Sequential updating via dynamic hierarchical models: A Bayesian approach to longitudinal data analysis

Most statistical analysis, theory and practice, is concerned with static models; models with a proposed set of parameters whose values are fixed across observational units. Static models implicitly assume that the quantified relationships remain the same across the design space of the data. While this is reasonable under many circumstances this can be a dangerous assumption when dealing with sequentially ordered data. The mere passage of time always brings fresh considerations and the interrelationships among parameters, or subsets of parameters, may need to be continually revised. ^ When data are gathered sequentially dynamic interim monitoring may be useful as new subject-specific parameters are introduced with each new observational unit. Sequential imputation via dynamic hierarchical models is an efficient strategy for handling missing data and analyzing longitudinal studies. Dynamic conditional independence models offers a flexible framework that exploits the Bayesian updating scheme for capturing the evolution of both the population and individual effects over time. While static models often describe aggregate information well they often do not reflect conflicts in the information at the individual level. Dynamic models prove advantageous over static models in capturing both individual and aggregate trends. Computations for such models can be carried out via the Gibbs sampler. An application using a small sample repeated measures normally distributed growth curve data is presented. ^

Evaluation of the accuracy of multilevel analysis parameter estimates for intra-cluster correlation in correlated binary data

Many studies in biostatistics deal with binary data. Some of these studies involve correlated observations, which can complicate the analysis of the resulting data. Studies of this kind typically arise when a high degree of commonality exists between test subjects. If there exists a natural hierarchy in the data, multilevel analysis is an appropriate tool for the analysis. Two examples are the measurements on identical twins, or the study of symmetrical organs or appendages such as in the case of ophthalmic studies. Although this type of matching appears ideal for the purposes of comparison, analysis of the resulting data while ignoring the effect of intra-cluster correlation has been shown to produce biased results.^ This paper will explore the use of multilevel modeling of simulated binary data with predetermined levels of correlation. Data will be generated using the Beta-Binomial method with varying degrees of correlation between the lower level observations. The data will be analyzed using the multilevel software package MlwiN (Woodhouse, et al, 1995). Comparisons between the specified intra-cluster correlation of these data and the estimated correlations, using multilevel analysis, will be used to examine the accuracy of this technique in analyzing this type of data. ^

Forecasting cost based on a stochastic utilization plan and a fixed cost function

The application of Markov processes is very useful to health-care problems. The objective of this study is to provide a structured methodology of forecasting cost based upon combining a stochastic model of utilization (Markov Chain) and deterministic cost function. The perspective of the cost in this study is the reimbursement for the services rendered. The data to be used is the OneCare database of claim records of their enrollees over a two-year period of January 1, 1996–December 31, 1997. The model combines a Markov Chain that describes the utilization pattern and its variability where the use of resources by risk groups (age, gender, and diagnosis) will be considered in the process and a cost function determined from a fixed schedule based on real costs or charges for those in the OneCare claims database. The cost function is a secondary application to the model. Goodness-of-fit will be used checked for the model against the traditional method of cost forecasting. ^

Risk Index Score (RISc)

The main objective of this study was to develop and validate a computer-based statistical algorithm based on a multivariable logistic model that can be translated into a simple scoring system in order to ascertain stroke cases using hospital admission medical records data. This algorithm, the Risk Index Score (RISc), was developed using data collected prospectively by the Brain Attack Surveillance in Corpus Christ (BASIC) project. The validity of the RISc was evaluated by estimating the concordance of scoring system stroke ascertainment to stroke ascertainment accomplished by physician review of hospital admission records. The goal of this study was to develop a rapid, simple, efficient, and accurate method to ascertain the incidence of stroke from routine hospital admission hospital admission records for epidemiologic investigations. ^ The main objectives of this study were to develop and validate a computer-based statistical algorithm based on a multivariable logistic model that could be translated into a simple scoring system to ascertain stroke cases using hospital admission medical records data. (Abstract shortened by UMI.)^

Predictors of survival in Alzheimer's disease

Alzheimer's disease (AD) is associated with greater mortality and reduced survival among individuals with Alzheimer's disease as compared to those without dementia. It is uncertain how these survival estimates change when the clinical signs and/or symptoms of comorbid conditions are present in individuals' with Alzheimer's disease. Cardiovascular risk factors such as hypertension, hyperlipidemia, congestive heart failure, coronary artery disease, and diabetes mellitus are common conditions in the aged population. Independently, these factors influence mortality and may have an additive effect on reduced survival in an individual with concomitant Alzheimer's disease. The bulk of the evidence from previous research efforts suggests an association between vascular co-morbidities and Alzheimer's disease incidence, but their role in survival remains to be elucidated. The objective of this proposed study was to examine the effects of cardiovascular comorbidities on the survival experience of individuals with probable Alzheimer's disease in order to identify prognostic factors for life expectancy following onset of disease. This study utilized data from the Baylor College of Medicine Alzheimer's Disease Center (ADC) longitudinal study of Alzheimer's disease and other memory disorders. Individuals between the ages of 55-69, 70-79, and ≥80 had a median survival from date of onset of 9.2 years, 8.0 years, and 7.2 years, respectively (p<0.001) and 5.5 years, 4.3 years, and 3.4 years from diagnosis. Sex was the strongest predictor of death from onset of AD, with females having a 30 percent lower risk compared to males. These findings further support the notion that age (both from onset and from diagnosis) and sex are the strongest predictors of survival among those with AD. ^

Optimal frequency of Imiquimod (Aldara(RTM)) 5% cream treatment of external genital warts in immunocompetent adults. Systematic review and meta-analysis

Genital warts are a sexually transmitted disease with high prevalence in the U.S. Imiquimod 5% cream is a self-applied treatment, prescribed three-times weekly, at bedtime, for 16 weeks. The post-marketing research addressed questions of imiquimod dosing frequency. MEDLINE, Embase, and the Cochrane Library were searched for randomized trials on efficacy and safety of imiquimod 5% cream with either three-times weekly or once-daily regimens to systemically review treatment options. Efficacy was evaluated by completely cleared warts at the end of treatment, and safety - by frequency of adverse events and at least one rest period taken from treatment. Six studies were selected for the analysis, including circumcised men, uncircumcised men, and women. The once-daily compared to three-times weekly regimen did not improve the efficacy, but resulted in increased incidence of local skin reactions and events, when at least one rest period was taken from treatment. The optimal regimen is three-times weekly.^

Breast cancer risk and heterocyclic amines and effect modification by NAT gene polymorphisms

Breast cancer is the most common cancer in women in the United States and is a leading cause of cancer-related deaths (1). Recently, dietary heterocyclic amines (HCAs) have been proposed to be a risk factor for breast cancer (2). This study uses the data collected for a case-control study conducted at the M.D. Anderson Cancer Center to assess the association between breast cancer risk and HCAs {2-amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo [4,5-f] quinoxaline (DiMeIQx) and mutagenicity of HCAs} and to examine if this association is modified by genetic polymorphisms of N-acetyl transferases (NAT1/NAT2). The NAT1/2 genotype was determined using Taqman technology. HCAs were estimated by using a meat preparation questionnaire on meat type, cooking method, and doneness, combined with a quantitative HCA database. Three hundred and fifty patients with breast cancer attending the Diagnostic Radiology Clinic at M. D. Anderson Cancer Center and fulfilling the eligibility criteria were compared to three hundred and fifty patients attending the same clinic for benign breast lesions to answer these questions. Logistic regression models were used to control for known risk factors and showed no statistically significant association between breast cancer versus benign breast cancer lesions and dietary intake of heterocyclic amines. There was no clear difference in their effect after subgroup analyses in different acetylator strata of NAT1/2 and no statistical interactions were found between NAT1/2 genotypes and HCAs, suggesting no effect modification by NAT1/2 acetylator status. These results suggest the need for further research to analyze if these null associations were because of the benign breast lesions sharing the risk factors with breast cancer or any other factors which haven't been explored yet.^

The association of sexual behavior with oropharyngeal cancer and correlations with HPV-16 serologic status

Objectives. This hospital-based case-case study compared the characteristics of sexual behavior in patients with cancer of the oropharynx to patients with cancers of other head and neck sites. Additionally, the prevalence of certain sexual behaviors of HPV-16 seropositive head and neck cancer patients was compared to that of seronegative patients. ^ Methods. One hundred sixty five oropharyngeal cancer patients and 86 patients with cancers of other head and neck sites completed a sexual history questionnaire. ^ Results. Oropharyngeal cancer patients were significantly more likely to have had a greater number of lifetime sex partners, to have engaged in oral-genital sex, and to have had a greater number of oral-genital sex partners than non-oropharyngeal cancer patients. Oral-genital sex was significantly more common in the HPV-16 seropositive group. ^ Conclusion. These findings add to the evidence that HPV-16 is sexually transmitted to the upper aerodigestive tract and that certain sexual behaviors increase the risk for HPV-associated oropharyngeal cancer. ^

Survey of VFC provider knowledge of catch-up regimens and contraindications to vaccination in Houston, Texas

In 2004, Houston had one of the lowest childhood immunization levels among major metropolitan cities in the United States at 65% for the 4:3:1:3:3 vaccination series. Delays in the receipt of scheduled vaccinations may be related to missed opportunities due to health care provider lack of knowledge about catch-up regimens and contraindications for pediatric vaccination. The objectives of this study are to identify, measure, and report on VFC provider-practice characteristics, knowledge of catch-up regimens and contraindications, and use of Reminder recall (R/R) and moved or gone elsewhere (MOGE) practices among providers with high (>80%) and low (<70%) immunization coverage among 19-35 month old children. The sampling frame consists of 187 Vaccines for Children (VFC) providers with 2004 clinic assessment software application (CASA) scores. Data were collected by personal interview with each participating practice provider. Only ten VFC providers were successful at maximizing vaccinations for every vignette and no provider administered the maximum possible number of vaccinations at visit 2 for all six vignettes. Both coverage groups administered polio conjugate vaccine (PCV), haemophilus influenza type b (Hib), and diphtheria, tetanus and acellular pertussis (DTaP) most frequently and omitted most frequently varicella zoster vaccine (VZV) and measles, mumps, and rubella (MMR) vaccine. ^

Phthalate exposure among US women, NHANES 1999--2002: Relationship to serum gonadotropin levels

Phthalates are industrial chemicals used primarily as plasticizers though they and are found in a myriad of consumer goods such as children's toys, food packaging, dental sealants, cosmetics, pharmaceuticals, perfumes, and building materials. US biomonitoring data show more than 75% of the population have exposure to mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl) hexyl phthalate (MEHP), and mono-benzyl phthalate (MBZP). Reproductive toxicity from phthalate exposure in animal models has raised concerns about similar effects on fertility in humans. This dissertation research focuses on phthalate exposures in the US population and investigates the plausibility of an exposure-response relationship between phthalates and endocrine hormones essential for ovulation among US women. The objective of this research is to determine the relationship between levels of gonadotropins, follicle stimulating hormone (FSH) and leutinizing hormone (LH), and urinary phthalate monoester metabolites: MBP, MEP, MEHP, MBZP among National Health and Nutrition Examination Survey (NHANES) 1999-2002 women aged 35 to 60 years. Using biomarker data from a one-third sub-sample of NHANES participants, log transformed serum FSH and serum LH, respectively were regressed on phthalates controlling for age, body mass index, smoking, and creatinine taking into consideration the complex survey design (n=385). Models were stratified by reproductive status: reproductive (n=185), menopause transition (n=49) and post-menopausal (n=125). A decrease in FSH associated with increasing MBzP (beta=-0.094, p<0.05) was observed for all participants but no statistical association between log FSH and MBP, MEP, or MEHP was seen. A decrease in LH (beta=-0.125, p<0.05) was also observed with increasing MBzP for all participants though there was no relationship between levels of LH and MBP, MEP, or MEHP. The observed associations between FSH, LH and MBzP did not persist when stratified by reproductive status. Thus, the present study shows a change in endocrine hormones related to ovulation with increasing urinary MBzP among a representative sample of US women from 1999-2002 though this observed exposure-response relationship does not remain after stratification by reproductive status. ^

Modifier genes and susceptibility to colorectal cancer in individuals with Lynch syndrome

Lynch syndrome, is caused by inherited germ-line mutations in the DNA mismatch repair genes resulting in cancers at an early age, predominantly colorectal (CRC) and endometrial cancers. Though the median age at onset for CRC is about 45 years, disease penetrance varies suggesting that cancer susceptibility may be modified by environmental or other low-penetrance genes. Genetic variation due to polymorphisms in genes encoding metabolic enzymes can influence carcinogenesis by alterations in the expression and activity level of the enzymes. Variation in MTHFR, an important folate metabolizing enzyme can affect DNA methylation and DNA synthesis and variation in xenobiotic-metabolizing enzymes can affect the metabolism and clearance of carcinogens, thus modifying cancer risk. ^ This study examined a retrospective cohort of 257 individuals with Lynch syndrome, for polymorphisms in genes encoding xenobiotic-metabolizing enzymes-- CYP1A1 (I462V and MspI), EPHX1 (H139R and Y113H), GSTP1 (I105V and A114V), GSTM1 and GSTT1 (deletions) and folate metabolizing enzyme--MTHFR (C677T and A1298C). In addition, a series of 786 cases of sporadic CRC were genotyped for CYP1A1 I462V and EPHX1 Y113H to assess gene-gene interaction and gene-environment interaction with smoking in a case-only analysis. ^ Prominent findings of this study were that the presence of an MTHFR C677T variant allele was associated with a 4 year later age at onset for CRC on average and a reduced age-associated risk for developing CRC (Hazard ratio: 0.55; 95% confidence interval: 0.36–0.85) compared to the absence of any variant allele in individuals with Lynch syndrome. Similarly, Lynch syndrome individuals heterozygous for CYP1A1 I462V A>G polymorphism developed CRC an average of 4 years earlier and were at a 78% increased age-associated risk (Hazard ratio for AG relative to AA: 1.78; 95% confidence interval: 1.16-2.74) than those with the homozygous wild-type genotype. Therefore these two polymorphisms may be additional susceptibility factors for CRC in Lynch syndrome. In the case-only analysis, evidence of gene-gene interaction was seen between CYP1A1 I462V and EPHX1 Y113H and between EPHX1 Y113H and smoking suggesting that genetic and environmental factors may interact to increase sporadic CRC risk. Implications of these findings are the ability to identify subsets of high-risk individuals for targeted prevention and intervention. ^

Correlation between dental care utilization and oral cavity cancer in a large sample of community-based United States residents

Cancer of the oral cavity and pharynx remains one of the ten leading causes of cancer death in the United States (US). Besides smoking and alcohol consumption, there are no well established risk factors. While poor dental care had been implicated, it is unknown if the lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past twelve months and the prevalence of oral cavity cancer. A cross-sectional design of the National Health Interview Survey of adult, non-institutionalized US residents (n=30,475) was used to assess the association between dental care utilization and self reported diagnosis of oral cavity cancer. Chi square statistic was used to examine the crude association between the predictor variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. There were statistically significant differences between those who utilized dental care during the past twelve months and those who did not with respect to education, income, age, marital status, and gender (p < 0.05), but not health insurance coverage (p = 0.53). Also, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% Confidence Interval (CI), 0.12–0.98. Further, higher income advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer, (p < 0.05), but health insurance coverage, alcohol use and smoking were not, p > 0.05. However, after simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did not attenuate nor persist. Thus, compared with those who did not use dental care, those who did wee 62% less likely to present with oral cavity cancer adjusted POR, 0.38, 95% CI, 0.13-1.10. Among US adults residing in community settings, use of dental care during the past twelve months did not significantly reduce the predisposition to oral cavity cancer. However, due to the nature of the data used in this study, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cancer development namely poor dental care, is needed. ^

Determinants of malnutrition in two states in Sudan

Nearly one in three children in the developing world is malnourished. Poor nutrition contributes to one out of two deaths (53%) associated with infectious diseases among children aged under five in developing countries. Using data from the 2005 World Food Program’s (WFP) Livelihood Vulnerability and Nutritional Assessment of Rural Kassala and Red Sea State this study examines the impact of female headed households and maternal education on malnutrition in children 6-59 months old. The dependent variable investigated in this study is moderate to severe wasting or less than -2 weight for height Z-score, also known as global acute malnutrition (GAM). ^ The study population consisted of 450 households in Kassala State and Red Sea State, Sudan. A total of 900 children 6-59 months of age were part of the households sampled from these states and one child per household (773 children) was randomly chosen for the analysis along with the child’s mother. Results of the study found that 18 percent of children between 6-59 months of age had GAM/wasting. Maternal education, main source of water, and income were strongly related to wasting. Gender of head of household was not found to have a significant relationship with GAM/wasting. Mothers with at least primary education were much less likely to have malnourished children, even after controlling for income and environmental conditions. Children in households with unsafe sources of water were 2.6 more likely to have wasting than those with piped in/tube wells as their main source of water. For every increase of 100 dinar in a household, the children in the household are approximately two-thirds times (.662) less likely to be wasted. ^ The results of this study support the alternate hypothesis that there is an association between maternal education on wasting of children 6-59 months old. The results do not, however, support the alternate hypothesis that there is an association between gender of head of household on wasting of children 6-59 months old. Better understanding of the association of wasting and other measures of malnutrition with maternal education levels can program managers and other health officials to target important nutritional and non-nutritional interventions. ^

Risk of adult-onset asthma in Mexican-American women employed in food preparation or food service

Existing literature examining the association between occupation and asthma has not been adequately powered to address this question in the food preparation or food service industries. Few studies have addressed the possible link between occupational exposure to cooking fumes and asthma. This secondary analysis of cohort study data aimed to investigate the association between adult-onset asthma and exposure to: (a) cooking fumes at work or (b) longest-held employment in food preparation or food service (e.g. waiters and waitresses, food preparation workers, non-restaurant food servers, etc.). Participants arose from a cohort of Mexican-American women residing in Houston, TX, recruited between July 2001 and June 2007. This analysis used Cox proportional-hazards regression to estimate the hazard ratio of adult-onset asthma given the exposures of interest, adjusting for age, BMI, smoking status, acculturation, and birthplace. We found a strong association between adult-onset asthma and occupational exposure to cooking fumes (hazard ratio [HR] = 1.77; 95% confidence interval [CI], 1.15, 2.72), especially in participants whose longest-held occupation was not in the food-related industry (HR = 2.12; 95% CI, 1.21, 3.60). In conclusion, adult-onset asthma is a serious public health concern for food industry workers. ^

Measuring the quality of life of patients with diabetes: Validating the tool and determining the effects on quality of life

There are several tools for measuring quality of life (QoL) and specifically, health-related quality of life (HRQoL) for persons with diabetes. A commonly-used measure, the Diabetes Quality of Life (DQOL) Survey, developed for the Diabetes Control and Complications Trial (DCCT), has been used in several experimental settings, and its reliability and validity are well-established. However, it is considered too long to be of practical use in clinical settings. Because of this, a shortened version of the tool was used recently in the Community Diabetes Education (CoDE) Project in Dallas, Texas, a clinic-based patient education program that uses a specially-trained community healthcare worker to provide patient education. However, the modified scale has never been tested for reliability and validity. Thus, one goal of this thesis was to measure these psychometric properties of the scale. After establishing the reliability and validity, the results of the scale were analyzed to determine the effects of the intervention on the subjects’ quality of life. The changes in QoL scales were compared with changes in physiologic measures which are most closely allied with diabetes, including blood glucose levels, weight/BMI, co-morbidities and health beliefs in order to determine if there is a relationship between such measures and quality of life. The results of the reliability and validity testing were not conclusive. Measures of reliability and criterion validity were established, but these contrasted with poor measures of repeatability and content validity. The effect of the intervention on quality of life, however, was more significant, particularly regarding the impact of diabetes. Those who received the counseling had significantly higher scores on the Impact scale than those who did not, and the former group had much greater improvement in scores over the twelve month period than the latter group. ^