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Full-Text Articles in Medicine and Health Sciences

Statistical Issues In Proteomic Research, Jeffrey S. Morris Dec 2007

Statistical Issues In Proteomic Research, Jeffrey S. Morris

Jeffrey S. Morris

No abstract provided.


Weight, Mortality, Years Of Healthy Life, And Active Life Expectancy In Older Adults, Paula Diehr Nov 2007

Weight, Mortality, Years Of Healthy Life, And Active Life Expectancy In Older Adults, Paula Diehr

Paula Diehr

OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults. DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults. SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline. MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years …


The Number Of Sick Persons In A Cohort, Paula Diehr Nov 2007

The Number Of Sick Persons In A Cohort, Paula Diehr

Paula Diehr

To see if the number of sick persons in a cohort was approximately constant over time, we calculated the number of sick persons in a “research” cohort of older adults followed for up to 14 years, and also in a synthetic birth cohort. Methods: In the research cohort, we calculated the actual number of persons in each health state over time, using eight different definitions of “sick”. For the birth cohort, we estimated the number of sick persons each year after birth. Results: The number of sick persons in the research cohort was approximately constant for 14 years, for all …


Statistical Methods For Analyzing Sequentially Randomized Trials, Oliver Bembom, Mark J. Van Der Laan Nov 2007

Statistical Methods For Analyzing Sequentially Randomized Trials, Oliver Bembom, Mark J. Van Der Laan

Oliver Bembom

In this issue of JNCI, Thall et al. present the results of a clinical trial that makes use of sequential randomization, a novel trial design that allows the investigator to study adaptive treatment strategies. Our aim is to complement this groundbreaking work by reviewing the current state of the art of statistical methods available for such analyses. Using the data collected by Thall et al. as an example, we focus on two different approaches for estimating the success rates of different adaptive treatment strategies of interest. By emphasizing the intuitive appeal and straightforward implementation of these methods and illustrating the …


Age-Specific Prevalence And Years Of Healthy Life In A System With 3 Health States, Paula Diehr Sep 2007

Age-Specific Prevalence And Years Of Healthy Life In A System With 3 Health States, Paula Diehr

Paula Diehr

Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an 'equilibrium' value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to the one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate …


Biomarker Discovery Using Targeted Maximum Likelihood Estimation: Application To The Treatment Of Antiretroviral Resistant Hiv Infection, Oliver Bembom, Maya L. Petersen, Soo-Yon Rhee, W. Jeffrey Fessel, Sandra E. Sinisi, Robert W. Shafer, Mark J. Van Der Laan Aug 2007

Biomarker Discovery Using Targeted Maximum Likelihood Estimation: Application To The Treatment Of Antiretroviral Resistant Hiv Infection, Oliver Bembom, Maya L. Petersen, Soo-Yon Rhee, W. Jeffrey Fessel, Sandra E. Sinisi, Robert W. Shafer, Mark J. Van Der Laan

Oliver Bembom

Researchers in clinical science and bioinformatics frequently aim to learn which of a set of candidate biomarkers is important in determining a given outcome, and to rank the contributions of the candidates accordingly. This article introduces a new approach to research questions of this type, based on targeted maximum likelihood estimation of variable importance measures. The methodology is illustrated using an example drawn from the treatment of HIV infection. Specifically, given a list of candidate mutations in the protease enzyme of HIV, we aim to discover mutations that reduce clinical virologic response to antiretroviral regimens containing the protease inhibitor lopinavir. …


Data-Adaptive Estimation Of The Treatment-Specific Mean, Yue Wang, Oliver Bembom, Mark Van Der Laan Jun 2007

Data-Adaptive Estimation Of The Treatment-Specific Mean, Yue Wang, Oliver Bembom, Mark Van Der Laan

Oliver Bembom

An important problem in epidemiology and medical research is the estimation of the causal effect of a treatment action at a single point in time on the mean of an outcome, possibly within strata of the target population defined by a subset of the baseline covariates. Current approaches to this problem are based on marginal structural models, i.e. parametric models for the marginal distribution of counterfactual outcomes as a function of treatment and effect modifiers. The various estimators developed in this context furthermore each depend on a high-dimensional nuisance parameter whose estimation currently also relies on parametric models. Since misspecification …


Estimating The Effect Of Vigorous Physical Activity On Mortality In The Elderly Based On Realistic Individualized Treatment And Intention-To-Treat Rules, Oliver Bembom, Mark J. Van Der Laan May 2007

Estimating The Effect Of Vigorous Physical Activity On Mortality In The Elderly Based On Realistic Individualized Treatment And Intention-To-Treat Rules, Oliver Bembom, Mark J. Van Der Laan

Oliver Bembom

The effect of vigorous physical activity on mortality in the elderly is difficult to estimate using conventional approaches to causal inference that define this effect by comparing the mortality risks corresponding to hypothetical scenarios in which all subjects in the target population engage in a given level of vigorous physical activity. A causal effect defined on the basis of such a static treatment intervention can only be identified from observed data if all subjects in the target population have a positive probability of selecting each of the candidate treatment options, an assumption that is highly unrealistic in this case since …


Analyzing Sequentially Randomized Trials Based On Causal Effect Models For Realistic Individualized Treatment Rules, Oliver Bembom, Mark J. Van Der Laan May 2007

Analyzing Sequentially Randomized Trials Based On Causal Effect Models For Realistic Individualized Treatment Rules, Oliver Bembom, Mark J. Van Der Laan

Oliver Bembom

In this paper, we argue that causal effect models for realistic individualized treatment rules represent an attractive tool for analyzing sequentially randomized trials. Unlike a number of methods proposed previously, this approach does not rely on the assumption that intermediate outcomes are discrete or that models for the distributions of these intermediate outcomes given the observed past are correctly specified. In addition, it generalizes the methodology for performing pairwise comparisons between individualized treatment rules by allowing the user to posit a marginal structural model for all candidate treatment rules simultaneously. If only a small number of candidate treatment rules are …


Supervised Detection Of Conserved Motifs In Dna Sequences With Cosmo, Oliver Bembom, Sunduz Keles, Mark J. Van Der Laan Feb 2007

Supervised Detection Of Conserved Motifs In Dna Sequences With Cosmo, Oliver Bembom, Sunduz Keles, Mark J. Van Der Laan

Oliver Bembom

A number of computational methods have been proposed for identifying transcription factor binding sites from a set of unaligned sequences that are thought to share the motif in question. We here introduce an algorithm, called cosmo, that allows this search to be supervised by specifying a set of constraints that the position weight matrix of the unknown motif must satisfy. Such constraints may be formulated, for example, on the basis of prior knowledge about the structure of the transcription factor in question. The algorithm is based on the same two-component multinomial mixture model used by MEME, with stronger reliance, however, …


The Causal Effect Of Recent Leisure-Time Physical Activity On All-Cause Mortality Among The Elderly, Oliver Bembom, Mark J. Van Der Laan, Ira B. Tager Feb 2007

The Causal Effect Of Recent Leisure-Time Physical Activity On All-Cause Mortality Among The Elderly, Oliver Bembom, Mark J. Van Der Laan, Ira B. Tager

Oliver Bembom

We analyze data collected as part of a prospective cohort study of elderly people living in and around Sonoma, CA, in order to estimate, for each round of interviews, the causal effect of leisure-time physical activity (LTPA) over the past year on the risk of mortality in the following two years. For each round of interviews, this effect is estimated separately for subpopulations defined based on past exercise habits, age, and whether subjects have had cardiac events in the past. This decomposition of the original longitudinal data structure into a series of point-treatment data structures corresponds to an application of …


Pre-Processing Mass Spectrometry Data, Kevin R. Coombes, Keith A. Baggerly, Jeffrey S. Morris Jan 2007

Pre-Processing Mass Spectrometry Data, Kevin R. Coombes, Keith A. Baggerly, Jeffrey S. Morris

Jeffrey S. Morris

No abstract provided.


Laser Capture Sampling And Analytical Issues In Proteomics, Howard Gutstein, Jeffrey S. Morris Jan 2007

Laser Capture Sampling And Analytical Issues In Proteomics, Howard Gutstein, Jeffrey S. Morris

Jeffrey S. Morris

Proteomics holds the promise of evaluating global changes in protein expression and post-translational modificaiton in response to environmental stimuli. However, difficulties in achieving cellular anatomic resolution and extracting specific types of proteins from cells have limited the efficacy of these techniques. Laser capture microdissection has provided a solution to the problem of anatomical resolution in tissues. New extraction methodologies have expanded the range of proteins identified in subsequent analyses. This review will examine the application of laser capture microdissection to proteomic tissue sampling, and subsequent extraction of these samples for differential expression analysis. Statistical and other quantitative issues important for …


Site Variation In Ems Treatment, Transport And Survival In Relation To Restoration Of Spontaneous Circulation (Rosc) For Adult Out-Of-Hospital Cardiac Arrest: The Resuscitation Outcomes Consortium (Roc) Epistry, Mohamud R. Daya, Kent M. Koprowicz, Dana M. Zive, Julie E. Cummins, Gena K. Sears, Terri A. Schmidt, Shannon W. Stephens, Ian G. Stiell Jan 2007

Site Variation In Ems Treatment, Transport And Survival In Relation To Restoration Of Spontaneous Circulation (Rosc) For Adult Out-Of-Hospital Cardiac Arrest: The Resuscitation Outcomes Consortium (Roc) Epistry, Mohamud R. Daya, Kent M. Koprowicz, Dana M. Zive, Julie E. Cummins, Gena K. Sears, Terri A. Schmidt, Shannon W. Stephens, Ian G. Stiell

Kent M Koprowicz

Introduction: EMS protocols outlining when to attempt and terminate resuscitation for non-traumatic out-of- hospital cardiac arrest (OHCA) vary substantially across North America. The ROC Epistry is a prospective population based cohort study with uniform Utstein-style data definitions from 11 sites in North America. The purpose of this study was to compare site variation in EMS treatment and transport percentages within the ROC Epistry. We also examined the differences in overall survival in relation to the presence of ROSC prior to transport. Methods: Analysis of ROC Epistry data from 7 sites for all patients > 20 years of age with OHCA between …