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.

Reference values for uterine artery mean pulsatility index throughout pregnancy customized by parity, transvaginal measurement and blood pressure.

INTRODUCTION: Population-specific reference ranges for uterine artery (UtA) mean pulsatility index (PI) throughout pregnancy have been shown to be of value in antenatal care. OBJECTIVE: To construct reference values for UtA mean PI throughout pregnancy, customized by maternal characteristics, transvaginal measurement and blood pressure in a Mexican population. METHODS: Cross-sectional study in 2286 normal singleton pregnancies in Mexico City. Blood pressure and UtA mean PI were measured using standardized methodology. Reference ranges by gestation were constructed. The effects of independent variables were tested by multiple linear regression. RESULTS: UtA mean PI median value between 11 and 41 weeks decreased from 1.714 to 0.523. The 95th percentile decreased from 2.600 to 0.653. Previous parity without preeclampsia had the main effect on UtA mean PI. Mean blood pressure had an effect on UtA mean PI by interaction with parity. Previous preeclampsia had an effect on UtA mean PI by interaction with maternal characteristics. A correction factor was obtained for transvaginal measurement. CONCLUSIONS: UtA mean PI usually decreases according to placentation and maternal adaptation to pregnancy. The effects of parity on blood pressure and UtA mean PI might reflect cardiovascular remodeling after gestation.

INTRODUCCIÓN: Los rangos de referencia de población específica para el índice de pulsatilidad medio de la arteria uterina (IPmAUt) durante el embarazo han demostrado valor en el cuidado prenatal. OBJETIVO: Construir valores de referencia para el IPmAUt durante el embarazo, personalizados por características maternas, medición transvaginal y presión arterial en una población mexicana. MÉTODOS: Estudio transversal de 2286 embarazos normales de feto único en la Ciudad de México. La presión arterial y el IPmAUt se midieron mediante metodología estandarizada. Se construyeron rangos de referencia por gestación. Los efectos de las variables independientes se probaron mediante regresión lineal múltiple. RESULTADOS: La mediana del IPmAUt entre las 11 y 41 semanas disminuyó de 1.714 a 0.523. El percentil 95 disminuyó de 2.600 a 0.653. La paridad sin preeclampsia previa representó el principal efecto sobre el IPmAUt. La presión arterial media tuvo efecto sobre el IPmAUt por interacción con la paridad. La preeclampsia previa tuvo efecto sobre el IPmAUt por interacción con las características maternas. Se obtuvo un factor de corrección para medición transvaginal. CONCLUSIONES: El IPmAUt disminuye normalmente según la placentación y adaptación materna al embarazo. Los efectos de la paridad sobre la presión arterial y el IPmAUt podrían reflejar remodelación cardiovascular posterior a la gestación.

Valores de referencia personalizados para el índice de pulsatilidad medio de la arteria uterina durante el embarazo según paridad, medición transvaginal y presión arterial / Reference values for uterine artery mean pulsatility index throughout pregnancy customized by parity, transvaginal measurement and blood pressure

Resumen Introducción: Los rangos de referencia de población específica para el índice de pulsatilidad medio de la arteria uterina (IPmAUt) durante el embarazo han demostrado valor en el cuidado prenatal. Objetivo: Construir valores de referencia para el IPmAUt durante el embarazo, personalizados por características maternas, medición transvaginal y presión arterial en una población mexicana. Métodos: Estudio transversal de 2286 embarazos normales de feto único en la Ciudad de México. La presión arterial y el IPmAUt se midieron mediante metodología estandarizada. Se construyeron rangos de referencia por gestación. Los efectos de las variables independientes se probaron mediante regresión lineal múltiple. Resultados: La mediana del IPmAUt entre las 11 y 41 semanas disminuyó de 1.714 a 0.523. El percentil 95 disminuyó de 2.600 a 0.653. La paridad sin preeclampsia previa representó el principal efecto sobre el IPmAUt. La presión arterial media tuvo efecto sobre el IPmAUt por interacción con la paridad. La preeclampsia previa tuvo efecto sobre el IPmAUt por interacción con las características maternas. Se obtuvo un factor de corrección para medición transvaginal. Conclusiones: El IPmAUt disminuye normalmente según la placentación y adaptación materna al embarazo. Los efectos de la paridad sobre la presión arterial y el IPmAUt podrían reflejar remodelación cardiovascular posterior a la gestación.

Abstract Introduction: Population-specific reference ranges for uterine artery (UtA) mean pulsatility index (PI) throughout pregnancy have been shown to be of value in antenatal care. Objective: To construct reference values for UtA mean PI throughout pregnancy, customized by maternal characteristics, transvaginal measurement and blood pressure in a Mexican population. Methods: Cross-sectional study in 2286 normal singleton pregnancies in Mexico City. Blood pressure and UtA mean PI were measured using standardized methodology. Reference ranges by gestation were constructed. The effects of independent variables were tested by multiple linear regression. Results: UtA mean PI median value between 11 and 41 weeks decreased from 1.714 to 0.523. The 95th percentile decreased from 2.600 to 0.653. Previous parity without preeclampsia had the main effect on UtA mean PI. Mean blood pressure had an effect on UtA mean PI by interaction with parity. Previous preeclampsia had an effect on UtA mean PI by interaction with maternal characteristics. A correction factor was obtained for transvaginal measurement. Conclusions: UtA mean PI usually decreases according to placentation and maternal adaptation to pregnancy. The effects of parity on blood pressure and UtA mean PI might reflect cardiovascular remodeling after gestation.

Fluidodinâmica Computacional na Avaliação do Risco Futuro de Aneurismas de Aorta Ascendente / Computational Fluid Dynamics to Assess the Future Risk of Ascending Aortic Aneurysms

Resumo Fundamentos Uma metodologia para identificação de pacientes portadores de aneurisma de aorta ascendente (AAAs) sob alto risco de remodelamento aórtico não está completamente definida. Objetivo Esta pesquisa objetiva caracterizar numericamente o fluxo sanguíneo aórtico, relacionando a distribuição do estresse mecânico resultante com o crescimento de AAAs. Métodos Estudo analítico, observacional, unicêntrico, em que um protocolo de fluidodinâmica computacional (CFD - Computacional Fluid Dynamics) foi aplicado a imagens de angiotomografia computadorizada (ATC) de aorta de pacientes portadores de AAAs. Duas ATC de aorta com pelo menos um ano de intervalo foram obtidas. Dados clínicos dos pacientes foram registrados e, a partir das imagens de ATC, foram gerados modelos tridimensionais. Foram realizados estudos do campo de velocidade e estruturas coerentes (vórtices) com o objetivo de relacioná-los ao crescimento ou não do aneurisma e, posteriormente, compará-los com os dados clínicos dos pacientes. O teste de Kolmogorov-Smirnov foi utilizado para avaliar a normalidade da amostra e o teste não-paramétrico Wilcoxon signed-rank foi aplicado para comparações de dados pareados entre os ângulos aórticos. A significância estatística foi fixada em 5%. Resultados Para o grupo que apresentou crescimento do aneurisma, a incidência do jato na parede aórtica gerou áreas de recirculação posterior ao jato, induzindo à formação de vórtices complexos, ocasionando um incremento na pressão média no endotélio aórtico. O grupo sem crescimento do aneurisma apresentou diminuição na pressão média. Conclusão Este estudo piloto mostrou que a CFD baseada em ATC pode, em um futuro próximo, ser uma ferramenta auxiliar na identificação dos padrões de fluxo associados ao processo de remodelamento de AAAs.

Abstract Background A methodology to identify patients with ascending aortic aneurysm (AsAA) under high risk for aortic growth is not completely defined Objetive This research seeks to numerically characterize the aortic blood flow by relating the resulting mechanical stress distribution with AsAA growth. Methods Analytical, observational, single-center study in which a computational fluid dynamics (CFD) protocol was applied to aortic computed tomography angiogram (CTA) images of patients with AsAA. Two CTA exams taken at a minimum interval of one year were obtained. From the CTA-gathered images, three-dimensional models were built, and clinical data were registered. Study of velocity field and coherent structures (vortices) was performed aiming to relate them to the presence or absence of aneurysm growth, as well as comparing them to the patients' clinical data. The Kolmogorov-Smirnov test was used to evaluate the normality of the distribution, and the non-parametric Wilcoxon signed-rank test, for non-normal distribution, was used to compare the paired data of the aortic angles. Statistical significance was set at 5%. Results The incident jet in the aortic wall generated recirculation areas in the posterior region of the jet, inducing complex vortices formation in the group with aneurysm growth, leading to an average pressure increase in the ascending aortic wall between exams. In the group without aneurysm growth, the average pressure decreased. Conclusion This pilot study showed that CFD based on CTA may in the near future be a tool to help identify flow patterns associated with AsAA remodeling process.

Direct resin composite restoration of endodontically-treated permanent molars in adolescents: bite force and patient-specific finite element analysis

Abstract Objective To evaluate the influence of three levels of dental structure loss on stress distribution and bite load in root canal-treated young molar teeth that were filled with bulk-fill resin composite, using finite element analysis (FEA) to predict clinical failure. Methodology Three first mandibular molars with extensive caries lesions were selected in teenager patients. The habitual occlusion bite force was measured using gnathodynamometer before and after endodontic/restoration procedures. The recorded bite forces were used as input for patient-specific FEA models, generated from cone-beam computed tomographic (CT) scans of the teeth before and after treatment. Loads were simulated using the contact loading of the antagonist molars selected based on the CT scans and clinical evaluation. Pre and post treatment bite forces (N) in the 3 patients were 30.1/136.6, 34.3/133.4, and 47.9/124.1. Results Bite force increased 260% (from 36.7±11.6 to 131.9±17.8 N) after endodontic and direct restoration. Before endodontic intervention, the stress concentration was located in coronal tooth structure; after rehabilitation, the stresses were located in root dentin, regardless of the level of tooth structure loss. The bite force used on molar teeth after pulp removal during endodontic treatment resulted in high stress concentrations in weakened tooth areas and at the furcation. Conclusion Extensive caries negatively affected the bite force. After pulp removal and endodontic treatment, stress and strain concentrations were higher in the weakened dental structure. Root canal treatment associated with direct resin composite restorative procedure could restore the stress-strain conditions in permanent young molar teeth.

Patient-specific instrumentation in total knee arthroplasty. Should we adopt it?

Total knee arthroplasty (TKA) is a surgical procedure of paramount relevance that restores a substantial degree of function in arthritic knees. Increased consideration has been given to the influence of limb alignment on longevity after TKA, as errors in component placement can be associated with inferior function and compromised long-term performance. Consequently, numerous studies comparing patient-specific instrumentation (PSI) to standard instruments (SI) have been published. Patient-specific approaches use preoperative imaging to create specific materials for each patient's anatomy and were designed to achieve a higher rate of success in TKA, causing the entire procedure to be more efficient and cost-effective. However, it is not clear to what degree these studies support the potential advantages of PSI. Thus, the present study aimed to review the current evidence comparing PSI to SI, concerning alignment, cost-effectiveness, and postoperative functional evaluation.

A artroplastia total do joelho (ATJ) é um procedimento cirúrgico de fundamental relevância que restaura boa parte da função de joelhos artríticos. Maior atenção tem sido dada à influência do alinhamento do membro na longevidade após a ATJ, uma vez que erros no posicionamento dos componentes podem estar associados à uma menor função e compromentimento do desempenho a longo prazo. Consequentemente, vários estudos compararam a instrumentação personalizada para cada paciente (IPP) com a instrumentação padrão (IP). As abordagens personalizadas usam imagens pré-operatórias para criar materiais específicos para a anatomia de cada paciente e foram projetados para atingir uma maior taxa de sucesso na ATJ, tornando todo o processo mais eficiente e rentável. No entanto, não está claro até que ponto tais estudos respaldam as vantagens potenciais da IPP. Assim, o presente estudo teve como objetivo avaliar as evidências atuais, comparando IPP e IP em respeito ao alinhamento, relação custo-benefício e avaliação funcional pós-operatória.

Patient-specific instrumentation in total knee arthroplasty. Should we adopt it? / Instrumentação personalizada na artroplastia total do joelho. Devemos adotá-la?

ABSTRACT Total knee arthroplasty (TKA) is a surgical procedure of paramount relevance that restores a substantial degree of function in arthritic knees. Increased consideration has been given to the influence of limb alignment on longevity after TKA, as errors in component placement can be associated with inferior function and compromised long-term performance. Consequently, numerous studies comparing patient-specific instrumentation (PSI) to standard instruments (SI) have been published. Patient-specific approaches use preoperative imaging to create specific materials for each patient's anatomy and were designed to achieve a higher rate of success in TKA, causing the entire procedure to be more efficient and cost-effective. However, it is not clear to what degree these studies support the potential advantages of PSI. Thus, the present study aimed to review the current evidence comparing PSI to SI, concerning alignment, cost-effectiveness, and postoperative functional evaluation.

RESUMO A artroplastia total do joelho (ATJ) é um procedimento cirúrgico de fundamental relevância que restaura boa parte da função de joelhos artríticos. Maior atenção tem sido dada à influência do alinhamento do membro na longevidade após a ATJ, uma vez que erros no posicionamento dos componentes podem estar associados a uma menor função e comprometimento do desempenho em longo prazo. Consequentemente, vários estudos compararam a instrumentação personalizada para cada paciente (IPP) com a instrumentação padrão (IP). As abordagens personalizadas usam imagens pré-operatórias para criar materiais específicos para a anatomia de cada paciente e foram projetados para atingir uma maior taxa de sucesso na ATJ e tornar todo o processo mais eficiente e rentável. No entanto, não está claro até que ponto tais estudos respaldam as vantagens potenciais da IPP. Assim, o presente estudo teve como objetivo avaliar as evidências atuais e comparar IPP e IP com respeito ao alinhamento, à relação custo-benefício e à avaliação funcional pós-operatória.

Posibilidad de aplicación de la simulación computacional de tejido óseo en niños con torsión tibial / Possibility of application of computational simulation of bone tissue in children with tibial torsion

Introducción: con el desarrollo de la informática surgen nuevos caminos a soluciones de problemas en la práctica clínica. La modelación de tejidos desempeña un papel importante en el desarrollo de la medicina; la experimentación en pacientes vivos dificulta la obtención de resultados, de ahí la necesidad de buscar alternativas para mejorar la calidad del servicio de salud.Objetivo: valorar la importancia de la modelación computacional de tejidos biológicos en niños con torsión tibial.Métodos: se entrevistaron 44 especialistas entre doctores, técnicos en imágenes médicas, ingenieros mecánicos e ingenieros cibernéticos. Fue empleada una encuesta no estructurada sin guion previo.Resultados: se aplicaron valores empíricos de cargas para corregir deformidades como la torsión tibial, el 81 por cientode los encuestados conocen acerca las ventajas de las simulaciones computacionales aplicadas a la salud, el 17 por ciento opina que faltan recursos informáticos en los hospitales para emplear estas técnicas, el 2 por ciento cree que se debe capacitar a los doctores en el empleo de estas herramientas para apoyar la toma de decisiones y el diagnóstico clínico.Conclusiones: la encuesta proporcionó datos conclusivos sobre la posibilidad e interés de la aplicación de los modelos computacionales en el diagnóstico, pronóstico y seguimiento de enfermedades ortopédicas(AU)

Introduction: the development of information brings new paths to solve problems in the clinical practice. Tissue modeling plays an important role in the development of medicine, experimentation on living patients makes it difficult to some extent the results, hence the need to seek alternatives to improve the quality of health service.Objective: assess the importance of computational modeling of biological tissues in pediatric orthopedics, specifically in children with tibial torsion.Methods: forty-four specialists were interviewed including physicians, technicians in medical imaging, mechanical engineers, and cyber engineers. It an unscripted survey unstructured was used.Results: empirical values of loads are applied to correct deformities such as tibial torsion; 81 percent of respondents know about the advantages of computer simulations for health, 17 percent think that missing computer resources in hospitals to employ these techniques, 2 percent believes that doctors should be trained in the use of these tools to support decision-making and clinical diagnosis.Conclusions: the survey provided conclusive data on the ability and interest of the application of computational models in the diagnosis, prognosis, and monitoring of orthopedic diseases(AU)

Posibilidad de aplicación de la simulación computacional de tejido óseo en niños con torsión tibial / Possible application de la modélisation assistée par ordinateur des tissus osseux chez des enfants atteints de torsion tibiale / Possibility of application of computational simulation of bone tissue in children with tibial torsion

Introducción: con el desarrollo de la informática surgen nuevos caminos a soluciones de problemas en la práctica clínica. La modelación de tejidos desempeña un papel importante en el desarrollo de la medicina; la experimentación en pacientes vivos dificulta la obtención de resultados, de ahí la necesidad de buscar alternativas para mejorar la calidad del servicio de salud. Objetivo: valorar la importancia de la modelación computacional de tejidos biológicos en niños con torsión tibial. Métodos: se entrevistaron 44 especialistas entre doctores, técnicos en imágenes médicas, ingenieros mecánicos e ingenieros cibernéticos. Fue empleada una encuesta no estructurada sin guion previo. Resultados: se aplicaron valores empíricos de cargas para corregir deformidades como la torsión tibial, el 81 por ciento de los encuestados conocen acerca las ventajas de las simulaciones computacionales aplicadas a la salud, el 17 por ciento opina que faltan recursos informáticos en los hospitales para emplear estas técnicas, el 2 por ciento cree que se debe capacitar a los doctores en el empleo de estas herramientas para apoyar la toma de decisiones y el diagnóstico clínico. Conclusiones: la encuesta proporcionó datos conclusivos sobre la posibilidad e interés de la aplicación de los modelos computacionales en el diagnóstico, pronóstico y seguimiento de enfermedades ortopédicas(AU)

Introduction: the development of information brings new paths to solve problems in the clinical practice. Tissue modeling plays an important role in the development of medicine, experimentation on living patients makes it difficult to some extent the results, hence the need to seek alternatives to improve the quality of health service. Objective: assess the importance of computational modeling of biological tissues in pediatric orthopedics, specifically in children with tibial torsion. Methods: forty-four specialists were interviewed including physicians, technicians in medical imaging, mechanical engineers, and cyber engineers. It an unscripted survey unstructured was used. Results: empirical values of loads are applied to correct deformities such as tibial torsion; 81 percent of respondents know about the advantages of computer simulations for health, 17 percent think that missing computer resources in hospitals to employ these techniques, 2 percent believes that doctors should be trained in the use of these tools to support decision-making and clinical diagnosis. Conclusions: the survey provided conclusive data on the ability and interest of the application of computational models in the diagnosis, prognosis, and monitoring of orthopedic diseases(AU)

Introduction: à fur et à mesure que l'informatique se développe, de nouvelles solutions aux problèmes de la pratique clinique apparaissent. La modélisation de tissus joue un rôle essentiel dans le développement de la médecine; l'expérimentation sur des patients vivants empêche l'obtention de résultats, il est pourtant nécessaire de chercher d'autres alternatives afin d'améliorer la qualité du service sanitaire. Objectif: le but de cette étude est d'évaluer l'importance de la modélisation assistée par ordinateur des tissus biologiques chez des enfants atteints de torsion tibiale. Méthodes: Quarante et quatre spécialistes, tels que médecins, techniciens en imagerie médicale, ingénieurs mécaniques et ingénieurs cybernétiques, ont été enquêtés. L'enquête utilisée n'avait aucune structure, aucun plan à suivre. Résultats: Des valeurs empiriques de charge ont été utilisées pour corriger des déformations, telles que la torsion tibiale; la majorité des enquêtés (81 pourcent) connaissent bien les bénéfices de la modélisation assistée par ordinateur appliqués à la santé ; la moitié (17 pourcent) considère qu'il y a un déficit de ressources informatiques dans les hôpitaux pour employer cette technique, tandis que la minorité (2 pourcent) croie qu'il faut que les médecins acquissent les habiletés nécessaires pour utiliser cet outil dans la prise de décisions et le diagnostic clinique. Conclusions: L'enquête a fourni des données incontestables sur la possibilité et l'intérêt à mettre en application la modélisation assistée par ordinateur dans le diagnostic, le pronostic et le suivi d'affections orthopédiques (AU)