Biostatistics Commons^™

The Cost-Effectiveness Of Diabetes Prevention: Results From The Diabetes Prevention Program And The Diabetes Prevention Program Outcomes Study, William Herman

GW Biostatistics Center

Background

The Diabetes Prevention Program (DPP) was a randomized, controlled clinical trial. It demonstrated that among high-risk individuals with impaired glucose tolerance, diabetes incidence was reduced by 58 % with lifestyle intervention and 31 % with metformin compared to placebo. During the Diabetes Prevention Program Outcomes Study (DPPOS), all DPP participants were unmasked to their treatment assignments, the original lifestyle intervention group was offered additional lifestyle support, the metformin group continued metformin, and all three groups were offered a group-implemented lifestyle intervention. Over the 10 years of combined DPP/DPPOS follow-up, diabetes incidence was reduced by 34 % in the lifestyle …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …

Abcc9 Gene Polymorphism Is Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Steven Estus, Erin L. Abner, Ishita Parikh, Manasi Malik, Janna H. Neltner, Eseosa Ighodaro, Wang-Xia Wang, Bernard R. Wilfred, Li-San Wang, Walter A. Kukull, Kannabiran Nandakumar, Mark L. Farman, Wayne W. Poon, Maria M. Corrada, Claudia H. Kawas, David H. Cribbs, David A. Bennett, Julie A. Schneider, Eric B. Larson, Paul K. Crane, Otto Valladares, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Charles D. Smith, Stephen W. Scheff, Joshua A. Sonnen, Jonathan L. Haines, Margaret A. Pericak-Vance, Richard Mayeux, Lindsay A. Farrer, Linda J. Van Eldik, Craig Horbinski, Robert C. Green, Marla Gearing, Leonard W. Poon, Patricia L. Kramer, Randall L. Woltjer, Thomas J. Montine, Amanda B. Partch, Alexander J. Rajic, Katierose Richmire, Sarah E. Monsell, Gerard D. Schellenberg, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer's Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer's Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer's Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically …

Partially-Latent Class Models (Plcm) For Case-Control Studies Of Childhood Pneumonia Etiology, Zhenke Wu, Maria Deloria-Knoll, Laura L. Hammitt, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In population studies on the etiology of disease, one goal is the estimation of the fraction of cases attributable to each of several causes. For example, pneumonia is a clinical diagnosis of lung infection that may be caused by viral, bacterial, fungal, or other pathogens. The study of pneumonia etiology is challenging because directly sampling from the lung to identify the etiologic pathogen is not standard clinical practice in most settings. Instead, measurements from multiple peripheral specimens are made. This paper considers the problem of estimating the population etiology distribution and the individual etiology probabilities. We formulate the scientific …

Dose Expansion Cohorts In Phase I Trials, Alexia Iasonos, John O'Quigley

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, frequently prolong the study and include dose expansion cohorts (DEC) with the goal to better characterize the toxicity profiles of experimental agents and to study disease specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD) and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is being collected. Current protocols typically do not specify whether the MTD will be updated …

The Impact Of Salsalate Treatment On Serum Levels Of Advanced Glycation End Products In Type 2 Diabetes., Joshua I Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E Shoelson, Allison B Goldfine, Christopher Strauch, Vincent M Monnier, Tinsal-T2d Research Consortium.

GW Biostatistics Center

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine …

Genetic Risk Of Progression To Type 2 Diabetes And Response To Intensive Lifestyle Or Metformin In Prediabetic Women With And Without A History Of Gestational Diabetes Mellitus., Shannon D Sullivan, Kathleen A. Jablonski, Jose C Florez, Dana Dabelea, Paul W Franks, Sam Dagogo-Jack, Catherine Kim, William C Knowler, Costas A Christophi, Robert Ratner, Diabetes Prevention Program Research Group.

GW Biostatistics Center

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS β-Cell function was …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …

Factors Associated With Parental Decision Making And Childhood Vaccination, Zuwen Qiu-Shultz

UNLV Theses, Dissertations, Professional Papers, and Capstones

In order to better understand factors affecting immunization status, logistic regression was used to assess the association of various socio-demographic factors and whether parents would have their child immunized if not a state mandate. Factors included in the study were race, household income, number of children in the household, number of adults in the household, if the child had a primary provider, if the child had a health check-up in the last twelve months, and medical insurance status of the child. The combined Nevada Kindergarten Health Survey Result of 2009-2010 (Year Two) and 2010-2011 (Year Three) conducted by the Nevada …

Predictors Of Treatments Acceptable To Patients For Late-Life Depression, Gerald J. Jogerst, Shimin Zheng, Erik Vanderlip

ETSU Faculty Works

Objectives. Describe older patients’ perceptions about depression and characteristics associated with acceptance of treatments. Design. Cross-sectional study. Setting. Three primary care clinics in Iowa. Participants. Consecutive sample of 529 primary care patients. Measurements. Depression screening tool (a 9-item patient health questionnaire [PHQ-9]) and questionnaire including sociodemographic data, patient attitudes about depression, and acceptability of different treatments. Results. Mean age was 71.9 years (range 60–93 years), 314 (59%) female. Among the 529 participants, 93 (17.5%) had history of depression and 60 (11.3%) had PHQ-9 scores of 10 or greater. Participants believed depression is a disease for which they would use medication …

Screening For Elder Mistreatment Among Older Adults Seeking Legal Assistance Services, Sheryl M. Strasser, Megan Smith, Scott Weaver, Shimin Zheng, Yan Cao

ETSU Faculty Works

Introduction: The aging population is a rapidly growing demographic in the United States. Isolation, limited autonomy, and declining physical and mental health render many older adults vulnerable to elder mistreatment (EM). The purpose of this study was to assess the prevalence and correlates of EM among a sample of older adults using legal assistance services in Atlanta, Georgia.

Methods: Researchers administered surveys to consenting older adults (aged 60þ) in 5 metro Atlanta community centers that hosted legal assistance information sessions as part of the Elderly Legal Assistance Program. The surveys screened for risk factors and prevalence of EM risk using …

The Morbidity & Mortality Of Prevalent Heart Failure, Jennifer Kwon

Loma Linda University Electronic Theses, Dissertations & Projects

The first study population included 292 unselected consecutive patients from the LLUMC heart failure clinic who were enrolled in the study from January to July 2006 and were followed up through the end of December 2010. The treatment policy at the clinic was to uptitrate dosages of beta-adrenergic blockade (β-blockers), angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) to the most tolerable levels in order to reach target dosages, as recommended by the Heart Failure Society of America (HFSA). Patients were classified into systolic heart failure (ejection fraction (EF) < 40%) or diastolic heart failure (EF≥40%). All dosages of β-blockers, ACEi and ARB were extracted through chart reviews and were used as the main predictors of the patients' survival. Results from analyses showed that reaching target dosages of β-blockers and ACEi/ARB may increase survival when compared to not reaching target among the systolic HF population (HR_{β_biockers}= 0.64, 95% CI 0.26-1.56 and HR_ACEi/ARB=0.50, …

Limited Sampling Estimates Of Epigallocatechin Gallate Exposures In Cirrhotic And Noncirrhotic Patients With Hepatitis C After Single Oral Doses Of Green Tea Extract., Dina Halegoua-De Marzio, Walter K. Kraft, Constantine Daskalakis, Xie Ying, Roy L Hawke, Victor J. Navarro

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential.

OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 …

A Systematic Selection Method For The Development Of Cancer Staging Systems, Yunzhi Lin, Richard Chappell, Mithat Gonen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

The tumor-node-metastasis (TNM) staging system has been the anchor of cancer diagnosis, treatment, and prognosis for many years. For meaningful clinical use, an orderly, progressive condensation of the T and N categories into an overall staging system needs to be defined, usually with respect to a time-to-event outcome. This can be considered as a cutpoint selection problem for a censored response partitioned with respect to two ordered categorical covariates and their interaction. The aim is to select the best grouping of the TN categories. A novel bootstrap cutpoint/model selection method is proposed for this task by maximizing bootstrap estimates of …

A Comparison Of Spatio-Temporal Prediction Methods Of Cancer Incidence In The U.S, Michelle Hamlyn

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer is the cause of one out of four deaths in the United States, and in 2009, researchers expected over 1.5 million new patients to be diagnosed with some form of cancer. People diagnosed with cancer, whether a common or rare type, need to undergo treatments, the amount and kind of which will depend on the severity of the cancer. So how do healthcare providers know how much funding is needed for treatment? What would better enable a pharmaceutical company to determine how much to allocate for research and development of drugs, the amount of each drug to manufacture, or …

Relationship Of Vitamin D Levels To Blood Pressure In A Biethnic Cohort, Rosario O. Sakamoto

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Serum hydroxyvitamin D [25(OH)D] has been well-accepted as not an ordinary vitamin but a pro-hormone that has many benefits beyond its well-known effects on bone. Cardiovascular risk factors such as hypertension remain a huge health burden and Blacks have been recognized to have higher prevalence of hypertension compared to non-Hispanic Whites. Despite increasing evidence of the benefits of vitamin D on blood pressure control, there is much more to be learned about the relationship of serum 25(OH)D to blood pressure among different ethnicities.

Purpose: The goal of this study was to determine whether vitamin D serum 25(OH)D levels were …

The Determinants Of Colorectal Cancer Survival Disparities In Nevada, Lucas N. Wassira

UNLV Theses, Dissertations, Professional Papers, and Capstones

Different population groups across Nevada and throughout the United States suffer disproportionately from colorectal cancer and its after-effects. Overcoming cancer health disparities is important for lessening the burden of cancer. There has been an overall decline in the incidence of and mortality from colorectal cancer (CRC). This is likely due, in part, to the increasing use of screening procedures such as Fecal Occult Blood Test (FOBT) and/or endoscopy, which can reduce the risk of CRC mortality by fifty percent. Nevertheless, screening procedures are routinely used by only fifty percent of Americans aged fifty years and older. Despite overall mortality decreasing …

Identification Of Neuroblastoma And Its Prognostic Markers Using Raman Spectroscopy, Rachel Kast

Wayne State University Dissertations

Introduction: Neuroblastoma is the most common cancer of infancy. It is one of several peripheral nervous system tumors, including ganglioneuroma, peripheral nerve sheath tumor, and pheochromocytoma. It is commonly situated on the adrenal gland. It displays similar histology to other small round blue cell tumors, including non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma. One method of judging neuroblastoma aggressiveness uses tumor histology factors, including mitosis-karyorrhexis index, Schwannian stromal development, degree of differentiation, and patient age. Tumor aggressiveness can also be judged based on the amplification of certain genes, including MYCN. Raman spectroscopy is a physics-based method which identifies the biochemical …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Incidence, Patterns And Severity Of Reported Unintentional Injuries In Pakistan For Persons Five Years And Older: Results Of The National Health Survey Of Pakistan 1990–94, Zafar Fatmi, Wilbur C. Hadden, Junaid A. Razzak, Huma Qureshi, Adnan A. Hyder, Gregory Pappas

Community Health Sciences

Background

National level estimates of injuries are not readily available for developing countries. This study estimated the annual incidence, patterns and severity of unintentional injuries among persons over five years of age in Pakistan.

Methods

National Health Survey of Pakistan (NHSP 1990–94) is a nationally representative survey of the household. Through a two-stage stratified design, 18, 315 persons over 5 years of age were interviewed to estimate the overall annual incidence, patterns and severity of unintentional injuries for males and females in urban and rural areas over the preceding one year. Weighted estimates were computed adjusting for complex survey design …

The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in …

Cultural And Psychological Influences On Diabetic Adherence, Keikilani Mcmillin-Williams

Loma Linda University Electronic Theses, Dissertations & Projects

Diabetes mellitus is a serious disease that poses a particular healthcare challenge because progression is considered controllable (Cox, et al, 1985; Vinicor, et al, 1996) yet treatment adherence, and thus outcome, is very poor (Gonder-Frederick, Cox, & Ritterband, 2002; Goodall, 1991). Culture is a lethal risk factor for diabetic contraction and treatment maintenance. Latinos within the United States are two-to-three times more likely to develop complications and die than non-Latinos (Haffner et al, 1996; Rubin, Peyrot, & Saudek, 1991) and are less likely to adhere to treatment (Lipton, Losey, Giachello, Mendez, & Girotti, 1998). Efforts to eliminate health disparities have …

Condylar Angulations As Related To Submental-Vertex Radiographs, Jady L. Chiakowsky

Loma Linda University Electronic Theses, Dissertations & Projects

Pretreatment submental-vertex radiographs were obtained for 637 adolescent patients (307 males, 330 females) who had presented themselves for orthodontic treatment. The purpose of this study was to: (1) determine the relationship between condylar angulations and depth of cut with the variables: age, sex, and race, and (2) establish normative values for the categories studied. The results indicated that no significant differences existed between the condylar angulations for the variables measured. However, significant differences did exist between the depth of cut for the variables measured and there was significant interaction between age and race with respect to the depth of cut. …

Decreased Triiodothyronine Binding To The Hepatic Nuclear Thyroid Hormone Receptor In The Diabetic Mouse, Thomas J. Dewind

Loma Linda University Electronic Theses, Dissertations & Projects

The diabetic C57BL/KsJ-db m mouse has abnormal thyroid hormone levels and indications of thyroid hormone resistance. To investigate the basis of these abnormalities, the hepatic nuclear thyroid hormone receptor was extracted with 0.4 M KCl, 1.1 mM MgCl₂, 20 mM Tris/HCl, pH 7.9 from hepatocyte nuclei of normal C57BL/KsJ, heterozygous C57BL/KsJ-db m (db/m), and diabetic C57BL/KsJ-db m (db/db) mice. Normal and heterozygous mice were grouped together as the controls. Triiodothyronine (T₃) binding studies at 4°C using nitrocellulose filtration to separate free T₃ from receptor bound T₃ demonstrated an …

Roentgenographic Evaluation Of Nasion-Menton And Sella-Gonion Measurements And Their Relationship To The Mandibular Plane Angle, David I. Asatani

Loma Linda University Electronic Theses, Dissertations & Projects

A convenience sample of 480 Caucasians using original diagnostic cephalometric films was selected to evaluate the nasion-menton and sella-gonion distances and their relationship to the mandibular plane angle.

The anterior facial height was represented by the nasion-menton plane. The posterior facial height was represented by sella-gonion plane. The facial depth was represented by sella-nasion and menton-gonion planes. The mandibular plane angle was represented by the intersection of the sella-nasion and menton-gonion planes.

The descriptive data, correlation analysis, and regression analysis was calculated for the following groups: total sample, females, males, prepubertal and postpubertal ages and various mandibular plane angles of …

The Relationship Of Central Venous Pressure To Hemorrhage In Open Heart Surgery, Mable Reynolds

Loma Linda University Electronic Theses, Dissertations & Projects

The problem of this study was to review 100 open heart surgical cases in a selected hospital to determine the changes occurring in central venous pressure in relation to blood loss.

The review of literature revealed that central venous pressure is an important factor in determining immediate postoperative care of open heart surgical patients. If central venous pressure falls below the normal range of 5 to 10 centimeters of water, hemorrhage is suspected. If central venous pressure is elevated between 15 and 20 centimeters of water, cardiac tamponade is suspected.

The descriptive survey method of research was used. Medical records …

A Study Of The Effect Of Varying Serum Phenylalanine Levels On Changes In Intelligence Quotient, Darlene Imai Manullang

Loma Linda University Electronic Theses, Dissertations & Projects

Data from thirty medical records of phenylketonuric children under treatment were investigated to determine at which serum phenylalanine level (0-3.9 mg. %, 4-7.9 mg %, 8-11.9 mg. %, greater than 12 mg. %) there would be the greatest increase in intelligence. The children involved in the study were divided into the following groups according to the age dietary treatment was initiated: 0 through 5 months, 6 through 11 months, 12 through 23 months, and over 2 years of age.

Among 6 patients who were placed on the diet during the first 5 months of life, it appears that the optimal …