de cápsulas ou comprimidos em formulações líquidas, como solução, suspensão ou xarope, assim como também na forma de soluções preparadas com base nos insumos farmacêuticos ativos. A manipulação de medicamentos tornou possível o tratamento medicamentoso em neonatologia, uma vez que tais medicamentos não possuem registro da forma farmacêutica líquida oral no país, apesar de integrarem a lista de medicamentos essenciais em pediatria da Organização Mundial da Saúde. Conclusões: Foi possível analisar o perfil dos medicamentos cardiovasculares manipulados prescritos na neonatologia no Brasil. Os resultados evidenciaram a necessidade do desenvolvimento de medicamentos adequados à população neonatal e à padronização dos procedimentos operacionais do preparo de formulações extemporâneas na neonatologia, para aumentar a segurança dos medicamentos.

Prevalence of Ivermectin use to prevent COVID-19 during the pandemic in Mato Grosso: cross-sectional home-based study / Prevalência do uso de ivermectina para prevenir COVID-19 durante a pandemia em Mato Grosso: estudo transversal de base domiciliar

ABSTRACT Objective: To analyze the use of ivermectin as COVID-19 prevention method by the population of Mato Grosso in 2020. Methods: This is a home-based survey, carried out between September and October 2020, in 10 pole cities of the socioeconomic regions of State. The use of ivermectin was evaluated through the question: "Did you take ivermectin to prevent COVID-19?". Sociodemographic variables (sex, age group, education, family income), current work situation, being benefitted by government financial programs, as well as symptoms, seroprevalence of antibodies against SARS-CoV-2, and previous diagnosis of COVID-19 were evaluated. Prevalence and their associations were estimated using the chi-square test. Results: 4.206 individuals were evaluated for prevalence of ivermectin use; 58.3% of the individuals responded positively, this rate being higher in the municipalities of the western region of the state (66.6%). There was no significant difference between sexes, but the prevalence was higher among people aged 50-59 years (69.7%), who were white (66.5%), with complete higher education or more (68.8%) and higher family income (≥3 minimum wages-64.2%). The use of this drug was even higher among participants who considered their knowledge of the disease good or very good (65.0%), who reported having symptoms of COVID-19 (75.3%), and who had been previously diagnosed with the disease (91.2%). Conclusion: There was a high prevalence of use of ivermectin as a method to prevent covid-19 by the population of Mato Grosso, indicating the need for strategies to inform the population about the risks of off-label use of drugs and to combat the advertising of drugs that are ineffective against COVID-19.

RESUMO Objetivo: Analisar a utilização de ivermectina como prevenção da COVID-19 pela população de Mato Grosso em 2020. Métodos: Trata-se de um inquérito de base domiciliar, realizado entre setembro e outubro de 2020, em dez municípios-polos das regiões socioeconômicas do estado. O uso da ivermectina foi avaliado por meio da pergunta: "Tomou ivermectina para prevenir a COVID-19?". Foram avaliadas as variáveis sociodemográficas (sexo, faixa etária, escolaridade, renda familiar), a situação de trabalho atual, o recebimento de benefícios financeiros governamentais, bem como sintomas, a soroprevalência de anticorpos contra SARS-CoV-2 e o diagnóstico prévio de COVID-19. As estimativas de prevalência e suas associações foram realizadas por meio do teste χ2. Resultados: Foram analisados 4.206 indivíduos, e a prevalência de uso de ivermectina foi de 58,3%, sendo maior nos municípios da região Oeste (66,6%). Não houve diferença significativa entre os sexos, a prevalência foi maior na da faixa etária de 50-59 anos (69,7%), em pessoas brancas (66,5%), com ensino superior completo ou mais (68,8%) e maior renda familiar (≥3 salários-mínimos — 64,2%). A utilização do medicamento ainda foi maior entre os que consideraram seu conhecimento sobre a doença como bom ou muito bom (65,0%), entre os que referiram ter apresentado sintomas de COVID-19 (75,3%) e que foram diagnosticados com a doença previamente (91,2%). Conclusão: Verifica-se a elevada a prevalência do uso de ivermectina para a prevenção da COVID-19 pela população de Mato Grosso, indicando a necessidade de estratégias para informar a população sobre os riscos do uso off-label de medicamentos e combater a publicidade de medicamentos sem eficácia contra COVID-19.

Evaluation of health warning labels for commercial locations vending sugar-sweetened beverages / 环境与职业医学

Background Long-term excessive consuming sugar-sweetened beverages have a negative impact on health. In order to decrease the consumption of sugar-sweetened beverages and create a healthy food environment, the Health Commission of Shenzhen Municipality pioneered to enforce health warning labels presented in commercial locations vending sugar-sweetened beverages based on relevant provisions of the Health Regulations of Shenzhen Special Economic Zone，but its effect has not yet been evaluated. Objective To evaluate the impact of presenting health warning labels in commercial locations vending sugar-sweetened beverages in Shenzhen. Methods A multi-stage stratified sampling method was used to randomly select one street in each of the 10 districts (excluding the Shenzhen Shantou Special Cooperation Zone) of Shenzhen followed by a convenience sampling to select sampling sites to conduct an undercover investigation on the presentation of health warning labels for sugar-sweetened beverages in six different types of venues (n=232) such as shopping malls, ordinary supermarkets/convenience stores, self-service vending machines, catering service places, medical institutions, and venues serving minors' education and activities. At the same time, 238 site managers, 1002 adult consumers, and 7396 child and adolescent consumers were interviewed. Results Among 213 commercial locations vending sugar-sweetened beverages, the rate of health warning label installation was 26.3%, with the highest installation rate in shopping malls (55.0%). Among site managers, 47.8% were aware that commercial locations were required to install health warning labels, and 50.0% were aware of the standards for setting up health warning labels. The higher the awareness of relevant regulations, the higher the rate of installation of health warning labels. More than half of site managers (55.3%) believed that after installing health warning labels, the sales of sugar-sweetened beverages and sugar-sweetened beverages in large-volume packages had decreased compared to the same period in previous years. Most of the interviewed consumers indicated that if they saw the health warning labels for sugar-sweetened beverages, they would buy less, give up purchasing, or choose low-sugar or sugar-free beverages, and also discourage their family members or friends from drinking such beverages. Compared with participants without awareness of the health warning labels, both adult and child and adolescent consumers with awareness of the health warning labels believed that the installation is beneficial to their good eating habits and reported a higher proportion of discouraging family members or friends from drinking such beverages, with a lower frequency of consuming sugar-sweetened beverages. Conclusion Health warning labels for sugar-sweetened beverages have a significant effect on promoting behavior changes, and both site managers and citizens have a high level of support for them. However, in view of the low voluntary compliance rate of commercial locations and the installation rate of health warning labels, the publicity and enforcement of the Health Regulations of Shenzhen Special Economic Zone should be enhanced.

Label-free target discovery technology of small molecule drug and its application in traditional Chinese medicines / 药学学报

The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.

Analysis on Ethical Issues in Off-label Use of Antitumor Drugs / 中国医学伦理学

The phenomenon of off-label use of antitumor drugs in the treatment of malignant tumors is relatively common. Although it is conducive to the development of clinical medical practice, but it is still necessary to pay attention to ethical issues such as medication risks and inadequate implementation of informed consent. Therefore, to effectively avoid ethical risks and standardize the rational use of off-label antitumor drugs, this paper proposed that pharmacists should actively participate in the process of off-label use of antitumor drugs, improve the evidence level of evidence-based medicine, implement patients’ right to informed consent, and improve the hospital’s supervision system of off-label drug use, so as to ensure the reasonable and legal use of drugs by patients.

Acceptance and effectiveness of the Healthier Choice Logo (HCL) among food industries in Malaysia

@#Introduction: The Healthier Choice Logo (HCL) was introduced in 2017 by the Ministry of Health Malaysia. This paper analysed acceptance of HCL, effectiveness of HCL in encouraging healthier product reformulation, and factors affecting reformulation among food industries. Methods: An online self-administered questionnaire consisting of four sections utilising multiple choice and 5-point Likert scale questions was distributed to food industries in Malaysia. Sample size calculation yielded 100 respondents. Results: Food industries had a higher acceptance of the processes and requirements involved in HCL implementation. HCL was highly effective in encouraging product reformulation among food industries in Malaysia. Meeting consumer demand, improving brand image, public health, more awareness around nutrition labelling, logo and national nutrition target, more technical knowledge and budget were found to motivate healthier product reformulation. However, product suitability, consumer acceptability, difficulties maintaining taste and shelf life, and limited budget were the challenges faced in product reformulation. There was no correlation between HCL acceptance and factors encouraging or inhibiting reformulation. Conclusion: These findings are expected to help relevant authorities or stakeholders make changes, if necessary, towards processes and requirements involved in HCL application to ensure wider HCL implementation. Future research should identify the relationship between HCL implementation and public health improvement among the Malaysian population.

Expert consensus on off-label drug use in the three Northeastern provinces of China（solid tumors and hematology） / 中国药房

OBJECTIVE To provide theoretical basis for the rational use of drugs in medical institutions， assist in improving the quality of pharmaceutical services， and thus meet clinical drug demands. METHODS Adopting consensus meetings， Liaoning Pharmaceutical Association，Jilin Pharmaceutical Association and Heilongjiang Pharmaceutical Association collaborated with clinical and pharmaceutical experts in the region to compile the expert consensus on off-label drug use in the three Northeastern provinces of China after many votes and discussions by collecting and collating the information related to off-label drug use in medical institutions from the three northeastern provinces of China，and referring to and citing off-label drug use stated in some expert consensus and medication catalog. RESULTS Finally， a total of 198 pieces of off-label drug use information for 70 drugs were included in the two sections of solid tumors and hematological diseases in Consensus of Experts on Drug Use beyond the Instructions in the Three Provinces of Northeast China. CONCLUSIONS Consensus of Experts on Off-label Drug Use in the Three Northeastern Provinces of Northeast China （solid tumors and hematology）offers a theoretical foundation for rational drug use in the treatment of solid tumors and hematological diseases within medical institutions，and has a positive significance in improving the effectiveness and safety of drug treatment.