ABSTRACT The present study aimed to establish a population pharmacokinetic (PopPK) modeling of benznidazole (BZD) in Brazilian patients with chronic Chagas disease. This was part of a Brazilian prospective cohort study with eight patients diagnosed with Chagas disease during the beginning of BZD treatment up to the 60th day. On the 15th day of treatment, a blood sampling was collected and analyzed. A one-compartment PK model was developed using Pmetrics. Patients with an average age of 50.3 (SD: 6.2) years old, 6 female patients and 2 males, 70.2 kg (14.2), receiving a 5 mg/Kg/day dose were included. PK parameters estimated for CL, V and Ka were 6.27 L/h, 38.97 L and 1.66 h-1, respectively. This is the first study to establish a population pharmacokinetic modeling of BZD in Brazilian patients with chronic Chagas disease. Therefore, further studies are needed to obtain the complete characterization of BZD pharmacokinetics.

Abstract The hospital pharmacy needs a constant process of evaluation and monitoring of its activities. In Brazil, several agencies establish tasks and duties for pharmacists, but little is known about the compliance and the perception of the professional regarding these policies. The present study aims to characterize the pharmacist’s perception of Brazilian hospital pharmacy policies according to the Basel Statements. A search was performed for the contacts of all medium and high complexity hospitals in the country. Subsequently, a questionnaire elaborated following the Basel Statements was sent by e-mail to hospital pharmacists throughout the country. The domain analyzed was "Human Resources, Training, and Development". Statistical analyses were performed using SPSS 19.0. Pharmacists representing a total of 111 hospitals from all Brazilian regions answered the survey questionnaire and showed that more than half of the hospital pharmacists perceive themselves as not complying, whether in the service of local, national, or pharmaceutical education. Besides updating the professionals in relation to national policies, it is necessary that the representative bodies of the pharmaceutical class be more present in the elaboration and evaluation of the policies directed to human resources, seeking uniformity and the possibility of carrying out the activities required.

Abstract To analyze microbiological effectiveness of vancomycin in children from a pediatric hospital through population pharmacokinetic modelling, as well as to propose dose adjustment, a cross- sectional study was performed in children under vancomycin treatment from the John Paul II Children’s Hospital, MG. In order to establish a model, concentrations versus time curves were analyzed using a population pharmacokinetic approach with Pmetrics®. Seventeen blood samples of 10 patients were collected. The best model to describe vancomycin population pharmacokinetic (PK) consisted of a two-compartment linear intravenous absorption model. The R² value and bias for population and individuals in observed versus predicted plot was 0.642 vs. 0.992 and the bias of 0.41 mg/L and 0.0778 mg/L, respectively. The covariables creatinine clearance, age, and body mass index were related to vancomycin PK. A relevant PK variability for vancomycin in pediatric patients was verified, which was significantly influenced by creatinine clearance, age, and body mass index. This result justifies the formulation of dosing recommendations for vancomycin in pediatric patients to achieve adequate pharmacodynamics targets.

Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the “Interchangeable Pharmaceutical Product in the Treatment of Epilepsies” questionnaire was applied. The questionnaires “Adverse Events Profile” and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event “problems with skin” incresead (p=0.023) and “upset stomach” decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: “energy/fatigue” (p=0.048) and “total score” (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients’ perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients’ life.

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.

Abstract Evidence on factors associated with the progression of chronic kidney disease (CKD) is still under construction. The present study aimed to evaluate sociodemographic, clinical, and drug use factors associated with the progression of CKD. A retrospective cohort study was conducted with 193 patients with CKD stages 3A to 5- non-dialysis followed for three years in a Brazilian city. The outcome was the evolution to renal replacement therapy (RRT) or death. A total of 52.3 % (n = 101) were men and 83.4 % (n = 161) elderly. The median age was 72.0 years, and 22.3 % (n = 44) progressed to RRT or death, and the three-year mortality rate was 20.2 %. Participants exposed to angiotensin converting enzyme inhibitors or angiotensin II receptor blockers had a lower risk of progressing to the outcome (hazard ratio (HR) 0.25; p = 0.003) and higher survival (p = 0.022) when compared to those not exposed to these drugs. Age (HR 1.06;) and use of omeprazole (HR 6.25; CI; p <0.01) and hydrochlorothiazide (HR 2.80; p = 0.028) increased the risks of RRT or death. The results highlight the importance of rational management of pharmacotherapy for patients with CKD.

ABSTRACT Introduction: According to data from the World Health Organization, stroke is the second leading cause of death in middle-income countries, accounting for 12.8% of death for all causes. Objective: To identify the main risk factors associated with accidente cerebrovascular and serum inpatients treated in a public hospital in Paraguay. The population studied consisted of 43 patients aged 30 to 80 in a hospital of Pedro Juan Caballero, Amambay - Paraguay, during the period from January to December2019. Methodology: This is a descriptive observational cross-sectional study on a population of 43 patients aged 30 to 80 years treated at a hospital in Pedro Juan Caballero, Amambay - Paraguay, during the period January to December2019. The measured variables were age, sex, Arterial Hypertension, Diabetes Mellitus, Dyslipidemia and Smoking. Results: The age of highest prevalence for events of Ischemic ACV is from the age of 50 years in both sexes and the higher prevalence risk factors associated with ischemic vascular brain accident in hospital patient hospital were high blood pressure, followed by dyslipidemia. Conclusion: The epidemiology of ischemic ACV is characterized by a multifactorial etiology involving risk factors of different weight that enhance each other, as can be seen in this study the presence of two or more associated risk factors

Resumen Introducción: Según datos de la Organización Mundial de la Salud, el accidente cerebrovascular es la segunda causa de muerte en los países con ingresos medios, representando el 12,8% de mortalidad por todas las causas. Objetivo: Identificar los principales factores de riesgo asociados a accidente cerebrovascular isquémico en pacientes tratados en un hospital público del Paraguay. La población estudiada estuvo constituida por 43 pacientes de 30 a 80 años de edad atendidos en un hospital de Pedro Juan Caballero, Amambay - Paraguay, durante el periodo de enero a diciembre del 2019. Metodología: Se realizó un estudio observacional descriptivo de corte transversal sobre una población de 43 pacientes de 30 a 80 años de edad atendidos en el Hospital de Pedro Juan Caballero, Amambay - Paraguay, durante el periodo de enero a diciembre del 2019. Las variables medidas fueron la edad, el sexo, la Hipertensión Arterial, la Diabetes Mellitus, la Dislipidemia y el Tabaquismo. Resultados: La edad de mayor prevalencia para eventos de ACV Isquémico es a partir de los 50 años en ambos sexos y los factores de riesgo de mayor prevalencia asociados al accidente cerebro vascular isquémico en pacientes internados en el hospital fueron la hipertensión arterial, seguido de la dislipidemia. Conclusión: La epidemiología del ACV isquémico se caracteriza por tener una etiología multifactorial en el que intervienen factores de riesgo de diferente peso que se potencian entre sí, como se puede ver en este estudio con estos factores de riesgo asociados

Os principais objetivos do corrente estudo consistiram na tradução e adaptação do Achievement Emotions Questionnaire - Elementary School (AEQ-ES) para Português e na análise das suas propriedades psicométricas. Uma amostra de 350 alunos portugueses do terceiro e quarto ano de escolaridade (com idades compreendidas entre os 7 e os 12 anos) completou a versão portuguesa do AEQ-ES (AEQ-ES-P). Tal como a versão original, o AEQ-ES-P mede o prazer, o aborrecimento e a ansiedade dos alunos em relação à matemática em três contextos académicos: assistir a aulas, fazer os trabalhos de casa e fazer testes. A análise fatorial confirmatória corroborou a estrutura hierárquica do AEQ-ES-P, que também se mostrou invariante entre géneros e anos de escolaridade. O instrumento mostrou também boa fiabilidade e estabilidade temporal. Foram encontradas correlações significativas na direção esperada entre o prazer, a ansiedade e o aborrecimento, bem como entre essas emoções, as perceções de competência dos alunos e a sua motivação intrínseca para a matemática, apoiando assim a validade interna e externa do questionário. Estes resultados indicam que o AEQ-ES-P apresenta boas propriedades psicométricas e é adequado para medir as emoções de realização de crianças portuguesas do terceiro e do quarto ano de escolaridade no domínio da matemática.

The main purposes of the current research were to translate and adapt the Achievement Emotions Questionnaire - Elementary School (AEQ-ES) into Portuguese and to analyze its psychometric properties. A sample of 350 Portuguese third and fourth graders (aged 7 to 12 years) completed the Portuguese version of the AEQ-ES (AEQ-ES-P). As does the original version, the AEQ-ES-P measures students’ enjoyment, boredom, and anxiety toward mathematics in three academic settings: attending class, doing homework, and taking tests. Confirmatory factor analysis corroborated the hierarchical structure of the AEQ-ES-P, which was also invariant across gender and grades. The instrument also showed good reliability and temporal stability. Significant correlations were found in the expected direction between enjoyment, anxiety, and boredom, as well as between these emotions, students’ perceptions of competence, and intrinsic motivation toward mathematics, thus supporting the internal and external validity of the questionnaire. These results indicate that the AEQ-ES-P presents good psychometric properties and is suitable to measure the achievement emotions of Portuguese elementary-school children of the third and fourth grades in the domain of mathematics.

ABSTRACT The present study aimed to review the existing literature and to evaluate the best dose regimen for benznidazole in adult patients with Chagas disease in the chronic phase. A systematic review was conducted followed by meta-analysis. Searches were performed in four databases, to include studies published until May 2019. The descriptors used were: “Chagas disease”, “benznidazole”, “Drug Therapy”, “Pharmacokinetics”, “Dose-response relationship, drug” and “Chronic disease”. The meta-analysis compared studies using the standard dose of 5 mg/kg/day for 30 or 60 days. A total of 608 articles were found, 23 of which were considered eligible for this review and nine were included in the meta-analysis. The studies selected and analyzed were published between 1996 and 2018, with various benznidazole dose regimens, ranging from 2.5 mg/kg/day to 10 mg/kg/day, for 30 to 80 days of treatment. The results pointed to a great diversity of dose regimens, thus there is no consensus on the optimal dose regimen for benznidazole in the chronic phase of Chagas disease.

RESUMO Objetivo Adaptar um software de ajuste de dose de antibióticos inicialmente elaborado em língua inglesa para o português e a conjuntura brasileira. Métodos Trata-se de estudo observacional, descritivo, em que foi utilizado o método Delphi para estabelecer consenso entre especialistas de diferentes áreas da saúde, com perguntas que abordaram os aspectos visuais e operacionais do software. Em uma segunda etapa, foi realizado um estudo piloto, experimental, com alocação aleatória dos pacientes, para avaliação e adaptação do software em ambiente real de uma unidade de tratamento intensivo, onde foram comparadas diferenças entre pacientes que utilizaram dose padronizada usual de piperacilina/tazobactam, e os que utilizaram a dose individualizada ajustada por meio do software Individually Designed Optimum Dosing Strategies. Resultados Participaram da primeira rodada 12 profissionais cujas sugestões foram encaminhadas ao desenvolvedor do software para adequação e ajustes, e posteriormente submetidas à segunda rodada. Oito especialistas participaram da segunda rodada. Foram obtidos índices de 80% e 90% de concordância entre os juízes, caracterizando uniformidade nas sugestões. Dessa forma, houve modificação no layout do software para adequação linguística e cultural, minimizando erros de entendimento e contradições. Na segunda etapa, foram incluídos 21 pacientes, e não houve diferenças entre doses de piperacilina nos grupos dose padronizada e dose ajustada. Conclusão A versão adaptada do software é segura e confiável para seu uso no Brasil.

ABSTRACT Objective To adapt an antibiotic dose adjustment software initially developed in English, to Portuguese and to the Brazilian context. Methods This was an observational, descriptive study in which the Delphi method was used to establish consensus among specialists from different health areas, with questions addressing the visual and operational aspects of the software. In a second stage, a pilot experimental study was performed with the random comparison of patients for evaluation and adaptation of the software in the real environment of an intensive care unit, where it was compared between patients who used the standardized dose of piperacillin/tazobactam, and those who used an individualized dose adjusted through the software Individually Designed and Optimized Dosing Strategies. Results Twelve professionals participated in the first round, whose suggestions were forwarded to the software developer for adjustments, and subsequently submitted to the second round. Eight specialists participated in the second round. Indexes of 80% and 90% of concordance were obtained between the judges, characterizing uniformity in the suggestions. Thus, there was modification in the layout of the software for linguistic and cultural adequacy, minimizing errors of understanding and contradictions. In the second stage, 21 patients were included, and there were no differences between doses of piperacillin in the standard dose and adjusted dose Groups. Conclusion The adapted version of the software is safe and reliable for its use in Brazil.

La percepción de competencias (PC) es una variable importante para la comprensión del rendimiento escolar de los alumnos en matemática. Desarrollamos dos estudios (E1, E2) cuyos objetivos fueron: 1) analizar las características psicométricas de la Escala de PC en Matemática (EPCM) para el 1.º ciclo de Educación Básica (E1); e 2) analizar un modelo explicativo de la relación entre PC y rendimiento y comparar medias según género (E2). En el E1 participaron 361 alumnos de 3.º y 4.º grado (52.4% masculino). Se realizó un análisis factorial confirmatorio para examinar la estructura de la EPCM y la invariancia de género. En el E2 participaron 79 alumnos de 3.º grado (55.7% masculino). El rendimiento fue calculado utilizando las notas de los profesores y de una prueba. La relación entre la PC yel rendimiento académico fue evaluada utilizando análisis de ecuaciones estructurales. Los resultados indican que la EPCM mostró buenas características psicométricas y invariancia de género. Además, se constató que existe una relación significativa entre PC y rendimiento matemático. Diferencias en la PC se observaron en ambos estudios, con las niñas mostrando menor PC, aunque su rendimiento fue semejante. Los resultados indican que las diferencias de género, identificadas en estudios previos con adolescentes, surgen precozmente en la escolaridad.

A perceção de competência (PC) tem-se mostrado como uma variável importante na compreensão do desempenho dos alunos na matemática. Desenvolvemos dois estudos (E1, E2) cujos objetivos foram: 1) analisar as caraterísticas psicométricas da Escala de PC na Matemática (EPCM) para o 1.º ciclo do Ensino Básico (E1); e 2) analisar um modelo explicativo da relação entre PC e desempenho e comparar médias segundo o género (E2). No E1 participaram 361 alunos do 3.º e 4.º ano (52.4% rapazes). Recorreu-se à análise fatorial confirmatória para examinar a estrutura da EPCM e a invariância de género. No E2 participaram 79 alunos do 3.º ano (55.7% rapazes). O desempenho foi calculado recorrendo à avaliação dos professores e classificações de um teste. Para testar a relação entre a PC e o desempenho recorreu-se à análise de equações estruturais. Os resultados indicaram que a EPCM apresenta boas caraterísticas psicométricas e invariância de género. Constatou-se ainda a existência de uma relação significativa entre a PC e o desempenho na matemática. Diferenças na PC foram observadas em ambos os estudos, com as raparigas evidenciando menor PC, apesar de o seu desempenho ser semelhante. Os resultados indicaram que as diferenças de género, identificadas em estudos prévios com adolescentes, surgem precocemente na escolaridade.

Perceived competence (PC) has been an important issue in understanding students' achievement in mathematics. We developed two studies (E1, E2), whose objectives were: 1) to analyze the psychometric characteristics of the PC in Mathematics Scale (EPCM) for elementary students (E1); 2) to analyze an explanatory model of the relation between PC and achievement and to compare averages according to gender (E2). E1 enrolled 361 third and fourth grade students (52.4% boys). We used confirmatory factor analysis to examine the EPCM structure and gender invariance. In E2, 79 students from the third grade (55.7% boys) participated. Achievement was calculated using teacher reports and test scores. To test the relationship between PC and performance, we used structural equation modeling. The results indicated that the EPCM presents good psychometric characteristics and gender invariance. We also found a significant relationship between PC and students' math achievement. Differences in PC were observed in both studies, with girls showing lower CP than boys, despite their performance being similar. The results indicate that gender differences, identified in previous studies with adolescents, appear early in schooling.

Diabetes mellitus type 2 (DM2) affects millions of people worldwide and causes several complications for the patient, consuming large sums of financial resources from the health services. This study aims to estimate the financial investment of DM2 treatment for glycemic control of the patient, from the point of view of the municipal Public Health System (SUS). The Delphi technique was used to validate the opinion of a team of judges, specialists in DM2, and health service managers, on the investment necessary for glycemic control of patients with DM2 through the application of questionnaires. In order for the patient to achieve glycated hemoglobin (A1c) < 7%, an investment of US$ 2,419.06 (value/patient/year) is necessary. As the value of A1c increases, investment is reduced. This result reveals the intention to allocate resources for the prevention of DM2 and its complications.

Abstract Background: Several studies have focused on the assessment of students' motivation because this construct is very important to understand students' learning and how to enhance it. The Academic Self-Regulation Questionnaire (SRQ-A), based on the self-determination theory is a self-report instrument developed to access the reasons why students do their school work. However, there is no Portuguese version of this questionnaire for late elementary students. The primary goal of this research was to analyze the psychometric properties of a Portuguese version of SRQ-A in the domain of Mathematics with elementary school children. Methods: Participants were 341 elementary school children ranging from 8 to 11 years old from the third and fourth grades. The Portuguese version of the SRQ-A included 24 items assessing four regulatory styles (external, introjected, identified, and intrinsic) in three behavioral categories (homework, classwork, and answering questions in mathematics lessons). To examine the psychometric properties of the instrument, we conducted an exploratory structural equation modeling (ESEM), measured gender and grade invariance, and calculated internal consistency indexes and temporal stability. Results: ESEM analyses supported the original multidimensional structure of the measure with four regulatory styles using a reduced version of the instrument with 16 items. Correlations between the four regulatory styles revealed a simplex pattern consistent with the continuum of self-determination theory. Results showed adequate internal consistency for all regulatory styles (α ≥ .73; CR ≥ .76) and temporal stability (4-month test-retest ≥ .43). The questionnaire showed measurement and structural invariance across gender and grade. Finally, some gender differences were observed; on average, boys scored higher than girls in external regulation. No differences were observed between grades. Conclusions: Our findings suggest that the Portuguese version of the SRQ-A has good psychometric properties providing adequate support for its use in educational research on motivational styles, including studies concerning gender and grade differences in self-regulation.

RESUMO Objetivo Analisar a efetividade microbiológica considerando a correlação farmacocinética/farmacodinâmica de vancomicina em crianças e propor uma estimativa de ajuste na dose. Métodos Trata-se de um estudo observacional, transversal, realizado em hospital pediátrico, no período de 1 ano (2016 a 2017). Foram incluídas crianças de 2 a 12 anos de ambos os sexos, tendo sido excluídas crianças queimadas ou submetidas à terapia renal substitutiva. Para análise farmacocinética, foram coletadas duas amostras de 2mL de sangue total, respeitando o intervalo de 2 horas entre cada coleta. Resultados Foram incluídos dez pacientes pediátricos com idade de 5,5 anos (mediana) e intervalo interquartil (IQ) de 3,2-9,0 anos, peso de 21kg (mediana; IQ: 15,5-24,0kg) e altura de 112,5cm (mediana; IQ: 95-133cm). Apenas uma criança alcançou concentrações mínimas entre 10µg/mL e 15µg/mL. Conclusão A utilização empírica de vancomicina na população de crianças não alcançou o alvo farmacocinético/farmacodinâmico terapêutico para concentração inibitória mínima de 1μg/mL.

ABSTRACT Objective Analyze the microbiological effectiveness, based on the pharmacokinetics/pharmacodynamics correlation of vancomycin in pediatric patients, and to propose dose adjustment. Methods This is an observational, cross-sectional study, conducted in a pediatric hospital, over a 1-year period (2016 to 2017). Children of both sexes, aged 2 to 12 years, were included in the study; burn children, and children in renal replacement therapy were excluded. For the pharmacokinetic analysis, two samples of 2mL of whole blood were collected, respecting the 2-hour interval between each withdrawal. Results Ten pediatric patients with median age of 5.5 years and interquartile range (IQR) of 3.2-9.0 years, median weight of 21kg (IQR: 15.5-24.0kg) and median height of 112.5cm (IQR: 95-133cm), were included. Only one child achieved trough concentrations between 10µg/mL and 15µg/mL. Conclusion The empirical use of vancomycin in the children studied did not achieve the therapeutic pharmacokinetic/pharmacodynamic target for minimum inhibitory concentration of 1µg/mL.