Prolonged Beta-Lactam Infusions in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess whether beta-lactam extended or continuous beta-lactam infusions (EI/CI) improve clinical outcomes in children with proven or suspected bacterial infections. STUDY DESIGN: We included observational and interventional studies that compared beta-lactam EI or CI with standard infusions in children less than 18 years old, and reported on mortality, hospital or intensive care unit length of stay, microbiological cure, and/or clinical cure. Data sources included PubMed, Medline, EBM Reviews, EMBASE, and CINAHL and were searched from January 1, 1980, to November 3, 2023. Thirteen studies (2945 patients) were included: 5 randomized control trials and 8 observational studies. Indications for antimicrobial therapies and clinical severity varied, ranging from cystic fibrosis exacerbation to critically ill children with bacteriemia. RESULTS: EI and CI were not associated with a reduction in mortality in randomized control trials (n = 1464; RR 0.93, 95% CI 0.71, 1.21), but were in observational studies (n = 833; RR 0.43, 95% CI 0.19, 0.96). We found no difference in hospital length of stay. Results for clinical and microbiological cures were heterogeneous and reported as narrative review. The included studies were highly heterogeneous, limiting the strength of our findings. The lack of shared definitions for clinical and microbiological cure outcomes precluded analysis. CONCLUSIONS: EI and CI were not consistently associated with reduced mortality or length of stay in children. Results were conflicting regarding clinical and microbiological cures. More well-designed studies targeting high-risk populations are necessary to determine the efficacy of these alternative dosing strategies.

Opioid prescribing for cancer pain in Latin America: systematic review.

OBJECTIVE: To explore opioid prescribing patterns for cancer pain in Latin America (LA). METHODS: A systematic review was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Relevant databases, including MEDLINE, EMBASE, PubMed, LILACS and Scielo, were searched from inception to June 2023. Empirical studies of opioid prescription patterns in adult palliative care patients with cancer pain were included. Methodological quality was assessed using the Effective Public Health Practice Project tool. Data were analysed using narrative synthesis. Descriptive statistical analyses were conducted using SPSS V.28 (IBM). Categorical variables were summarised using frequencies and percentages and continuous variables as means or medians. RESULTS: Seventeen studies from six countries were included. Ten were observational, while seven were experimental, including five randomised controlled trials (RCT) and two non-RCT. Most were low or moderate methodological quality. Out of 7809 patients, morphine (54%) and tramadol (18%) were the most prescribed opioids. The median of morphine equivalent daily dose was 26 mg (IQR 26-41). CONCLUSION: Latin America shows lower opioid consumption rates compared with high-income countries for control pain management (CPM). More rigorous research on CPM in LA is needed. Additionally, a comprehensive review of opioid prescription patterns, including non-cancer diagnoses, is necessary.

Efficacy of different routes of acetaminophen administration for postoperative pain in children: a systematic review and network meta-analysis.

PURPOSE: Acetaminophen is the most common drug used to treat acute pain in the pediatric population, given its wide safety margin, low cost, and multiple routes for administration. We sought to determine the most efficacious route of acetaminophen administration for postoperative acute pain relief in the pediatric surgical population. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that included children aged between 30 days and 17 yr who underwent any type of surgical procedure and that evaluated the analgesic efficacy of different routes of administration of acetaminophen for the treatment of postoperative pain. We searched MEDLINE, CENTRAL, Embase, CINAHL, LILACs, and Google Scholar databases for trials published from inception to 16 April 2023. We assessed the risk of bias in the included studies using the Cochrane Risk of Bias 1.0 tool. We performed a frequentist network meta-analysis using a random-effects model. Our primary outcome was postoperative pain using validated pain scales. RESULTS: We screened 2,344 studies and included 14 trials with 829 participants in the analysis. We conducted a network meta-analysis for the period from zero to two hours, including six trials with 496 participants. There was no evidence of differences between intravenous vs rectal routes of administration of acetaminophen (difference in means, -0.28; 95% confidence interval [CI], -0.62 to 0.06; very low certainty of the evidence) and intravenous vs oral acetaminophen (difference in means, -0.60; 95% CI, -1.20 to 0.01; low certainty of the evidence). For the comparison of oral vs rectal routes, we found evidence favouring the oral route (difference in means, -0.88; 95% CI, -1.44 to -0.31; low certainty of the evidence). Few trials reported secondary outcomes of interest; when comparing the oral and rectal routes in the incidence of nausea and vomiting, there was no evidence of differences (relative risk, 1.20; 95% CI, 0.81 to 1.78). CONCLUSION: The available evidence on the effect of the administration route of acetaminophen on postoperative pain in children is very uncertain. The outcomes of postoperative pain control and postoperative vomiting may differ very little between the oral and rectal route. Better designed and executed RCTs are required to address this important clinical question. STUDY REGISTRATION: PROSPERO (CRD42021286495); first submitted 19 November 2021.

RéSUMé: OBJECTIF: Compte tenu de sa large marge de sécurité, de son faible coût et de ses multiples voies d'administration, l'acétaminophène est le médicament le plus couramment utilisé pour traiter la douleur aiguë dans la population pédiatrique. Nous avons cherché à déterminer la voie d'administration d'acétaminophène la plus efficace pour le soulagement de la douleur aiguë postopératoire dans la population chirurgicale pédiatrique. MéTHODE: Nous avons réalisé une revue systématique d'études randomisées contrôlées (ERC) qui ont inclus des enfants âgé·es de 30 jours à 17 ans ayant bénéficié de n'importe quel type d'intervention chirurgicale et qui ont évalué l'efficacité analgésique de différentes voies d'administration d'acétaminophène pour le traitement de la douleur postopératoire. Nous avons mené des recherches dans les bases de données MEDLINE, CENTRAL, Embase, CINAHL, LILAC et Google Scholar pour en tirer les études publiées depuis leur création jusqu'au 16 avril 2023. Le risque de biais dans les études incluses a été évalué à l'aide de l'outil de Risque de biais 1.0 de Cochrane. Nous avons réalisé une méta-analyse de réseau fréquentiste à l'aide d'un modèle à effets aléatoires. Notre critère d'évaluation principal était la douleur postopératoire mesurée à l'aide d'échelles de douleur validées. RéSULTATS: Nous avons passé en revue 2344 études et inclus 14 études incluant un total de 829 enfants dans l'analyse. Nous avons mené une méta-analyse en réseau pour une période allant de zéro à deux heures, comprenant six études avec 496 participant·es. Il n'y avait aucune preuve de différences entre les voies d'administraion intraveineuse vs rectale de l'acétaminophène (différence de moyennes, −0,28; intervalle de confiance [IC] à 95 %, −0,62 à 0,06; très faible certitude des données probantes) et entre les voies intraveineuse vs orale (différence de moyennes, −0,60; IC 95 %, −1,20 à 0,01; faible certitude des données probantes). Pour la comparaison des voies orale vs rectale, nous avons trouvé des données probantes en faveur de la voie orale (différence de moyennes, −0,88; IC 95 %, −1,44 à −0,31; faible degré de certitude des données probantes). Peu d'études ont rapporté des résultats secondaires d'intérêt; en comparant les voies orale et rectale dans l'incidence des nausées et des vomissements, il n'y avait aucune preuve de différences (risque relatif, 1,20; IC 95 %, 0,81 à 1,78). CONCLUSION: Les données probantes disponibles sur l'effet de la voie d'administration de l'acétaminophène sur la douleur postopératoire chez les enfants sont très incertaines. Les résultats de contrôle de la douleur postopératoire et de vomissements postopératoires peuvent différer très peu entre la voie orale et la voie rectale. Des ERC mieux conçues et mieux exécutées sont nécessaires pour répondre à cette importante question clinique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021286495); première soumission le 19 novembre 2021.

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

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

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

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

Clinical pharmacy in hospital palliative medicine: non-randomised clinical trial.

OBJECTIVE: To assess the impact of pharmaceutical care on hospital indicators and clinical outcomes of palliative care (PC) patients admitted to a secondary hospital. METHODS: A non-randomised clinical trial was carried out in the PC ward of a secondary hospital in São Paulo, Brazil. Pharmaceutical care for all patients aged 18 and above, admitted between October 2021 and March 2022, with stays exceeding 48 hours, was provided. The interventions required were performed in collaboration with healthcare teams, patients and caregivers. Assessments occurred at admission and discharge, using PC performance scales and pharmacotherapy tools, with Research Ethics Committee approval. RESULTS: Over 6 months, 120 hospitalisations were analysed, primarily involving women (58.9%), averaging 71.0 years, with neoplasm diagnoses (20.5%). A total of 170 drug-related problems were identified in 68.3% of patients. Following assessment, 361 interventions were performed, with a 78.1% acceptance rate, including medication dose adjustments, additions and discontinuations. Addressing unintentional pharmacotherapy discrepancies at admission led to reduced hospital stays (p<0.05). Pharmaceutical interventions also decreased pharmacotherapy complexity (p<0.001), inappropriate medications for the older people (p<0.001) and improved symptom management, such as pain (p<0.05). CONCLUSIONS: Pharmaceutical care services integrated within the multiprofessional health team contributed to reducing drug-related problems associated with polypharmacy as well as improved the management PC symptoms in end-of-life patients, which reduced hospitalisation time.

The Potential of Films as Transmucosal Drug Delivery Systems.

Pharmaceutical films are polymeric formulations used as a delivery platform for administration of small and macromolecular drugs for local or systemic action. They can be produced by using synthetic, semi-synthetic, or natural polymers through solvent casting, electrospinning, hot-melt extrusion, and 3D printing methods, and depending on the components and the manufacturing methods used, the films allow the modulation of drug release. Moreover, they have advantages that have drawn interest in the development and evaluation of film application on the buccal, nasal, vaginal, and ocular mucosa. This review aims to provide an overview of and critically discuss the use of films as transmucosal drug delivery systems. For this, aspects such as the composition of these formulations, the theories of mucoadhesion, and the methods of production were deeply considered, and an analysis of the main transmucosal pathways for which there are examples of developed films was conducted. All of this allowed us to point out the most relevant characteristics and opportunities that deserve to be taken into account in the use of films as transmucosal drug delivery systems.

Evaluation of the economic benefits, administration times, and patient preferences associated with the use of biotechnological drugs administered subcutaneously and intravenously in patients with cancer: a systematic review.

INTRODUCTION: Cancer imposes a high economic burden with medical care and medication costs. We evaluate the costs, the use of resources, the administration time, and the patient preferences associated with the use of biotechnological drugs in SC and IV presentations. METHODOLOGY: A systematic literature search was conducted in PubMed, Embase, and seven additional databases. The search was carried out in September 2021 and included only studies directly comparing SC and IV presentations. Evidence was synthesized narratively. RESULTS: 34 references were included, which only analyzed bortezomib, daratumumab, rituximab, and trastuzumab. Reduction in preparation costs of SC compared to IV presentations ranged from 6.6% to 50.1%, and in administration costs from 4.5% to 95.3%. SC administration of rituximab and trastuzumab resulted in less productivity loss. More than 68% of patients reported greater satisfaction with the SC route. A reduction of time in the infusion chair, lower costs of resources for preparation, and health personnel for the administration process were identified with SC administration. CONCLUSIONS: The use of SC daratumumab, rituximab, and trastuzumab in patients with cancer reduces direct and indirect costs and adverse events compared to IV use. Patients prefer the SC administration, perceiving more comfort, and less pain at the administration site.

Why Are We Still a Worm World in the 2020s? An Overview of Risk Factors and Endemicity for Soil-Transmitted Helminthiasis.

PURPOSE: Soil-transmitted helminthiasis (STH) is one of the most common chronic infections in developing countries associated with poor socioeconomic and sanitary conditions. The main objective of this overview was to evaluate the influence of environmental factors, risk factors related to the host, and control strategies on the prevalence of STH in different regions of the world. METHODS: LILACS, PubMed, Web of Knowledge, Embase, the Cochrane Library, and Clinical Trials (gray literature) databases were used to obtain the systematic reviews published until December 2020. The methodological quality of systematic reviews was assessed using the standard criteria recommended by AMSTAR. RESULTS: The initial results of the bibliographic search identified 1448 articles, of which 66 studies were read in full and 16 met the inclusion criteria. All the reviews included in this overview associated variations in the global prevalence of STH with at least one of the factors related to the environment, host, and/or control strategies. Climate, temperature, soil moisture, precipitation, mass drug administration, lack of access to water, sanitation and hygiene (WASH), and non-use of footwear were considered the main factors associated with the prevalence of STH. Socioeconomic factors, low educational level, and wearing shoes were universal factors related to prevalence, regardless of the location studied. CONCLUSION: The combination of environmental factors, with factors associated with hosts that predispose infection and reinfection of helminths, as well as the adoption of control strategies based on the treatment of target populations instead of the entire population, influenced the prevalence of STH in all the continents evaluated.

Pharmacological Modulation of Temporal Discounting: A Systematic Review.

Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.

Incorporação de esomeprazol em um hospital universitário: uma análise de custo-minimização / Incorporation of esomeprazole in a university hospital: a cost-minimization analysis

Introdução: Inibidores de bomba de prótons (IBP) são amplamente utilizados na profilaxia de úlceras de estresse. O omeprazol é o IBP mais prescrito no Brasil, porém, sua formulação oral convencional é inadequada para administração por sonda devido ao risco de obstrução. A apresentação injetável de omeprazol possui custo muito superior à formulação oral. O esomeprazol, por ser constituído de microgrânulos, é uma alternativa ao omeprazol injetável, pois pode ser administrado por sonda e ainda possibilitaria redução de custos. Objetivo: Analisar por meio de custo-minimização o impacto financeiro da incorporação do esomeprazol em um hospital universitário secundário. Material e Métodos: Estudo observacional transversal retrospectivo para identificar e analisar o consumo e custo relacionado ao uso de omeprazol injetável e esomeprazol nos anos de 2021 e 2022. A partir dos dados levantados, foi realizada análise de custo-minimização e determinado o impacto financeiro após incorporação do esomeprazol. Resultados: Houve redução de 76,7% no consumo de omeprazol injetável no ano de 2022. A análise de custo-minimização apontou um custo real de R$20.374,96 no ano de 2022, referente às 906 doses utilizadas no período, destas, 46,4% eram de omeprazol injetável e 53,6% de esomperazol. Considerando o cenário com terapia exclusiva com omeprazol injetável, o custo simulado foi de R$ 41.252,05. O impacto financeiro foi de R$ -20.877,09, resultando em economia de recursos de 50,6%. Conclusão: A incorporação de esomeprazol no elenco de medicamentos de um hospital universitário gerou redução significativa de custo, implicando em economia de mais de 50% no consumo global de IBP e de mais de 70% no consumo de omeprazol injetável, no ano de 2022.

Introduction: Proton pump inhibitors (PPIs) are widely used in stress ulcers prophylaxis. Omeprazole is the most prescribed PPI in Brazil, but its conventional oral formulation is unsuitable for administration through a tube due to the risk of obstruction. The injectable presentation of omeprazole has a much higher cost than the oral formulation. Esomeprazole, composed of microgranules, is an alternative to injectable omeprazole as it can be administered through a tube and could potentially lead to a cost reduction. Objective: To analyze, through cost minimization, the financial impact of incorporating esomeprazole in a secondary university hospital. Material and Methods: A retrospective cross-sectional observational study was conducted to identify and analyze the consumption and cost related to the use of injectable omeprazole and esomeprazole in the years 2021 and 2022. Cost-minimization analysis was performed based on the collected data, to determine the financial impact after incorporating esomeprazole. Results: There was a 76.7% reduction in the consumption of injectable omeprazole in 2022. The cost-minimization analysis indicated a real cost of R$20,374.96 in 2022 for the 906 doses used during the period, of which 46.4% were injectable omeprazole and 53.6% were esomeprazole. Considering the scenario with exclusive therapy using injectable omeprazole, the simulated cost was R$41,252.05. The financial impact was R$-20,877.09, resulting in a resource saving of 50.6%. Conclusion: The incorporation of esomeprazole into the list of medications at a university hospital led to a significant cost reduction, resulting in over 50% savings in PPI consumption and over 70% in injectable omeprazole consumption, in 2022.

Evolution of pediatric pharmaceutical forms for treatment of Hansen's disease (leprosy).

INTRODUCTION: Leprosy is a neglected, infectious, granulomatous and chronic disease caused by the pathological agent Mycobacterium leprae. The course of the disease is more aggressive in patients under 15 years of age, but the current treatment offered worldwide consists of solid forms, by the combination of antibiotics such as rifampicin, clofazimine and dapsone. This represents results in lack of adherence in pediatric patients and drug therapy failure, although numerous formulations and technologies have already been developed. AREA COVERED: This study aims to analyze the technological evolution of the pharmaceutical treatment of leprosy, aimed at children. A review of patents around the world was conducted to look for technical and clinical aspects of formulations and devices. EXPERT OPINION: Innovative formulations for pediatric patients were classified according to the routes of administration as oral, inhalable, injectable and transdermal. The formulations were organized as alternatives for pediatric therapy, taking into account the physicochemical aspects of drugs and the physiological aspects of pediatric patients. Among the difficulties for the patented formulations to reach the market, of special note is the low stability of the physicochemical characteristics of the drugs. Optimization of formulations would favor the pediatric treatment of leprosy, aiming at therapeutic success.

En casos de escabiosis ¿Cuál es la efectividad de tratar farmacológicamente al grupo familiar y contactos comunitarios versus tratar solo al grupo familiar?: síntesis rápida de evidencia / In cases of scabies, what is the effectiveness of pharmacologically treating the family group and community contacts versus treating only the family group?: rapid evidence synthesis

ANTECEDENTES Y OBJETIVO La escabiosis tiene una prevalencia estimada en 200 millones de personas alrededor del mundo. Su tratamiento consiste en alternativas de uso tópico y administración oral. Sin embargo, la prevención de contagios se dificulta cuando la escabiosis es endémica, ya que las condiciones de higiene y de hacinamiento favorecen la reinfección incluso cuando los contactos familiares han sido tratados previamente. Considerando lo anterior, ha cobrado relevancia como estrategia de control de la escabiosis, la administración masiva de medicamentos, que consiste en la administración del agente farmacológico a comunidades completas, independiente de si las personas presentan o no la enfermedad. En este contexto, el Departamento de Enfermedades Transmisibles ha solicitado el desarrollo de una síntesis de evidencia, con el objetivo de informar sobre el efecto que puede tener tratar a la comunidad versus solo a los contactos familiares. METODOLOGÍA Se formuló una estrategia de búsqueda para ser utilizada en las bases de datos MEDLINE y EMBASE a través de OVID y en Epistemonikos, Pubmed, BEIC, JBI y BVS con fecha 23 enero 2023. Se utiliza la metodología de la certeza de evidencia GRADE. Se incluyen documentos que aborden a la población general, el efecto de tratar farmacológicamente a contactos versus contactos comunitarios en Sarna/Escabiosis, outcomes de infección o reinfección. Se excluyen estudios que comparen la efectividad de medicamentos. RESULTADOS La cantidad de revisiones sistemáticas recuperadas fueron 2, de las que se obtuvieron los siguientes resultados - No se encontró evidencia que respondiera directamente a la pregunta por lo que se incluyeron estudios que evaluaban la efectividad de la Administración Masiva de Medicamentos. - No es posible establecer el efecto de tratar a los contactos comunitarios y familia sobre la prevalencia de escabiosis en comparación al tratamiento solo al grupo familiar, debido a que la certeza de la evidencia existente es muy baja. - La escasa evidencia identificada proviene de contextos endémicos de escabiosis, de comunidades pequeñas y aisladas por lo que la aplicabilidad de la evidencia a un contexto más amplio habría que evaluarla con precaución.

Administração de medicamentos por via intramuscular: caracterização dos vídeos brasileiros veiculados no YouTube® / Intramuscular drug administration: characterization of Brazilian videos on YouTube®

RESUMO Objetivo caracterizar os vídeos que contém a demonstração do procedimento de administração de medicamentos por via intramuscular em indivíduos adultos. Métodos estudo de corte transversal descritivo, foram selecionados 44 vídeos brasileiros disponíveis no YouTube® que abordavam o procedimento de administração de medicamentos por via intramuscular. Resultados a maioria dos vídeos selecionados é de origem pessoal (86,4%), tem como autor um técnico de Enfermagem (59,1%), adota a região dorsoglútea como local de injeção (54,5%), foi produzido em ambiente de saúde utilizando um paciente para a demonstração do procedimento (52,3%). Nenhum vídeo apresentou a completude do procedimento, sendo identificada grande frequência de erros em todas as etapas do procedimento. Observou-se uma diferença estatisticamente significante entre os testes de confiabilidade e popularidade dos vídeos (p=0,042). Conclusão os vídeos que abordam o procedimento de administração de medicamentos por via intramuscular disponíveis na plataforma YouTube® foram considerados atuais, de pouca relevância, elaborados por fontes não confiáveis, de baixa acurácia e frágil finalidade. Contribuições para a prática os vídeos disponíveis na plataforma YouTube® sobre a administração de medicamentos por via intramuscular não devem ser indicados como material educativo para a formação ou atualização profissional.

ABSTRACT Objective to characterize videos that contain a demonstration of the procedure for administering drugs intramuscularly to adults. Methods a descriptive cross-sectional study, 44 Brazilian videos available on YouTube® were selected which addressed the procedure of intramuscular drug administration. Results the majority of the videos selected are of personal origin (86.4%), were made by a Nursing technician (59.1%), used the dorsal gluteal region as the injection spot (54.5%), and were produced in a healthcare environment using a patient to demonstrate the procedure (52.3%). No video showed the completeness of the procedure, and a high frequency of errors was identified at all stages of the procedure. There was a statistically significant difference between the reliability and popularity tests of the videos (p=0.042). Conclusion the videos on intramuscular drug administration available on the YouTube® platform were considered to be up-to-date, of little relevance, produced by unreliable sources, of low accuracy, and with a weak purpose. Contributions to practice the videos available on the YouTube® platform on intramuscular drug administration should not be used as educational material for professional training or updating.

Trends and Perspectives of Biological Drug Approvals by the FDA: A Review from 2015 to 2021.

Despite belonging to a relatively new class of pharmaceuticals, biological drugs have been used since the 1980s, when they brought about a breakthrough in the treatment of chronic diseases, especially cancer. They conquered a large space in the pipeline of the pharmaceutical industry and boosted the innovation portfolio and arsenal of therapeutic compounds available. Here, we report on biological drug approvals by the US Food and Drug Administration (FDA) from 2015 to 2021. The number of drugs included in this class grew over this period, totaling 90 approvals, with an average of 13 authorizations per year. This figure contrasts with previous periods, which registered between 2 and 8 approvals per year. We highlight the great potential and advantages of biological drugs. In this context, these therapeutics show high efficacy and high selectivity, and they have brought about a significant increase in patient survival and a reduction of adverse reactions. The development and production of biopharmaceuticals pose a major challenge because these processes require cutting-edge technology, thereby making the drugs very expensive. However, we believe that, in the near future, biological medicines will be more accessible and new drugs belonging to this class will become available as new technologies emerge. Such advances will enhance the production of these biopharmaceuticals, thereby making the process increasingly profitable and less expensive, thereby bringing about greater availability of these drugs.

Transição de via de linezolida endovenosa para via oral: uma análise de custo-minimização / Switching from intravenous to oral linezolid therapy: a cost-minimization analysis

Objetivo: Comparar custos da terapia endovenosa exclusiva com linezolida com os custos da terapia iniciada por via endovenosa com transição para via oral após 72 horas, como estratégia de intervenção em programas de gestão de antimicrobianos. Métodos: Avaliação econômica de custo-minimização comparando custos diretos da terapia endovenosa exclusiva com linezolida com a terapia endovenosa seguida de transição para via oral em cenário simulado, sob a perspectiva do Sistema Único de Saúde (SUS), com árvore de decisão como modelo para tomada de decisão. Resultados: A alternativa englobando a transição de via mostrou-se a mais econômica em todos os cenários analisados. Para 28 dias de tratamento com linezolida, houve redução de 22% nos custos, considerando o paciente internado. Ao considerar alta após o sexto dia de tratamento, a redução de custos variou de 26%, com financiamento pelo SUS do restante do tratamento, a 84%, com financiamento do tratamento pós-alta pelo paciente. Conclusão: Conclui-se que a transição de via de linezolida é uma importante estratégia nos programas de gerenciamento de antimicrobianos, capaz de gerar economia significativa para a instituição. As avaliações econômicas de custo-minimização, nesse contexto, são uma importante ferramenta para demonstrar o aspecto econômico com potencial para sensibilizar gestores e tomadores de decisão.

Objective: To compare the direct costs of linezolid intravenous therapy with the costs of intravenous therapy switching to oral therapy after 72 hours as an intervention strategy in antimicrobial stewardship programs. Methods: Economic evaluation cost-minimization comparing direct costs of exclusive linezolid intravenous therapy with intravenous therapy for 72 hours and after switching to oral therapy in a simulated scenario, from the perspective of the National Health Service, with a decision tree as a decision modeling. Results: The alternative encompassing the therapy transition proved to be the most economical in all analyzed scenarios. For 28 days of treatment with linezolid, there was a 22% reduction in costs, considering the hospitalized patient. When considering discharge after the sixth day of treatment, the cost reduction ranged from 26%, with funding from the National Health Service for the rest of the treatment, to 84%, with funding for the post-discharge treatment by the patient. Conclusion: It was concluded that the linezolid therapy transition is an important strategy in antimicrobial management programs, capable of generating significant savings for the institution. In this context, economic cost-minimization assessments are an important tool to demonstrate the economic aspect with the potential to raise awareness among managers and decision-makers.

Etramp5 as a useful serological marker in children to assess the immediate effects of mass drug campaigns for malaria.

INTRODUCTION: Serological methods provide useful metrics to estimate age-specific period prevalence in settings of low malaria transmission; however, evidence on the use of seropositivity as an endpoint remains scarce in studies to evaluate combinations of malaria control measures, especially in children. This study aims to evaluate the immediate effects of a targeted mass drug administration campaign (tMDA) in Haiti by using serological markers. METHODS: The tMDA was implemented in September-October 2018 using sulfadoxine-pyrimethamine and single low-dose primaquine. A natural quasi-experimental study was designed, using a pretest and posttest in a cohort of 754 randomly selected school children, among which 23% reported having received tMDA. Five antigens were selected as outcomes (MSP1-19, AMA-1, Etramp5 antigen 1, HSP40, and GLURP-R0). Posttest was conducted 2-6 weeks after the intervention. RESULTS: At baseline, there was no statistical difference in seroprevalence between the groups of children that were or were not exposed during the posttest. A lower seroprevalence was observed for markers informative of recent exposure (Etramp5 antigen 1, HSP40, and GLURP-R0). Exposure to tMDA was significantly associated with a 50% reduction in the odds of seropositivity for Etramp5 antigen 1 and a 21% reduction in the odds of seropositivity for MSP119. CONCLUSION: Serological markers can be used to evaluate the effects of interventions against malaria on the risk of infection in settings of low transmission. Antibody responses against Etramp5 antigen 1 in Haitian children were reduced in the 2-6 weeks following a tMDA campaign, confirming its usefulness as a short-term marker in child populations.

Systemic, Intrathecal, and Intracerebroventricular Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models.

CTK 01512-2 toxin is a recombinant peptide of the Phα1ß version derived from the venom of the Phoneutria nigriventer spider. It acts as an N-type voltage-gated calcium channel (VGCC) blocker and shows a prolonged effect on preventing and reducing nociception. Herein, CTK 01512-2 was tested on two models of persistent pain, the chronic post-ischemia pain (CPIP) and the paclitaxel-induced peripheral neuropathy, to evaluate its systemic, intrathecal, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia. Glial cell viability was also investigated using the MTT test. The results showed that CTK 01512-2 intrathecal and systemic treatments reduced the mechanical hypersensitivity induced by CPIP, mainly between 1-4 h after its administration. Additionally, intrathecal treatment reduced the CPIP-induced thermal allodynia. In its turn, the intracerebroventricular treatment showed mechanical antihyperalgesic and thermal antiallodynic effects in the paclitaxel-induced peripheral neuropathy. These data reinforce the therapeutic potential of CTK 01512-2 to treat persistent pain conditions and offer a perspective to use the systemic route. Moreover, CTK 01512-2 increased the glial cell viability in the MTT reduction assay, and it may indicate a new approach to managing chronic pain. The results found in this study help to pave new perspectives of pain relief treatments to patients affected by chronic pain.

A Systematic Review on Cannabinoids for Neuropathic Pain Administered by Routes Other than Oral or Inhalation.

The use of cannabis and cannabinoid products for the treatment of neuropathic pain is a growing area of research. This type of pain has a high prevalence, limited response to available therapies and high social and economic costs. Systemic cannabinoid-based therapies have shown some unwanted side effects. Alternative routes of administration in the treatment of neuropathic pain may provide better acceptance for the treatment of multiple pathologies associated with neuropathic pain. To examine the efficacy, tolerability, and safety of cannabinoids (individualized formulations, phytocannabinoids, and synthetics) administered by routes other than oral or inhalation compared to placebo and/or conventional medications in the management of neuropathic pain. This systematic review of the literature reveals a lack of clinical research investigating cannabis by routes other than oral and inhalation as a potential treatment for neuropathic pain and highlights the need for further investigation with well-designed clinical trials. There is a significant lack of evidence indicating that cannabinoids administered by routes other than oral or inhaled may be an effective alternative, with better tolerance and safety in the treatment of neuropathic pain. Higher quality, long-term, randomized controlled trials are needed to examine whether cannabinoids administered by routes other than inhalation and oral routes may have a role in the treatment of neuropathic pain.

Macrocyclic lactone resistance in nematodes of cattle in Brazil: Blame it to the ticks!

Strategic helminth control in adult cattle would hardly impose sufficient selection pressure to parasite populations but reports of resistance against macrocyclic lactone (ML) based-products have been confirmed worldwide. The objective of this study was to evaluate the scientific literature of ML resistance (< 90.0% efficiency) in helminths of cattle from 2001 (the first report) to 2020 in Brazil. Additional to the data, we studied the correlation of parasite control practices based on a questionnaire given to 32 farmers. The search returned 246 reports and 21 full articles were selected. From these, a Wordcloud and a Keyword Co-occurrence Network graph were created. The published data revealed that most of the studies (19/21) reported multi-species (Cooperia spp., Haemonchus sp., Oesophagostomum radiatum, Trichostrongylus sp.) resistance to ML. None of the reports described the treatment frequency in the tested farms. As for the questionnaire, the majority of farmers (> 70.0%) responded that they rotate products after treatment, animals are treated monthly or biweekly (58.0%), treatments are based on visual evaluation (coat condition, ectoparasite infestation), and that in 94.0% of the times farmers treat all animals. Moreover, farmers use ML in association with potent acaricides (cypermethrin, chlorpyriphos, fluazuron) in more than 90.0% of the times (15/16). It was observed that this regimen was used to prevent and control the cattle-tick Rhipicephalus microplus (90.0%) and the horn-fly, Haematobia irritans (30.0%) infestations. We conclude that the most important factor for nematode resistance was the high level of ML exposure of up to 16 times/year, in combination with acaricides to control ticks and to a lesser extent to control horn-flies. Therefore, selection of helminth populations in cattle in Brazil can be considered secondary to ectoparasite control. The present analysis is critical, as one the most widespread recommendations to avoid drug resistance is to reduce the use of long-acting compounds, due to their extended persistent periods, increasing parasite selection. Moreover, a more serious attitude must be taken regarding parasite control strategies for livestock, reinforcing that health protocols should be based on single acaricidal products whenever possible. Complementary, selective evaluations based on transient threshold population abundance must be enforced to reduce treatment frequency, reducing parasite selection and animal distress.

In vitro transdermal drug permeation tests: a regulatory scenario evaluation

SUMMARY Introduction: The Transdermal Drug Delivery Systems (TDDS) could circumvent the inconveniences of oral administration, increasing treatment adhesion. Meanwhile, despite being highly widespread systems, there are discrepancies between the performance and quality control methodologies recommended by the leading regulatory agencies, which is an issue for the pharmaceutical industry. Aim: To identify and to compare the requirements for TDDS regulatory approval by important agencies, focusing on the in vitro release and drug permeation studies, which are crucial tests for the evaluation of safety, efficacy, and performance of these systems. Methods: The documents that regulate the scope of TDDS in FDA, EMA and Anvisa were analyze, as well as the contributions of OECD. In addition, an approaching regarding the pharmacopeial requirements was made regarding USA, Europe, and Brazil. Results and conclusion: Concerning the regulatory approval aspects, the FDA is reviewing its documents because the current guidance is not specific to transdermal systems. On the other hand, the EMA presents a unique guideline that includes specific requirements for TDDS. The USA and the European Pharmacopoeias have specific mentions to performance and quality control of TDDS, while the Brazilian Pharmacopoeia does not mention this dosage form. Recently, Anvisa published a guide, which helps Brazilian manufacturers concerning the tests required for the regulatory approval of a new TDDS. The launch of this standardized national statute associated with the use of a validated in vitro release and permeation tests represents a remarkable breakthrough regarding TDDS.

Introducción: los sistemas de administración de fármacos transdérmicos (TDDS) podrían sortear los inconvenientes de la administración por vía oral, aumentando la adherencia al tratamiento. Mientras tanto, a pesar de ser sistemas muy extendidos, existen discrepancias entre las metodologías de desempeño y control de calidad recomendadas por las principales agencias reguladoras, lo cual es un problema para la industria farmacéutica. Objetivo: identificar y comparar los requisitos para la aprobación regulatoria de TDDS por parte de las principales agencias reguladoras, enfocándose en los estudios de liberación in vitro y premiación de fármacos. Métodos: se analizaron los documentos que regulan el alcance de la TDDS en la FDA, EMA y Anvisa, así como los aportes de la OCDE. Además, se realizó un planteamiento sobre los requisitos de las farmacopeas de los Estados Unidos, Europa y Brasil. Resultados y conclusión: la FDA está revisando los aspectos de aprobación regulatoria porque la guía actual no es específica para los sistemas transdérmicos. Por otro lado, la EMA presenta una guía única que incluye requisitos específicos para TDDS. Las farmacopeas de los Estados Unidos e Europa tienen menciones específicas al rendimiento y control de calidad de TDDS, mientras que la Farmacopea brasileña no menciona esta forma de dosificación. Recientemente, Anvisa publicó una guía que ayuda a los fabricantes brasileños en cuanto a las pruebas requeridas para la aprobación regulatoria de un nuevo TDDS. El lanzamiento de este estatuto nacional estandarizado asociado con el uso de pruebas validadas de liberación y premiación in vitro representa un avance notable con respecto a TDDS.

Introdução: os sistemas de liberação transdérmica (SLT) são capazes de contornar as desvantagens da administração oral de medicamentos, aumentando a adesão ao tratamento. Entretanto, apesar de serem sistemas difundidos, existem discrepâncias entre as metodologias de desempenho e controle de qualidade recomendadas pelas agências regulatórias, dificultando o desenvolvimento destes pela indústria farmacêutica. Objetivo: identificar e comparar os requisitos para aprovação regulatória de SLT por importantes agências regulatórias, com foco nos estudos de liberação e permeação de fármacos in vitro, testes fundamentais para avaliação da segurança, eficácia e desempenho desses sistemas. Métodos: foram analisados os documentos que regulam o escopo dos SLT publicados pela FDA, EMA e Anvisa e as contribuições da OCDE. Além disso, foi realizada a abordagem sobre os requisitos farmacopeicos nos Estados Unidos, Europa e Brasil. Resultados e conclusão: FDA está revisando os aspectos de aprovação regulatória, pois os documentos atuais não são específicos para os SLT. Em contraponto, a EMA apresenta uma diretriz única que inclui requisitos específicos para estes sistemas. Em relação às farmacopeias, enquanto EUA e Europa apresentam recomendações específicas para desempenho e controle de qualidade dos SLT, a Farmacopeia brasileira não menciona esta forma farmacêutica. Recentemente, a Anvisa publicou um guia com os testes necessários para o registro destes sistemas. O lançamento de tal publicação, associado a ensaios devidamente validados representam um avanço notável no escopo regulatório dos SLT.