ABSTRACT
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.
Subject(s)
Humans , Child , Pharmacokinetics , Multivariate AnalysisABSTRACT
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.
ABSTRACT
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.
Subject(s)
Humans , Aortic Aneurysm/diagnostic imaging , Hydrodynamics , Aorta/diagnostic imaging , Pilot Projects , Hemodynamics/physiologyABSTRACT
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.
Subject(s)
Humans , Child , Bite Force , Composite Resins/chemistry , Tooth, Nonvital/therapy , Dental Restoration, Permanent/methods , Molar , Reference Values , Tensile Strength , Reproducibility of Results , Treatment Outcome , Composite Resins/therapeutic use , Tooth, Nonvital/diagnostic imaging , Compressive Strength , Finite Element Analysis , Dental Stress Analysis , Cone-Beam Computed Tomography , Elastic Modulus , Patient-Specific ModelingABSTRACT
The physiomic approach is now widely used in the diagnosis of cardiovascular diseases. There are two possible methods for cardiovascular physiome: the traditional mathematical model and the machine learning (ML) algorithm. ML is used in almost every area of society for various tasks formerly performed by humans. Specifically, various ML techniques in cardiovascular medicine are being developed and improved at unprecedented speed. The benefits of using ML for various tasks is that the inner working mechanism of the system does not need to be known, which can prove convenient in situations where determining the inner workings of the system can be difficult. The computation speed is also often higher than that of the traditional mathematical models. The limitations with ML are that it inherently leads to an approximation, and special care must be taken in cases where a high accuracy is required. Traditional mathematical models are, however, constructed based on underlying laws either proven or assumed. The results from the mathematical models are accurate as long as the model is. Combining the advantages of both the mathematical models and ML would increase both the accuracy and efficiency of the simulation for many problems. In this review, examples of cardiovascular physiome where approaches of mathematical modeling and ML can be combined are introduced.
Subject(s)
Humans , Cardiovascular Diseases , Diagnosis , Jurisprudence , Machine Learning , Models, Theoretical , Patient-Specific ModelingABSTRACT
OBJECTIVES: The association between obstructive sleep apnea (OSA) and mortality or serious cardiovascular events over a long period of time is not clearly understood. The aim of this observational study was to estimate the clinical effectiveness of continuous positive airway pressure (CPAP) treatment on an outcome variable combining mortality, acute myocardial infarction (AMI), and cerebrovascular insult (CVI) during a follow-up period of 15.5 years (186 ± 58 months). METHODS: The data set consisted of 978 patients with an apnea-hypopnea index (AHI) ≥5.0. One-third had used CPAP treatment. For the first time, a data-driven causal Bayesian network (DDBN) and a hypothesis-driven causal Bayesian network (HDBN) were used to investigate the effectiveness of CPAP. RESULTS: In the DDBN, coronary heart disease (CHD), congestive heart failure (CHF), and diuretic use were directly associated with the outcome variable. Sleep apnea parameters and CPAP treatment had no direct association with the outcome variable. In the HDBN, CPAP treatment showed an average improvement of 5.3 percentage points in the outcome. The greatest improvement was seen in patients aged ≤55 years. The effect of CPAP treatment was weaker in older patients (>55 years) and in patients with CHD. In CHF patients, CPAP treatment was associated with an increased risk of mortality, AMI, or CVI. CONCLUSIONS: The effectiveness of CPAP is modest in younger patients. Long-term effectiveness is limited in older patients and in patients with heart disease (CHD or CHF).
Subject(s)
Humans , Bayes Theorem , Continuous Positive Airway Pressure , Coronary Disease , Dataset , Follow-Up Studies , Heart Diseases , Heart Failure , Mortality , Myocardial Infarction , Observational Study , Outcome Assessment, Health Care , Patient-Specific Modeling , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Treatment OutcomeABSTRACT
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.
Subject(s)
Arthroplasty , Arthroplasty, Replacement, Knee , Knee Prosthesis , Patient-Specific ModelingABSTRACT
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)