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1.
Alzheimers Res Ther ; 15(1): 176, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37838690

RESUMEN

Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years from the initial diagnosis. Diagnosis of cognitive impairment in dementia is typically based on clinical evaluation, neuropsychological assessments, cerebrospinal fluid (CSF) biomarkers, and neuroimaging. The main goal of diagnosing MCI is to determine its cause, particularly whether it is due to Alzheimer's disease (AD). However, only a limited percentage of the population has access to etiological confirmation, which has led to the emergence of peripheral fluid biomarkers as a diagnostic tool for dementias, including MCI due to AD. Recent advances in biofluid assays have enabled the use of sophisticated statistical models and multimodal machine learning (ML) algorithms for the diagnosis of MCI based on fluid biomarkers from CSF, peripheral blood, and saliva, among others. This approach has shown promise for identifying specific causes of MCI, including AD. After a PRISMA analysis, 29 articles revealed a trend towards using multimodal algorithms that incorporate additional biomarkers such as neuroimaging, neuropsychological tests, and genetic information. Particularly, neuroimaging is commonly used in conjunction with fluid biomarkers for both cross-sectional and longitudinal studies. Our systematic review suggests that cost-effective longitudinal multimodal monitoring data, representative of diverse cultural populations and utilizing white-box ML algorithms, could be a valuable contribution to the development of diagnostic models for AD due to MCI. Clinical assessment and biomarkers, together with ML techniques, could prove pivotal in improving diagnostic tools for MCI due to AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/genética , Estudios Transversales , Progresión de la Enfermedad , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Aprendizaje Automático , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo
2.
Stat Med ; 42(27): 4952-4971, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-37668286

RESUMEN

In this work, we propose an extension of a semiparametric nonlinear mixed-effects model for longitudinal data that incorporates more flexibility with penalized splines (P-splines) as smooth terms. The novelty of the proposed approach consists of the formulation of the model within the stochastic approximation version of the EM algorithm for maximum likelihood, the so-called SAEM algorithm. The proposed approach takes advantage of the formulation of a P-spline as a mixed-effects model and the use of the computational advantages of the existing software for the SAEM algorithm for the estimation of the random effects and the variance components. Additionally, we developed a supervised classification method for these non-linear mixed models using an adaptive importance sampling scheme. To illustrate our proposal, we consider two studies on pregnant women where two biomarkers are used as indicators of changes during pregnancy. In both studies, information about the women's pregnancy outcomes is known. Our proposal provides a unified framework for the classification of longitudinal profiles that may have important implications for the early detection and monitoring of pregnancy-related changes and contribute to improved maternal and fetal health outcomes. We show that the proposed models improve the analysis of this type of data compared to previous studies. These improvements are reflected both in the fit of the models and in the classification of the groups.


Asunto(s)
Algoritmos , Programas Informáticos , Femenino , Humanos , Embarazo , Resultado del Embarazo , Modelos Estadísticos , Estudios Longitudinales
3.
Biostatistics ; 24(1): 209-225, 2022 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-34296256

RESUMEN

Across several medical fields, developing an approach for disease classification is an important challenge. The usual procedure is to fit a model for the longitudinal response in the healthy population, a different model for the longitudinal response in the diseased population, and then apply Bayes' theorem to obtain disease probabilities given the responses. Unfortunately, when substantial heterogeneity exists within each population, this type of Bayes classification may perform poorly. In this article, we develop a new approach by fitting a Bayesian nonparametric model for the joint outcome of disease status and longitudinal response, and then we perform classification through the clustering induced by the Dirichlet process. This approach is highly flexible and allows for multiple subpopulations of healthy, diseased, and possibly mixed membership. In addition, we introduce an Markov chain Monte Carlo sampling scheme that facilitates the assessment of the inference and prediction capabilities of our model. Finally, we demonstrate the method by predicting pregnancy outcomes using longitudinal profiles on the human chorionic gonadotropin beta subunit hormone levels in a sample of Chilean women being treated with assisted reproductive therapy.


Asunto(s)
Teorema de Bayes , Femenino , Humanos , Cadenas de Markov , Método de Montecarlo , Análisis por Conglomerados , Probabilidad
4.
Entropy (Basel) ; 25(1)2022 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-36673197

RESUMEN

Mixture cure rate models have been developed to analyze failure time data where a proportion never fails. For such data, standard survival models are usually not appropriate because they do not account for the possibility of non-failure. In this context, mixture cure rate models assume that the studied population is a mixture of susceptible subjects who may experience the event of interest and non-susceptible subjects that will never experience it. More specifically, mixture cure rate models are a class of survival time models in which the probability of an eventual failure is less than one and both the probability of eventual failure and the timing of failure depend (separately) on certain individual characteristics. In this paper, we propose a Bayesian approach to estimate parametric mixture cure rate models with covariates. The probability of eventual failure is estimated using a binary regression model, and the timing of failure is determined using a Weibull distribution. Inference for these models is attained using Markov Chain Monte Carlo methods under the proposed Bayesian framework. Finally, we illustrate the method using data on the return-to-prison time for a sample of prison releases of men convicted of sexual crimes against women in England and Wales and we use mixture cure rate models to investigate the risk factors for long-term and short-term survival of recidivism.

5.
Stat Methods Med Res ; 27(4): 1153-1167, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-27405324

RESUMEN

Consider longitudinal observations across different subjects such that the underlying distribution is determined by a non-linear mixed-effects model. In this context, we look at the misclassification error rate for allocating future subjects using cross-validation, bootstrap algorithms (parametric bootstrap, leave-one-out, .632 and [Formula: see text]), and bootstrap cross-validation (which combines the first two approaches), and conduct a numerical study to compare the performance of the different methods. The simulation and comparisons in this study are motivated by real observations from a pregnancy study in which one of the main objectives is to predict normal versus abnormal pregnancy outcomes based on information gathered at early stages. Since in this type of studies it is not uncommon to have insufficient data to simultaneously solve the classification problem and estimate the misclassification error rate, we put special attention to situations when only a small sample size is available. We discuss how the misclassification error rate estimates may be affected by the sample size in terms of variability and bias, and examine conditions under which the misclassification error rate estimates perform reasonably well.


Asunto(s)
Sesgo , Análisis Discriminante , Estudios Longitudinales , Muestreo , Adulto , Investigación Biomédica/estadística & datos numéricos , Femenino , Humanos , Dinámicas no Lineales , Embarazo , Resultado del Embarazo , Adulto Joven
6.
Stat Med ; 36(13): 2120-2134, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28215052

RESUMEN

We propose a semiparametric nonlinear mixed-effects model (SNMM) using penalized splines to classify longitudinal data and improve the prediction of a binary outcome. The work is motivated by a study in which different hormone levels were measured during the early stages of pregnancy, and the challenge is using this information to predict normal versus abnormal pregnancy outcomes. The aim of this paper is to compare models and estimation strategies on the basis of alternative formulations of SNMMs depending on the characteristics of the data set under consideration. For our motivating example, we address the classification problem using a particular case of the SNMM in which the parameter space has a finite dimensional component (fixed effects and variance components) and an infinite dimensional component (unknown function) that need to be estimated. The nonparametric component of the model is estimated using penalized splines. For the parametric component, we compare the advantages of using random effects versus direct modeling of the correlation structure of the errors. Numerical studies show that our approach improves over other existing methods for the analysis of this type of data. Furthermore, the results obtained using our method support the idea that explicit modeling of the serial correlation of the error term improves the prediction accuracy with respect to a model with random effects, but independent errors. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Estudios Longitudinales , Modelos Estadísticos , Resultado del Embarazo/epidemiología , Interpretación Estadística de Datos , Femenino , Hexaclorociclohexano/sangre , Humanos , Embarazo/sangre , Trimestres del Embarazo/sangre
7.
Rev. chil. pediatr ; 87(5): 351-358, oct. 2016. ilus
Artículo en Español | LILACS | ID: biblio-830163

RESUMEN

El desarrollo infantil temprano es un determinante de la salud física, mental y social de poblaciones. Conocer la situación de desarrollo de base, previo a la instalación de «Chile Crece Contigo¼, es clave para efectos de su evaluación. Objetivo: Comparar el desarrollo infantil temprano y factores asociados de preescolares del sector público y del sector privado de salud en la línea de base. Pacientes y método: Una muestra de 1.045 niños de la Región Metropolitana, de 30 a 58 meses, 52% hombres, 671 del sector público y 380 del privado de salud. Se evaluaron mediante el Inventario de Desarrollo Battelle-1 y una encuesta psicosocial en sus hogares aplicada al cuidador principal. Resultados: El 14,4% del sector privado y el 30,4% de la red pública tenían desarrollo alterado. No hubo diferencias en el área adaptativa entre ambos grupos (26,3% vs 29,2%). En las áreas cognitiva (8,8% vs 12,1%), personal-social (13,2% vs 32,5%), motriz (19,2% vs 35,3%) y comunicación (19,0% vs 36,8%) las diferencias fueron estadísticamente significativas. Mediante regresión logística se determinó que, independiente del nivel socioeconómico, son factores de riesgo: Apgar < 7 (OR: 5,4; IC 95%: 1,24-23,84), tener enfermedades crónicas de la infancia (OR: 1,3; IC 95%: 1,11-1,42); protector es: hogar con recursos para el aprendizaje y juego (OR: 0,8; IC 95%: 0,76-0,89). Conclusión: Estos resultados son un aporte al conocimiento de la situación del desarrollo infantil y para relevar su importancia para las políticas sociales en pediatría.


Early child development is a population determinant of physical, mental and social health. To know the base line situation prior to the implementation of "Chile grows with you" (Chile Crece Contigo) is key to its evaluation. Objective: To compare early child development and associated factors at baseline in pre-school children from public and private health sectors. Patients and method: The sample consisted of 1045 children aged 30-58 months, 52% male, and 671 from the public and 380 from the private sector of the metropolitan region in Chile were evaluated using Battelle Developmental Inventory-1 and a household interview of primary carer. Results: Abnormal child development was found in 14.4% of children in the private sector compared to 30.4% in the public sector. There were no differences in adaptive area (26.3% vs 29.2%), but there were statistically significant differents in cognitive (8.8% vs 12.1%), social-personal (13.2% vs 32.5%), motor (19.2% vs 35.3%), and communication (19% vs 36.8%) development. The logistic regression showed that, independent of socioeconomic level, the risk factors are: Apgar < 7 (OR: 5.4; 95% CI: 1.24-23.84); having childhood chronic diseases (OR: 1.3; 95% CI: 1.11-1.42). Protective factor is: home with resources to learn and play (OR: 0.8; 95% CI: 0.76-0.89).


Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Desarrollo Infantil/fisiología , Discapacidades del Desarrollo/epidemiología , Disparidades en el Estado de Salud , Factores Socioeconómicos , Modelos Logísticos , Chile/epidemiología , Enfermedad Crónica/epidemiología , Factores de Riesgo , Sector Público , Sector Privado , Cognición/fisiología , Factores Protectores
8.
J Multivar Anal ; 143: 94-106, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27274601

RESUMEN

Joint models for a wide class of response variables and longitudinal measurements consist on a mixed-effects model to fit longitudinal trajectories whose random effects enter as covariates in a generalized linear model for the primary response. They provide a useful way to assess association between these two kinds of data, which in clinical studies are often collected jointly on a series of individuals and may help understanding, for instance, the mechanisms of recovery of a certain disease or the efficacy of a given therapy. When a nonlinear mixed-effects model is used to fit the longitudinal trajectories, the existing estimation strategies based on likelihood approximations have been shown to exhibit some computational efficiency problems (De la Cruz et al., 2011). In this article we consider a Bayesian estimation procedure for the joint model with a nonlinear mixed-effects model for the longitudinal data and a generalized linear model for the primary response. The proposed prior structure allows for the implementation of an MCMC sampler. Moreover, we consider that the errors in the longitudinal model may be correlated. We apply our method to the analysis of hormone levels measured at the early stages of pregnancy that can be used to predict normal versus abnormal pregnancy outcomes. We also conduct a simulation study to assess the importance of modelling correlated errors and quantify the consequences of model misspecification.

9.
Rev Chil Pediatr ; 87(5): 351-358, 2016.
Artículo en Español | MEDLINE | ID: mdl-27079995

RESUMEN

Early child development is a population determinant of physical, mental and social health. To know the base line situation prior to the implementation of "Chile grows with you" (Chile Crece Contigo) is key to its evaluation. OBJECTIVE: To compare early child development and associated factors at baseline in pre-school children from public and private health sectors. PATIENTS AND METHOD: The sample consisted of 1045 children aged 30-58 months, 52% male, and 671 from the public and 380 from the private sector of the metropolitan region in Chile were evaluated using Battelle Developmental Inventory-1 and a household interview of primary carer. RESULTS: Abnormal child development was found in 14.4% of children in the private sector compared to 30.4% in the public sector. There were no differences in adaptive area (26.3% vs 29.2%), but there were statistically significant differents in cognitive (8.8% vs 12.1%), social-personal (13.2% vs 32.5%), motor (19.2% vs 35.3%), and communication (19% vs 36.8%) development. The logistic regression showed that, independent of socioeconomic level, the risk factors are: Apgar<7 (OR: 5.4; 95% CI: 1.24-23.84); having childhood chronic diseases (OR: 1.3; 95% CI: 1.11-1.42). Protective factor is: home with resources to learn and play (OR: 0.8; 95% CI: 0.76-0.89). CONCLUSION: These results are another input about early child development situation and its importance for paediatric social policy.


Asunto(s)
Desarrollo Infantil/fisiología , Discapacidades del Desarrollo/epidemiología , Disparidades en el Estado de Salud , Preescolar , Chile/epidemiología , Enfermedad Crónica/epidemiología , Cognición/fisiología , Femenino , Humanos , Modelos Logísticos , Masculino , Sector Privado , Factores Protectores , Sector Público , Factores de Riesgo , Factores Socioeconómicos
10.
BMC Public Health ; 16: 122, 2016 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-26847446

RESUMEN

BACKGROUND: Maule Cohort (MAUCO), a Chilean cohort study, seeks to analyze the natural history of chronic diseases in the agricultural county of Molina (40,000 inhabitants) in the Maule Region, Chile. Molina´s population is of particular interest because in the last few decades it changed from being undernourished to suffering excess caloric intake, and it currently has the highest national rates of cardiovascular diseases, stomach cancer and gallbladder cancer. Between 2009 and 2011 Molina´s poverty rate dropped from 24.1 % to 13.5 % (national average 20.4 %); in this period the county went from insufficient to almost complete basic sanitation. Despite these advances, chemical pollutants in the food and air are increasing. Thus, in Molina risk factors typical of both under-developed and developed countries coexist, generating a unique profile associated with inflammation, oxidative stress and chronic diseases. METHODS/DESIGN: MAUCO is the core project of the recently established Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Católica de Chile. In this study, we are enrolling and following 10,000 adults aged 38 to 74 years over 10 years. All eligible Molina residents will be enrolled. Participants were identified through a household census. Consenting individuals answer an epidemiological survey exploring risk factors (psycho-social, pesticides, diet, alcohol, and physical activity), medical history and physical and cognitive conditions; provide fasting blood, urine, and saliva samples; receive an electrocardiogram, abdominal ultrasound and bio-impedance test; and take a hand-grip strength test. These subjects will be re-interviewed after 2, 5 and 7 years. Active surveillance of health events is in place throughout the regional healthcare system. The MAUCO Bio-Bank will store 30 to 50 aliquots per subject using an NIH/NCI biorepository system for secure and anonymous linkage of samples with data. DISCUSSION: MAUCO´s results will help design public health interventions tailored to agricultural populations in Latin America.


Asunto(s)
Enfermedad Crónica/epidemiología , Salud Pública , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Enfermedades Cardiovasculares/epidemiología , Chile/epidemiología , Dieta , Ingestión de Energía , Ejercicio Físico , Femenino , Neoplasias de la Vesícula Biliar/epidemiología , Humanos , América Latina , Masculino , Persona de Mediana Edad , Plaguicidas/análisis , Pobreza/estadística & datos numéricos , Estudios Prospectivos , Proyectos de Investigación , Factores de Riesgo , Población Rural , Factores Socioeconómicos , Neoplasias Gástricas/epidemiología
11.
Biometrics ; 71(2): 333-43, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25639332

RESUMEN

We propose a classification method for longitudinal data. The Bayes classifier is classically used to determine a classification rule where the underlying density in each class needs to be well modeled and estimated. This work is motivated by a real dataset of hormone levels measured at the early stages of pregnancy that can be used to predict normal versus abnormal pregnancy outcomes. The proposed model, which is a semiparametric linear mixed-effects model (SLMM), is a particular case of the semiparametric nonlinear mixed-effects class of models (SNMM) in which finite dimensional (fixed effects and variance components) and infinite dimensional (an unknown function) parameters have to be estimated. In SNMM's maximum likelihood estimation is performed iteratively alternating parametric and nonparametric procedures. However, if one can make the assumption that the random effects and the unknown function interact in a linear way, more efficient estimation methods can be used. Our contribution is the proposal of a unified estimation procedure based on a penalized EM-type algorithm. The Expectation and Maximization steps are explicit. In this latter step, the unknown function is estimated in a nonparametric fashion using a lasso-type procedure. A simulation study and an application on real data are performed.


Asunto(s)
Interpretación Estadística de Datos , Modelos Estadísticos , Algoritmos , Teorema de Bayes , Biometría , Gonadotropina Coriónica Humana de Subunidad beta/metabolismo , Simulación por Computador , Femenino , Humanos , Funciones de Verosimilitud , Modelos Lineales , Estudios Longitudinales , Dinámicas no Lineales , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/metabolismo , Resultado del Embarazo
12.
Rev. chil. infectol ; 31(6): 721-728, dic. 2014. ilus, tab
Artículo en Español | LILACS | ID: lil-734766

RESUMEN

Introduction: Febrile neutropenia (FN) is a common complication of patients undergoing chemotherapy (QMT). Clinical presentation is varied, from mild fever to severe sepsis with invasive bacterial infection (IBI) or invasive fungal infection (IFI), with great impact on prognosis and patient mortality. Patients and Methods: Prospective cohort study of FN episodes in adult patients with acute leukemia (AL) or lymphoma (L), diagnosed and treated at the Hospital Clínico Universidad Católica and Hospital Dr. Sótero del Río in Santiago from April 2010 to January 2012. Results: 130 patients were included with 105 episodes of NF, with an incidence of 0.65 per 100 days of observation, higher in AL than L (1.31 vs 0.25, p = 0.001). Etiology or clinical focus was documented in 67 (63.8%) episodes, with IBI in 33 (31.4%) and IFI in 21 (20%) cases. Mortality related to infection occurred in 4 (6.2%) patients. Conclusions: This study reports that the FN incidence and frequency of IBI and IFI during episodes are higher in AL vs. L. It is necessary to evaluate the impact of interventions to reduce its incidence, including the benefit and risk of using antibacterial and antifungal prophylaxis in high-risk subgroups.


Introducción: La neutropenia febril (NF) es una complicación frecuente de pacientes sometidos a quimioterapia (QMT). Su presentación clínica es amplia, desde cuadros leves a sepsis grave con infección bacteriana invasora (IBI) o infección fúngica invasora (IFI), con gran impacto en el pronóstico y mortalidad de los pacientes. Pacientes y Métodos: Estudio prospectivo de episodios de NF en cohorte de pacientes adultos con leucemia aguda (LA) o linfoma (L) diagnosticados y tratados en el Hospital Clínico Pontificia Universidad Católica de Chile y Hospital Dr. Sótero del Río en Santiago, desde abril de 2010 hasta enero de 2012. Resultados: Se reclutaron 130 pacientes que presentaron 105 episodios de NF, con incidencia de 0,65 por 100 días de observación, mayor en LA que en L (1,31 vs 0,25, p: 0,001), documentándose etiología o foco infeccioso en 67 (63,8%) de los episodios, con 33 (31,4%) IBI y 21 (20%) IFI. Hubo mortalidad relacionada a infección en 4 (6,2%) pacientes. Conclusiones: Se define la incidencia de NF (LA > L) y frecuencia de IBI e IFI durante el episodio (LA > L). Es necesario evaluar el impacto de intervenciones destinadas a disminuir la incidencia de NF, entre las que se debe incluir el beneficio y riesgo del uso sistemático de profilaxis antibacteriana y antifúngica en los subgrupos de mayor riesgo.


Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Enfermedad Aguda , Chile/epidemiología , Hospitales Privados , Hospitales Públicos , Incidencia , Leucemia/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Estudios Prospectivos
13.
Pharm Stat ; 13(1): 81-93, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24106083

RESUMEN

A common assumption in nonlinear mixed-effects models is the normality of both random effects and within-subject errors. However, such assumptions make inferences vulnerable to the presence of outliers. More flexible distributions are therefore necessary for modeling both sources of variability in this class of models. In the present paper, I consider an extension of the nonlinear mixed-effects models in which random effects and within-subject errors are assumed to be distributed according to a rich class of parametric models that are often used for robust inference. The class of distributions I consider is the scale mixture of multivariate normal distributions that consist of a wide range of symmetric and continuous distributions. This class includes heavy-tailed multivariate distributions, such as the Student's t and slash and contaminated normal. With the scale mixture of multivariate normal distributions, robustification is achieved from the tail behavior of the different distributions. A Bayesian framework is adopted, and MCMC is used to carry out posterior analysis. Model comparison using different criteria was considered. The procedures are illustrated using a real dataset from a pharmacokinetic study. I contrast results from the normal and robust models and show how the implementation can be used to detect outliers.


Asunto(s)
Teorema de Bayes , Dinámicas no Lineales , Humanos , Funciones de Verosimilitud , Distribución Normal , Teofilina/farmacocinética
14.
Rev Chilena Infectol ; 31(6): 721-8, 2014 Dec.
Artículo en Español | MEDLINE | ID: mdl-25679930

RESUMEN

INTRODUCTION: Febrile neutropenia (FN) is a common complication of patients undergoing chemotherapy (QMT). Clinical presentation is varied, from mild fever to severe sepsis with invasive bacterial infection (IBI) or invasive fungal infection (IFI), with great impact on prognosis and patient mortality. PATIENTS AND METHODS: Prospective cohort study of FN episodes in adult patients with acute leukemia (AL) or lymphoma (L), diagnosed and treated at the Hospital Clínico Universidad Católica and Hospital Dr. Sótero del Río in Santiago from April 2010 to January 2012. RESULTS: 130 patients were included with 105 episodes of NF, with an incidence of 0.65 per 100 days of observation, higher in AL than L (1.31 vs 0.25, p = 0.001). Etiology or clinical focus was documented in 67 (63.8%) episodes, with IBI in 33 (31.4%) and IFI in 21 (20%) cases. Mortality related to infection occurred in 4 (6.2%) patients. CONCLUSIONS: This study reports that the FN incidence and frequency of IBI and IFI during episodes are higher in AL vs. L. It is necessary to evaluate the impact of interventions to reduce its incidence, including the benefit and risk of using antibacterial and antifungal prophylaxis in high-risk subgroups.


Asunto(s)
Neutropenia Febril Inducida por Quimioterapia/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Chile/epidemiología , Femenino , Hospitales Privados , Hospitales Públicos , Humanos , Incidencia , Leucemia/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
15.
Biom J ; 53(5): 735-49, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21770044

RESUMEN

In many studies, the association of longitudinal measurements of a continuous response and a binary outcome are often of interest. A convenient framework for this type of problems is the joint model, which is formulated to investigate the association between a binary outcome and features of longitudinal measurements through a common set of latent random effects. The joint model, which is the focus of this article, is a logistic regression model with covariates defined as the individual-specific random effects in a non-linear mixed-effects model (NLMEM) for the longitudinal measurements. We discuss different estimation procedures, which include two-stage, best linear unbiased predictors, and various numerical integration techniques. The proposed methods are illustrated using a real data set where the objective is to study the association between longitudinal hormone levels and the pregnancy outcome in a group of young women. The numerical performance of the estimating methods is also evaluated by means of simulation.


Asunto(s)
Estudios Longitudinales , Dinámicas no Lineales , Análisis de Varianza , Gonadotropina Coriónica Humana de Subunidad beta/farmacología , Femenino , Humanos , Funciones de Verosimilitud , Modelos Logísticos , Embarazo , Curva ROC , Procesos Estocásticos
16.
PLoS One ; 6(6): e19934, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21695122

RESUMEN

INTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. SUBJECTS AND METHODS: This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. RESULTS: No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103-rs1543873 (p = 0.06), rs6014646-rs6024730 (p = 0.05) and rs3746619-rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. CONCLUSION: The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans.


Asunto(s)
Alelos , Dieta con Restricción de Grasas , Obesidad/dietoterapia , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Receptor de Melanocortina Tipo 3/genética , Pérdida de Peso/genética , Tejido Adiposo/efectos de los fármacos , Adulto , Animales , Dieta Reductora , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/farmacología , Metabolismo Energético/efectos de los fármacos , Femenino , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Ratones , Persona de Mediana Edad , Circunferencia de la Cintura/efectos de los fármacos , Circunferencia de la Cintura/genética , Pérdida de Peso/efectos de los fármacos , Adulto Joven
19.
J Clin Endocrinol Metab ; 95(3): 1069-75, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20097707

RESUMEN

CONTEXT: The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear. OBJECTIVE: The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED). DESIGN: This was a prospective, controlled, nonrandomized study. SETTING: The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital. PARTICIPANTS: PARTICIPANTS included three groups of eight patients with similar body mass indexes (RYGB 37.8 +/- 0.8, SG 35.3 +/- 0.7, and MED 39.1 +/- 1.7 kg/m(2), P = NS) and eight lean controls (body mass index 21.7 +/- 0.7 kg/m(2)). MAIN OUTCOME MEASURES: Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured. RESULTS: At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 +/- 3, 14.9 +/- 2.4, 16.6 +/- 4%, respectively, P = NS). PYY AUC increased in RYGB (P < 0.001) and SG (P < 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P < 0.05). Hunger AUC decreased in RYGB (P < 0.05). Satiety AUC increased in RYGB (P < 0.05) and SG (P < 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r = 0.35, P < 0.05). CONCLUSION: RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety.


Asunto(s)
Hambre/fisiología , Obesidad/sangre , Obesidad/terapia , Péptido YY/sangre , Saciedad/fisiología , Pérdida de Peso/fisiología , Adulto , Análisis de Varianza , Área Bajo la Curva , Índice de Masa Corporal , Dietoterapia , Ejercicio Físico , Femenino , Gastrectomía , Derivación Gástrica , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Estudios Prospectivos , Radioinmunoensayo , Análisis de Regresión , Factores de Tiempo
20.
Biom J ; 51(4): 588-609, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19629998

RESUMEN

We have considered a Bayesian approach for the nonlinear regression model by replacing the normal distribution on the error term by some skewed distributions, which account for both skewness and heavy tails or skewness alone. The type of data considered in this paper concerns repeated measurements taken in time on a set of individuals. Such multiple observations on the same individual generally produce serially correlated outcomes. Thus, additionally, our model does allow for a correlation between observations made from the same individual. We have illustrated the procedure using a data set to study the growth curves of a clinic measurement of a group of pregnant women from an obstetrics clinic in Santiago, Chile. Parameter estimation and prediction were carried out using appropriate posterior simulation schemes based in Markov Chain Monte Carlo methods. Besides the deviance information criterion (DIC) and the conditional predictive ordinate (CPO), we suggest the use of proper scoring rules based on the posterior predictive distribution for comparing models. For our data set, all these criteria chose the skew-t model as the best model for the errors. These DIC and CPO criteria are also validated, for the model proposed here, through a simulation study. As a conclusion of this study, the DIC criterion is not trustful for this kind of complex model.


Asunto(s)
Teorema de Bayes , Gonadotropina Coriónica/sangre , Interpretación Estadística de Datos , Modelos Biológicos , Dinámicas no Lineales , Embarazo/sangre , Chile/epidemiología , Simulación por Computador , Femenino , Humanos , Modelos Estadísticos , Crecimiento Demográfico , Embarazo/estadística & datos numéricos , Resultado del Embarazo , Análisis de Regresión
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