Medicine and Health Sciences Commons^™

Uncertainty And The Value Of Diagnostic Information With Application To Axillary Lymph Node Dissection In Breast Cancer, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

In clinical decision making, it is common to ask whether, and how much, a diagnostic procedure is contributing to subsequent treatment decisions. Statistically, quantification of the value of the information provided by a diagnostic procedure can be carried out using decision trees with multiple decision points, representing both the diagnostic test and the subsequent treatments that may depend on the test's results. This article investigates probabilistic sensitivity analysis approaches for exploring and communicating parameter uncertainty in such decision trees. Complexities arise because uncertainty about a model's inputs determines uncertainty about optimal decisions at all decision nodes of a tree. We …

Survival Model Predictive Accuracy And Roc Curves, Patrick Heagerty, Yingye Zheng

UW Biostatistics Working Paper Series

The predictive accuracy of a survival model can be summarized using extensions of the proportion of variation explained by the model, or R^2, commonly used for continuous response models, or using extensions of sensitivity and specificity which are commonly used for binary response models.

In this manuscript we propose new time-dependent accuracy summaries based on time-specific versions of sensitivity and specificity calculated over risk sets. We connect the accuracy summaries to a previously proposed global concordance measure which is a variant of Kendall's tau. In addition, we show how standard Cox regression output can be used to obtain estimates of …

Semiparametric Estimation Of Time-Dependent: Roc Curves For Longitudinal Marker Data, Yingye Zheng, Patrick Heagerty

UW Biostatistics Working Paper Series

One approach to evaluating the strength of association between a longitudinal marker process and a key clinical event time is through predictive regression methods such as a time-dependent covariate hazard model. For example, a time-varying covariate Cox model specifies the instantaneous risk of the event as a function of the time-varying marker and additional covariates. In this manuscript we explore a second complementary approach which characterizes the distribution of the marker as a function of both the measurement time and the ultimate event time. Our goal is to flexibly extend the standard diagnostic accuracy concepts of sensitivity and specificity to …

The Relation Of Dietary Patterns To Future Survival, Health, And Cardiovascular Events In Older Adults, Paula Diehr

Paula Diehr

BACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns. METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later. RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly …

Optimization Of Breast Cancer Screening Modalities, Yu Shen, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

Mathematical models and decision analyses based on microsimulations have been shown to be useful in evaluating relative merits of various screening strategies in terms of cost and mortality reduction. Most investigations regarding the balance between mortality reduction and costs have focused on a single modality, mammography. A systematic evaluation of the relative expenses and projected benefit of combining clinical breast examination and mammography is not at present available. The purpose of this report is to provide methodologic details including assumptions and data used in the process of modeling for complex decision analyses, when searching for optimal breast cancer screening strategies …

Modeling The Incubation Period Of Anthrax, Ron Brookmeyer, Elizabeth Johnson, Sarah Barry

Johns Hopkins University, Dept. of Biostatistics Working Papers

Models of the incubation period of anthrax are important to public health planners because they can be used to predict the delay before outbreaks are detected, the size of an outbreak and the duration of time that persons should remain on antibiotics to prevent disease. The difficulty is that there is little direct data about the incubation period in humans. The objective of this paper is to develop and apply models for the incubation period of anthrax. Mechanistic models that account for the biology of spore clearance and germination are developed based on a competing risks formulation. The models predict …

Comparison Of Bracket Bond Strength By Total, Self-Etch And Laser Treatment, Kyo Sung Shawn Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Laser etching of enamel surfaces alters the physical and chemical characteristics of the enamel. These changes in characteristics enhance the bonding to enamel. The purpose of this study was to compare the shear and tensile bond strength of Er,Cr:YSGG hydrokinetic laser system (Biolase) with 37% phosphoric acid and self etching primer 30 minutes and 72 hours after bonding. Four different laser power output setting was observed: 1.5W, 2.0W, 2.5W, and 3.0W. Two hundred forty bovine teeth free of defect, caries, and dentin exposure were mounted in acrylic resin and divided into 24 groups of 10 teeth. Sixteen groups of 10 …

Clinical Effectiveness Of A Subperiosteal Anchorage Device, Monica Anne Witte

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this pilot study was to evaluate the clinical efficacy of a subperiosteal anchorage device, the palatal OnPlant™, during orthodontic retraction of protruding anterior teeth in cases requiring maxillary premolar extraction. Seven subjects (5 female, 2 male), ages 13 to 55, were selected for the study. The OnPlant was surgically placed in the mid-palatal region through a well-defined subperiosteal tunnel. Following the manufacturer recommended osseointegration period of four months, the OnPlant was uncovered and attached to the first molars by means of a transpalatal bar. Standard orthodontic treatment then commenced to retract the anterior teeth after the first …

A Bond Strength Comparison Of Led And Halogen Light Curing Units, John Richard Kavanagh

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this research was to compare the tensile bond strength of orthodontic flat based buttons bonded to bovine teeth with four commercial light-emitting diode (LED) curing lights and one conventional quartz tungsten halogen (QTH) curing light.

The dental market has recently been introduced to a number of commercially available light-emitting diode (LED) curing lights. Tensile bond strength was evaluated for LED curing lights (Rembrandt® Allegro^TM, Den-Mat Corp, Santa Maria, CA), (LEDemetron, Kerr/Demetron Corp, Danbury, Conn), (Ortholux LED, 3M^TMESPE^TM, St. Paul, MN),and (FLASH-lite 1001, Discus Dental, Culver City, CA) are compared with one …

Modeling The Optimum Duration Of Antibiotic Prophylaxis In An Anthrax Outbreak, Ron Brookmeyer, Elizabeth Johnson, Robert Bollinger

Ron Brookmeyer

A critical consideration in effective and measured public health responses to an outbreak of inhalational anthrax is the optimum duration of antibiotic prophylaxis. We develop a competing-risks model to address the duration of antibiotic prophylaxis and the incubation period that accounts for the risks of spore germination and spore clearance. The model predicts the incubation period distribution, which is confirmed by empirical data. The optimum duration of antibiotic prophylaxis depends critically on the dose of inhaled spores. At high doses, we show that exposed persons would need to remain on antibiotic prophylaxis for at least 4 months, and considerable morbidity …

Statistical Models And Bioterrorism: Application To The U.S. Anthrax Outbreak, Ron Brookmeyer, Natalie Blades

Ron Brookmeyer

In the fall of 2001 an outbreak of inhalational anthrax occurred in the United States that was the result of bioterrorism. Letters contaminated with anthrax spores were sent through the postal system. In response to the outbreak, public health officials treated over 10,000 persons with antibiotic prophylaxis in the hopes of preventing further morbidity and mortality. No persons receiving the antibiotics subsequently developed disease. The question arises as to how many cases of disease may actually have been prevented by the public health intervention of antibiotic prophylaxis. A statistical model is developed to answer this question by relating to the …

Time-Series Studies Of Particulate Matter, Michelle L. Bell, Jonathan M. Samet, Francesca Dominici

Johns Hopkins University, Dept. of Biostatistics Working Papers

Studies of air pollution and human health have evolved from descriptive studies of the early phenomena of large increases in adverse health effects following extreme air pollution episodes, to time-series analyses and the development of sophisticated regression models. In fact, advanced statistical methods are necessary to address the many challenges inherent in the detection of a small pollution risk in the presence of many confounders. This paper reviews the history, methods, and findings of the time-series studies estimating health risks associated with short-term exposure to particulate matter, though much of the discussion is applicable to epidemiological studies of air pollution …

Smooth Quantile Ratio Estimation With Regression: Estimating Medical Expenditures For Smoking Attributable Diseases, Francesca Dominici, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In this paper we introduce a semi-parametric regression model for estimating the difference in the expected value of two positive and highly skewed random variables as a function of covariates. Our method extends Smooth Quantile Ratio Estimation (SQUARE), a novel estimator of the mean difference of two positive random variables, to a regression model.

The methodological development of this paper is motivated by a common problem in econometrics where we are interested in estimating the difference in the average expenditures between two populations, say with and without a disease, taking covariates into account. Let Y1 and Y2 be two positive …

A Corrected Pseudo-Score Approach For Additive Hazards Model With Longitudinal Covariates Measured With Error, Xiao Song, Yijian Huang

UW Biostatistics Working Paper Series

In medical studies, it is often of interest to characterize the relationship between a time-to-event and covariates, not only time-independent but also time-dependent. Time-dependent covariates are generally measured intermittently and with error. Recent interests focus on the proportional hazards framework, with longitudinal data jointly modeled through a mixed effects model. However, approaches under this framework depend on the normality assumption of the error, and might encounter intractable numerical difficulties in practice. This motivates us to consider an alternative framework, that is, the additive hazards model, under which little has been done when time-dependent covariates are measured with error. We propose …

Smooth Quantile Ratio Estimation, Francesca Dominici, Leslie Cope, Daniel Q. Naiman, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In a study of health care expenditures attributable to smoking, we seek to compare the distribution of medical costs for persons with lung cancer or chronic obstructive pulmonary disease (cases) to those without (controls) using a national survey which includes hundreds of cases and thousands of controls. The distribution of costs is highly skewed toward larger values, making estimates of the mean from the smaller sample dependent on a small fraction of the biggest values. One approach to deal with the smaller sample is to rely on a simple parametric model such as the log-normal, but this makes the undesirable …

Rejoinder To "“Wavelet-Based Nonparametric Modeling Of Hierarchical Functions In Colon Carcinogenesis.”, Jeffrey S. Morris, Marina Vannucci, Philip J. Brown, Raymond J. Carroll

Jeffrey S. Morris

No abstract provided.

Quality Control And Peak Finding For Proteomics Data Collected From Nipple Aspirate Fluid Using Surface Enhanced Laser Desorption And Ionization., Jeffrey S. Morris, Kevin R. Coombes, Herbert A. Fritsche, Charlotte Clarke, Jeng-Neng Chen, Keith A. Baggerly, Lian-Chun Xiao, Mien-Chie Hung, Henry M. Kuerer

Jeffrey S. Morris

Background: Recently, researchers have been using mass spectroscopy to study cancer. For use of proteomics spectra in a clinical setting, stringent quality-control procedures will be needed.

Methods: We pooled samples of nipple aspirate fluid from healthy breasts and breasts with cancer to prepare a control sample. Aliquots of the control sample were used on two spots on each of three IMAC ProteinChip® arrays (Ciphergen Biosystems, Inc.) on 4 successive days to generate 24 SELDI spectra. In 36 subsequent experiments, the control sample was applied to two spots of each ProteinChip array, and the resulting spectra were analyzed to determine how …

Imputation Of Missing Longitudinal Data: A Comparison Of Methods, Paula Diehr, Jean Mundahl Engels

Paula Diehr

BACKGROUND AND OBJECTIVES: Missing information is inevitable in longitudinal studies, and can result in biased estimates and a loss of power. One approach to this problem is to impute the missing data to yield a more complete data set. Our goal was to compare the performance of 14 methods of imputing missing data on depression, weight, cognitive functioning, and self-rated health in a longitudinal cohort of older adults. METHODS: We identified situations where a person had a known value following one or more missing values, and treated the known value as a "missing value." This "missing value" was imputed using …

A Varying-Coefficient Cox Model For The Effect Of Age At A Marker Event On Age At Menopause, Bin Nan, Xihong Lin, Lynda D. Lisabeth, Sioban D. Harlow

The University of Michigan Department of Biostatistics Working Paper Series

. It is of recent interest in reproductive health research to investigate the validity of a marker event for the onset of menopausal transition and to estimate age at menopause using age at the marker event. We propose a varying coefficient Cox model to investigate the association between age at a marker event, denned as a specific bleeding pattern change, and age at menopause, where both events are subject to censoring and their association varies with age at the marker event. Estimation proceeds using the regression spline method. The proposed method is applied to the Tremin Trust Data to evaluate …

Wavelet-Based Nonparametric Modeling Of Hierarchical Functions In Colon Carcinogenesis., Jeffrey S. Morris, Marina Vannucci, Philip J. Brown, Raymond J. Carroll

Jeffrey S. Morris

In this article we develop new methods for analyzing the data from an experiment using rodent models to investigate the effect of type of dietary fat on O6-methylguanine-DNA-methyltransferase (MGMT), an important biomarker in early colon carcinogenesis. The data consist of observed profiles over a spatial variable contained within a two-stage hierarchy, a structure that we dub hierarchical functional data. We present a new method providing a unified framework for modeling these data, simultaneously yielding estimates and posterior samples for mean, individual, and subsample-level profiles, as well as covariance parameters at the various hierarchical levels. Our method is nonparametric in that …

Trajectories Of Health For Older Adults Over Time: Accounting Fully For Death, Paula Diehr

Paula Diehr

The process of healthy aging can best be described by plotting the trajectory of health-related variables over time. Unfortunately, graphs including data only from survivors may be misleading because they may confuse patterns of mortality with patterns of change in health. Two approaches for creating graphs that account for death in such situations are 1) to incorporate a category or value for death into the longitudinal health variable and 2) to measure time in years before death or some other event. The first approach has been applied to self-rated health (excellent to poor) and the 36-Item Short-Form Health Survey (SF-36). …

The Radiopacity Of 29 Resin Restorative Materials Compared To Enamel, Peter Lubisich Iv

Loma Linda University Electronic Theses, Dissertations & Projects

The radiodensity of a composite resin can greatly influence a clinician's ability to analyze a restoration for failure. The purpose of this study was to determine the relative radiopacities of 29 resin restorative materials compared to enamel, and to verify the comparable radiopacity between shades of 23 of the restorative composite resin materials. Composite resin discs measuring >5mm in diameter and 2 mm in thickness were made and polymerized. Radiographs were taken of the composite resin discs, which included an aluminum step wedge for calibration and a densitometer was used to measure the radiodensity of the composite resin samples. The …

Quantification Of Bone Deposition In Onlay Bone Grafting, Gregory Alan Kammeyer

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to quantitatively evaluate; 1) mandibular posterior mono-cortical block onlay bone graft success rates 2) the amount of grafted bone retained after initial resorption in radiographic projections. Seven consecutive patients with 14 mandibular posterior implant sites requiring bone augmentation for implants of a standard 3.8mm x 10mm dimension were sought. Mono-cortical block bone grafts from the ipsilateral ascending ramus were placed then observed with two standardized CT scans, dividing them into two groups: Group A had the first CT at 4 weeks after graft placement and a second taken before Prosthodontic reconstruction, 36.7 weeks later. …

The Psychological Characteristics Of Obese Children, Thomas Taylor Mitchell

Loma Linda University Electronic Theses, Dissertations & Projects

Several studies along with the surgeon general of the United States have identified obesity as a national health issue. Research indicates that adult obesity treatment has relatively poor long-term effects. Consequently increased attention has been given to addressing obesity in children. This focus is particularly vital due to the fact that children are one of the populations showing the most rapid increase in overweight and obesity. The purpose of this study was to identify the some of the unique psychological characteristics of obese children by analyzing the intake data of children and adolescents attending the Loma Linda University Growing Fit …

Cross-Calibration Of Stroke Disability Measures: Bayesian Analysis Of Longitudinal Ordinal Categorical Data Using Negative Dependence, Giovanni Parmigiani, Heidi W. Ashih, Gregory P. Samsa, Pamela W. Duncan, Sue Min Lai, David B. Matchar

Johns Hopkins University, Dept. of Biostatistics Working Papers

It is common to assess disability of stroke patients using standardized scales, such as the Rankin Stroke Outcome Scale (RS) and the Barthel Index (BI). The Rankin Scale, which was designed for applications to stroke, is based on assessing directly the global conditions of a patient. The Barthel Index, which was designed for general applications, is based on a series of questions about the patient’s ability to carry out 10 basis activities of daily living. As both scales are commonly used, but few studies use both, translating between scales is important in gaining an overall understanding of the efficacy of …

An Extended General Location Model For Causal Inference From Data Subject To Noncompliance And Missing Values, Yahong Peng, Rod Little, Trivellore E. Raghuanthan

The University of Michigan Department of Biostatistics Working Paper Series

Noncompliance is a common problem in experiments involving randomized assignment of treatments, and standard analyses based on intention-to treat or treatment received have limitations. An attractive alternative is to estimate the Complier-Average Causal Effect (CACE), which is the average treatment effect for the subpopulation of subjects who would comply under either treatment (Angrist, Imbens and Rubin, 1996, henceforth AIR). We propose an Extended General Location Model to estimate the CACE from data with non-compliance and missing data in the outcome and in baseline covariates. Models for both continuous and categorical outcomes and ignorable and latent ignorable (Frangakis and Rubin, 1999) …

Adjusting For Non-Ignorable Verification Bias In Clinical Studies For Alzheimer’S Disease, Xiao-Hua Zhou, Pete Castelluccio

UW Biostatistics Working Paper Series

A common problem for comparing the relative accuracy of two screening tests for Alzheimer’s disease (D) in a two-stage design study is verification bias. If the verification bias can be assumed to be ignorable, Zhou and Higgs (2000) have proposed a maximum likelihood approach to compare the relative accuracy of screening tests in a two-stage design study. However, if the verification mechanism also depends on the unobserved disease status, the ignorable assumption does not hold. In this paper, we discuss how to use a profile likelihood approach to compare the relative accuracy of two screening tests for AD without assuming …

A New Confidence Interval For The Difference Between Two Binomial Proportions Of Paired Data, Xiao-Hua Zhou, Gengsheng Qin

UW Biostatistics Working Paper Series

Motivated by a study on comparing sensitivities and specificities of two diagnostic tests in a paired design when the sample size is small, we first derived an Edgeworth expansion for the studentized difference between two binomial proportions of paired data. The Edgeworth expansion can help us understand why the usual Wald interval for the difference has poor coverage performance in the small sample size. Based on the Edgeworth expansion, we then derived a transformation based confidence interval for the difference. The new interval removes the skewness in the Edgeworth expansion; the new interval is easy to compute, and its coverage …

A Comprehensive Approach To The Analysis Of Maldi-Tof Proteomics Spectra From Serum Samples., Keith A. Baggerly, Jeffrey S. Morris, Jing Wang, David Gold, Lian-Chun Xiao, Kevin R. Coombes

Jeffrey S. Morris

For our analysis of the data from the First Annual Proteomics Data Mining Conference, we attempted to discriminate between 24 disease spectra (group A) and 17 normal spectra (group B). First, we processed the raw spectra by (i) correcting for additive sinusoidal noise (periodic on the time scale) affecting most spectra, (ii) correcting for the overall baseline level, (iii) normalizing, (iv) recombining fractions, and (v) using variable- width windows for data reduction. Also, we identified a set of polymeric peaks (at multiples of 180.6 Da) that is present in several normal spectra (B1–B8). After data processing, we found the intensities …

The Effect Of Ultrasonics On Fibroblast Cells, Sheila A. Harris

Loma Linda University Electronic Theses, Dissertations & Projects

The field of dentistry uses the debriding properties of ultrasonic vibration. It is unknown if this property is detrimental to the periodontal ligament (PDL) of an avulsed tooth. This information is important when a clinician is faced with a debris-covered avulsed tooth following a traumatic event. The purpose of this study was to determine the effect that ultrasonic vibration has on those PDL cells most numerous and most vital to a successful tooth replantation, namely, the fibroblasts.

Several fibroblast cell sources were exposed to varying ultrasonic times. These included a commercially available cell line of human foreskin fibroblast (HFF), a …