Evaluation of proactive therapeutic drug monitoring application in infliximab users in ulcerative colitis

Objective: To evaluate the application of proactive pro-drug therapy (TDM) at week six in users of infliximab therapy in ulcerative colitis patients and to analyze the need for further disease optimization. Method: This is a retrospective analysis that will be carried out simultaneously at the Hospital de Clínicas de Passo Fundo and at the Endoclin Diagnostic Center in the city of Passo Fundo, with secondary data collection between January 2020 and May 2022. The sample included patients from both sexes, regardless of age, who are being followed up in the services mentioned above, by signing the informed Free and Clarified Consent Term. Results: 63.2% of patients required optimization of their treatment based on the serum level assessment at week six. Conclusion: Proactive TDM performed at week six benefits patients in order to complete indications for treatment to avoid lack of drug response and complications from the disease. (AU)

Therapeutic drug monitoring in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a problem that directly affects the quality of life of patients suffering from this condition. Monitoring the serum level of infliximab (IFX) (TDM) is an important tool for guiding therapeutic decisions in IBD patients. The purpose of this study was to determine the significance of quantitatively measuring the serum level of IFX (TDM) and antibody to IFX (ATI). Methods and materials: Prospective observational study involving 40 IBD patients on IFX therapy, including 14 Proactive (week 06 of the induction phase) and 26 Reactive (maintenance phase). Immediately prior to the infusion, blood samples were drawn and measured using a Bulhlmann rapid test instrument. Serum concentrations of IFX were categorized as supratherapeutic (>7.0 micrograms/ml), therapeutic (between 3.0 and 7.0 micrograms/ml), and subtherapeutic (3.0 micrograms/ml). When the serum concentration of IFX was 3 mcg/ml (subtherapeutic), the ATI was measured. 25 patients with CD and 15 patients with UC were evaluated. Only three of the twenty patients with subtherapeutic serum levels had a positive ATI, and both were reactive; two had CD and one had UC. There was a statistically significant difference between reactive and proactive patients with respect to levels of CRP (p = 0.042), with proactive DNS patients suffering greater alterations in CRP and albumin. (AU)

Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases / 中国实验血液学杂志

OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. In this way, the objective is analyzing the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients' records, in which the patient's profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (± 5.4) different medicines after the transplantation, and 7.4 (± 4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs' effects were related to, mainly, increase their immunosuppressant activity. Conclusion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs' effects to prevent and minimize side effects in transplanted recipients.

Therapeutic drug monitoring of gabapentin: the applicability in patients with neuropathic pain

Abstract Gabapentin is an antiepileptic drug prescribed for several neuropathic pain conditions. This study aimed to evaluate gabapentin (GAB) trough plasma concentration range and the applicability of therapeutic drug monitoring in patients with neuropathic pain. Fifty-three patients with neuropathic pain, aged 20 to 75, received gabapentin as treatment for at least 7 days. Gabapentin plasma concentration was sampled before GAB administration and quantified by liquid chromatography with a UV detector. GAB trough plasma concentration ranged between 0.40 and 11.94 µg/mL in patients with chronic neuropathic pain. No differences were observed in terms of GAB plasma concentrations between responsive and non-responsive patients. Our data suggest that the reference ranges suggested in the literature for patients with epilepsy should not be used for patients with neuropathic pain. Therapeutic drug monitoring of GAB was shown to be an important tool to assess treatment adherence.

Identifying adverse drug events in patients at a pediatric ward in a Brazilian hospital: application and performance of the triggers / Identificação de eventos adversos a medicamentos em pacientes de enfermaria pediátrica em um hospital brasileiro: aplicação e desempenho de rastreadores

Abstract Objectives: to evaluate the performance of a trigger tool in identifying adverse drug events (ADE) in hospitalized children. Methods: a retrospective cohort study review on 133 medical records at a federal maternal and child reference hospital in Rio de Janeiro in 2016. A list of 14 triggers was developed to detect ADE in the pediatric population. Three steps were performed: (1) search for triggers; (2) selection of suspected cases of ADE and (3) final determination of ADE by experts' consensus. Results: 360 triggers were identified in 100 hospitalizations (75.2%), with an average of 2.7 triggers/ hospitalization. The most frequent triggers were "abrupt medication stop" (79.7%); "antiemetics use" (8.9%) and "laxatives use" (7.2%); while the "diphenhydramine use", "phytomenadione use" and "excessive sedation/lethargy/fall/hypotension" obtained the highest performance indicating ADE every time they occurred. Thirty-one ADE were identified in 12.8% of the hospitalizations; 11 (35.5%) ADE were detected without the aid of the triggers thus, pruritus and diarrhea were the most frequent. Conclusion: the trigger tool proved to be useful in identifying ADE in hospitalized children, especially if high performance and high frequency triggers are used in identifying the events. The inclusion of the triggers "diarrhea" and "pruritus", may favor the identification of ADE in patients at pediatric wards.

Resumo Objetivos: avaliar o desempenho de uma ferramenta de rastreamento de eventos adversos a medicamentos (EAM) em crianças hospitalizadas. Métodos: estudo de coorte retrospectivo com revisão de 133 prontuários de hospital federal de referência materno infantil no Rio de Janeiro, em 2016. Uma lista de 14 rastreadores foi usada para detecção de EAM na população pediátrica. Foram realizadas 3 etapas: (1) busca de rastreadores; (2) seleção dos casos suspeitos de EAM e (3) determinação final do EAM por consenso entre especialistas. Resultados: foram identificados 360 rastreadores em 100 internações (75,2%), com média de 2,7 rastreadores/internação. Os rastreadores mais frequentes foram "interrupção abrupta da medicação" (79,7%); "uso de antieméticos" (8,9%) e "uso de laxantes" (7,2%) enquanto que "uso de difenidramina", "uso de fitomenadiona" e "excesso de sedação/letargia/queda/hipotensão" obtiveram o maior rendimento indicando EAM em todas as vezes que ocorreram. Trinta e um EAM foram identificados em 12,8% das internações; 11(35,5%) EAM foram detectados sem auxílio dos rastreadores, sendo prurido e diarreia os mais frequentes. Conclusão: a ferramenta de rastreadores mostrou-se útil para a identificação de EAM em crianças hospitalizadas, principalmente se forem utilizados rastreadores com alto rendimento e alta frequência na identificação de eventos. A inclusão dos rastreadores diarreia e prurido pode favorecer a identificação de EAM em pacientes de enfermaria pediátrica.

Impacto del monitoreo terapéutico de vancomicina y amikacina en la optimización de dosis de antimicrobianos en pacientes pediátricos / Impact of the vancomycin and amikacin therapeutic monitoring in the optimization of antimicrobial dose in pediatric patients

INTRODUCCIÓN: La monitorización de antimicrobianos mediante sus concentraciones plasmáticas permite determinar la posología óptima de éstos, conducta esencial en pediatría. OBJETIVOS: Describir la monitorización de concentraciones plasmáticas de antimicrobianos y el ajuste de dosis en población pediátrica para determinar si las dosis utilizadas alcanzan rangos terapéuticos. PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo, utilizando una base de datos con medición de concentraciones plasmáticas de amikacina y vancomicina en pacientes pediátricos del Hospital San Borja Arriarán, entre 2015-2018. Se determinó el número de pacientes que alcanzó rango terapéutico con dosis inicial, cuántos requirieron ajuste y sus características. RESULTADOS: Se monitorizó 104 concentraciones totales. Para vancomicina 65 concentraciones plasmáticas eran basales encontrándose fuera de rango terapéutico 56,5%; de los que requirieron ajuste, 25% fueron neonatos con mayor probabilidad de estar fuera de rango versus otros (p = 0,022). Para amikacina la Cpeak estuvo en rango en 60% de mediciones; 15,4% requirió ajuste incluyendo pacientes con fibrosis quística y oncológicos. No fue necesario efectuar ajustes en pacientes sin co-morbilidad. CONCLUSIÓN: La medición de concentraciones plasmáticas es necesaria para ajustar de forma individualizada la dosis, especialmente en pacientes pediátricos con fibrosis quística, oncológicos y en neonatología, donde es más probable no alcanzar rango terapéutico con las dosis iniciales.

BACKGROUND: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics. AIM: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges. METHODS: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined. RESULTS: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity. CONCLUSION: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.

Consideraciones sobre los eventos trombóticos posteriores a la administración de la vacuna de AstraZeneca contra COVID-19 en Europa / Considerations for Thrombotic Events Following AstraZeneca COVID-19 Vaccine Administration in Europe

En las campañas de vacunación, como en la actual situación de COVID-19, es habitual que los países señalen posibles efectos adversos después de la vacunación. Esto no significa necesariamente que los eventos estén relacionados con la vacunación en sí, pero es necesario investigarlos. También muestra que el sistema de vigilancia funciona y que existen controles efectivos. La Organización Mundial de la Salud (OMS) está en contacto regular con la Agencia Europea de Medicamentos (EMA) y otras autoridades reguladoras del mundo para obtener la información más reciente sobre la seguridad de todas las vacunas para COVID-19.

Utilização da monitorização terapêutica com níveis séricos de infliximabe nas doenças inflamatórias intestinais: um algoritmo simplificado baseado em evidências / Induction therapeutic drug monitoring regimen with infliximab: a simplified evidence-based algorithm for inflammatory bowel disease

ABSTRACT Therapeutic drug monitoring (TDM) of infliximab (IFX) has been recognized as an important strategy in the management of secondary loss of response to this agent, guiding clinical decision-making in the management of inflammatory bowel diseases (IBD). Although most of the data on the application of TDM for IFX refer to the maintenance phase of treatment, many studies have associated higher drug concentrations, specially in the induction phase, with achievement of important treatment targets, such as clinical remission and mucosal healing. This brief communication aims to summarize the literature on the use of TDM during induction phase of IFX and propose application of a simplified approach which can be useful into clinical practice, aiming better outcomes to IBD patients.

RESUMO A monitorização terapêutica dos níveis séricos (Therapeutic drug monitoring - TDM) de infliximabe (IFX) é uma estratégia reconhecida na tomada de decisão clínica frente a perda de resposta secundária a esta droga no manejo das doenças inflamatórias intestinais (DII). Embora a maioria dos dados sobre a aplicação dessa estratégia para IFX se refira à fase de manutenção do tratamento, muitos estudos associaram concentrações mais altas de IFX, especialmente na fase de indução, com o alcance de importantes alvos de tratamento, como remissão clínica e cicatrização da mucosa. Este artigo visa resumir as evidências da literatura sobre o uso de níveis séricos durante a fase de indução do IFX e propor a aplicação de uma abordagem simplificada que pode ser extremamente útil na prática clínica, visando melhores resultados para os pacientes.

Principios de estadística Bayesiana y su relación con la farmacocinética aplicada / Principles of Bayesian statistics and its relationship with applied pharmacokinetics

La metodología estadística Bayesiana permite, si se conoce la probabilidad poblacional de que un suceso ocurra, modificar su valor cuando se dispone de nueva información individual. Aunque las metodologías Bayesiana y frecuentista (clásica) tienen idénticos campos de aplicación, la primera se aplica cada vez más en investigación científica y análisis de big data. En la farmacoterapia moderna, la farmacocinética clínica ha sido responsable de la expansión de la monitorización, facilitada por desarrollos técnico-analíticos y matemático-estadísticos. La farmacocinética poblacional ha permitido identificar y cuantificar las características fisiopatológicas y de tratamiento en una población de pacientes determinada, en particular en pediatría y neonatología, y otros grupos vulnerables, explicando la variabilidad farmacocinética interindividual. Asimismo, la estimación Bayesiana resulta importante como herramienta estadística aplicada en programas informáticos de optimización farmacoterapéutica cuando la monitorización farmacológica se basa en la interpretación farmacocinética clínica. Aunque con ventajas y limitaciones, la optimización farmacoterapéutica basada en la estimación Bayesiana es cada vez más usada en la actualidad, siendo el método de referencia. Esto es particularmente conveniente para la práctica clínica de rutina debido al limitado número de muestras requeridas por parte del paciente, y a la flexibilidad en cuanto a los tiempos de muestreo de sangre para cuantificación de fármacos. Así, la aplicación de los principios Bayesianos a la práctica de la farmacocinética clínica resulta en la mejora de la atención farmacoterapéutica.

If one knows the probability of an event occurring in a population, Bayesian statistics allows mo difying its value when there is new individual information available. Although the Bayesian and frequentist (classical) methodologies have identical fields of application, the first one is increasin gly applied in scientific research and big data analysis. In modern pharmacotherapy, clinical phar macokinetics has been used for the expansion of monitoring, facilitated by technical-analytical and mathematical-statistical developments. Population pharmacokinetics has allowed the identification and quantification of pathophysiological and treatment characteristics in a specific patient popu lation, especially in the pediatric and neonatal population and other vulnerable groups, explaining interindividual variability. Likewise, Bayesian estimation is important as a statistical tool applied in pharmacotherapy optimization software when pharmacological monitoring is based on clinical phar macokinetic interpretation. With its advantages and despite its limitations, pharmacotherapeutic op timization based on Bayesian estimation is increasingly used, becoming the reference method today. This characteristic is particularly convenient for routine clinical practice due to the limited number of samples required from the patient and the flexibility it shows regarding blood sampling times for drug quantification. Therefore, the application of Bayesian principles to the practice of clinical phar macokinetics has led to the improvement of pharmacotherapeutic care.

Implementação de um protocolo de monitorização terapêutica de vancomicina em adultos / Implementation of a vancomycin therapeutic monitoring protocol in adults / Implementación de un protocolo de monitoreo terapéutico de vancomicina en adultos

Justificativa e objetivos: A Monitorização Terapêutica de Fármacos (MTF) é uma importante ferramenta na otimização da terapia com vancomicina, utilizada no tratamento de infecções graves causadas por bactérias Gram-positivas. O objetivo deste estudo foi implementar um protocolo de monitoramento terapêutico de vancomicina em um hospital e descrever as características clínicas, laboratoriais e de uso deste medicamento após sua implementação. Métodos: Para o desenvolvimento do protocolo, foram utilizados os consensos internacionais sobre MTF de vancomicina. Os dados dos pacientes adultos foram coletados dos prontuários e das estimativas do software farmacocinético. Resultados: O protocolo de vancomicina foi implementado na instituição hospitalar e disponibilizado ao corpo clínico. Foram avaliados 49 pacientes. A vancomicina foi indicada principalmente para tratar pneumonia 15 (30,6%). Entre os microrganismos identificados, Staphylococcus aureus foi o mais presente ­ 8 (50%), e 9 (56,3%) das culturas eram resistentes à oxacilina. Média de uso de vancomicina foi 10,6 (± 6,6) dias, e dose de ataque foi administrada em 33 (67,3%) dos pacientes. Apresentaram insuficiência renal aguda 5 (11,1%) pacientes. O monitoramento das concentrações mínimas no vale (Cmin) de vancomicina ocorreu em 43 (87,8%) pacientes. Na primeira medição, 16 deles (37,2%) apresentaram Cmin inferiores a 10 mcg/dL, e 11 (25,6%), superiores a 20 mcg/dL, dados considerados fora da faixa terapêutica. Conclusão: A elaboração de um protocolo de MTF para a vancomicina orienta o uso racional e seguro desse antibiótico. Formação continuada em recursos humanos e investimento em softwares farmacocinéticos para ajustes de doses podem contribuir para a otimização da terapia com vancomicina.(AU)

Background and objectives: Therapeutic Drug Monitoring (TDM) is an important tool in optimizing vancomycin therapy, a drug used to treat serious infections caused by gram-positive bacteria. The aim of this study was to implement a protocol for the therapeutic monitoring of vancomycin in hospitals and to describe the clinical, laboratory and use characteristics of this drug after its implementation. Methods: The international consensus on vancomycin TDM was used for protocol development. Patient data were collected from medical records and pharmacokinetic software estimates. Results: The vancomycin protocol was implemented at a hospital and made available to the clinical staff. We evaluated 49 patients. Vancomycin was prescribed mainly to treat pneumonia 15 (30.6%). Among the identified microorganisms, Staphylococcus aureus was the most common with 8 cases (50%), and 9 (56.3%) patients were resistant to oxacillin. The average use of vancomycin was 10.6 (± 6.6) days and the loading dose was administered in 33 (67.3%) patients. A total of 5 (11.1%) patients had acute renal failure. Monitoring of Minimal Concentrations in the vancomycin valley (Cmin) occurred in 43 (87.8%) patients. In the first measurement, 16 of them (37.2%) presented Cmin below 10 mcg/dL and 11 (25.6%) above 20 mcg/dL, data considered outside the therapeutic range. Conclusion: The elaboration of an MTF protocol for vancomycin guides the rational and safe use of this antibiotic. Continued training in human resources and investment in dose-adjusting pharmacokinetic software may contribute to the optimization of vancomycin therapy.(AU)

Justificación y objetivos: La monitorización terapéutica de medicamentos (MTF) es una importante herramienta para optimizar la terapia con vancomicina, utilizada para tratar infecciones graves causadas por bacterias grampositivas. El objetivo de este estudio fue implementar un protocolo de MTF de vancomicina en el hospital y describir las características clínicas, de laboratorio y de uso de vancomicina después de su implementación. Métodos: El consenso internacional sobre vancomicina MTF se utilizó para el desarrollo del protocolo. Los datos de los pacientes adultos se obtuvieron de los registros médicos y las estimaciones del software farmacocinético. Resultados: El protocolo se implementó en el hospital y se puso a disposición al personal clínico. Se evaluaron 49 pacientes. La vancomicina fue indicada para pneumonía 15 (30,6%). Entre los microorganismos identificados, Staphylococcus aureus fue el más presente 8 (50%) y 9 (56,3%) de los cultivos fueron resistentes a oxacilina. El promedio del uso de vancomicina fue de 10,6 (± 6,6) días, y la dosis de ataque se administró en 33 (67,3%) pacientes. La insuficiencia renal aguda se encontró en 5 (11,1%) pacientes. El monitoreo de concentraciones mínimas en el valle de vancomicina (Cmin) ocurrió en 43 (87,8%) pacientes. En la primera medición, 16 de ellos (37,2%) presentaron Cmin por debajo de 10 mcg/dL, y 11 (25,6%), por encima de 20 mcg/dL, datos considerados fuera del rango terapéutico. Conclusión: La elaboración de un protocolo de MTF para vancomicina guía el uso racional y seguro de ese antibiótico. La capacitación continua en recursos humanos y la inversión en softwares farmacocinéticos de ajuste de dosis pueden contribuir a la optimización de la terapia con vancomicina.(AU)

Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units

Abstract Purpose The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. Methods Intermittent therapy was administered for 60 minutes and prescribed as a loading dose of 30 mg/kg and continued with 15 mg/kg q12 h. Continuous infusion was prescribed as a loading dose of 30 mg/kg followed by 30 mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1 h before third dose, 1 h, 8 h and 24 h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1 h after loading dose, 12 h, 24 h, 36 h, and 48 h after continuous infusion initiation. Results Median serum concentration of continuous infusion group at 24-hour was 23.59 µg/mL [14.52-28.97], while of intermittent infusion group at 23-hour was 12.30 µg/mL [7.27-18.12] and on 25-hour was 17.58 µg/mL [12.5-22.5]. Medians AUC24-48h were 357.2 mg.h/L and 530.2 mg.h/L for intermittent infusion and continuous infusion groups, respectively (p = 0.559). Conclusion Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.

Estudio del índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida / Study of the level/dose index of phenytoin in volunteer epileptic patients from Mérida

INTRODUCCIÓN La fenitoína es usada con mucha frecuencia en nuestro medio, por lo que se requiere hacer estudios de monitorización terapéutica, que contribuya a minimizar los efectos adversos y optimizar la terapia farmacológica. En ese contexto, nuestro objetivo ha sido determinar el índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida. MÉTODOS Se realizó un estudio descriptivo, observacional y por reclutamiento consecutivo concurrente, conformado por 30 pacientes voluntarios con diagnóstico de epilepsia. Las muestras de suero se obtuvieron en niveles mínimos de pacientes que estaban en tratamiento con fenitoína durante 1 mes. Los niveles del fármaco se cuantificaron por el método de Inmunoensayo de enzima donante clonada en el equipo Indiko Thermo Scientific. RESULTADOS El índice nivel/dosis fue de 1,4 y 1,6, la concentración plasmática de 4,8mg/l y 8,0mg/l, la capacidad metabólica de 388,4 y 462,9mg/día, respectivamente en mujeres y hombres. Mientras que el nivel de la concentración plasmática en el estado estacionario fue de 6,5mg/l y 5,5mg/l, la dosis de carga máxima de 237,3mg y de 395,6mg, respectivamente en mujeres y hombres con epilepsia de la ciudad de Mérida. CONCLUSIONES Nuestros resultados sugieren que se debe individualizar la dosis en base al índice nivel/dosis de cada paciente, ya que no se puede extrapolar para todos los pacientes con epilepsia, debido a diversos factores como al fenotipo metabólico y al uso de fármacos inductores e inhibidores enzimáticos.

INTRODUCTION Phenytoin is used very frequently in our environment, so it is necessary to do studies of therapeutic monitoring, which helps to minimize adverse drug reaction and optimize pharmacological therapy. In this context, our objective was to determine the level/dose index of phenytoin in volunteer epileptic patients from Mérida. METHODS A descriptive, observational and consecutive concurrent recruitment study was carried out, consisting of 30 volunteer patients with a diagnosis of epilepsy. The serum samples were obtained in minimum levels from patients who were in treatment with phenytoin for 1 month. The levels of the drug were quantified by the method of donor enzyme immunoassay cloned in the Indiko Thermo Scientific equipment. RESULTS The level/dose index was 1,4 and 1,6, the plasma concentration of 4,8mg/l and 8,0mg/l, the metabolic capacity of 388,4 and 462,9mg/day, respectively in women and men. While the level of plasma concentration at steady state was 6,5mg/l and 5,5mg/l, the maximum loading dose of 237,3mg and 395,6mg, respectively in women and men with epilepsy of the city of Mérida. CONCLUSIONS Our results suggest that the dose should be individualized based on the level/dose index of each patient, since it can not be extrapolated for all patients with epilepsy, due to various factors such as the metabolic phenotype and the use of enzyme-inducing drugs and inhibitors.

Monitoring compliance with Clinical Protocol and Therapeutic Guidelines for Alzheimer's disease / Monitoramento do cumprimento do protocolo clínico e diretrizes terapêuticas da doença de alzheimer

ABSTRACT Dementia is a chronic neurodegenerative disease and Alzheimer's disease (AD) is the most prevalent type. Objective: To describe the drug monitoring of patients enrolled in a Clinical Protocol and Therapeutic Guidelines of Alzheimer's Disease (PCDTDA) in Brazil. Methods: A descriptive study based on interviews conducted in 2017 was performed. Patients diagnosed with Alzheimer's disease (AD) enrolled on the PCDTDA were included. The variables assessed were age, sex, time since diagnosis, clinical parameters of Mini-Mental State Exam (MMSE) and Clinical Dementia Rating (CDR), drug therapy used and AD drug collection. Results: The drug monitoring of 143 patients was evaluated. Observing the requirements of the screening tests for patient enrolment on the PCDTDA, all patients had scores for at least one MMSE and CDR assessment at protocol admission. None of the patients underwent the first reassessment of the effectiveness of AD drug therapy or the semiannual reassessment. Conclusion: Although PCDTDA provides the best evidence of AD treatment, the data showed failures in the monitoring of the effectiveness of AD drug therapy at dispensing.

RESUMO A demência é uma doença crônica e neurodegenerativa, e a doença de Alzheimer (DA) é a mais prevalente. Objetivo: Descrever o monitoramento da farmacoterapia de pacientes inseridos no Protocolo Clínico e Diretrizes Terapêuticas da Doença de Alzheimer (PCDTDA), Brasil. Métodos: Estudo descritivo, conduzido por meio de entrevistas em 2017. Foram incluídos pacientes com diagnóstico da doença de Alzheimer (DA) inseridos no PCDTDA. As variáveis foram idade; sexo; tempo de diagnóstico e farmacoterapia da DA; os parâmetros clínicos Mini-exame do estado mental (MEEM) e Clinical Dementia Rating (CDR); e farmacoterapia em uso. Resultados: O monitoramento de 143 pacientes foi avaliado. Considerando a exigência dos testes de rastreio para a inserção do paciente no PCDTDA, observou-se que todos os pacientes tinham pelo menos um escore no MEEM e no CDR na admissão no protocolo. Nenhum paciente foi submetido à primeira reavaliação da efetividade da farmacoterapia da DA e nem à reavaliação semestral. Conclusão: Apesar do PCDTDA ser a maior evidência do tratamento da DA, dados evidenciam falhas no monitoramento da efetividade da farmacoterapia da DA na dispensação.

Development and validation of a method for phenobarbital in serum: anticonvulsant pharmacotherapy monitoring

The therapeutic drug monitoring (TDM) is an important strategy for the effectiveness and safety of long-term pharmacotherapy, such as the use of phenobarbital as an anticonvulsant drug in epilepsy. In this sense, HLPC has been presented as a technique for the measurement of phenobarbital in serum. However, the ideal conditions for carrying out the method must be established for each laboratory reality. An analytical method using HPLC was developed and validated in order to identify and quantify Phenobarbital in blood. The chromatographic conditions were C-18 column (Shimpack XR-ODS 50L x 3.0), acetonitrile-water mobile phase (30:70, v v-1), 0.2 mL min-1 flow and reading wavelength of 210 nm. Linearity was established in the range of 2.5 to 80 µg mL-1, the linear correlation coefficient was 0.9981. The average of the coefficient of variation of the precision was 5.30%. The relative standard error of the accuracy was -2.17% and of the recovery coefficient was 97.83%. In all eleven patients, phenobarbital concentrations were below the therapeutic range. The tested method was selective, linear, precise, accurate and showed good recovery.(AU)

Análise da notificação de eventos adversos através da pesquisa de cultura de segurança do paciente / Adverse event notification analysis through patient safety culture research / Análisis de la notificación de eventos adversos a través de la investigación de cultura de seguridad del paciente

Objetivo: a avaliação da cultura de segurança do paciente permite aos hospitais identificar e gerir prospectivamente questões relevantes de segurança em suas rotinas de trabalho. Método: estudo quantitativo, transversal e descritivo, ocorrida no ano de 2017 na Unidade de Terapia Intensiva Adulta em um hospital privado, localizado em Niterói/RJ. A população foram os profissionais médicos e equipe de enfermagem, utilizando análise estatística por meio de programa R, com a interface Rcmdr. Resultados: baseados nas respostas às perguntas sobre notificação de eventos aplicada com a Pesquisa de Cultura de Segurança do Paciente a 97 profissionais, com uma taxa de resposta de 85,6%, correspondendo a 83 profissionais. Menos de 45% dos participantes da pesquisa sempre notificam um erro, engano ou falha, que afete ou não o paciente, 59,0% não fizeram nenhuma notificação nos últimos 12 meses antecedentes à pesquisa e não houve diferença significativa na quantidade de notificação que destacasse uma categoria profissional, graduados ou não. Discussão: houve maior adesão à notificação de eventos pelos com maior tempo de hospital e com maior tempo naquela terapia intensiva. Não se encontrou correlação do número de notificações relatadas com o tempo de profissão e com a carga horária de trabalho. Conclusão: no que tange à conscientização de incrementar a adesão à notificação de eventos, a análise realizada contribuiu para a melhoria da segurança do paciente

Objective: ealuating the patient's safety culture allows hospitals to identify and manage relevant safety issues prospectively in their work routines. Method: a quantitative, transversal and descriptive study, carried out in 2017 at the Adult Intensive Care Unit in a private hospital, located in Niterói / RJ. The population were medical professionals and nursing staff, using statistical analysis through program R, with the Rcmdr interface. Results: based on responses to questions about event notification applied with the Patient Safety Culture Survey to 97 professionals, with a response rate of 85.6%, corresponding to 83 professionals. Less than 45% of respondents report an error, deception, or failure, affecting the patient, 59.0% did not report in the last 12 months prior to the survey, and there was no significant difference in the amount of notification that stood out a professional category, graduates or not. Discussion: there was greater adherence to the notification of events by those with longer hospital time and with more time in that intensive therapy. There was no correlation between the number of reports reported with the time of profession and the workload. Conclusion: with regard to the awareness of increasing adherence to event notification, the analysis performed contributed to the improvement of patient safety

Objetivo: la evaluación de la cultura de seguridad del paciente permite a los hospitales identificar y gestionar prospectivamente cuestiones relevantes de seguridad en sus rutinas de trabajo. Método: estudio cuantitativo, transversal y descriptivo, ocurrido en el año 2017 en la Unidad de Terapia Intensiva Adulta en un hospital privado, ubicado en Niterói / RJ. La población fueron los profesionales médicos y equipo de enfermería, utilizando análisis estadístico por medio del programa R, con la interfaz Rcmdr. Resultados: basados en las respuestas a las preguntas sobre notificación de eventos aplicada con la Encuesta de Cultura de Seguridad del Paciente a 97 profesionales, con una tasa de respuesta del 85,6%, correspondiendo a 83 profesionales. En la mayoría de los casos, la mayoría de las personas que sufren de la enfermedad de Alzheimer, una categoría profesional, graduados o no. Discusión: hubo mayor adhesión a la notificación de eventos por los con mayor tiempo de hospital y con mayor tiempo en aquella terapia intensiva. No se encontró correlación del número de notificaciones relatadas con el tiempo de profesión y con la carga horaria de trabajo. Conclusión: en lo que concierne a la concientización de incrementar la adhesión a la notificación de eventos, el análisis realizado contribuyó a la mejora de la seguridad del paciente