The association between vancomycin trough concentrations and nephrotoxicity in the paediatric intensive care unit / A associação entre concentrações no vale de vancomicina e nefrotoxicidade em uma unidade de terapia intensiva pediátrica

Objective: To analyze and describe the pharmacokinetic aspects of vancomycin usage in a cohort of critically ill children and to construct a pharmacokinetic model for this population. Method: We conducted an observational study in a pediatric intensive care unit from September 2017 to March 2019. Children receiving vancomycin with at least one serum measurement were included. Variables with a p-value lower than 0.2 in univariate analysis, and biologically plausible for inducing nephrotoxicity and not correlated with other predictors, were incorporated into logistic regression. Additionally, pharmacokinetic modeling was performed using the PMETRICS® package for patients with creatinine clearance (CLCR) > 30 mL/min. Result: The study included 70 children, with an average vancomycin dose of 60 mg/kg/day. Only eleven children achieved vancomycin levels within the target range (15-20 mg/L). No significant differences in doses/mg/kg/day were observed among children above, within, or below the vancomycin target range. In the multivariate model, children above the recommended serum range had an odds ratio of 4.6 [95% CI 1.4 ­ 17.2] for nephrotoxicity. A pharmacokinetic model was proposed using data from 15 children, estimating PK parameters for CLCR and V as 0.94 L/h and 5.71 L, respectively. Conclusion: Nephrotoxicity was associated with vancomycin plasma concentrations equal to or exceeding 15 mg/L. The developed model enhanced understanding of the drug's behavior within this population, potentially aiding clinical practice in dose calculations and estimation of the area under the curve ­ a recommended parameter for vancomycin monitoring.

Objetivo: Analisar e descrever os aspectos farmacocinéticos do uso de vancomicina em uma coorte de crianças sob cuidados intensivos e elaborar um modelo farmacocinético para essa população. Método: Estudo observacional em uma unidade de terapia intensiva pediátrica conduzido entre setembro de 2017 a março de 2019. Inclui-se crianças em uso de vancomicina com pelo menos uma mensuração sérica desse antimicrobiano. As variáveis com valor de p < 0,2 na análise univariada e com plausibilidade biológica para propiciar nefrotoxicidade, não correlacionadas com outras preditoras, foram incluídas na regressão logística. Adicionalmente, uma modelagem farmacocinética foi realizada usando o programa PMETRICS® para pacientes com clearance de creatinina (CLCR) > 30 mL/min. Resultado: Foram incluídas 70 crianças no estudo. A dose média de vancomicina foi de 60 mg/kg/dia. Apenas onze crianças apresentaram vancocinemia dentro da faixa alvo (15-20 mg/L). Não foram observadas diferenças significativas entre as doses administradas e a observação de vancocinemia acima, dentro ou abaixo da faixa preconizada. No modelo multivariado, crianças acima da faixa sérica preconizada apresentaram odd ratio de 4,6 [IC 95% 1,4 ­ 17,2] para nefrotoxicidade. Um modelo farmacocinético com os dados de 15 crianças foi proposto, no qual os parâmetros de PK estimados para CLCR e Volume de distribuição foram de 0,94 L/h e 5,71 L, respectivamente. Conclusão: A nefrotoxicidade mostrou-se associada às concentrações plasmáticas de vancomicina iguais ou maiores a 15 mg/L. O modelo desenvolvido permitiu entender o comportamento do fármaco nessa população e pode ser útil na prática clínica para o monitoramento do uso de vancomicina.

Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.

BACKGROUND: Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality. METHODS: A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis. RESULTS: Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients. CONCLUSIONS: ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.

Redução da taxa de filtração glomerular em pacientes críticos em uso de vancomicina: um estudo transversal / Decrease of the glomerular filtration rate in critically ill patients using vancomycin: a cross-sectional study

Objetivo: o presente trabalho teve como objetivo avaliar os fatores clínicos e medicamentosos relacionados com a redução da Taxa de Filtração Glomerular (TFG) em pacientes críticos em uso de vancomicina. Métodos: trata-se de um estudo transversal em que pacientes em uso de vancomicina, maiores de 18 anos, hospitalizados em terapia intensiva, foram selecionados no período de agosto a dezembro de 2019. Foram excluídos os pacientes que tiveram permanência inferior a 48h na unidade, aqueles com doença renal crônica e/ou que tiveram antimicrobiano suspenso nas primeiras 48h. Os dados clínicos e laboratoriais foram coletados do prontuário nas mesmas datas das coletas de amostras sanguíneas. As amostras de sangue foram coletadas no vale a partir do terceiro dia de tratamento. Os níveis de vancomicina foram medidos usando VANC VITROS ®. Os dados foram analisados através do software R. Resultados: 54 pacientes foram incluídos, sendo 68,5% do sexo masculino, 98,1% em ventilação mecânica, com foco respiratório (51,2%) e isolado Acinetobacter baumanni (38,0%). As concentrações de vancomicina variaram entre 5,0 e 50,0µg/mL, média 21,6 (DP: 10,6) µg/mL; 50% dos pacientes apresentaram concentração acima de 20µg/mL e 66,7% piora da TFG após o tratamento. A concentração de vancomicina foi a única variável diretamente relacionada com o desenvolvimento da alteração na função renal (p=0.0037). Não foi possível estabelecer a influência da comedicação na redução da taxa de filtração glomerular (TFG). Conclusão: as doses usuais de vancomicina ajustadas por meio da função renal não atingiram os níveis séricos terapêuticos recomendados de vancomicina, sendo relacionados à nefrotoxicidade.

Objective: we aimed to evaluate clinical and drug factors related to the Glomerular Filtration Rate (GFR) reduction in critically ill patients using vancomycin. Methods: This is a cross-sectional study where critically ill patients using vancomycin, aged over 18 years, were selected from August to December 2019. Patients were excluded when hospitalized for less than 48 hours in the unit, those with chronic kidney disease, and/or who had their antimicrobial suspended in the first 48 hours. Clinical and laboratory data were collected from the medical record on the same days as the blood sample collection. All blood samples were collected at the trough during the third day of vancomycin treatment. Vancomycin levels were measured using VANC VITROS ®. Data analysis was analyzed by R software. Results: 54 patients were included, 68.5% male, 98.1% mechanical ventilation, respiratory focus (51.2%), and isolation of Acinetobacter baumanni (38.0%). Vancomycin concentrations ranged between 5.0 and 50.0µg/mL, mean of 21.6 (SD: 10.6) µg/mL; 50% of patients with concentrations above 20µg/mL and 66.7% worsened GFR after vancomycin treatment. Vancomycin concentration was the only variable directly related to the development of renal malfunction (p=0.0037). It was not possible to establish the influence of co-medication in the reduction of the glomerular filtration rate (GFR). Conclusion: the usual doses of vancomycin adjusted by renal function did not reach the recommended therapeutic serum levels of vancomycin, being related to nephrotoxicity.

Instrumento sobre conhecimento, atitudes e práticas da automedicação em estudantes universitários

Objetivo: construir e validar instrumento para investigar os conhecimentos, atitudes e práticas de estudantes universitários brasileiros sobre a automedicação. Método: estudo metodológico realizado em universidade pública do centro oeste mineiro, Brasil. Um comitê de juízes avaliou clareza, pertinência e abrangência e o pré-teste realizado com público alvo para avaliar compreensão e aceitabilidade. O índice de validade de conteúdo (IVC) foi utilizado para avaliar a proporção de concordância e o coeficiente alfa de Cronbach (a) para mensurar a confiabilidade. Resultados: o instrumento foi composto por 38 itens divididos em três seções: caracterização dos participantes (13 itens); conhecimentos e práticas da automedicação (3 itens); e crenças e atitudes (22 itens). A média do IVC de todas as seções do instrumento foi de 0,97 e o coeficiente alfa de Cronbach da seção crenças e atitudes >0,70. Conclusão: o instrumento foi considerado válido para avaliar conhecimento, prática, crenças e atitudes sobre automedicação em estudantes universitários.

SUMMARY Objective: To build and validate an instrument to investigate the knowledge, attitudes and practices of Brazilian university students about self-medication. Method: Methodological study carried out at a public university in the center of western Minas Gerais, Brazil. A committee of judges assessed clarity, relevance and comprehensiveness and the pre-test carried out with a target audience to assess understanding and acceptability. The content validity index (CVI) was used to assess the proportion of agreement and Cronbach's alpha coefficient (a) to measure reliability. Results: The instrument consisted of 38 items divided into three sections: characterization of participants (13 items); knowledge and practices of self-medication (3 items); and beliefs and attitudes (22 items). The mean CVI for all sections of the instrument was 0.97 and the Cronbach's alpha coefficient for the beliefs and attitudes section >0.70. Conclusion: The instrument was considered valid to assess knowledge, practice, beliefs and attitudes about self-medication in university students.

Objetivo: construir y validar un instrumento para investigar los conocimientos, actitudes y prácticas de estudiantes universitarios brasileños sobre la automedicación. Método: estudio metodológico realizado en una universidad pública del centro del occidente de Minas Gerais, Brasil. Un comité de jueces evaluó la claridad, la relevancia y la exhaustividad y la prueba previa se llevó a cabo con un público objetivo para evaluar la comprensión y la aceptabilidad. El índice de validez de contenido (IVC) se utilizó para evaluar la proporción de acuerdo y el coeficiente alfa de Cronbach (a) para medir la confiabilidad. Resultados: el instrumento constaba de 38 ítems divididos en tres apartados: caracterización de los participantes (13 ítems); conocimientos y prácticas de automedicación (3 ítems); y creencias y actitudes (22 ítems). El CVI medio para todas las secciones del instrumento fue 0,97 y el coeficiente alfa de Cronbach para la sección de creencias y actitudes> 0,70. Conclusión: el instrumento se consideró válido para evaluar conocimientos, prácticas, creencias y actitudes sobre la automedicación en estudiantes universitarios.

Avaliação econômica de uma estratégia individual de empoderamento farmacoterapêutico: um modelo em longo prazo aplicado do diabetes mellitus tipo II / Economic evaluation of an individual pharmacotherapeutic empowerment strategy: an applied long-term model for type II diabetes mellitus

Objetivos: contribuir para a geração de dados de avaliação econômica de estratégias de empoderamento farmacoterapêutico para pacientes com Diabetes Mellitus tipo 2 (DM tipo 2). Métodos: este estudo farmacoeconômico é aninhado a um ensaio clínico com controle não randomizado que incluiu pacientes ≥18 anos de idade, cadastrados no HIPERDIA. Os pacientes foram alocados em um modelo de Markov conforme valores de hemoglobina glicada do acompanhamento. As probabilidades do surgimento de complicações relativas ao DM, incluindo-se óbito, foram estimadas por dez anos. Cada complicação do DM tipo 2 teve seu custo estabelecido para determinação do custo anual. Resultados: entre os participantes da intervenção, não ocorrem óbitos ocasionados por DM tipo 2, e a progressão de complicações mantém-se estável durante os anos simulados, enquanto, no grupo controle, 60% dos pacientes podem evoluir para óbito nos dez anos, e a probabilidade de serem acometidos por complicações relacionadas ao DM tipo 2 é crescente. Com relação aos custos, ao final de dez anos, os pacientes que participaram da Estratégia Individual de Empoderamento Farmacoterapêutico (EIEF) tiveram um custo médio de UU$134,45 poupando a vida de 100% dos pacientes, e os pacientes do atendimento convencional um custo médio de UU$237,12 e 40% dos pacientes acompanhados chegariam ao final do ciclo com vida. Conclusão: a EIEF parece ser uma alternativa economicamente viável em longo prazo, bem como para a promoção do controle glicêmico.

Objectives: contribute to the data generation for the economic evaluation of pharmacotherapeutic empowerment strategies for type 2 diabetes mellitus patients (type 2 DM). Method: This pharmacoeconomic study is nested in a clinical trial with non-randomized control that included patients ≥18 years old, registered in HIPERDIA. The patients were allocated to a Markov model according to the follow-up glycated hemoglobin values. The probabilities of the appearance of complications related to DM, including death, have been estimated for ten years. Each complication of type 2 DM had its cost established to determine the annual cost. Results: Among the participants in the intervention, there are no deaths caused by type 2 DM, and the progression of complications remains stable during the simulated years, whereas in the control group, 60% of the patients can progress to death in ten years and the probability of being affected by complications related to type 2 DM is increasing. Regarding costs, at the end of ten years, patients who participated in Individual Pharmacotherapeutic Empowerment Strategy (IPES) had an average cost of US$ 134.45, saving 100% of patient's lives, and conventional care patients cost an average of US$ 237.12 and 40% of the patients followed would reach the end of the life cycle. Conclusion: The IPES seems like an economically viable and long-term economic alternative and promotes glycemic control.

Mechanisms involved in resistance to carbapenems among Acinetobacter baumannii isolates recovered in Brazil: A systematic review and meta-analysis

SUMMARY Introduction: Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a health problem due to the limited therapeutic options available. This study was carried out to evaluate the main mechanisms of resistance of carbapenems in CRAB in the last 10 years in Brazil and to describe the susceptibility profile to tigecycline and polymyxins in these isolates. Material and methods: A systematic review was carried out according to Prisma in PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) and Cochrane Library. Data regarding enzyme resistance to carbapenems were evaluated by meta-analysis according to the random effect. Results: 21 articles were selected according to inclusion and exclusion criteria that evaluated 1096 CRAB. Most of the studies were carried out in the southern (33.3 %) and southeast (23.8 %) regions of Brazil (33.3 %) and in 2016 and 2018. According to the meta-analyzes, OXA-type carbapenemase was the main mechanism involved in the low susceptibility to carbapenems in CRAB (98%; 95% CI: 0.91, 0.99; I2 = 95%), with bla OXA-23-like (91 %; 95 % CI: 0.76; 0.97; I2 = 97 %) or bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0.15, 0.99; I2 = 98 %) genes, followed by metallo-ß-lactamases (MBL) (12 %, 95 % CI: 0.09, 0.15, I2 = 99 %) and Klebsiella pneumoniae carbapenemase (KPC) (6 %, 95 % CI: 0.04; 0.08; I2 = 87 %). Conclusion: The included studies showed that susceptibility to colistin (99 %) and tigecy-cline (93 %) remains high and was not affected by carbapenem resistance.

Introducción: Las infecciones por Acinetobacter baumannii resistente a carbapenémicos (CRAB) es un problema de salud debido a las limitadas opciones terapéuticas disponibles. Este estudio se realizó para evaluar los principales mecanismos de resistencia de los carbapenémicos en CRAB en los últimos 10 años en Brasil y describir el perfil de susceptibilidad a tigeciclina y polimixinas en estos aislados. Material y métodos: Se realizó una revisión sistemática de acuerdo con Prisma en PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) y Cochrane Library. Los datos referentes a resistencia enzimática a los carbapenémicos se evaluaron mediante metaanálisis según el efecto aleatorio. Resultados: Se seleccionaron 21 artículos según criterios de inclusión y exclusión que evaluaron 1.096 CRAB. La mayoría de los estudios se llevaron a cabo en las regiones sur (33,3%) y sureste (23,8 %) de Brasil (33,3 %) y en los años 2016 y 2018. Según los metaanálisis, la carbapenemasa tipo OXA fue el principal mecanismo implicado en la baja susceptibilidad a los carbapenémicos en CRAB (98 %; IC 95 %: 0,91; 0,99; I² = 95 %), con bla OXA-23-like (91 %; 95 % CI: 0,76; 0,97; I² = 97 %) o bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0,15; 0,99 ; I² = 98 %) genes, seguida de metalo-ß-lactamasas (MBL ) (12 %; IC95 %: 0,09; 0,15; I² = 99 %) y Klebsiella pneumoniae carbapenemase (KPC) (6 %; IC95 %: 0,04; 0,08; I² = 87 %). Conclusión: Los estudios incluidos mostraron que la susceptibilidad a la colistina (99 %) y tigeciclina (93 %) sigue siendo alta y no se ve afectada por la resistencia a los carbapenémicos.

Introdução: As infecções causadas por Acinetobacter baumannii resistente aos carbapenémicos (CRAB) são um problema de saúde devido às limitadas opções terapêuticas disponíveis. Este estudo foi realizado para avaliar os principais mecanismos de resistência aos carbapenêmicos em CRAB nos últimos 10 anos no Brasil e descrever o perfil de susceptibilidade à tigeciclina e às polimixinas nesses isolados. Material e métodos: Foi conduzida uma revisão sistemática segundo o Prisma nas bases de dados PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) e Biblioteca Cochrane. Os dados relativos à resistência enzimática aos carbapenêmicos foram avaliados por meta-análises de acordo com o efeito aleatório. Resultados: Foram selecionados 21 artigos de acordo com os critérios de inclusão e exclusão que avaliaram 1.096 CRAB. A maioria dos estudos foi realizada nas regiões Sul (33,3 %) e Sudeste (23,8 %) do Brasil e nos anos de 2016 e 2018. De acordo com as metanálises, a carbapenemase do tipo OXA foi o principal mecanismo envolvido na baixa susceptibilidade aos carbapenêmicos em CRAB (98 %; 95% IC: 0.91, 0.99; I² = 95 %), com bla OXA-23-like (91 %; 95 %; IC: 0,76; 0,97; I² = 97 %) ou bla OXA -51-like / ISAba1 (84 %; 95 % IC: 0.15, 0.99; I² = 98 %) genes, seguidos por metalo-ß-lactamases (MBL) (12 %, 95 % IC: 0,09, 0,15, I² = 99 %) e Klebsiella pneumoniae carbapenemase (KPC) (6 %, IC 95 %: 0,04; 0,08; I² = 87 %). Conclusão: Os estudos incluídos mostraram que a susceptibilidade à colistina (99 %) e tigeciclina (93 %) permanece alta e não foi afetada pela resistência aos carbapenêmicos.

Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation.

Objectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by HPLC-UV. Population pharmacokinetic modelling was conducted using Pmetrics. Empiric dose of 4 g IV 6- and 8-hourly were simulated for 50 and 100% fT > MIC and the probabil-ity of target attainment (PTA) and the fractional target attainment (FTA) determined. Results: A two-compartment model was designed to describe the pharmacokinetics of critically ill Brazillian patients. Clearance and volume of distribution were (mean ± SD) 3.33 ± 1.24 L h−1 and 10.69 ± 4.50 L, respectively. Creatinine clearance was positively correlated with piperacillin clearance and a high creatinine clearance was associated with lower values of PTA and FTA. An external vali-dation was performed using data from two different ethnic ICU populations (n = 30), resulting in acceptable bias and precision. Conclusion: The primary pharmacokinetic parameters obtained from critically ill Brazilian patients were similar to those observed in studies performed in critically ill patients of other ethnicities. Based on our results, the use of dose adjustment based on creati-nine clearance is required in Brazilian patients.

Population pharmacokinetic modeling of benznidazole in Brazilian patients with chronic Chagas disease.

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.

Perception of pharmacists regarding human resources, training, and development of a national hospital pharmacy: a preliminary report on Basel Statements

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.

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

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.

Interchangeability among carbamazepine formulations: the impact over epilepsy patients

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.

Progression of chronic kidney disease in non- dialysis patients: a retrospective cohort

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

Population pharmacokinetic modeling of benznidazole in Brazilian patients with chronic Chagas disease

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.

Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study.

BACKGROUND: Tuberculosis (TB) patients admitted to intensive care units (ICU) have high mortality rates. It is uncertain whether the pharmacokinetics of first-line TB drugs in ICU patients are different from outpatients. This study aims to compare the pharmacokinetics of oral ethambutol in TB patients in ICU versus TB outpatients and to determine whether contemporary dosing regimens achieve therapeutic exposures. METHODS: A prospective population pharmacokinetic study of ethambutol was performed in Amazonas State, Brazil. Probability of target attainment was determined using AUC/MIC > 11.9 and Cmax/MIC > 0.48 values. Optimized dosing regimens were simulated at steady state. RESULTS: Ten ICU patients and 20 outpatients were recruited. Ethambutol pharmacokinetics were best described using a two-compartment model with first-order oral absorption. Neither ICU patients nor outpatients consistently achieved optimal ethambutol exposures. The absorption rate for ethambutol was 2-times higher in ICU patients (p < 0.05). Mean bioavailability for ICU patients was >5-times higher than outpatients (p < 0.0001). Clearance and volume of distribution were 93% (p < 0.0001) and 53% (p = 0.002) lower in ICU patients, respectively. CONCLUSIONS: ICU patients displayed significantly different pharmacokinetics for an oral fixed-dose combination administration of ethambutol compared to outpatients, and neither patient group consistently achieved pre-defined therapeutic exposures.

Factors associated with the occurrence of adverse events to antiretroviral therapy in adults and elderly living with HIV

Objectives: This study identifies the factors associated with the occurrence of adverse events in adults and elderly on antiretroviral therapy. Methods: This is a cross-sectional study carried out with adults and elderly patients, attended by the Specialized Assistance Service between September 2016 and August 2017. Adverse events were measured through self-reports collected in interviews, information collected in medical records, and changes identified in laboratory tests, with the degree of causality being assessed using the Naranjo Algorithm. Univariate analysis, with results expressed as odds ratio (OR) and their respective confidence intervals (CI 95%), was performed to estimate the association between sociodemographic, pharmacotherapeutic, and clinical characteristics (explanatory variables) with the occurrence of four or more adverse events to antiretroviral therapy (response variable). For multivariate analysis, multiple logistic regression was considered in order to verify the permanence or absence of associations previously found in the univariate analysis. Results: Prevalence of adverse events to antiretroviral therapy was 92.6%, with the median of adverse events being four (IQR 25%: 2 ; IQR 75%: 5) and two (IQR 25%: 2 ; IQR 75%: 4), respectively, among adults and elderly (p <0.05). Additionally, 340 adverse events were identified, among which nightmares (15.0%) and vertigo (13.5%) were the most frequent. Most of the adverse events identified were classified as possible (96.2% / n = 327). In the initial univariate analysis, factors such receipt of guidance on adverse events and age were associated with a higher occurrence of adverse events to antiretroviral therapy. Contrary to expectations, the elderly were considered less susceptible to have adverse events when compared to adults (OR = 0.363; CI 95% = 0.164-0.801). However, the final multivariate analysis model revealed "receipt of guidance on adverse events" as the only variable significantly associated with the presence of four or more adverse events to antiretroviral therapy (OR = 4.183 ; CI 95% = 1.775-9.855). Conclusions: Results suggest difference in perception of adverse events between patients who received and those who did not receive guidance in this regard, which indicates the importance of health professionals to provide specific information to their patients regarding adverse events to antiretroviral therapy. Thus the patient can understand the effects generated by the treatment and inform these professionals for the notification of adverse events, in order to improve pharmacovigilance actions and promote patient safety.

Can parabens be added to cosmetics without posing a risk to human health? A systematic review of its toxic effects Pode adicionar parabenos a cosméticos sem risco para a saúde humana? Uma revisão sistemática de seus efeitos tóxicos

Objective: To summarize evidence regarding the toxic potential of administering parabenscontaining cosmetics in humans. Methods: The systematic review followed the methodology proposed in Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). Electronic searches of the PubMed, Virtual Health Library (BVS), and Science Direct databases were performed between October 1st and 31st, 2018. No language restriction was determined. Original articles reporting observational, in vitro and in silico studies of toxicity caused by parabens in human or human cells were considered for eligibility. Two independent reviewers performed data extraction and assessed the methodological quality and risk of bias of articles by using the Downs & Black Scale. Score levels greater than 70% were assumed to reflect good methodological quality. The Kappa coefficient was calculated. Results: A total of 254 studies were found. Following the eligibility evaluation, 22 studies were included for the qualitative synthesis. The concordance between the reviewers was substantial (Kappa coefficient = 0.650). The meaningful reported outcomes were: high concentrations of parabens in the body; apoptosis damage to sperm DNA; oxidative stress; DNA damage; irritative potential; interference in the control of adipogenesis; estrogenic activity; genotoxicity; necrosis; role in carcinogenesis of breast cancer; harmful effects on human skin when exposed to the sun; stimulation of oncogenes expression; and interference with DNA transcription. Despite most included articles presenting appreciable methodological quality, remarkable limitations were observed and the mechanisms by which parabens exert toxicity on humans remained unclear. Conclusions: The accumulation of parabens in the human organism following repeated cosmetics administration on the skin is noteworthy. However overall, the evidence so far does not make it possible to determine whether, and in what extent, the use of paraben-containing cosmetics can disturb human health. Further investigations are still required for clarifying these issues.

Análise do perfil e da frequência de erros de dispensação de medicamentos em um hospital de médio porte nos anos de 2009 a 2019 / Analysis of the profile and frequency of medication dispensing errors in a medium-sized hospital in the years 2009 to 2019

Objetivo: avaliar o perfil e a frequência de erros de dispensação de medicamentos entre os anos de 2009 e 2019 em um hospital de médio porte. Métodos: neste trabalho descritivo documental de abordagem quantitativa, os medicamentos envolvidos em erros de dispensação foram classificados de acordo com Anatomical Therapeutic Chemical (ATC) e medicamentos potencialmente perigosos. E os erros foram categorizados segundo guia da Política Nacional de Segurança do Paciente (PNSP). Resultados: os resultados demonstraram que os erros aumentaram no decorrer dos anos, apresentando 28 erros/mês no primeiro ano e 58,6 erros/mês no último, e que os tipos de erros mais frequentes são de omissão do envio (n=1532; 39,0%) e dispensação com dose ou quantidade errada (n=827; 21,0%). A classe de medicamento prescrita mais envolvida em erros foi a de agentes anti-infecciosos de uso sistêmico (n=806; 20,5%). Entre os medicamentos potencialmente perigosos, os de ação no sistema nervoso (n=271; 32,8%) foram os mais dispensados de forma errada, tendo, também, como principal tipo de erro, a omissão, e seu principal representante foi o diazepam (n=84; 31,0%). Conclusões: a quantidade de erros de dispensação (mais de um por dia, em média) evidencia a importância do profissional farmacêutico como potencializador para transformar esse cenário, tanto no âmbito gerencial ao propor barreiras de segurança, quanto clínico, ao acompanhar o processo de uso dos medicamentos.

Objetctive: to evaluate the profile and frequency of medication dispensing errors between the years of 2009 to 2019 in a medium-sized hospital. Methods: In this descriptive documentary work of quantitative approach, the drugs involved in dispensing errors were classified according to the Anatomical Therapeutic Chemical (ATC) and potentially dangerous drugs. The errors were categorized according to the guidelines of the National Policy for Patient Safety (NPPS). Results: The results showed that errors increased over the years, presenting 28 errors/month in the first year and 58.6 errors/month in the last, and that the most frequent types of errors are shipment omission (n = 1532; 39.0%) and dispensing with wrong dose or amount (n = 827; 21.0%). The medication class prescribed most involved in errors was anti-infective agents for systemic use (n = 806; 20.5%). Among the potentially dangerous drugs, those with action on the nervous system (n = 271; 32.8%) were the most misdispensed, also having omission as the main type of error, and its main representative was diazepam (n = 84; 31.0%). Conclusions: The amount of dispensing errors (more than one per day, on average) highlights the importance of the professional pharmacist as a potential generator to transform this scenario, both managerially, by proposing safety barriers, and clinically, by monitoring the process of medication use.

Epidemiological profile of isolated bacteria in a public pediatric hospital / Perfil epidemiológico de bactérias isoladas em um hospital pediátrico público / Perfil epidemiológico de bacterias aisladas en un hospital pediátrico público

Justificativa e objetivos: nos últimos anos, a incidência de bactérias resistentes tem aumentado significativamente e, no Brasil, existem poucas pesquisas sobre o tema, em hospitais pediátricos. Portanto, este estudo teve como objetivo analisar o perfil epidemiológico das principais bactérias recuperadas de amostras biológicas de um hospital pediátrico brasileiro. Métodos: trata-se de um estudo descritivo documental e retrospectivo. O estudo foi conduzido em 24 meses a partir de laudos de exames microbiológicos emitidos pelo serviço de controle de infecção hospitalar de um hospital pediátrico localizado no Centro-Oeste de Minas Gerais. Resultados: foram recuperadas de amostras biológicas, neste período, 4.286 bactérias, sendo 1.107 (25,82%) responsáveis por infecções relacionadas à assistência à saúde (IRAS) na instituição de origem. Os principais microrganismos identificados foram Pseudomonas aeruginosa (10.4%), Acinetobacter baumannii (7.8%), Staphylococcus aureus (4.3%), Escherichia coli (4.3%) e Klebsiella pneumoniae (3.5%). Os isolados que apresentaram concentração inibitória mínima (CIM) ≥ 4mg/L foram considerados resistentes. Conclusão: o conhecimento do perfil epidemiológico local tem se mostrado efetivo nas estratégias estabelecidas pelas instituições para redução das infecções relacionadas à assistência à saúde. O perfil de prevalência das bactérias recuperadas das amostras biológicas foi similar a outros estudos conduzidos em âmbito nacional e internacional.(AU)

Background and objectives: in recent years, the incidence of resistant bacteria has increased significantly, and in Brazil there is little research on the subject regarding pediatric hospitals. Therefore, this study aimed to analyze the epidemiological profile of the main bacteria recovered from biological samples of a Brazilian pediatric hospital. Methods: this is a descriptive and retrospective study. The study was conducted over 24 months based on reports of microbiological tests issued by the infection control service of a pediatric hospital located in the Center-West of the Brazilian state of Minas Gerais. Results: a total of 4286 bacteria were recovered from biological samples, of which 1107 (25.82 %) were responsible for healthcare- associated infection (HAI) at the institution of origin. The main microorganisms identified were Pseudomonas aeruginosa (10.4%), Acinetobacter baumannii (7.8%), Staphylococcus aureus (4.3%), Escherichia coli (4.3%), and Klebsiella pneumoniae (3.5%). Isolates with minimal inhibitory concentration (MIC) ≥ 4mg/L were considered resistant. Conclusion: knowledge of the local epidemiological profile has been shown to be effective in the strategies established by the institutions to reduce infections related to health care. The prevalence profile of bacteria recovered from biological samples was similar to other studies conducted at national and international levels.(AU)

Justificación y objetivos: en los últimos años, la incidencia de bacterias resistentes ha aumentados significativamente y en Brasil hay poca investigación sobre el tema con respecto a los hospitales pediátricos. Por lo tanto, este estudio tuvo como objetivo analizar el perfil epidemiológico de las principales bacterias recuperadas de muestras biológicas de un hospital pediátrico brasileño. Métodos: este es un estudio descriptivo y retrospectivo. El estudio se realizó durante 24 meses en base a informes de pruebas microbiológicas emitidas por el servicio de control de infecciones de un hospital pediátrico ubicado en el centro oeste del estado brasileño de Minas Gerais. Resultados: se recuperaron un total de 4286 bacterias de muestras biológicas, de las cuales 1107 (25.82%) fueron responsables de infecciones relacionadas con la atención médica (IRAS) en la institución de origen. Los principales microorganismos identificados fueron Pseudomonas aeruginosa (10.4%), Acinetobacter baumannii (7.8%), Staphylococcus aureus (4.3%), Escherichia coli (4.3%) y Klebsiella pneumoniae (3.5%). Los aislamientos con concentración mínima inhibitoria (MIC) ≥ 4 mg/L se consideraron resistentes. Conclusiones: el conocimiento del perfil epidemiológico local se ha mostrado efectivo en las estrategias establecidas por las instituciones para reducir las infecciones relacionadas con la atención de la salud.(AU)

Factores de riesgo asociados a Accidente Cerebro-Vascular Isquémico en pacientes atendidos en un hospital público en el Paraguay

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

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

Fatores associados para potenciais interações medicamentosas clinicamente significantes em terapia intensiva adulto / Associated factors for potential clinically significant drug-drug interactions in adult intensive care

RESUMO: Modelo do estudo: Estudo transversal. Objetivo: caracterizar as interações medicamentosas potenciais (IMp) maiores e contraindicadas em terapia intensiva adulto e determinar sua prevalência, medicamentos e fatores associados à exposição dessas interações. Métodos: a amostra foi composta por 309 pacientes internados em uma unidade de terapia intensiva adulto de um hospital da Região Centro-Oeste de Minas Gerais, Brasil. Os dados demográficos-clínicos e perfil medicamentoso foram coletados, prospectivamente. As IMp foram caracterizadas pela base Micromedex 2.0 quanto à gravidade, prevalência e implicação clínica. Realizaram-se análises descritivas para as variáveis qualitativas e contínuas. Modelos Lineares Generalizados com distribuição Gama e Poisson foram utilizados para avaliar a relação entre um conjunto de variáveis independentes e a prevalência de IMp maiores e contraindicadas (p<0.05). Resultados:Um total de 81,8% (n=251) foi exposto a, no mínimo, uma IMp maior ou contraindicada. Mais de um terço (37,4%) destes participantes foram expostos a seis ou mais IMp. Medicamentos com ação no sistema nervoso colaboraram para maior probabilidade de IMp maiores e/ou contraindicadas. Pessoas idosas (p=0,006), do sexo masculino (p=0,028) e polimedicadas (<0,001) tiveram maior probabilidade de serem expostas ao menos a uma IMp maior ou contraindicada. Conclusão: Interações medicamentosas potenciais maiores e contraindicadas apresentaram alta frequência. Pessoas idosas, do sexo masculino e polimedicadas foram mais expostas às IMp maiores e/ou contraindicadas. É importante que profissionais da saúde conheçam os riscos e potenciais eventos adversos relacionados às IMp maiores e contraindicadas, para que sejam implementadas medidas para promoção da segurança do paciente. (AU)

ABSTRACT: Study Design: Cross-sectional. Objective: characterizing major and contraindicated potential drug-drug interactions (PDDI) in adult intensive care as well as determining their prevalence, risk factors, and potentially high-risk medications. Methods: The sample was composed of 309 patients hospitalized in an adult intensive care unit in the Midwest Region of Minas Gerais state, Brazil. Clinical data and drug profile were prospectively collected. The PDDI were characterized using the Micromedex 2.0 as to severity, prevalence, and clinical implications. Descriptive analyses were performed for qualitative and continuous variables. Generalized Linear Models with Gamma and Poisson distribution were used to assess the relationship between a set of independent variables and the prevalence of major and contraindicated PDDI (p<0.05). Results: A total of 81.8% (n = 251) were exposed to, at least, a major or contraindicated PDDI. More than a third (37.4%) of these participants were exposed to six or more IMp. Drugs with action on the nervous system contributed to a greater probability of major and/or contraindicated PDDI. Elderly (p = 0.006), male (p = 0.028), and polymedicated (<0.001) people were more likely to be exposed to at least a higher or contraindicated PDDI. Conclusion: Potentially major and contraindicated drug interactions showed high frequency. Elderly, male, and polymedicated people were more exposed to larger and/or contraindicated PDDI. It is important that health professionals are aware of the risks and potential adverse events related to major and contraindicated PDDI so that measures might be implemented to promote patient safety. (AU)