Publications by authors named "Alejandro Jara"

13 Publications

  • Page 1 of 1

The role of body mass index at diagnosis of colorectal cancer on Black-White disparities in survival: a density regression mediation approach.

Biostatistics 2020 Sep 24. Epub 2020 Sep 24.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Building 2, 4th Floor, Boston, MA 02115, USA.

The study of racial/ethnic inequalities in health is important to reduce the uneven burden of disease. In the case of colorectal cancer (CRC), disparities in survival among non-Hispanic Whites and Blacks are well documented, and mechanisms leading to these disparities need to be studied formally. It has also been established that body mass index (BMI) is a risk factor for developing CRC, and recent literature shows BMI at diagnosis of CRC is associated with survival. Since BMI varies by racial/ethnic group, a question that arises is whether differences in BMI are partially responsible for observed racial/ethnic disparities in survival for CRC patients. This article presents new methodology to quantify the impact of the hypothetical intervention that matches the BMI distribution in the Black population to a potentially complex distributional form observed in the White population on racial/ethnic disparities in survival. Our density mediation approach can be utilized to estimate natural direct and indirect effects in the general causal mediation setting under stronger assumptions. We perform a simulation study that shows our proposed Bayesian density regression approach performs as well as or better than current methodology allowing for a shift in the mean of the distribution only, and that standard practice of categorizing BMI leads to large biases when BMI is a mediator variable. When applied to motivating data from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium, our approach suggests the proposed intervention is potentially beneficial for elderly and low-income Black patients, yet harmful for young or high-income Black populations.
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http://dx.doi.org/10.1093/biostatistics/kxaa034DOI Listing
September 2020

Marginal Bayesian Semiparametric Modeling of Mismeasured Multivariate Interval-Censored Data.

J Am Stat Assoc 2018 26;114(525):129-145. Epub 2018 Oct 26.

Statistician, Medtronic, Inc., 710 Medtronic Parkway N.E., Minneapolis, MN 55432 USA

Motivated by data gathered in an oral health study, we propose a Bayesian nonparametric approach for population-averaged modeling of correlated time-to-event data, when the responses can only be determined to lie in an interval obtained from a sequence of examination times and the determination of the occurrence of the event is subject to misclassification. The joint model for the true, unobserved time-to-event data is defined semiparametrically; proportional hazards, proportional odds, and accelerated failure time (proportional quantiles) are all fit and compared. The baseline distribution is modeled as a flexible tailfree prior. The joint model is completed by considering a parametric copula function. A general misclassification model is discussed in detail, considering the possibility that different examiners were involved in the assessment of the occurrence of the events for a given subject across time. We provide empirical evidence that the model can be used to estimate the underlying time-to-event distribution and the misclassification parameters without any external information about the latter parameters. We also illustrate the effect on the statistical inferences of neglecting the presence of misclassification.
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http://dx.doi.org/10.1080/01621459.2018.1476240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711609PMC
October 2018

A flexible AFT model for misclassified clustered interval-censored data.

Biometrics 2016 06 7;72(2):473-83. Epub 2015 Oct 7.

Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University in Prague, Sokolovska 83, CZ-186 75 Praha 8 ' Karlín, Czech Republic.

Motivated by a longitudinal oral health study, we propose a flexible modeling approach for clustered time-to-event data, when the response of interest can only be determined to lie in an interval obtained from a sequence of examination times (interval-censored data) and on top of that, the determination of the occurrence of the event is subject to misclassification. The clustered time-to-event data are modeled using an accelerated failure time model with random effects and by assuming a penalized Gaussian mixture model for the random effects terms to avoid restrictive distributional assumptions concerning the event times. A general misclassification model is discussed in detail, considering the possibility that different examiners were involved in the assessment of the occurrence of the events for a given subject across time. A Bayesian implementation of the proposed model is described in a detailed manner. We additionally provide empirical evidence showing that the model can be used to estimate the underlying time-to-event distribution and the misclassification parameters without any external information about the latter parameters. We also provide results of a simulation study to evaluate the effect of neglecting the presence of misclassification in the analysis of clustered time-to-event data.
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http://dx.doi.org/10.1111/biom.12424DOI Listing
June 2016

MODELLING COUNTY LEVEL BREAST CANCER SURVIVAL DATA USING A COVARIATE-ADJUSTED FRAILTY PROPORTIONAL HAZARDS MODEL.

Ann Appl Stat 2015 Mar;9(1):43-68

University of South Carolina.

Understanding the factors that explain differences in survival times is an important issue for establishing policies to improve national health systems. Motivated by breast cancer data arising from the Surveillance Epidemiology and End Results program, we propose a covariate-adjusted proportional hazards frailty model for the analysis of clustered right-censored data. Rather than incorporating exchangeable frailties in the linear predictor of commonly-used survival models, we allow the frailty distribution to flexibly change with both continuous and categorical cluster-level covariates and model them using a dependent Bayesian nonparametric model. The resulting process is flexible and easy to fit using an existing R package. The application of the model to our motivating example showed that, contrary to intuition, those diagnosed during a period of time in the 1990s in more rural and less affluent Iowan counties survived breast cancer better. Additional analyses showed the opposite trend for earlier time windows. We conjecture that this anomaly has to be due to increased hormone replacement therapy treatments prescribed to more urban and affluent subpopulations.
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http://dx.doi.org/10.1214/14-AOAS793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520441PMC
March 2015

BM-BC: a Bayesian method of base calling for Solexa sequence data.

BMC Bioinformatics 2012 24;13 Suppl 13:S6. Epub 2012 Aug 24.

Center for Clinical and Research Informatics, Northshore University HealthSystem, Evanston, IL 60091, USA.

Base calling is a critical step in the Solexa next-generation sequencing procedure. It compares the position-specific intensity measurements that reflect the signal strength of four possible bases (A, C, G, T) at each genomic position, and outputs estimates of the true sequences for short reads of DNA or RNA. We present a Bayesian method of base calling, BM-BC, for Solexa-GA sequencing data. The Bayesian method builds on a hierarchical model that accounts for three sources of noise in the data, which are known to affect the accuracy of the base calls: fading, phasing, and cross-talk between channels. We show that the new method improves the precision of base calling compared with currently leading methods. Furthermore, the proposed method provides a probability score that measures the confidence of each base call. This probability score can be used to estimate the false discovery rate of the base calling or to rank the precision of the estimated DNA sequences, which in turn can be useful for downstream analysis such as sequence alignment.
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http://dx.doi.org/10.1186/1471-2105-13-S13-S6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426806PMC
May 2013

A Bayesian Semiparametric Temporally-Stratified Proportional Hazards Model with Spatial Frailties.

Bayesian Anal 2011 ;6(4):1-48

Department of Statistics, University of South Carolina, Columbia, SC 29208 ( ).

Incorporating temporal and spatial variation could potentially enhance information gathered from survival data. This paper proposes a Bayesian semiparametric model for capturing spatio-temporal heterogeneity within the proportional hazards framework. The spatial correlation is introduced in the form of county-level frailties. The temporal effect is introduced by considering the stratification of the proportional hazards model, where the time-dependent hazards are indirectly modeled using a probability model for related probability distributions. With this aim, an autoregressive dependent tailfree process is introduced. The full Kullback-Leibler support of the proposed process is provided. The approach is illustrated using simulated and data from the Surveillance Epidemiology and End Results database of the National Cancer Institute on patients in Iowa diagnosed with breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255564PMC
January 2011

The Polya Tree Sampler: Towards Efficient and Automatic Independent Metropolis-Hastings Proposals.

J Comput Graph Stat 2011 Mar;20(1):41-62

Department of Statistics, University of South Carolina, Columbia, SC 29208.

We present a simple, efficient, and computationally cheap sampling method for exploring an un-normalized multivariate density on ℝ(d), such as a posterior density, called the Polya tree sampler. The algorithm constructs an independent proposal based on an approximation of the target density. The approximation is built from a set of (initial) support points - data that act as parameters for the approximation - and the predictive density of a finite multivariate Polya tree. In an initial "warming-up" phase, the support points are iteratively relocated to regions of higher support under the target distribution to minimize the distance between the target distribution and the Polya tree predictive distribution. In the "sampling" phase, samples from the final approximating mixture of finite Polya trees are used as candidates which are accepted with a standard Metropolis-Hastings acceptance probability. Several illustrations are presented, including comparisons of the proposed approach to Metropolis-within-Gibbs and delayed rejection adaptive Metropolis algorithm.
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http://dx.doi.org/10.1198/jcgs.2010.09115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226339PMC
March 2011

DPpackage: Bayesian Non- and Semi-parametric Modelling in R.

J Stat Softw 2011 Apr;40(5):1-30

Universidad de Concepción.

Data analysis sometimes requires the relaxation of parametric assumptions in order to gain modeling flexibility and robustness against mis-specification of the probability model. In the Bayesian context, this is accomplished by placing a prior distribution on a function space, such as the space of all probability distributions or the space of all regression functions. Unfortunately, posterior distributions ranging over function spaces are highly complex and hence sampling methods play a key role. This paper provides an introduction to a simple, yet comprehensive, set of programs for the implementation of some Bayesian non- and semi-parametric models in R, DPpackage. Currently DPpackage includes models for marginal and conditional density estimation, ROC curve analysis, interval-censored data, binary regression data, item response data, longitudinal and clustered data using generalized linear mixed models, and regression data using generalized additive models. The package also contains functions to compute pseudo-Bayes factors for model comparison, and for eliciting the precision parameter of the Dirichlet process prior. To maximize computational efficiency, the actual sampling for each model is carried out using compiled FORTRAN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142948PMC
April 2011

Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance.

Eur Heart J 2009 Jan 10;30(1):116-24. Epub 2008 Sep 10.

Department of Pediatric Neurology, University Hospitals Leuven, Herestraat, Leuven, Belgium.

Aims: Duchenne muscular dystrophy (DMD) is a severe and still incurable disease, with heart failure as a leading cause of death. The identification of a disease-modifying therapy may require early-initiated and long-term administration, but such type of therapeutic trial is not evident in humans. We have performed such a trial of SNT-MC17/idebenone in the mdx mouse model of DMD, based on the drug's potential to improve mitochondrial respiratory chain function and reduce oxidative stress.

Methods And Results: In this study, 200 mg/kg bodyweight of either SNT-MC17/idebenone or placebo was given from age 4 weeks until 10 months in mdx and wild-type mice. All evaluators were blinded to mouse type and treatment groups. Idebenone treatment significantly corrected cardiac diastolic dysfunction and prevented mortality from cardiac pump failure induced by dobutamine stress testing in vivo, significantly reduced cardiac inflammation and fibrosis, and significantly improved voluntary running performance in mdx mice.

Conclusion: We have identified a novel potential therapeutic strategy for human DMD, as SNT-MC17/idebenone was cardioprotective and improved exercise performance in the dystrophin-deficient mdx mouse. Our data also illustrate that the mdx mouse provides unique opportunities for long-term controlled prehuman therapeutic studies.
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http://dx.doi.org/10.1093/eurheartj/ehn406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639086PMC
January 2009

Variables associated with longitudinally registered plaque accumulation in a cohort of Flemish schoolchildren.

Quintessence Int 2007 Jul-Aug;38(7):555-64

Department of Paediatric Dentistry and Special Care-PaeCaMed-research, Ghent University, Ghent, Belgium.

Objectives: To analyze the change in pattern of plaque accumulation on buccal and occlusal surfaces of permanent teeth and associated variables in a cohort of 4,468 children examined on a yearly basis between the ages of 7 and 12 years.

Method And Materials: Oral hygiene level on buccal surfaces was assessed using the Plaque Index of Silness and Loe; for occlusal surfaces, a simplified version of the index as described by Carvalho et al was used. Data on oral health habits were collected using questionnaires completed by the parents and by the school health care center. Multiple ordinal logistic regression models using first-order generalized estimating equations were fitted to estimate population average effects taking into account the correlated structure of the data.

Results: Girls brushed significantly more frequently than boys (as reported by the parents) and presented with significantly less dental plaque. In all survey years, starting to brush at a young age, no daily consumption of sugar-containing drinks, and brushing at least twice a day were significantly associated with lower plaque accumulation scores. Parental help did not seem to influence the accumulation of occlusal plaque, but it did influence the amount of buccal plaque on incisors and premolars at older ages. The presence of sealants was significantly associated with less dental plaque.

Conclusion: Regarding future policies for preventive strategies in schoolchildren, help with brushing at older ages can be recommended. Application of sealants can be encouraged, but further research is needed to confirm whether the presence of sealants improves oral cleanliness.
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September 2007

CINRG pilot trial of oxatomide in steroid-naïve Duchenne muscular dystrophy.

Eur J Paediatr Neurol 2007 Nov 24;11(6):337-40. Epub 2007 Apr 24.

University Hospitals KU Leuven, Leuven, Herestraat 49, B-3000 Leuven, Belgium.

The authors report a pilot open-label two-center therapeutic trial of oxatomide in 14 steroid-naive DMD boys aged 5-10 years. Comparison of linear evolutions between 3 months medication-free lead-in periods and 6 months treatment periods showed no significant differences in quantitative (QMT) and manual (MMT) measurements of muscle strength and timed functional tests. A modest mitigation of strength deterioration over time cannot be excluded.
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http://dx.doi.org/10.1016/j.ejpn.2007.02.009DOI Listing
November 2007

Gastric cancer is related to early Helicobacter pylori infection in a high-prevalence country.

Cancer Epidemiol Biomarkers Prev 2007 Apr;16(4):662-7

Departamento de Salud Pública, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 434, Santiago, Chile.

Background And Aims: Chile ranks fifth in the world among countries with the highest incidence of gastric cancer. The aim was to quantify the association between Helicobacter pylori infection and gastric cancer mortality at the county of residence.

Methods: A cross-sectional household survey, a probability sample of the Chilean adult population, provided 2,615 participants in whom serum H. pylori IgG antibodies were measured (ELISA). The spatial pattern of 48,367 deaths due to gastric cancer which occurred from 1985 to 2002 was analyzed using a hierarchical Poisson regression model; 333 counties were categorized as low, medium, and high gastric cancer mortality with median gastric cancer death rates of 11.4, 19.1, and 26.0 per 100,000 inhabitants, respectively. The association between H. pylori positivity and gastric cancer mortality in the county of residence was assessed by multivariate Poisson regression for complex samples.

Results: H. pylori prevalence was 73.0% [95% confidence intervals (CI), 70.0-76.0], higher in men [prevalence rate ratio (PRR), 1.1 (95% CI, 1.01-1.20)], peaked at ages 45 to 64, and dropped after age 65. It was higher among residents in counties with high gastric cancer mortality (79.7%; 95% CI, 76.4-82.6) compared to counties with low gastric cancer mortality (62.3%; 95% CI, 53.8-70.2; corresponding PRR, 1.3; 95% CI, 1.1-1.5); under age 24, H. pylori infection was 79.7% (95% CI, 72.2-85.6) versus 39.8% (95% CI, 19.6-64.2) among residents in counties with high and low gastric cancer mortalities, respectively (PRR, 2.0; 95% CI, 1.1-3.7).

Conclusions: The high prevalence of H. pylori at younger ages was associated with high gastric cancer mortality in the base population.
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http://dx.doi.org/10.1158/1055-9965.EPI-06-0514DOI Listing
April 2007

Population-based prevalence and age distribution of human papillomavirus among women in Santiago, Chile.

Cancer Epidemiol Biomarkers Prev 2004 Dec;13(12):2271-6

Department of Public Health, School of Medicine, P Catholic University, Depto. de Salud Pública, Marcoleta, 434, Santiago, Santiago 6510259, Chile.

Unlabelled: More than 18 types of human papillomavirus (HPV) are associated with cervical cancer, the relative importance of the HPV types may vary in different populations.

Objective: To investigate the types of HPV, age distribution, and risk factors for HPV infection in women from Santiago, Chile.

Methods: We interviewed and obtained two cervical specimens from a population-based random sample of 1,038 sexually active women (age range, 15-69 years). Specimens were tested for the presence of HPV DNA using a GP5+/6+ primer-mediated PCR and for cervical cytologic abnormalities by Papanicolaou smears.

Results: 122 women tested positive for HPV DNA, 87 with high risk types (HR), and 35 with low risks (LR) only. Standardized prevalence of HPV DNA was 14.0% [95% confidence interval (95% CI), 11.5-16.4]. HR HPV by age showed a J reverse curve, whereas LR HPV showed a U curve, both statistically significant in comparison with no effect or with a linear effect. We found 34 HPV types (13 HR and 21 LR); HPV 16, 56, 31, 58, 59, 18, and 52 accounted for 75.4% of HR infections. Thirty-four (3.6%) women had cytologic lesions. Main risk factor for HPV and for cytologic abnormalities was number of lifetime sexual partners, odds ratios for > or =3 versus 1 were 2.8 (95% CI, 1.6-5.0) and 3.8 (95% CI, 1.3-11.4), respectively.

Conclusions: LR HPV presented a clear bimodal age pattern; HR HPV presented a J reverse curve. HPV prevalence was similar to that described in most Latin American countries.
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December 2004