Carolyn M. Ervin

Bio: Carolyn M. Ervin is an academic researcher from University of Southern California. The author has contributed to research in topics: Randomized controlled trial & Nicotine. The author has an hindex of 4, co-authored 7 publications receiving 331 citations.

Effect of Highly Active Antiretroviral Therapy on Time to Acquired Immunodeficiency Syndrome or Death using Marginal Structural Models

Abstract: To estimate the net (i.e., overall) effect of highly active antiretroviral therapy (HAART) on time to acquired immunodeficiency syndrome (AIDS) or death, the authors used inverse probability-of-treatment weighted estimation of a marginal structural model, which can appropriately adjust for time-varying confounders affected by prior treatment or exposure. Human immunodeficiency virus (HIV)-positive men and women (n = 1,498) were followed in two ongoing cohort studies between 1995 and 2002. Sixty-one percent (n = 918) of the participants initiated HAART during 6,763 person-years of follow-up, and 382 developed AIDS or died. Strong confounding by indication for HAART was apparent; the unadjusted hazard ratio for AIDS or death was 0.98. The hazard ratio from a standard time-dependent Cox model that included time-varying CD4 cell count, HIV RNA level, and other time-varying and fixed covariates as regressors was 0.81 (95% confidence interval: 0.61, 1.07). In contrast, the hazard ratio from a marginal structural survival model was 0.54 (robust 95% confidence interval: 0.38, 0.78), suggesting a clinically meaningful net benefit of HAART. Standard Cox analysis failed to detect a clear net benefit, because it does not appropriately adjust for time-dependent covariates, such as HIV RNA level and CD4 cell count, that are simultaneously confounders and intermediate variables.

The immediate and long-term effects of exercise and patient education on physical, functional, and quality-of-life outcome measures after single-level lumbar microdiscectomy: a randomized controlled trial protocol.

Abstract: Low back pain remains a costly quality-of-life-related health problem Microdiscectomy is often the surgical procedure of choice for a symptomatic, single-level, lumbar disc herniation in younger and middle-aged adults The question of whether a post-microdiscectomy exercise program enhances function, quality of life, and disability status has not been systematically explored Thus, the overall purpose of this study is to assess immediate and long-term outcomes of an exercise program, developed at University of Southern California (USC), targeting the trunk and lower extremities (USC Spine Exercise Program) for persons who have undergone a single-level microdiscectomy for the first time One hundred individuals between the ages of 18 and 60 who consent to undergo lumbar microdiscectomy will be recruited to participate in this study Subjects will be randomly assigned to one of two groups: 1) one session of back care education, or 2) a back care education session followed by the 12-week USC Spine Exercise Program The outcome examiners (evaluators), as well as the data managers, will be blinded to group allocation Education will consist of a one-hour "one-on-one" session with the intervention therapist, guided by an educational booklet specifically designed for post-microdiscectomy care This session will occur four to six weeks after surgery The USC Spine Exercise Program consists of two parts: back extensor strength and endurance, and mat and upright therapeutic exercises This exercise program is goal-oriented, performance-based, and periodized It will begin two to three days after the education session, and will occur three times a week for 12 weeks Primary outcome measures include the Oswestry Disability Questionnaire, Roland-Morris Disability Questionnaire, SF-36® quality of life assessment, Subjective Quality of Life Scale, 50-foot Walk, Repeated Sit-to-Stand, and a modified Sorensen test The outcome measures in the study will be assessed before and after the 12-week post-surgical intervention program Long-term follow up assessments will occur every six months beginning one year after surgery and ending five years after surgery Immediate and long-term effects will be assessed using repeated measures multivariate analysis of variance (MANOVA) If significant interactions are found, one-way ANOVAs will be performed followed by post-hoc testing to determine statistically significant pairwise comparisons We have presented the rationale and design for a randomized controlled trial evaluating the effectiveness of a treatment regimen for people who have undergone a single-level lumbar microdiscectomy

The Physical Therapy Clinical Research Network (PTClinResNet) : Methods, Efficacy, and Benefits of a Rehabilitation Research Network

Abstract: This article describes the vision, methods, and implementation strategies used in building the infrastructure for PTClinResNet, a clinical research network designed to assess outcomes for health-related mobility associated with evidence-based physical therapy interventions across and within four different disability groups. Specific aims were to (1) create the infrastructure necessary to develop and sustain clinical trials research in rehabilitation, (2) generate evidence to evaluate the efficacy of resistance exercise-based physical interventions designed to improve muscle performance and movement skills, and (3) provide education and training opportunities for present and future clinician-researchers and for the rehabilitation community at-large in its support of evidence-based practice. We present the network's infrastructure, development, and several examples that highlight the benefits of a clinical research network. We suggest that the network structure is ideal for building research capacity and fostering multisite, multiinvestigator clinical research projects designed to generate evidence for the efficacy of rehabilitation interventions.

Multiethnic Prediction of Nicotine Biomarkers and Association with Nicotine Dependence

Abstract: Background The nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers will extend biomarker studies to cohorts without measured biomarkers and enable tobacco-related behavioral and exposure research. Methods We screened genetic variants genome-wide using marginal scans and applied statistical learning algorithms on top-ranked genetic variants and age, ethnicity and sex, and cigarettes per day (CPD) (in additional modeling) to build prediction models for the urinary nicotine metabolite ratio (uNMR) and creatinine-standardized total nicotine equivalents (TNE) in 2,239 current cigarette smokers in five ethnic groups. We predicted these nicotine biomarkers using model ensembles, and evaluated external validity using behavioral outcomes in 1,864 treatment-seeking smokers in two ethnic groups. Results The genomic regions with the most selected and trained variants for measured biomarkers were chr19q13.2 (uNMR, without and with CPD) and chr15q25.1 and chr10q25.3 (TNE, without and with CPD). We observed ensemble correlations between measured and predicted biomarker values for the uNMR and TNE without (with CPD) of 0.67 (0.68), and 0.65 (0.72) in the training sample. We observed inconsistency in penalized regression models of TNE (with CPD) with fewer variants at chr15q25.1 selected and trained. In treatment-seeking smokers, predicted uNMR (without CPD) was significantly associated with CPD, and predicted TNE (without CPD) with CPD, Time-To-First-Cigarette, and Fagerstrom total score. Conclusions Nicotine metabolites, genome-wide data and statistical learning approaches develop novel robust predictive models for urinary nicotine biomarkers in multiple ethnic groups. Predicted biomarker associations help define genetically-influenced components of nicotine dependence. IMPLICATIONS We demonstrate development of robust models and multiethnic prediction of the urinary nicotine metabolite ratio and total nicotine equivalents using statistical and machine learning approaches. Trained variants in models for both biomarkers include top-ranked variants in multiethnic genome-wide studies of smoking behavior, nicotine metabolites and related disease. Association of the two predicted nicotine biomarkers with Fagerstr□m Test for Nicotine Dependence items support models of nicotine biomarkers as predictors of physical dependence and nicotine exposure. Predicted nicotine biomarkers may facilitate tobacco-related disease and treatment research in samples with genomic data and limited nicotine metabolite or tobacco exposure data.

Constructing Inverse Probability Weights for Marginal Structural Models

Abstract: The method of inverse probability weighting (henceforth, weighting) can be used to adjust for measured confounding and selection bias under the four assumptions of consistency, exchangeability, positivity, and no misspecification of the model used to estimate weights. In recent years, several published estimates of the effect of time-varying exposures have been based on weighted estimation of the parameters of marginal structural models because, unlike standard statistical methods, weighting can appropriately adjust for measured time-varying confounders affected by prior exposure. As an example, the authors describe the last three assumptions using the change in viral load due to initiation of antiretroviral therapy among 918 human immunodeficiency virus-infected US men and women followed for a median of 5.8 years between 1996 and 2005. The authors describe possible tradeoffs that an epidemiologist may encounter when attempting to make inferences. For instance, a tradeoff between bias and precision is illustrated as a function of the extent to which confounding is controlled. Weight truncation is presented as an informal and easily implemented method to deal with these tradeoffs. Inverse probability weighting provides a powerful methodological tool that may uncover causal effects of exposures that are otherwise obscured. However, as with all methods, diagnostics and sensitivity analyses are essential for proper use.

Registries for Evaluating Patient Outcomes: A User's Guide

Abstract: This user’s guide is intended to support the design, implementation, analysis, interpretation, and quality evaluation of registries created to increase understanding of patient outcomes. For the purposes of this guide, a patient registry is an organized system that uses observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves one or more predetermined scientific, clinical, or policy purposes. A registry database is a file (or files) derived from the registry. Although registries can serve many purposes, this guide focuses on registries created for one or more of the following purposes: to describe the natural history of disease, to determine clinical effectiveness or costeffectiveness of health care products and services, to measure or monitor safety and harm, and/or to measure quality of care.

Estimating causal effects from epidemiological data

Abstract: In ideal randomised experiments, association is causation: association measures can be interpreted as effect measures because randomisation ensures that the exposed and the unexposed are exchangeable. On the other hand, in observational studies, association is not generally causation: association measures cannot be interpreted as effect measures because the exposed and the unexposed are not generally exchangeable. However, observational research is often the only alternative for causal inference. This article reviews a condition that permits the estimation of causal effects from observational data, and two methods -- standardisation and inverse probability weighting -- to estimate population causal effects under that condition. For simplicity, the main description is restricted to dichotomous variables and assumes that no random error attributable to sampling variability exists. The appendix provides a generalisation of inverse probability weighting.

Activated Injectable Vitamin D and Hemodialysis Survival: A Historical Cohort Study

Abstract: Patients with ESRD commonly experience secondary hyperparathyroidism, a condition primarily managed with activated injectable vitamin D. The biologic effects of vitamin D, however, are widespread, and it is possible that activated injectable vitamin D alters survival in ESRD. This hypothesis was tested in a historical cohort study of incident hemodialysis patients who lived throughout the United States between January 1996 and December 1999. The primary outcome was 2-yr survival among those who survived for at least 90 d after initiation of chronic hemodialysis. During this period, 51,037 chronic hemodialysis patients survived for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr, 37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr, mortality rates were 13.8/100 person-years in the group that received injectable vitamin D compared with 28.6/100 person-years in the group that did not (P < 0.001). Cox proportional hazards analyses adjusting for several potential confounders and examining injectable vitamin D therapy as a time-dependent exposure suggested that compared with patients who did not receive injectable vitamin D, the 2-yr survival advantage associated with the group that did receive injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76 to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person-years in the injectable vitamin D group, compared with 14.6/100 person-years in the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus, situations in which injectable vitamin D is often withheld. Repeating the entire analysis using marginal structural models to adjust for time-dependent confounding by indication yielded a survival advantage of 26% (hazard ratio, 0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable vitamin D group. In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not. Randomized clinical trials would permit definitive conclusions.