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.

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.

Prevalencia de dolor y su abordaje terapéutico en niños pasibles de cuidados paliativos asistidos en un centro de referencia de Uruguay / Prevalence of pain and its therapeutic approach in children eligible for assisted palliative care in a reference hospital center in Uruguay / Prevalência de dor e sua abordagem terapêutica em crianças submetidas a cuidados paliativos atendidas em um centro hospitalar de referência no Uruguai

Introducción: el tratamiento del dolor es un derecho humano y constituye un pilar de los cuidados paliativos (CP). Este síntoma en niños suele ser subestimado e insuficientemente tratado. Objetivo: conocer la prevalencia del dolor y describir el perfil de uso de fármacos analgésicos, coadyuvantes y procedimientos invasivos en niños asistidos en la Unidad de Cuidados Paliativos Pediátricos del Centro Hospitalario Pereira Rossell (UCPP-CHPR) durante el período 2019-2021. Metodología: se realizó un estudio observacional, descriptivo y retrospectivo mediante revisión de historias clínicas. Resultados: se incluyeron 317 niños, 58% de sexo masculino, con una mediana de edad 6,9 años. Eran portadores de enfermedades neurológicas severas no evolutivas 64%, utilizaban prótesis o tecnología médica 51%. Se encontró registro de presencia de dolor en 35%, de tipo crónico 87%, mixto 55% y de fuentes múltiples 54%. Se detectó uso de escala para evaluación del dolor en 61%, la más utilizada fue r-FLACC. En el grupo de niños con dolor se encontró prescripción de analgésicos en 43% (48/111) y de coadyuvantes 87% (97/111), gabapentina en 78. En todos la vía de administración fue la oral/enteral. Se encontró uso off label de fármacos en 79% y polifarmacia en 82%. Se registraron efectos adversos en 10%. Conclusión: un tercio de los niños asistidos por la UCPP-CHPR, presentaba registros de presencia dolor. La mayoría de tipo crónico, mixto y de fuentes múltiples. Se encontró amplio uso de escalas validadas para evaluación del dolor y alta prescripción de coadyuvantes en relación a la de analgésicos.

Introduction: pain treatment is a human right and a pillar of palliative care (PC). This symptom in children is often underestimated and insufficiently treated. Objective: learn about the prevalence of pain and describe the analgesic drugs' usage profile, adjuvants and invasive procedures in children assisted in the Pediatric Palliative Care Unit of the Pereira Rossell Hospital Center (UCPP-CHPR) during the period 2019-2021. Methodology: observational, descriptive and retrospective study based on the review of medical records. Results: 317 children were included, 58% male, with a median age of 6.9 years. 64% were carriers of severe non-progressive neurological diseases, 51% used prosthetics or medical technology. A record of the presence of pain was found in 35%, chronic type 87%, mixed 55% and multiple sources 54%. The use of a pain assessment scale was detected in 61%, the most used was r-FLACC. In the group of children with pain, analgesics were prescribed in 43% (48/111) and adjuvants in 87% (97/111), gabapentin in 78. In all of them, the administration route was oral/enteral. Off-label use of drugs was found in 79% and polypharmacy in 82%. Adverse effects were recorded in 10%. Conclusion: a third of the children assisted by the UCPP-CHPR showed records of pain presence. Most chronic type, mixed and multiple sources. We found a vast use of validated scales for pain assessment and high prescription of adjuvants in relation to analgesics.

Introdução: o tratamento da dor é um direito humano e constitui um pilar dos Cuidados Paliativos (CP). Este sintoma em crianças é geralmente subestimado e insuficientemente tratado. Objetivo: conhecer a prevalência da dor e descrever o perfil do uso de medicamentos analgésicos, adjuvantes e procedimentos invasivos em crianças atendidas na Unidade de Cuidados Paliativos Pediátricos do Centro Hospitalar Pereira Rossell (UCPP-CHPR) durante o período de 2019-2021. Metodologia: foi realizado um estudo observacional, descritivo e retrospectivo por meio de revisão de prontuários. Resultados: foram incluídas 317 crianças, 58% do sexo masculino, com idade mediana de 6,9 anos. 64% eram portadores de doenças neurológicas graves não evolutivas, 51% usavam próteses ou tecnologia médica. Registro da presença de dor foi encontrado em 35%, do tipo crônica 87%, mista 55% e de origem múltipla 54%. A utilização de escala para avaliação da dor foi detectada em 61%, sendo a mais utilizada a r-FLACC. No grupo de crianças com dor, a prescrição de analgésicos foi encontrada em 43% (48/111) e adjuvantes em 87% (97/111), gabapentina em 78. Ao todo, a via de administração foi oral/enteral. Uso off-label de medicamentos foi encontrado em 79% e polifarmácia em 82%. Efeitos adversos foram registrados em 10%. Conclusão: um terço das crianças atendidas pela UCPP-CHPR apresentou registro da presença de dor. A maioria do tipo crônica, mista e de fontes múltiplas. Encontrou-se ampla utilização de escalas validadas para avaliação da dor e elevada prescrição de coadjuvantes em relação aos analgésicos.

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.

Uso de micofenolato mofetilo fuera de registro en enfermedades inmunomediadas / Off-label use of mycophenolate mofetil in immune-mediated diseases

BACKGROUND: Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). AIM: To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. MATERIAL AND METHODS: A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. RESULTS: MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. CONCLUSIONS: Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

Use of tigecycline at a teaching hospital / Uso da tigeciclina em hospital de ensino

INTRODUCTION: Tigecycline is an antimicrobial agent, approved for the treatment of complicated skin and soft tissue infections, hospital-acquired and community-acquired pneumonia, intra-abdominal infections and anaerobic or atypical infections. OBJECTIVE: To describe the use of tigecycline in a teaching hospital and to compare data from patients who had their prescriptions audited by the hospital infection committee with those who did not have audited prescriptions. METHODS: Retrospective observational cohort study conducted at a teaching hospital from April 2012 to March 2014 including patients who received tigecycline. Demographic variables, comorbidities, microbiological findings, prescribed antibiotics and technical opinions issued by the Hospital Infection Control Service were collected. RESULTS: 71 patients were included, aged between 13 and 92 years, 63.4% were male and 56.3% were non-white. Tigecycline was the first antimicrobial choice in 19.7% (14/71) of the cases, while the use associated with other antibiotics was observed in 66.2% (45/71) of the prescriptions. mainly with meropenem (28.9%). Empirical use was performed in 69.0% of cases, after culture and the antibiogram in 31.0% and off label use in 81.7%. The microorganisms frequently identified by the culture tests were Enterococcus faecalis (17.6%), Pseudomonas aeruginosa (14.7%) and Klebsiella penumoniae (11.8%). CONCLUSION: The study demonstrated that empirical and off label use is common in clinical practice and few prescriptions were guided by the results of the culture and the antibiogram, demonstrating the need for prescribers to evaluate the benefits/ risks of using this antibiotic, risk of resistance, adverse effects and drug interactions, in addition to cost.

INTRODUÇÃO: A tigeciclina é agente antimicrobiano, aprovada para o tratamento de infecções complicadas na pele e tecidos moles, pneumonia hospitalar e adquirida na comunidade, infecções intra-abdominal e infecções anaeróbias ou atípicas. OBJETIVO: Descrever o uso da tigeciclina em hospital de ensino e comparar dados de pacientes que tiveram suas prescrições auditadas pela comissão de infecção hospitalar com os que não tiveram prescrições auditadas. MÉTODOS: Estudo de coorte retrospectivo observacional realizado em hospital de ensino de abril de 2012 a março de 2014 incluindo pacientes que receberam tigeciclina. Foram coletadas variáveis ​​demográficas, comorbidades, achados microbiológicos, antibióticos prescritos e pareceres técnicos emitidos pelo Serviço de Controle de Infecção Hospitalar. RESULTADOS: Foram incluídos 71 pacientes, com idade entre 13 e 92 anos, 63,4% eram do sexo masculino e 56,3% eram não brancos. A tigeciclina foi primeira escolha antimicrobiana em 19,7% (14/71) dos casos, enquanto o uso associado a outros antibióticos foi observado em 66,2% (45/71) das prescrições. principalmente com meropenem (28,9%). O uso empírico foi realizado em 69,0% dos casos, após cultura e o antibiograma em 31,0% e o uso off label em 81,7%. Os microrganismos frequentemente identificados pelos testes de cultura foram Enterococcus faecalis (17,6%), Pseudomonas aeruginosa (14,7%) e Klebsiella penumoniae (11,8%). CONCLUSÃO: O estudo demonstrou que o uso empírico e off label é comum na prática clínica e poucas prescrições foram orientadas pelos resultados da cultura e do antibiograma, demonstrando necessidade de prescritores avaliarem os benefícios/riscos do uso desse antibiótico, risco de resistência, efeitos adversos e interações medicamentosas, além do custo.

Medicamentos off-label e não licenciados no âmbito pediátrico: uma revisão descritiva dos últimos dez anos / Off-label and unlicensed drugs in the pediatric field: a descriptive review of the last ten years

A falta de medicamentos contendo bulas prevendo o tratamento de pacientes pediátricos representa um problema frequentemente observado em hospitais, principalmente nos setores de unidade de terapia intensiva (UTI) pediátrica e neonatais. Sabe-se que, para que um tratamento seja considerado seguro e eficaz, uma série de estudos clínicos são necessários, no entanto, relata-se um baixo número dessas pesquisas envolvendo crianças, principalmente devido a questões éticas que dificultam a condução das mesmas. Assim, poucos são os medicamentos que provam ser adequados para o tratamento desses pacientes, tornando necessário recorrer ao uso de medicamentos off-label e não licenciados. Os medicamentos são classificados como off-label quando seu uso se dá de maneira que difere de suas especificações aprovadas, por sua vez, produtos não licenciados são classificados desta forma por não possuírem aprovação para sua comercialização no país ou não possuírem comprovação de segurança e eficácia. O preparo de protocolos de estudo organizados, relato de informações aos pais e à criança de maneira clara e objetiva, aproximação entre pesquisadores e pais para o estabelecimento de uma relação de confiança e a condução das pesquisas em momentos de disponibilidade da família demonstram-se estratégias importantes para facilitar a realização dos ensaios clínicos.

The lack of medicines containing drug information leaflets considering the treatment of pediatric patients is a problem frequently observed in hospitals, especially in the pediatric and neonatal intensive care unit (ICU) sectors. It is known that, for a treatment to be considered safe and effective, a series of clinical studies are necessary; however, a low number of these studies involving children are reported, mainly due to ethical issues that make conducting them difficult. Thus, few drugs prove to be suitable for treating these patients, making it necessary to resort to using off-label and unlicensed drugs. Drugs are classified as off-label when their use differs from their approved specifications, in turn, unlicensed products are classified in this way due to not having approval for marketing in the country or do not have proof of safety and efficacy. Preparation of organized study protocols, reporting information to parents and the child in a clear and objective way, bringing researchers and parents closer to establish a relationship of trust and conducting research at moments when the family is available are important strategies to facilitate conducting clinical trials.

Percepções e uso do metilfenidato entre universitários da área da Saúde em Ceilândia, DF, Brasil / Perceptions and use of methylphenidate among health students in Ceilândia, DF, Brazil / Percepciones y uso del metilfenidato entre universitarios del área de la salud en Ceilândia, Distrito Federal - DF, Brasil

As percepções e o uso de metilfenidato entre universitários foram investigados em estudo descritivo realizado em duas etapas. A primeira, quantitativa, foi realizada por meio do preenchimento de um questionário semiestruturado on-line. Para a segunda etapa, qualitativa, foi realizado um grupo focal. Dos 337 participantes da primeira etapa, 14,5% relataram usar o metilfenidato. Entre os usuários, a prevalência de uso sem prescrição foi maior para o sexo masculino (65,3%), após ingresso na faculdade (57,1%), e 61,2% relataram eventos adversos. O principal motivo de uso foi o doping intelectual (65,3%). Já na etapa qualitativa, além de reforçar os achados anteriores, foram identificados tópicos temáticos como a pressão externa exercida por familiares, sociedade e a rotina universitária. Esses achados apontam para a necessidade de medidas de apoio e orientação aos universitários e de reformulação do processo ensino-aprendizagem.(AU)

This descriptive study investigated the use and perceptions of methylphenidate among university students. The study was conducted in two stages. In the first stage (quantitative), the students completed an online semi-structured questionnaire. The second stage (qualitative) consisted of focus group discussions. Of the 337 participants in the first stage, 14.5% reported using methylphenidate. The prevalence of methylphenidate use without a prescription was greater among men (65.3%) and after starting university (57.1%); 61.2% of the students reported adverse events. The main reason for using the drug was intellectual doping (65.3%). In the qualitative stage, which reinforced the findings of the quantitative stage, we identified themes such as external pressure from family, society and university routine. The findings underline the need to provide student support and advice and reformulate the teaching and learning process.(AU)

Se investigaron las percepciones y el uso del metilfenidato entre universitarios, en un estudio descriptivo realizado en dos etapas. La primera, cuantitativa, se realizó por medio del llenado de un cuestionario semiestructurado online. Para la segunda etapa, cualitativa, se realizó un grupo focal. De los 337 participantes de la primera etapa, el 14,5% relató que usaba metilfenidato. Entre los usuarios, la prevalencia de uso sin prescripción fue mayor para el sexo masculino (65,3%), después del ingreso en la facultad (57,1%) y el 61,2% relataron eventos adversos. El principal motivo de uso fue el dopping intelectual (65,3%). En la etapa cualitativa, además de reforzar los hallazgos anteriores, se identificaron tópicos temáticos tales como la presión externa ejercida por los familiares, la sociedad y la rutina universitaria. Esos hallazgos señalan la necesidad de medidas de apoyo y orientación a los universitarios y de reformulación del proceso enseñanza-aprendizaje.(AU)

Manifestations cliniques et traitements des diastemes chez les personnes adultes à l'hopital national Donka / Clinical manifestations and treatments of diastemas among people adults at hospital national Donka

Le diastème du grec diastèmà (interstice) se définit comme étant l'existence d'espace entre les dents d'une même arcade. Les objectifs de l'étude étaient de déterminer le profil épidémiologique des diastèmes; décrire les formes cliniques rencontrées, assurer une prise en charge. PATIENTS ET MÉTHODE: Il s'agissait d'une étude prospective de type descriptif effectuée à l'hôpital national Donka, elle avait duré sept mois, allant du 1er Mars au 30 septembre 2019. RÉSULTATS: Le sexe féminin prédominait avec 77,7% contre 22,2 % de sexe masculin, donnant un ratio (f/h) = 3,5. La tranche d'âge de 21-23 ans (tout sexe confondu) était la plus représentée avec un pourcentage de 44,4%. La tonicité du frein labial médian avec 29,62% était l'étiologie principale du diastème inter incisif. Le diastème était plus fréquent au maxillaire avec des valeurs respectives de 33,33% de diastème des dents du bloc incisivo canin et 29,62% de diastème inter incisif soit au total 62,96 %. Le traitement fut chirurgical, orthodontique et prothétique. CONCLUSION:Le diastème reste l'une des anomalies orthodontiques fréquente dans nos pays. Considéré par certains comme un excès de place sur l'arcade dentaire, il est cependant apprécié par d'autres, surtout en Afrique de l'ouest où il est souvent considéré par la population comme signe de chance, de beauté, d'où son impact socio-culturel.

Analysis on off-label use of drugs in pediatric guidelines and consensus published by Chinese authors / 中华儿科杂志

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.

Expert consensus on off-label use of small molecule anti-angiogenic drugs in the treatment of metastatic breast cancer / 中华肿瘤杂志

Breast cancer is the most common cancer in the world, and 5-year survival rate of metastatic breast cancer is about 20%. The treatment of metastatic breast cancer is mainly chemotherapy, endocrine therapy and targeted therapy. However, after multiline treatment, patients with MBC especially the triple negative breast cancer face the problem of drug resistance. Tumor angiogenesis theory suggests that blocking angiogenesis can inhibit tumor growth and migration. Based on this, angiogenesis treatment strategy is proposed. Antiangiogenic drugs mainly include biological macromolecular drugs targeting vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) and small molecule VEGFR inhibitors. Angiogenesis is known to play a key role in the growth and metastasis of breast cancer. Therefore, anti-angiogenetic therapy has potential in metastatic breast cancer patients. Since the approval of tumor drug indications by NPMA in China is often later than the release of the latest research data, the National Health Commission issued "the guiding principles for the clinical application of new antitumor drugs" in 2020. The principle pointed out that under special circumstances such as the absence of better treatment, medical institutions should manage the usage of drugs that are not clearly defined in the instructions but have evidence-based data. Based on the latest research progress in breast cancer, the consensus writing expert group collated published reports, international academic conferences, conducted analysis, discussion and summary, collected data on the use of small molecule anti-vascular targeting drugs for advanced breast cancer, and formulated "expert consensus on the application of small molecule anti-angiogenic drugs in the treatment of advanced breast cancer" . For clinicians' reference only.

Off-label drug use in an adult intensive care unit of a Brazilian hospital

Abstract The objective of this study was to determine the prevalence and describe the factors associated with off-label drug use in an adult intensive care unit (ICU) of a Brazilian hospital. An analytical, cross-sectional, prospective study was conducted in the adult ICU population from March 2018 to May 2018. Off-label use of medication was classified by indication, dosage, route of administration, type and volume of diluent, and duration of administration. Most patients were female (57.89%), non-elderly (56.14%), and had a mean age of 54.44 ± 17.15 years. The prevalence of off-label drug use was 70.31%, but was not associated with the clinical severity of the patients. A statistically significant association was observed between label use of drugs and prescribing potentially inappropriate medicines (PIM). The most common reasons for off-label drug use were therapeutic indication (19.58%) and volume of diluent (23.30%). Drug administration by enteral tubes accounted for the largest number of off-label uses due to route of administration (90.85%). There was a higher prevalence of off-label use of systemic antimicrobials (14.44%) and norepinephrine (9.28%). Our study provided a broad characterization of off-label drug use in an adult ICU and showed why it is important for health professionals to evaluate the specific risks and benefits of this practice

Prescrição de medicamentos off-label e sem licença para prematuros de unidade de terapia intensiva neonatal / Prescription of off-label and unlicensed drugs for preterm infants in a neonatal intensive care unit

RESUMO Objetivo: Avaliar o uso de medicamentos off-label e sem licença em recém-nascidos prematuros hospitalizados em unidade de terapia intensiva neonatal. Métodos: Estudo de coorte não concorrente, incluindo prematuros admitidos em três unidades de terapia intensiva neonatais, nos anos de 2016 e 2017, acompanhados durante o período neonatal. O uso de medicamentos e o número foram registrados para todo o período e classificados segundo a Anatomical Therapeutic Chemical. Foram realizadas análises descritivas e bivariadas dos dados para avaliar associações entre o número de medicamentos utilizados (total, off-label e sem licença) e as variáveis explicativas de interesse. Resultados: Os 400 neonatos prematuros utilizaram 16.143 medicamentos, com 86 especialidades diferentes; 51,9% desses itens foram classificados como off-label e 23,5% como sem licença. Os mais prescritos foram gentamicina e ampicilina (17,5% e 15,5% dos off-label, respectivamente) e cafeína (75,5% dos não licenciados). O estudo demonstrou associações significativas do uso de medicamentos off-label com a menor idade gestacional, baixo peso ao nascer, menor escore de Apgar no quinto minuto, manobra de reanimação avançada em sala de parto e óbito. Com os medicamentos não licenciados, foram verificadas associações com a menor idade gestacional, baixo peso ao nascer e escore de Apgar no quinto minuto menor que 7. Conclusão: Os neonatos internados em unidades de terapia intensiva neonatais são muito expostos ao uso de medicamentos off-label e sem licença. Tornam-se necessários mais investimentos em estudos para alcançar maior segurança e qualidade da terapêutica medicamentosa empregada em neonatologia.

ABSTRACT Objective: To evaluate the use of off-label and unlicensed medications in preterm infants hospitalized in a neonatal intensive care unit. Methods: This nonconcurrent cohort study included preterm infants admitted to 3 neonatal intensive care units in 2016 and 2017 who were followed up during the neonatal period. The type and number of medications used were recorded for the entire period and classified based on the Anatomical Therapeutic Chemical. Descriptive and bivariate data analyses were performed to assess associations between the number of drugs used (total, off-label and unlicensed) and the explanatory variables of interest. Results: Four hundred preterm infants received 16,143 prescriptions for 86 different pharmaceuticals; 51.9% of these medications were classified as off-label and 23.5% as unlicensed. The most prescribed drugs were gentamicin and ampicillin (17.5% and 15.5% among off-label, respectively) and caffeine (75.5% among unlicensed). The results indicated significant associations between the use of off-label drugs and lower gestational age, low birth weight, lower 5-minute Apgar score, advanced resuscitation maneuver in the delivery room and death. The prescription of unlicensed drugs was associated with lower gestational age, low birth weight and 5-minute Apgar score below 7. Conclusion: Neonates admitted to neonatal intensive care units are highly exposed to off-label and unlicensed medications. Further studies are needed to achieve greater safety and quality of drug therapy used in neonatology.

Suplementación de testosterona durante el climaterio en mujeres con trastorno por deseo sexual hipoactivo / Testosterone supplementation during the climacteric period in women with hypoactive sexual desire disorder

A partir del caso de una paciente con trastorno por deseo sexual hipoactivo durante su climaterio y a través del resumen de los resultados de dos revisiones sistemáticas, los autores de este artículo revisan la evidencia sobre la suplementación con andrógenos para el tratamiento de esta condición clínica. Concluyen que su uso sería relativamente seguro a corto plazo, aunque su eficacia no alcanzaría la relevancia clínica y no contamos aún con mayor información sobre la seguridad en el largo plazo. Los autores destacan además que el abordaje de las pacientes con este problema de salud debería ser realizado en forma integral, incluyendo opciones terapéuticas no farmacológicas e informando sobre las incertidumbres todavía presentes. (AU)

Based on the case of a patient with hypoactive sexual desire disorder during her climacteric period and through the summary of the results of two systematic reviews, the authors of this article review the evidence supporting androgen supplementation for the treatment of this clinical condition. They conclude that its use would be relatively safe in the short term, although its efficacy would not reach clinical relevance and no further information on long-term safety is available. The authors also highlight that patients with this health problem should be approached comprehensively, including non-pharmacological therapeutic options and providing information on the uncertainties still present. (AU)

Use of off-label medications in a neonatal intensive care unit / Uso de medicamentos off-label em unidade de terapia intensiva neonatal

ABSTRACT Objective: This paper aims to analyze the use of off label (OL) medicines, according to the National Regulatory Agency, in a neonatal intensive care unit of a high-risk maternity hospital in Northeast Brazil. Methods: A cross-sectional study was carried out, using a convenience sample of newborns that used mechanical ventilation at the Intensive Care Unit. As a reference, OL medications were considered for those without an approval for newborn usage by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA) and by the Food and Drugs Administration (FDA). Results: The sample consisted of 158 newborns, 58.3% male, 87.7% premature, and 70.2% of low or very low birth weight. According to ANVISA, 440 out of the 1,167 prescriptions analyzed were OL, with 98.1% of newborns exposed to at least one of these drugs. According to the FDA, 484 prescriptions were OL, with 75.8% of newborns exposed to at least one of them. Anti-infectives were the most prescribed OL medications. Neonates who presented respiratory failure and pneumonia used these drugs more often; and there was no relation between their use and the number of deaths. Conclusions: Nearly all newborns at the Intensive Care Units, mainly preterm infants, are exposed to at least one off-label (OL) medication during hospital stay, according to the national and international regulatory agencies. No association was found between off-label prescriptions and the frequency of complications or neonatal deaths.

RESUMO Objetivo: Analisar o uso de medicamentos off-label (OL), segundo a agência reguladora nacional, em unidade de terapia intensiva neonatal de uma maternidade de alto risco em Aracaju. Métodos: Foi realizado um estudo transversal, utilizando amostra de conveniência de recém-nascidos (RN) da Unidade Intensiva, que fizeram uso de ventilação mecânica. Consideramos OL o medicamento que não era liberado para uso em RN nos bulários eletrônicos da Agência Nacional de Vigilância Sanitária (ANVISA) e da U.S. Food and Drug Administration (FDA). Resultados: A amostra consistiu de 158 neonatos, sendo 58,3% do sexo masculino, 87,7% prematuros e 70,2% com baixo ou muito baixo peso. De acordo com a ANVISA, das 1.167 prescrições analisadas, 440 foram OL, com 98,1% dos RN expostos a pelo menos um desses medicamentos. Já para a FDA, 484 prescrições foram OL, com 75,8% dos neonatos expostos a pelo menos um deles. As medicações OL mais prescritas foram os anti-infecciosos. Neonatos que apresentaram insuficiência respiratória e pneumonia fizeram mais uso deles e não houve relação entre o seu uso e o número de óbitos. Conclusões: Quase todos os RN internados, principalmente os prematuros, foram expostos a pelo menos um medicamento OL, de acordo com a agência reguladora nacional e internacional, durante a internação. Entretanto, isso não teve relação com a frequência de complicações nem de óbitos neonatais.

Prescripción e indicaciones de uso de fluoroquinolonas en un grupo de pacientes ambulatorios de Colombia / Prescription and indications for the use of fluoroquinolones in a group of outpatients in Colombia

Introducción. Existen evidencias sobre el uso indiscriminado de antibióticos en el tratamiento de diversas enfermedades. Objetivo. Determinar los patrones de prescripción y de indicaciones de uso de las fluoroquinolonas en un grupo de pacientes ambulatorios en Colombia. Materiales y métodos. Se llevó a cabo un estudio descriptivo farmacoepidemiológico del tipo de prescripción e indicaciones de uso a partir de una base de datos poblacionales que incluía pacientes con prescripciones ambulatorias de fluoroquinolonas entre mayo y octubre de 2018. Se recabó la información sobre las variables sociodemográficas, farmacológicas y clínicas (diagnóstico según la Clasificación Internacional de Enfermedades, versión 10) y se estableció la proporción del uso de fluoroquinolonas en indicaciones aprobadas y no aprobadas por las agencias reguladoras. Resultados. Se identificaron 23.373 pacientes que habían recibido fluoroquinolonas; su edad media era de 47,9 ± 18,1 años y 15.767 eran mujeres (67,5 %). La ciprofloxacina fue el medicamento más prescrito (n=19.328; 82,7 %), seguida de la norfloxacina (n=3.076; 13,2 %), la levofloxacina (n=573; 2,5 %) y la moxifloxacina (n=394; 1,7 %). Las principales indicaciones fueron la infección de las vías urinarias en sitio no especificado (n=10.777; 46,1 %), la diarrea y la gastroenteritis de presunto origen infeccioso (n=3.077, 13,2 %) y la cistitis aguda (n=956; 4,2 %). El 76 % (n=17.759) de las prescripciones correspondía a indicaciones aprobadas y el resto a usos no aprobados, como la rinofaringits o las infecciones de tejidos blandos. El ser hombre (odds ratio, OR=1,26; IC95%: 1,18-1,34) y tener menos de 35 años (OR=1,92; IC95%:1,48-1,50) se asociaron con una mayor probabilidad de uso de fluoroquinolonas en indicaciones no aprobadas. Conclusión. Las fluoroquinolonas, en particular la ciprofloxacina, se están prescribiendo especialmente a mujeres con infecciones de las vías urinarias, pero hasta la cuarta parte de los pacientes las recibieron para usos no aprobados por las agencias reguladoras.

Introduction: There is evidence of the indiscriminate use of antibiotics for different pathologies. Objective: To determine the prescription patterns and indications for the use of fluoroquinolones in a group of outpatients in Colombia. Materials and methods: We conducted a descriptive pharmaco-epidemiological study on prescription-indication using a population database where patients with outpatient fluoroquinolone prescriptions were included from May to October, 2018. We obtained the information on sociodemographic, pharmacological, and clinical variables, as well as on the diagnosis according to the International Classification of Diseases, version 10, and we established if the use was approved by the regulatory agencies or if it was off-label. Results: A total of 23,373 patients were identified who were using fluoroquinolones; their mean age was 47.9 ± 18.1 years and women predominated (n=15,767, 67.5%). Ciprofloxacin was the medication most commonly prescribed (n=19,328, 82.7%), followed by norfloxacin (n=3076, 13.2%), levofloxacin (n=573, 2.5%), and moxifloxacin (n=394; 1.7%). The main indications were urinary tract infection in unspecified site (n=10,777, 46.1%), diarrhea and gastroenteritis of presumed infectious origin (n=3077, 13.2%), and acute cystitis (n=956; 4.2%). The prescriptions followed approved indications in 76% (n=17,759) of cases while the rest were used off-label or without indication for nasopharyngitis or soft-tissue infections, for example. Being male (OR=1.26, 95%CI:1.18-1.34) and under 35 years of age (OR=1.92, 95%CI:1.48-1.50) were associated with a greater probability of using fluoroquinolones in unapproved indications. Conclusions: Fluoroquinolones, particularly ciprofloxacin, are being prescribed especially to women with urinary tract infections, but up to a quarter of the patients received them for unapproved indications by regulatory agencies.

Lineamientos técnicos para la farmacovigilancia de los medicamentos de uso off-label utilizados en pacientes ingresados por COVID-19 / Technical guidelines for pharmacovigilance of off-label drugs used in patients admitted for COVID-19

El presente documento describe los aspectos técnicos y logísticos necesarios a tener en cuenta para implementar la farmacovigilancia especial intrahospitalaria, sobre el uso de medicamentos off-label autorizados, según el "plan de acciones reguladoras para la implementación de opciones 8 terapéuticas y diagnósticas en situaciones de riesgo sanitario en El Salvador" para el manejo clínico de pacientes con enfermedad COVID-19; también, es una herramienta de apoyo para los profesionales de la salud que estarán en la primera línea de atención hospitalaria para la detección, identificación o sospecha de posibles reacciones adversas, interacciones medicamentosas u otros riesgos asociados al uso de estos, así mismo para la prevención de errores de medicación en el manejo de los pacientes y la notificación oportuna de dichos eventos

This document describes the technical and logistical aspects necessary to take into account to implement special intra-hospital pharmacovigilance, on the use of authorized off-label drugs, according to the "regulatory action plan for the implementation of therapeutic and diagnostic options in situations of health risk in El Salvador "for the clinical management of patients with COVID-19 disease; It is also a support tool for health professionals who will be in the first line of hospital care for the detection, identification or suspicion of possible adverse reactions, drug interactions or other risks associated with the use of these, as well as for prevention of medication errors in the management of patients and the timely notification of such events

Análisis del uso de fármacos fuera de indicación autorizada en hematología y oncología / Analysis of the "Off label" drug use in hematology and oncology

Resumen Objetivo: El uso de medicamentos en condiciones diferentes a las autorizadas es el uso de medicamentos en condiciones distintas a las incluidas en su ficha técnica. El objetivo del presente trabajo es analizar las solicitudes de medicamentos fuera de ficha técnica y sus resultados, realizadas por el Servicio de Oncología y Hematología en un hospital de segundo nivel. Materiales y métodos: Se realiza un estudio observacional retrospectivo de todas las peticiones de fármacos "off label" recibidas por el Servicio de Farmacia. Los medicamentos se clasifican según impacto económico, una clasificación propia según el tipo de fármaco y motivo de petición y según su grado de evidencia. Se analiza para cada solicitud los datos demográficos, de diagnóstico y de tratamiento de los pacientes. Se presenta un seguimiento de los efectos adversos, mediana de supervivencia libre de progresión y mediana de supervivencia global. Resultados: Se aprueban 85 solicitudes de tratamiento. La mayoría de los tratamientos son de alto impacto dirigidos principalmente a patologías raras y últimas opciones de tratamiento. Un 22% de las solicitudes presentan alto grado de evidencia. La media de supervivencia libre de progresión (SLP) es de 6,6 meses (IC 95% 5,2-8) y la supervivencia global (SG) es de 9,7 meses (IC95% 8,2-11,2). Un 18,7% de pacientes presentan toxicidad de grado 3-4 al recibir el tratamiento. Conclusiones: A pesar de la heterogeneidad de las patologías, y la baja evidencia, los resultados obtenidos en SLP y SG, junto a la escasa toxicidad obliga a seguir avanzando en la evaluación de este tipo de tratamientos.

Abstract Background and objective: the use of off-label drugs is the use of medications in conditions other than those included in its prescribing information. The objective of this paper is to analyze the off-label drugs applications and their results, performed by the Oncology and Hematology services in a second level hospital. Materials and methods: A retrospective observational study of all requests for "off label" drugs received by the Pharmacy Service is carried out. The drugs are classified according to economic impact, a classification according to the type of drug and the reason for the request and according to the degree of evidence. The demographic, diagnostic and treatment data of the patients are analyzed for each request. A follow-up of adverse effects, median progression-free survival and median overall survival is presented. Results: 85 treatment requests are approved. Most of the treatments are high impact, mainly aimed at rare pathologies and last treatment options. 22% of the requests have a high degree of evidence. Progression free survival (PFS) and overall survival (OS) are 6.6 (95% CI 5.2-8) and 9.7 months (95% CI 8.2-11.2). 18.7% of patients have grade 3-4 toxicity when receiving treatment. Conclusions: Despite the heterogeneity of the pathologies, and the low evidence, the results obtained in SLP and SG, together with the low toxicity, force us to continue advancing in the evaluation of this type of treatments.