Tracking of plasma lipids and lipoproteins, within-person and year-to-year variability in plasma cholesterol levels among participants from age 8 to 18 in Project HeartBeat!

Coronary heart disease remains the leading cause of death in the United States and increased blood cholesterol level has been found to be a major risk factor with roots in childhood. Tracking of cholesterol, i.e., the tendency to maintain a particular cholesterol level relative to the rest of the population, and variability in blood lipid levels with increase in age have implications for cholesterol screening and assessment of lipid levels in children for possible prevention of further rise to prevent adulthood heart disease. In this study the pattern of change in plasma lipids, over time, and their tracking were investigated. Also, within-person variance and retest reliability defined as the square root of within-person variance for plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides and their relation to age, sex and body mass index among participants from age 8 to 18 years were investigated. ^ In Project HeartBeat!, 678 healthy children aged 8, 11 and 14 years at baseline were enrolled and examined at 4-monthly intervals for up to 4 years. We examined the relationship between repeated observations by Pearson's correlations. Age- and sex-specific quintiles were calculated and the probability of participants to remain in the uppermost quintile of their respective distribution was evaluated with life table methods. Plasma total cholesterol, HDL-C and LDL-C at baseline were strongly and significantly correlated with measurements at subsequent visits across the sex and age groups. Plasma triglyceride at baseline was also significantly correlated with subsequent measurements but less strongly than was the case for other plasma lipids. The probability to remain in the upper quintile was also high (60 to 70%) for plasma total cholesterol, HDL-C and LDL-C. ^ We used a mixed longitudinal, or synthetic cohort design with continuous observations from age 8 to 18 years to estimate within person variance of plasma total cholesterol, HDL-C, LDL-C and triglycerides. A total of 5809 measurements were available for both cholesterol and triglycerides. A multilevel linear model was used. Within-person variance among repeated measures over up to four years of follow-up was estimated for total cholesterol, HDL-C, LDL-C and triglycerides separately. The relationship of within-person and inter-individual variance with age, sex, and body mass index was evaluated. Likelihood ratio tests were conducted by calculating the deviation of −2log (likelihood) within the basic model and alternative models. The square root of within-person variance provided the retest reliability (within person standard deviation) for plasma total cholesterol, HDL-C, LDL-C and triglycerides. We found 13.6 percent retest reliability for plasma cholesterol, 6.1 percent for HDL-cholesterol, 11.9 percent for LDL-cholesterol and 32.4 percent for triglycerides. Retest reliability of plasma lipids was significantly related with age and body mass index. It increased with increase in body mass index and age. These findings have implications for screening guidelines, as participants in the uppermost quintile tended to maintain their status in each of the age groups during a four-year follow-up. The magnitude of within-person variability of plasma lipids influences the ability to classify children into risk categories recommended by the National Cholesterol Education Program. ^

Statistical characterization and development of summary measures of non-normal distributions of nuclear morphometry data from prostate cancer cells for use as prognostic indicators

Nuclear morphometry (NM) uses image analysis to measure features of the cell nucleus which are classified as: bulk properties, shape or form, and DNA distribution. Studies have used these measurements as diagnostic and prognostic indicators of disease with inconclusive results. The distributional properties of these variables have not been systematically investigated although much of the medical data exhibit nonnormal distributions. Measurements are done on several hundred cells per patient so summary measurements reflecting the underlying distribution are needed.^ Distributional characteristics of 34 NM variables from prostate cancer cells were investigated using graphical and analytical techniques. Cells per sample ranged from 52 to 458. A small sample of patients with benign prostatic hyperplasia (BPH), representing non-cancer cells, was used for general comparison with the cancer cells.^ Data transformations such as log, square root and 1/x did not yield normality as measured by the Shapiro-Wilks test for normality. A modulus transformation, used for distributions having abnormal kurtosis values, also did not produce normality.^ Kernel density histograms of the 34 variables exhibited non-normality and 18 variables also exhibited bimodality. A bimodality coefficient was calculated and 3 variables: DNA concentration, shape and elongation, showed the strongest evidence of bimodality and were studied further.^ Two analytical approaches were used to obtain a summary measure for each variable for each patient: cluster analysis to determine significant clusters and a mixture model analysis using a two component model having a Gaussian distribution with equal variances. The mixture component parameters were used to bootstrap the log likelihood ratio to determine the significant number of components, 1 or 2. These summary measures were used as predictors of disease severity in several proportional odds logistic regression models. The disease severity scale had 5 levels and was constructed of 3 components: extracapsulary penetration (ECP), lymph node involvement (LN+) and seminal vesicle involvement (SV+) which represent surrogate measures of prognosis. The summary measures were not strong predictors of disease severity. There was some indication from the mixture model results that there were changes in mean levels and proportions of the components in the lower severity levels. ^

A process evaluation of the childhood lead poisoning prevention program in Houston, Texas, 1992--1995

A process evaluation of the Houston Childhood Lead Poisoning Prevention Program, 1992-1995, was conducted. The Program's goal is to reduce lead poisoning prevalence. The study proposed to determine to what extent the Program was implemented as planned by measuring how well Program services were actually: (1) received by the intended target population; (2) delivered to children with elevated blood lead levels; (3) delivered in compliance with the Centers for Disease Control and Prevention and Program guidelines and timetables; and (4) able to reduce lead poisoning prevalence among those rescreened. Utilizing a program monitoring design, the Program's pre-collected computer records were reviewed. The study sample consisted of 820 children whose blood lead levels were above 15 micrograms per deciLiter, representing approximately 2.9% of the 28,406 screened over this period. Three blood lead levels from each participant were examined: the initial elevated result; the confirmatory result; and the next rescreen result, after the elevated confirmatory level. Results showed that the Program screened approximately 18% (28,406 of 161,569) of Houston's children under age 6 years for lead poisoning. Based on Chi-square tests of significance, results also showed that lead-poisoned participants were more likely to be younger than 3 years, male and Hispanic, compared to those not lead poisoned. The age, gender and ethnic differences observed were statistically significant (p =.01, p =.00, p =.00). Four of the six Program services: medical evaluations, rescreening, environmental inspections and confirmation, had satisfactory delivery completion rates of 71%-98%. Delivery timetable compliance rates for three of the six services examined: outreach contacts, home visits and environmental inspections were below 32%. However, dangerously elevated blood lead levels fell and lead poisoning prevalence dropped from 3.3% at initial screening to 1.2% among those rescreened, after intervention. From a public health perspective, reductions in lead poisoning prevalence are very meaningful. Based on these findings, the following are recommendations for future research: (1) integrate Program database files by utilizing a computer database management program; (2) target services at Hispanic male children under age 3 years living in the highest risk neighborhoods; (3) increase resources to: improve tracking and documentation of service delivery and provide more non-medical case management and environmental services; and (4) share the evaluation methodology/findings with the Centers for Disease Control and Prevention administrators; the implications may be relevant to other program managers conducting such assessments. ^

GENERAL WELL-BEING AND USE OF SOCIAL SUPPORT

Research interest on well-being and social support has focused largely on social factors as related to attaining and maintaining well-being, self-perceptions of well-being and to a lesser extent the relationship of current level of self-perceived well-being to use of formal or informal sources of social support. This study analyzed responses to the General Well-Being Schedule of 6,913 subjects (25-74 years) interviewed during the National Health and Nutrition Examination Survey (1971-1975). The purpose of this analysis was to relate the level of GWBS scores to the use of social support, both informal (family and friends) and formal (community professionals).^ Study questions addressed were whether well-being level was related to selection of a specific social support resource and/or rate of use of resources and whether gender differences were apparent in level of well-being and social support use. Because age, sex, race, socioeconomic status (income and education) and marital status may confound the relation between level of GWB and type of social support chosen, the association between these variables with GWB and use of social support were considered. For analysis, test scores were grouped into four categories and for detailed analysis, two categories: low (0-70) and high (71-110). Cross tabulations and percentages were computed and the chi-square test of significance was used.^ Although 16 to 25 percent of the sample population reported low well-being, less than 10 percent used formal resources to discuss emotional, mental or behavior problems. Medical resources, mostly physicians, were the most used formal social supports. Informal social support was important for all well-being levels where 65-77% of each category reported using this resource.^ While well-being level does not appear to serve as a screener/selector of type of formal social support used, it is related to rates of use. Females reported slightly lower well-being than males, and except in the lowest well-being group, had higher rates of social support use. Findings support the conclusion that perceived well-being is related to use of social support such that the lower the well-being, the greater tendency to use formal and/or informal social support. ^

Association of self-reported physical activity and performance in the physical fitness assessment among Airmen

The U.S. Air Force, as with the other branches of military services, has physical fitness standards imposed on their personnel. These standards ensure a healthy and fit combat force. To meet these standards, Airmen have to maintain a certain level of physical activity in their lifestyle. Objective. This was a cross sectional (prevalence) study to evaluate the association of Airmen's self-reported physical activity and their performance in the Air Force Physical Fitness Assessment in 2007. Methods. The self-reported physical activity data were obtained from the Air Force Web Health Assessment (AF WEB HA), a web-based health questionnaire completed by the Airmen during their annual Preventive Health Assessment. The physical activity levels were categorized as having met or not having met the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) physical activity recommendations. Physical Fitness scores were collected from the Air Force Fitness Management System (AFFMS), a repository of physical fitness test data. Results. There were 49,029 Airmen who answered the AF WEB HA in 2007 and also took their physical fitness test. 94.4% (n = 46,304) of Airmen met the recommended physical activity guidelines and 79.9% (n = 39,178) passed the fitness test. Total Airmen who both met the physical activity recommendations and passed the fitness test was 75.6% (n = 37,088). Airmen who did not meet the activity recommendations and also failed the fitness test totaled 635 or 1.3% of the study group. The Mantel-Haenszel Chi-Square analysis of the data on the activity levels and the physical fitness test relationship was the following χ2 = 18.52, df 1, and p = <0.0001. The Odds Ratio (OR) was 1.22 (95% CI 1.12, 1.34). Conclusion. The study determined that there was a positive association between Airmen's self-reported physical activity and their performance in the physical fitness assessment.^

A systematic review of economic evaluations for interventions of cardiovascular diseases

Background. Cardiovascular disease (CVD) exhibits the most striking public health significance due to its high prevalence and mortality as well as huge economic burdens all over the world, especially in industrialized countries. Major risk factors of CVDs have been the targets of population-wide prevention in the United States. Economic evaluations provide structured information in regard to the efficiency of resource utilization which can inform decisions of resource allocation. The main purpose of this review is to investigate the pattern of study design of economic evaluations for interventions of CVDs. ^ Methods. Primary journal articles published during 2003-2008 were systematically retrieved via relevant keywords from Medline, NHS Economic Evaluation Database (NHS EED) and EBSCO Academic Search Complete. Only full economic evaluations for narrowly defined CVD interventions were included for this review. The methodological data of interest were extracted from the eligible articles and reorganized in Microsoft Access database. Chi-square tests in SPSS were used to analyze the associations between pairs of categorical data. ^ Results. One hundred and twenty eligible articles were reviewed after two steps of literature selection with explicit inclusion and exclusion criteria. Descriptive statistics were reported regarding the evaluated interventions, outcome measures, unit costing and cost reports. The chi-square test of the association between prevention level of intervention and category of time horizon showed no statistical significance. The chi-square test showed that sponsor type was significantly associated with whether new or standard intervention being concluded as more cost effective. ^ Conclusions. Tertiary prevention and medication interventions are the major interests for economic evaluators. The majority of the evaluations were claimed from either a provider’s or a payer’s perspective. Almost all evaluations adopted gross costing strategy for unit cost data rather than micro costing. EQ-5D is the most commonly used instrument for subjective outcome measurement. More than half of the evaluations used decision analytic modeling techniques. The lack of consistency in study design standards in published evaluations appears in several aspects. Prevention level of intervention is not likely to be a factor for evaluators to decide whether to design an evaluation in a lifetime horizon or not. Published evaluations sponsored by industry are more likely to conclude that new intervention is more cost effective than standard intervention.^

Adolescent tobacco use: Studies of prevalence, factorial validity, and factorial invariance between African Americans and Whites

In the last thirty years, increasing efforts have been made to reduce the prevalence of adolescent tobacco use in the United States. Although the prevalence has declined dramatically over the past decade, there are still sharp differences in adolescent smoking-initiation rates across racial/ethnic groups. Large-scale surveys frequently assess smoking-related attitudes, self-efficacy, and intentions to explain the differences in smoking rates between African Americans and Whites. However, there is little agreement about which constructs are significant. Moreover, the psychometric properties of smoking-related attitude, self-efficacy, and intention constructs have not been fully examined. More studies are needed to understand existing patterns of tobacco use and to validate and fully exploit the constructs' relationship to adolescent smoking initiation across racial/ethnic groups. ^ This dissertation reports on a secondary analysis of data from a large multi-ethnic convenience sample of sixth- through eighth-grade students in 22 schools in East Texas and the city of Houston. The specific aims of this dissertation were to (1) describe smoking and alternate tobacco product use rates by race/ethnicity, gender, age, and grade level (Article 1); (2) test the factorial validity of smoking-related attitudes, self-efficacy, and intentions using confirmatory factor analysis techniques (Article 2); and (3) test the factorial invariance of smoking-related attitudes, self-efficacy, and intentions between African Americans and Whites (Article 3). ^ The prevalence findings confirm the disparities in tobacco use among African American, Hispanic, and White adolescents that other surveys have reported (Article 1). This study also demonstrates the usefulness of examining use patterns of not only cigarettes but also alternative tobacco products in younger multiethnic populations, as well as of providing epidemiological data estimates about different phases of smoking. The confirmatory factor analysis provides evidence of construct validity of attitude, self-efficacy, and intention scales for the multiethnic sample (Article 2). Finally, the factorial invariance analyses indicates that some measures representing smoking-related attitudes, self-efficacy, and intentions may not be appropriate for use among both African Americans and Whites (Article 3). Additional research is needed to further our understanding of the patterns and predictors of youth tobacco use initiation. ^

Tp53-dependent repression of cell cycle target genes: Global and mechanistic analysis

Most studies of p53 function have focused on genes transactivated by p53. It is less widely appreciated that p53 can repress target genes to affect a particular cellular response. There is evidence that repression is important for p53-induced apoptosis and cell cycle arrest. It is less clear if repression is important for other p53 functions. A comprehensive knowledge of the genes repressed by p53 and the cellular processes they affect is currently lacking. We used an expression profiling strategy to identify p53-responsive genes following adenoviral p53 gene transfer (Ad-p53) in PC3 prostate cancer cells. A total of 111 genes represented on the Affymetrix U133A microarray were repressed more than two fold (p ≤ 0.05) by p53. An objective assessment of array data quality was carried out using RT-PCR of 20 randomly selected genes. We estimate a confirmation rate of >95.5% for the complete data set. Functional over-representation analysis was used to identify cellular processes potentially affected by p53-mediated repression. Cell cycle regulatory genes exhibited significant enrichment (p ≤ 5E-28) within the repressed targets. Several of these genes are repressed in a p53-dependent manner following DNA damage, but preceding cell cycle arrest. These findings identify novel p53-repressed targets and indicate that p53-induced cell cycle arrest is a function of not only the transactivation of cell cycle inhibitors (e.g., p21), but also the repression of targets that act at each phase of the cell cycle. The mechanism of repression of this set of p53 targets was investigated. Most of the repressed genes identified here do not harbor consensus p53 DNA binding sites but do contain binding sites for E2F transcription factors. We demonstrate a role for E2F/RB repressor complexes in our system. Importantly, p53 is found at the promoter of CDC25A. CDC25A protein is rapidly degraded in response to DNA damage. Our group has demonstrated for the first time that CDC25A is also repressed at the transcript level by p53. This work has important implications for understanding the DNA damage cell cycle checkpoint response and the link between E2F/RB complexes and p53 in the repression of target genes. ^

A constellation of factors associated with premature births among African American women

A cohort, cross-sectional, historical study design was used to study factors related to spontaneous premature birth outcomes among African American women. The cohort consisted of 4,294 mothers drawn from the 1988 National Maternal and Infant Health Survey conducted by the National Center for Health Statistics. The objectives of the study were: (1) to examine the distribution of gestational ages of African American infants for selected variables reported for their families and (2) to describe risk factors associated with birth at 20–31 weeks of gestational age and at 32–36 weeks of gestational age. Risk factors examined include maternal age, maternal marital status, maternal living arrangements, maternal education, maternal work status, household income, gestational bleeding, month prenatal began, adequacy of prenatal care, parity, previous viable preterm birth, and behavioral factors of attitude toward pregnancy, smoking, drug, and alcohol use during pregnancy. Frequency distributions, cross tabulations, stratified analysis, and logistic regression analysis were used. ^ Risk factors associated with a 50 percent or more increase in preterm birth were cocaine use, low maternal education, teenaged mother, prenatal care deficits or overuse, and bleeding during the second half of pregnancy. The other risk factors of not living with the baby's father, smoking cigarettes and having a mistimed pregnancy carried statistically significance but lower strength of association. ^ Health care services, educational systems, and community organizations can develop and evaluate comprehensive health education and information campaigns that address preventable risk factors during pregnancy. Although preterm birth cannot always be prevented, preconception care can help identify and modify maternal risk and promote optimum health before conception. Quality care should include continued risk assessment, health promotion, and interventions. ^

The assessment of standardized training programs in public health preparedness

The Texas Bioterrorism Continuing Education Consortium (BCE) provided National Disaster Life Support (NDLS) training courses throughout the state of Texas in 2005, to help improve knowledge and skills pertaining to bioterrorism and other public health emergencies. The NDLS training courses include curriculum in Basic Disaster Life Support (BDLS) and Core Disaster Life Support (CDLS). A course evaluation which included items assessing ability and willingness of training participants, role of responders, and other variables was mailed to all NDLS participants who provided contact information. An analysis was conducted to determine whether the survey respondents participated in the Hurricanes Katrina and/or Rita relief efforts, as well as to evaluate the impact of the NDLS training courses on the participant's ability and willingness to respond during a disaster. The study population (n = 2150) consisted mostly of nurses (50%) (n=1074). A chi-square test of analysis indicated the following results. Among the survey respondents who took the CDLS course, there was no statically significant difference by occupation pertaining to ability or willingness to respond (x2 [df = 5] = 4.02, p= 0.546); (x2 [df = 5] = 2.45, p = .783). However, there was a statistically significant difference among those respondents who took the BDLS course with respect to ability, and a slightly significant difference with respect to willingness (x2 [df = 5] = 13.35, p = .020 and (x2 = [df = 5] = 10.299, p = .067). These findings are similar to previous studies assessing willingness to respond to a disaster.^ A second analysis was conducted with these survey data to evaluate the implications for disaster response training for the NDLS courses. Results indicated that the majority of disaster responders served in the role for which they were professionally trained (Physicians=68%; Nurses = 50.4%). Nurses, EMT, and Fire professionals served in multiple roles. These results suggest the importance of developing training programs that will prepare professionals to serve in multiple roles. The development of standardized evaluation methods would fill an important gap in assessing impact of national training programs. ^

Impact of maternal Tdap vaccination on pertussis infection in young infants

Undiagnosed infected mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention (CDC) recommends Tdap vaccine for post-partum women before hospital discharge. This intervention has been implemented at Ben Taub General Hospital (BTGH) in Houston, TX since January 2008. Our objective was to compare the proportion of infants born at BTGH and developing pertussis to the total number of pertussis cases before and after the intervention. Methods. We conducted a cross-sectional comparative study between the pre-intervention (7/2000 to 12/2007) and post-intervention (1/2008 to 5/2009) periods. Information on pertussis diagnosis was determined using ICD-9 codes, infection control records, and molecular microbiology reports from Texas Children's Hospital (TCH) and BTGH. Only patients ≤ 6 months of age with laboratory-confirmed B. pertussis infection were included in the study. Results. 481 infants had pertussis illness; 353 (73.3%) during pre-intervention and 128 (26.6%) during post-intervention years. The groups were comparable in all measures including age (median 73 vs. 62.5 days; p=0.08), gender (males 54.2%; p=0.47), length of hospitalization (median 9.8 vs. 4 9.5 days; p=0.5), outcomes (2 deaths in each period; p=0.28) and pertussis illness at TCH (95.2% vs. 95.3%; p=0.9). The proportion of pertussis patients born at BTGH, and thus amenable to protection by the intervention, was not statically different between the two periods after adjusting for age, gender and ethnicity (7.3% vs. 9.3%; an OR=1.05, 95% CI 0.5-2.1, p=0.88). Conclusions. Vaccinating only mothers with Tdap in the post-partum period does not reduce the proportion of pertussis in infants age ≤ 6 months. Efforts should be directed at Tdap immunization of not only mothers, but also all household and key contacts of newborns to protect them against pertussis illness before the primary DTaP series is completed.^

Classification of cellular malignancy associated changes in cervical cancer

Cervical cancer is the leading cause of death and disease from malignant neoplasms among women in developing countries. Even though the Pap smear has significantly decreased the number of deaths from cervical cancer in the past years, it has its limitations. Researchers have developed an automated screening machine which can potentially detect abnormal cases that are overlooked by conventional screening. The goal of quantitative cytology is to classify the patient's tissue sample based on quantitative measurements of the individual cells. It is also much cheaper and potentially can take less time. One of the major challenges of collecting cells with a cytobrush is the possibility of not sampling any existing dysplastic cells on the cervix. Being able to correctly classify patients who have disease without the presence of dysplastic cells could improve the accuracy of quantitative cytology algorithms. Subtle morphologic changes in normal-appearing tissues adjacent to or distant from malignant tumors have been shown to exist, but a comparison of various statistical methods, including many recent advances in the statistical learning field, has not previously been done. The objective of this thesis is to use different classification methods applied to quantitative cytology data for the detection of malignancy associated changes (MACs). In this thesis, Elastic Net is the best algorithm. When we applied the Elastic Net algorithm to the test set, we combined the training set and validation set as "training" set and used 5-fold cross validation to choose the parameter for Elastic Net. It has a sensitivity of 47% at 80% specificity, an AUC 0.52, and a partial AUC 0.10 (95% CI 0.09-0.11).^