Overprescription of short-acting β2 agonists: reflections from the SABINA study in Brazil / Prescrição excessiva de β2-agonistas de curta duração: reflexões a partir do estudo SABINA no Brasil

ABSTRACT Objective: To assess prescription patterns for short-acting b2 agonists (SABAs) and other asthma medications in asthma patients treated by specialists and participating in the SABA use IN Asthma (SABINA) study in Brazil. Methods: This was an observational, cross-sectional study conducted at five sites in different regions of Brazil. The primary endpoints were to record SABA prescriptions and obtain data on over-the-counter (OTC) SABA purchases at the pharmacy. Results: Data on 218 asthma patients were analyzed. Of those 218 patients, 80.3% were prescribed SABAs in addition to their maintenance therapy, with a mean of 11.2 SABA canisters in the previous 12 months. Of those patients, 71.4% were prescribed ≥ 3 canisters and 42.2% were prescribed ≥ 10 canisters. None of the patients were prescribed SABA monotherapy. A total of 14.2% of the patients reported purchasing SABAs OTC at a pharmacy without a prescription. Of those, 48.4% purchased ≥ 3 SABA canisters. A fixed-dose combination of an inhaled corticosteroid and a long-acting b2 agonist was prescribed to 95.0% of the patients. In the year before the study visit, 45.0% of the patients received at least one course of oral corticosteroid burst treatment. Asthma was well controlled in 43.1% of the patients, partly controlled in 34.9%, and uncontrolled in 22.0%. Patients reported a mean of 1.1 severe asthma exacerbations, with 49.1% experiencing 1 or more severe exacerbations. Conclusions: Overprescription and OTC purchases of SABAs are common in Brazil, possibly leading to the need for courses of oral corticosteroids. The health care community should collaborate to implement evidence-based recommendations and promote health education to improve asthma management in Brazil.

RESUMO Objetivo: Avaliar os padrões de prescrição de short-acting b2 agonists (SABAs, b2-agonistas de curta duração) e outros medicamentos para asma em pacientes tratados por especialistas e participantes do estudo SABA use IN Asthma (SABINA) no Brasil. Métodos: Trata-se de um estudo transversal observacional realizado em cinco locais em diferentes regiões do Brasil. Os desfechos primários foram registrar as prescrições de SABAs e obter dados a respeito da compra de SABAs sem receita médica na farmácia. Resultados: Foram analisados dados a respeito de 218 pacientes com asma. Dos 218 pacientes, 80,3% receberam prescrição de SABA além da terapia de manutenção, com uma média de 11,2 frascos de SABA nos 12 meses anteriores. Destes, 71,4% receberam prescrição de ≥ 3 frascos e 42,2% receberam prescrição de ≥ 10 frascos. Nenhum dos pacientes recebeu prescrição de monoterapia com SABA. Do total de pacientes, 14,2% relataram que compraram SABAs sem receita médica na farmácia. Destes, 48,4% compraram ≥ 3 frascos de SABA. Foram prescritas doses fixas combinadas de corticosteroide inalatório e b2-agonista de longa duração para 95,0% dos pacientes. No ano anterior à visita do estudo, 45,0% dos pacientes receberam pelo menos um ciclo de tratamento de curta duração com corticosteroide oral. A asma estava bem controlada em 43,1% dos pacientes, parcialmente controlada em 34,9% e não controlada em 22,0%. Os pacientes relataram uma média de 1,1 exacerbações graves da asma, sendo que 49,1% apresentaram uma ou mais exacerbações graves. Conclusões: A prescrição excessiva e a compra de SABAs sem receita médica são comuns no Brasil e possivelmente levam à necessidade de uso de corticosteroides orais. A comunidade de profissionais de saúde deve colaborar para implantar recomendações baseadas em evidências e promover a educação em saúde para melhorar o manejo da asma no Brasil.

Transfusion of packed red blood cells in adults with sickle cell anemia treated at an emergency hospital

SUMMARY OBJECTIVE: The aim of this study was to analyze the prescription of packed red blood cells performed by emergency physicians for adults with sickle cell anemia. METHODS: Transfusions performed in adults with sickle cell anemia treated at an emergency service in São Bernardo do Campo, São Paulo Brazil, between January 2018 and January 2022 were evaluated. For data comparison, the chi-square2 test was used. The significance level adopted was 5%. RESULTS: A total of 114 transfusions were performed. The mean age was 41.8±16.4 years, and pretransfusion hemoglobin was 6.1±1.23 g/dL. Regarding the indication, the adequacy of transfusions performed in symptomatic individuals was significantly higher compared to asymptomatic individuals (100% vs. 3.9%, p<0.001). Symptomatic individuals received excessive volumes of packed red blood cells less frequently than asymptomatic individuals (17.5% vs. 56.9%, p<0.001). The filtered subtype, indicated for sickle cell anemia, was prescribed in only a quarter of the patients. However, non-indicated subtypes were frequently prescribed. CONCLUSION: This study found low adequacy in the indication and calculation of the transfusion volume of packed red blood cells in asymptomatic individuals. Few patients received filtered red blood cells, resulting in increased risks of transfusion reactions. On the contrary, non-indicated subtypes were prescribed in a quarter of transfusions, which resulted in higher costs and delay in receiving packed red blood cells.

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.

Prescrição, oferta e acesso aos medicamentos para disfunção erétil: um paradoxo na saúde pública? / Prescription, offer and access to medications for erectile dysfunction: a paradox in public health?

Resumo Trata-se de um artigo embasado em opinião que procura refletir sobre o antagonismo estabelecido entre a Política Nacional de Atenção Integral à Saúde do Homem (PNAISH) com o recorte específico para DE (Disfunção Erétil) direcionado ao acesso de medicamentos. É notório que a PNAISH apresenta objetivos que vão além da saúde sexual e reprodutiva, sobretudo, mesmo após 13 anos de sua publicação, não houve incorporação de medicamentos para tratar DE no âmbito SUS. O artigo foi desenvolvido com base no cenário observado no dia a dia de atendimento aos pacientes que recebem cuidados no Serviço Ambulatorial da Saúde Masculina de um Hospital de Alta Complexidade. Isto por constatar a dificuldade dos médicos em prescreverem medicamentos para DE, por ausência de padronização no contexto SUS. Importante ressaltar, nesta perspectiva, que a prescrição de medicamentos no âmbito SUS deve seguir fidedignamente a Rename; conforme preconiza o Decreto 7.508 e, se atentar à Resolução SS-83 de 2015, vigente no estado de São Paulo. Ela estabelece que o custo da dispensação de medicamentos não contemplados na Rename, por meio da judicialização, prescritos por médico da rede estadual de saúde, poderá ser custeado pela instituição ao qual este esteja vinculado.

Abstract This is an opinion-based article that aims to reflect on the antagonism established between the National Policy of Integral Attention to Men's Health (PNAISH) with specific focus on ED (Erectile Dysfunction), directed to access to medication. It is well-known that PNAISH presents objectives that go beyond sexual and reproductive health, especially, even after 13 years of its publication, since there was no incorporation of medications to treat ED within the SUS. This article was developed based on the scenario observed in the daily care of patients who undergo treatment in the Men's Health Outpatient Service of a High-Complexity Hospital. According to this perspective, it is important to emphasize, that the prescription of medications within the SUS should faithfully follow the Rename; as recommended by Decree 7,508, observing the Resolution SS-83 of 2015, in the state of São Paulo. This establishes that the cost of dispensing medications not included in the SUS pharmaceutical assistance protocols, through judicialization, prescribed by a physician in the state health network, may be funded by the institution to which this physician is affiliated.

Compatibility Theory of Yiqi Zengmian Prescription as Vaccine Adjuvant / 中国实验方剂学杂志

ObjectiveThis study explored the application of Yiqi Zengmian prescription as a vaccine adjuvant， aiming to provide a new scheme for the prevention and control of corona virus disease 2019（COVID-19） with traditional Chinese medicine （TCM）. By analyzing the compatibility and efficacy， this paper examines the compatibility effect of Yiqi Zengmian prescription， which is modified from the classic tonifying agent Si Junzitang， as a vaccine adjuvant. MethodUsing the Database of Ancient Classical Prescriptions， this paper analyzed the composition of Yiqi Zengmian prescription and probed into the theoretical basis for the compatibility of this prescription from the properties， medicine combination， and efficacy. Furthermore， the compatibility effect of this prescription with vaccines was analyzed. ResultAs a TCM prescription， Yiqi Zengmian prescription focuses on the lung and spleen and enhances the Qi in the two organs. The lung governs Qi movement. The body breathes fresh air through the lungs and exchanges the turbid gas in the lungs， and the gas circulates alternately in the lungs to ensure the normal breathing of the human body. The spleen governing transportation and transformation is the hub for Qi movement， and Qi is the embodiment of metabolic function. By regulating qi movement and enhancing the functions of Qi and blood， Yiqi Zengmian prescription can enhance the immunogenicity of the vaccine， which provides a theoretical basis for enhancing the immune effects of vaccines. ConclusionYiqi Zengmian prescription has the effects of replenishing Qi and invigorating spleen， regulating Qi and drying dampness， and enhancing immunity. The in-depth analysis of the TCM theory of Yiqi Zengmian prescription as a vaccine adjuvant and the results of clinical and laboratory studies suggest that Yiqi Zengmian prescription may enhance the induction of immune response after vaccination and maintain the immune memory. However， the mechanism of Yiqi Zengmian prescription in regulating the complex immune network remains to be elucidated.

Network Pharmacology in Research on Efficacy of Traditional Chinese Medicine and Compound Prescriptions / 中国实验方剂学杂志

The efficacy of traditional Chinese medicine （TCM） and compound prescriptions is confirmed based on practical experience. It is a highly generalized expression of the clinical characteristics and scope of prescriptions and a unique expression of the medical effects of TCM. Network pharmacology， as a cross-disciplinary field based on the theory of systems biology and multi-level analysis of biological systems， has become a common virtual screening tool in TCM research and gradually developed with the progress in big data and artificial intelligence. In the context of modern medicine， the efficacy of TCM compound prescriptions has a vague concept and lacks scientific evidence. Elucidating the connotation of TCM efficacy and guiding TCM theoretical research has become one of the hotspots and difficulties in TCM research. This article explores the feasibility of using network pharmacology for the research on the efficacy of TCM compound prescriptions and investigates whether the research results can represent part of the efficacy of prescriptions. Furthermore， the research platforms and algorithms in this field are summarized. The research ideas and existing problems in this field are proposed from the aspects of efficacy concept embodiment， target screening， result verification， efficacy network building， and homogenization avoiding of network pharmacology research results. Finally， the future development directions are prospected. This article is expected to provide a reference for exploring the modern biological basis of the efficacy of TCM and compound prescriptions and for the clinical application and theoretical research of TCM.

Uso de inhaladores para la enfermedad pulmonar obstructiva crónica en un grupo de pacientes colombianos

Introducción: En Colombia son escasos los datos sobre el uso de los inhaladores en pacientes con EPOC. Objetivo: Describir la técnica de uso de inhaladores de dosis medida y polvo seco en pacientes de un hospital colombiano. Materiales y métodos: Estudio descriptivo en pacientes mayores de 40 años con EPOC atendidos en un hospital en La Virginia, Risaralda, Colombia, entre el 1 de septiembre de 2019 al 31 de enero de 2020. La unidad de análisis fueron los pacientes. Se incluyeron variables sociodemográficas, clínicas y lista de chequeo para uso de inhaladores. Se aplicaron frecuencias y proporciones para variables discretas, estadísticas de tendencia central y dispersión para variables continuas. Resultados: Se incluyeron 104 pacientes con edad media de 73,6 ± 10,1 años; 57 eran mujeres (54,8 %). Además, 48 pacientes estaban clasificados como GOLD-D (46,2 %). Igualmente, 89 pacientes manifestaron haber recibido educación sobre el uso de broncodilatadores (85,6 %). Los más frecuentes fueron los inhaladores de dosis medida (DM) en 95 casos (91,3 %), seguido de los de polvo seco unidosis (7,7 %). Así mismo, 37 pacientes que usaron DM sin inhalocámara (35,6 %) no cumplieron los pasos de la lista de chequeo. En el sistema multidosis, el más realizado fue cerrar de manera adecuada el inhalador y el menos ejecutado, expulsar el aire lentamente evitando hacerlo cerca del inhalador (n = 6; 5,7 %). Discusión: Se lograron describir las características de la técnica de uso de los inhaladores en pacientes con EPOC. A pesar de que ningún paciente logró utilizar el inhalador de forma "perfecta", la mayoría han recibido educación por parte de los profesionales de la salud. Conclusión: Un alto porcentaje de pacientes usa inadecuadamente los dispositivos para suministrar los broncodilatadores. Esto puede impactar negativamente en el control de la enfermedad.

Introduction: In Colombia, there is limited data on the use of inhalers in patients with COPD. Objective: The objective was to describe the technique of using metered-dose inhalers and dry powder in patients in a Colombian hospital. Methods: Observational, descriptive study of patients over 40 years of age with COPD, treated in a hospital in La Virginia, Risaralda, Colombia, between September 1st, 2019 and January 31st, 2020. The unit of analysis were patients in consultation. Sociodemographic and clinical variables, and a checklist for use of inhalers were included. Frequencies and proportions were applied for discrete variables, statistics of central tendency and dispersion for continuous variables. Results: A total of 104 patients with an average age of 73.6 ± 10.1 years were included; 57 were women (54.8%). In addition, 48 patients were classified as GOLD-D (46.2%). Similarly, 89 patients reported having received education on the use of bronchodilators (85.6%). The most common were metered-dose (MD) inhalers in 95 cases (91.3%), followed by single-dose dry powder inhalers in eight patients (7.7%). Likewise, 37 patients who used DM without inhalochamber (35.6%) did not comply with the steps of the checklist. In the multidose system, the most performed was to properly close the inhaler and the least performed was to expel the air slowly, avoiding doing so near the inhaler (n=6; 5.7%). Discussion: The characteristics of the technique of using inhalers in patients with COPD were described. Although no patient was able to use the inhaler "perfectly", most have received education from health professionals. Conclusion: A high percentage of patients misuse the devices to deliver bronchodilators. This can negatively impact the control of the disease.

Prescripción del ejercicio en paciente post operatorio de cirugía bariátrica 2010-2020: Revisión exploratoria

El ejercicio sigue siendo una intervención necesaria para la pérdida y mantenimiento del peso en pacientes postquirúrgicos de cirugía bariátrica. Sin embargo, los principios básicos de su prescripción luego de este tipo de intervenciones son aún controversiales en la literatura. En este contexto, el objetivo de este estudio fue describir los principales componentes de la prescripción del ejercicio en pacientes postquirúrgicos de cirugía bariátrica y sus beneficios asociados. Se realizó una revisión exploratoria usando las bases de datos Pubmed, PEDro, Springer, Science Direct, y Scielo. Se utilizó un algoritmo de búsqueda con los términos clave "cirugía bariátrica", "obesidad", "ejercicio", "post-quirúrgico", "prescripción del ejercicio" y "actividad física", en inglés y español. Fueron incluidos ensayos clínicos y estudios observacionales publicados entre 2010-2020, donde hubo prescripción del ejercicio posterior a cirugía bariátrica. Un total de 13 estudios fueron analizados. Los parámetros recomendados incluyeron la frecuencia de 3 a 5 veces por semana, intensidad aeróbica entre el 60-85% de la FCmáx o 60-70% de VO2máx, intensidad anaeróbica entre el 60-85% de 1 repetición máxima (1RM), y duración entre 12 y 18 semanas. El ejercicio es una herramienta importante para mantener y reducir el peso, atenuar el sedentarismo y mejorar la calidad de vida en paciente postquirúrgicos de cirugía bariátrica con resultados seguros y eficaces siempre y cuando se garanticen los niveles de intensidad, frecuencia, duración, tipo y progresión sugeridos.

Exercise remains a necessary intervention for weight loss and weight maintenance in post-bariatric surgery patients. However, the basic principles of its prescription after this type of interventions are still controversial in the literature. In this context, our objective was to describe the main components of exercise prescription in post-bariatric surgery patients and its associated benefits. A scoping review was carried out using the Pubmed, PEDro, Springer, Science Direct, and Scielo databases. A search algorithm was used with the terms "bariatric surgery", "obesity", "exercise", "post-surgical", "exercise prescription" and "physical activity", in English and Spanish. Clinical trials and observational studies published between 2010-2020, where there was exercise prescription after bariatric surgery, were included. A total of13 studies were analyzed. The recommended parameters included frequency 3 to 5 times per week, aerobic intensity between 60-85% of HRmax or 60-70% of VO2max, anaerobic intensity between 60-85% of 1 repetition maximum (1RM), and duration period between 12 and 18 weeks. Exercise is an important tool to maintain and reduce weight, attenuate sedentary lifestyle and improve quality of life in post-bariatric surgery patients with safe and effective results as long as the suggested levels of intensity, frequency, duration, type and progression are guaranteed.

Evaluation of Antibiotic Prophylaxis Prescriptions for Infectious Endocarditis Before Oral Procedures Between Cardiologists and Dentists

Abstract Background Infective endocarditis (IE) is a serious disease with a high mortality rate. Antibiotic prophylaxis for bacterial endocarditis before invasive procedures has been recommended in patients with predisposing cardiac conditions since 1960, but contemporary guidelines worldwide have proposed changes. Objective To evaluate the knowledge and pattern of prescription by cardiologists and dentists regarding antibiotic prophylaxis for bacterial endocarditis before risky oral procedures. Methods This is an observational and cross-sectional study. Data were obtained from an online questionnaire, sent to cardiologists and dentists linked to specialty societies, in the first semester of 2021. Data analysis was performed using descriptive statistics, and comparisons between variables were done in an exploratory approach. The significance level adopted was 5%. Results From 613 responders, 82.5% of cardiologists and 79.5% of dentists reported prescribing antibiotic prophylaxis for patients at high and moderate risk for IE. Of dental procedures capable of generating bacteremia, all were correctly identified by more than 50.0% of the sample. As for the habits of daily living, flossing and toothbrushing had almost 50.0% of correct answers, chewing had only 17.3%, and 40.9% reported that none of the actions presented a risk of bacteremia. When comparing variables, the correct prescription of amoxicillin (2 g, 30-60 minutes before the procedure) was more prevalent among cardiologists and in responders with less than 20 years of graduation (p<0.01). Conclusion In the present study, the prescription of antibiotic prophylaxis for IE were frequent for high- and moderate-risk patients, before oral/dental procedures. Partial knowledge was found about endocarditis, which highlights the need for continuous medical/dental education.

Avaliação de prescrições médicas de medicamentos em uma emergência hospitalar / Evaluation of drug prescriptions in a hospital emergency department / Evaluación de la prescripción de medicamentos en un servicio de urgencias hospitalario

RESUMO Objetivo: avaliar a adesão das prescrições médicas de medicamentos às recomendações para segurança do paciente por meio do checklist - Lista de Verificação de Segurança na Prescrição de Medicamentos. Método: trata-se de um estudo observacional, transversal, realizado entre maio a junho de 2022, com 341 prescrições médicas de medicamentos, numa emergência hospitalar no interior da Bahia - Brasil, cujos dados foram analisados através de análise descritiva. Resultados: 80% a 89% das prescrições tiveram adesão às recomendações de segurança; o item de maior adesão foi identificação da data da prescrição, menor adesão foi possuir medicamentos com nomes semelhantes identificados com caixa alta ou negrito. Cerca de 18,63% (n=514) dos medicamentos prescritos fazem parte da lista de medicamentos potencialmente perigosos de uso hospitalar. Conclusão: a avaliação das prescrições médicas de medicamentos evidenciou barreiras existentes na prática clínica, o que possibilita a elaboração de mecanismos mais efetivos para promoção da segurança do paciente.

ABSTRACT Objective: To evaluate the adherence of medical prescriptions to patient safety recommendations using the Medication Prescription Safety Checklist. Method: This is an observational, cross-sectional study carried out between May and June 2022, with 341 medical prescriptions for medicines in a hospital emergency room in the interior of Bahia - Brazil, whose data were analyzed through descriptive analysis. Results: 80% to 89% of the prescriptions adhered to the safety recommendations; the item with the highest adherence was identification of the date of the prescription, and the lowest adherence was having drugs with similar names identified in upper case or bold. Around 18.63% (n=514) of the drugs prescribed are on the list of potentially dangerous drugs for hospital use. Conclusion: The evaluation of medical prescriptions for medicines highlighted existing barriers in clinical practice, which makes it possible to develop more effective mechanisms to promote patient safety.

RESUMEN Objetivo: Evaluar la adhesión de las prescripciones médicas a las recomendaciones de seguridad del paciente utilizando la checklist - Lista de verificación de la Seguridad de la Prescripción de Medicamentos. Método: Se trata de un estudio observacional, transversal, realizado entre mayo y junio de 2022, con 341 prescripciones médicas de medicamentos, en la sala de urgencias de un hospital del interior de Bahia - Brasil, cuyos datos fueron analizados mediante análisis descriptivo. Resultados: Entre el 80% y el 89% de las prescripciones cumplieron las recomendaciones de seguridad; el punto con mayor cumplimiento fue la identificación de la fecha de la prescripción, y el de menor cumplimiento, que los medicamentos con nombres similares se identificaran en mayúsculas o en negrita. Alrededor del 18,63% (n=514) de los medicamentos prescriptos figuran en la lista de medicamentos potencialmente peligrosos de uso hospitalario. Conclusiones: La evaluación de las prescripciones médicas de medicamentos puso de manifiesto los obstáculos existentes en la práctica clínica, lo que permite desarrollar mecanismos más eficaces para promover la seguridad de los pacientes.

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.

Comparison of Application Strategies of Patent Applicants of Classic Traditional Chinese Medicine Prescriptions Between China and Japan / 中国实验方剂学杂志

A total of 290 prescriptions in Treatise on Typhoid and Miscellaneous Diseases （《伤寒杂病论》） and Synopsis of the Golden Chamber （《金匮要略》） and 191 prescriptions in Prescriptionology were selected as representatives of classical prescriptions of traditional Chinese medicine （TCM）， which were translated into Chinese and Japanese. The prescription names were used as keywords for search， and the patent application data up to June 2022 were retrieved. The retrieved results underwent data cleaning and manual noise reduction. Taking the important applicants as the starting point， the key technologies were divided and indexed according to the technical improvement characteristics of classic TCM prescriptions， and the intelligence information of patent applications for classic TCM prescriptions in the two countries was deeply excavated. The differences in the patent applications and layout strategies of classic TCM prescriptions between China and Japan were further compared. This paper drew up an accurate and targeted search strategy for more accurate and comprehensive retrieval， collation， and statistics of patent data of classic TCM prescriptions of representative patent applicants in China and Japan. At the same time， this paper deeply explored the information on Chinese patent applications in Japan and compared the differences in patent application strategies and patent protection of classic TCM prescriptions and Chinese prescriptions in Japan taking the layout of classic TCM prescriptions of representative patent applicants in China and Japan as the entry point. On one hand， it can accurately grasp the current patent application status of classic TCM prescriptions in the two countries， and on the other hand， it can also provide some references for the secondary development and research， patent application， and layout of classic prescriptions of enterprises， universities， and research institutions in China.

Treatment of thyroid nodules based on Chaihu constitution / 国际中医中药杂志

Thyroid nodule is a common endocrine system disease in clinic. Its onset is mostly related to affect-mind internal damage. The core pathogenesis is dysfunction of the liver and liver-qi stagnation, and the main pathological changes are qi stagnation, phlegm turbidity and blood stasis. Constitution is inherited from the natural factors and nourished from the postnatal factors, which is closely related to the occurrence of diseases, the transformation of syndromes and the transmission of diseases. Chaihu constitution refers to the type of constitution suitable for long-term use of Bupleuri Radix and prescriptions about Bupleuri Radix. The characteristics of patients with Chaihu constitution are similar to those of patients with thyroid nodules in clinic, and the risk of developing thyroid nodules is higher. Chaihu constitution is the internal basis of thyroid nodules. When treating thyroid nodule patients with Chaihu constitution, the dominant position of Bupleuri Radix should be highlighted, and Bupleuri Radix and prescriptions about Bupleuri Radix should be used flexibly. The dosage of Bupleuri Radix is mostly between 6-15 g, and according to the change of pathogenesis, it is often combined with Chinese materia medica with the efficacy of soothing liver and promoting qi, resolving phlegm and removing turbidity, promoting blood circulation and removing blood stasis, in order to prevent the occurrence and development of thyroid nodules.

Connotation， Key Scientific Issues， and System Building of Classical Herbal Formulae for Critical Care Medicine / 中国实验方剂学杂志

In contemporary clinical practice of traditional Chinese medicine （TCM）， there is a strong emphasis on treating chronic difficult diseases and preventing diseases before they occur （"pre-disease" treatment）. However， the treatment of critical care medicine has not received as much attention and is even facing a trend of diminishing influence in the field of emergency medicine and critical care. Critical care medicine refers to a class of diseases that are characterized by rapid onset， severity， quick progression， and high mortality rates in clinical practice. The growth and development of renowned TCM experts throughout history have invariably been honed through practical experiences in managing critical care medicine. Treatise on Cold Damage （《伤寒论》） is a dedicated work for treating critical care medicine， and the classic prescriptions in Treatise on Cold Damage are particularly central to the treatment of these diseases. In the current clinical context， it is important to break through the prevailing mindset that the strengths of TCM lie solely in treating chronic diseases and maintenance-type illnesses， identify the entry point of TCM in the clinical advantages in the field of critical care medicine， explore the interdisciplinary relationship between Treatise on Cold Damage and critical care medicine， enhance the ability to treat critical care medicine using classic prescriptions， establish a disciplinary system for prescription-based treatment of critical care medicine， reveal clinical evidence for prescription-based treatment of these diseases， and elevate the contribution of TCM in the domain of critical care medicine. These have become a strong call and demand in contemporary TCM clinical practice. Regarding key scientific issues， the system of using classic prescriptions to treat critical care medicine encompasses traditional core theories such as the nature of cold damage， the essence of the six meridians， the implications of specific clauses， and the dosages of classic prescriptions. In the context of future academic inheritance and system construction， it is recommended to focus on clinical challenges， break away from the current limitations of traditional classical disciplinary systems， such as their singular patterns and weak innovative and translational capabilities， suggest defining diseases in critical care medicine responding specifically to TCM， advocate a research model based on combining disease mechanisms with pathology and combining medicinal properties with pharmacology， establish a comprehensive multidisciplinary thinking mode， and encourage collaborative innovative research among medical， educational， research， and manufacturing institutions. This will help chart the path and address key aspects of constructing a comprehensive system for prescription-based treatment of critical care medicine.

Medication and prescription rules for treating spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary / 数字中医药（英文）

@#【Objective】   To explore the prescriptions related to the treatment of spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary (Tai Ping Hui Min He Ji Ju Fang,《太平惠民和剂局方》, TPHMHJJF), and investigate the medication and prescription rules. 【Methods】   The prescriptions of TPHMHJJF for treating spleen and stomach diseases were screened, and the data set was established by entering the prescriptions and standardized drug names using WPS Excel 2019. Herb frequency statistics, efficacy categorization, property, flavor, meridian tropism, association rules, cluster analysis, factor analysis, and complex network analysis were performed using Python 3.6.8 programming language and Gephi 0.9.2 visualization software. 【Results】   A total of 239 prescriptions were included after the screening, and the dosage forms were mainly pills and powders. The study involved 200 herbal medicines, among which 40 herbs had a frequency of ≥ 12. The herb with the highest frequency was Ganjiang (Zingiber Rhizoma). The herb properties were mainly warm in nature, with the most pungent herbs. Most herbs were attributed to the spleen and stomach meridians, and tonifying medicine were the main species. The association rule analysis identified 26 second-order association rules and 16 third-order association rules, with "Renshen (Ginseng Radix et Rhizoma) → Fuling (Poria)" as the leading rule in the former and "Fuling (Poria) + Baizhu (Atractylodis Macrocephalae Rhizome) → Renshen (Ginseng Radix et Rhizoma)" as the leading rule in the latter. Also, cluster analysis divided the top 30 herbs into six herb combinations that can warm the middle, move Qi, and dry dampness effectively. Factor analysis extracted 13 common factors, with Renshen (Ginseng Radix et Rhizoma), Fuling (Poria), and Baizhu (Atractylodis Macrocephalae Rhizome) as the highest contributing factors. Lastly, complex network analysis yielded the core prescription of 14 herbs, with Ganjiang (Zingiber Rhizoma), Renshen (Ginseng Radix et Rhizoma), Gancao (Glycyrrhizae Radix et Rhizome), and Chenpi (Citri Reticulatae Pericarpium) among the herbs with a higher weighting degree. 【Conclusion】  TPHMHJJF is mainly based on the use of warming herbs to treat spleen and stomach diseases, and its medication rule can be summarized into three aspects: (i) primarily using warming and tonifying to warm the middle and dissipate cold, (ii) using the method of moving Qi with aromatic nature to delight the spleen and appetize the stomach, and (iii) emphasizing the regulation of Qi and blood to calm the five zang-organs.

Historical Evolution and Herbal Textual Research of Jupi Zhurutang / 中国实验方剂学杂志

Jupi Zhurutang originated from Synopsis of the Golden Chamber （《金匮要略》）， which consists of Pericarpium Citri Reticulatae， Caulis Bambusae in Taenia， Ginseng Radix et Rhizoma， Zingiberis Rhizoma Recens， Jujubae Fructus， and Glycyrrhizae Radix et Rhizoma and is used to treat retching. It has been put on the list of Catalogue of Ancient Classical Prescription （First Batch） released by National Administration of Traditional Chinese Medicine. With the bibliometric method， we searched the medical classics containing Jupi Zhurutang and systematically examined the information on the origin of the prescription， the indications， compatibility rule， medicinals in the prescription， dosage and usage， processing method， and decocting method. It was found that there are many versions of Jupi Zhurutang， and there are common grounds of main symptoms， pathogenesis， composition and dosage between the same prescription with different names and different prescriptions with the same name. The prescription which is closest to the original version in Synopsis of the Golden Chamber is mainly used for the treatment of stomach deficiency and qi counterflow without obvious cold or heat. According to the weights and measures， ratio of Pericarpium Citri Reticulatae， Caulis Bambusae in Taenia， Radix Ginseng， Rhizoma Zingiberis Recens， and Radix Ginseng in Synopsis of the Golden Chamber is approximately 6∶2∶8∶5∶1. The Jupi Zhurutang derived from other ancient classics such as Yanshi Jisheng Fang（《严氏济生方》） is a different prescription for hiccups caused by the stomach heat， and the ratio of Pericarpium Citri Reticulatae to Caulis Bambusae in Taenia in this prescription is about 1∶1. It is also found that cold herbs such as Red Poria， Eriobotryae Folium and Ophiopogon Japonicus are added to the formula in later generations. Therefore， the Jupi Zhurutang used in modern times is mostly modified and different from that in Synopsis of the Golden Chamber. This study summarizes the historical evolution of Jupi Zhurutang and identifies the key information， with a view to providing a reference for the rational modification of this prescription in clinical settings and further research.

Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review / 中国中药杂志

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Class concept: annotation and application in classical prescriptions / 中国中药杂志

The study of classical prescriptions should probe into not only the history but also the formation methodology. As a representative of the logic thoughts in ancient China, the class concept has gone through long history, with the theoretical system completed by Biemo in the late Warring States period. The Mohist school, proposing the class concept, plays an important role in the history of Chinese logic and world logic, and its theory has also been inherited and developed by scholars of the same era and later generations. The study of the class concept will contribute to the integration of scientific methodologies between the east and the west. Exploring the impact of the class concept on traditional Chinese medicine(TCM), especially the application in classical prescriptions, may be a path worth exploring for further studying the thought of the Treatise on Febrile and Miscellaneous Diseases(Shang Han Za Bing Lun).

Network Meta-analysis of single Hirudo prescriptions in treatment of ischemic cerebrovascular disease / 中国中药杂志

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment>Maixuekang Capsules+conventional treatment>Naoxuekang Capsules+conventional treatment>conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.

Análise das intervenções farmacêuticas clínicas em Unidade de Terapia Intensiva de um hospital de urgência e trauma / Analysis of clinical pharmaceutical interventions in the Intensive Care Unit of an emergency and trauma hospital

Analisar o perfil das intervenções farmacêuticas providas pelos farmacêuticos clínicos por meio da análise de prescrições médicas em uma Unidade de Terapia Intensiva (UTI) adulto generalista. Metodologia: Trata-se de um estudo transversal, prospectivo e observacional, com abordagem quantitativa, realizado na UTI de um hospital público referência em urgência e trauma do estado de Goiás. Os dados foram coletados no período de junho a agosto do ano de 2022, por meio da análise diária das prescrições. Resultados: A população estudada compreendeu 74 pacientes, em sua maioria do sexo masculino (68,92%), hipertensos (27,03%), e diabéticos (14,86%). Foram analisadas 568 prescrições, e identificados 489 problemas relacionados a medicamentos, sendo os mais prevalentes: medicamento inapropriado/desnecessário ou contraindicado (30,67%) e necessidade de medicamento adicional (24,34%). As classes de medicamentos mais envolvidas nos problemas foram: anti-infecciosos gerais para uso sistêmico (23,72%), e agentes do sistema nervoso (23,11%). Das intervenções farmacêuticas promovidas, 84,25% foram aceitas, com maior frequência: suspender medicamento (30,67%) e iniciar terapia medicamentosa (23,72%). Conclusão: Diante dos resultados apresentados, nota-se a boa taxa de aceitabilidade das intervenções, destacando a importância da atuação do farmacêutico clínico dentro da UTI na prevenção de problemas relacionados à farmacoterapia, bem como na melhoria dos desfechos terapêuticos

To analyze the profile of pharmaceutical interventions provided by clinical pharmacists through the analysis of medical prescriptions in a generalist adult Intensive Care Unit (ICU). Methodology: This is a cross-sectional, prospective and observational study, with a quantitative approach, conducted in the ICU of a public hospital that is a reference in emergency and trauma in the state of Goiás. Data were collected from June to August of 2022, through the daily analysis of prescriptions. Results: The population being studied comprised 74 patients, mostly male (68.92%), hypertensive (27.03%), and diabetic (14.86%). 568 prescriptions were analyzed, and 489 problems related to medication were identified, the most prevalent being: inappropriate/unnecessary or contraindicated medication (30.67%) and need for additional medication (24.34%). The drug classes most involved in the problems were: general anti-infectives for systemic use (23.72%) and nervous system agents (23.11%). Of the promoted pharmaceutical interventions, 84.25% were accepted, most frequently: discontinuing medication (30.67%) and starting medication therapy (23.72%). Conclusion: In view of the results presented, there is a good rate of acceptability of the interventions, highlighting the importance of the role of the clinical pharmacist within the ICU in preventing problems related to pharmacotherapy, as well as in improving therapeutic outcomes