Long Term Follow-up of Morbidity and Quality of Life Associated with Isolated Gastroschisis

Gastroschisis is a birth defect in which an opening in the abdominal wall allows herniation of the viscera. Prenatal counseling regarding gastroschisis typically discusses that, although these infants often endure a difficult neonatal course, they experience few long-term complications. However, information regarding long-term outcomes is based on limited studies that lack specificity. Therefore, we aimed to study the long-term morbidity and quality of life in children born with gastroschisis in a large and diverse population drawn from the Texas Birth Defects Registry (TBDR). Study packets with informed consent, a questionnaire, and the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL 4.0) in English and Spanish were mailed to 1,112 parents of children born with isolated gastroschisis in Texas between 1999 and 2008 via the TBDR. Information was abstracted from the TBDR for 58 mothers of children with gastroschisis who returned study materials. Three hundred fifty five packets were returned to sender, giving a response rate of 7.7%. Children born with gastroschisis had quality of life scores that were not significantly different than expected (p = 0.981). However, factors such as having a learning disability (p = 0.001) and missing school due to gastrointestinal issues (p = 0.020) were found to significantly decrease quality of life. Overall, children with gastroschisis had a significantly increased risk for learning disabilities regardless of whether they were preterm (p = 0.021) or full term (p = 0.021). Additionally, there appeared to be an increased risk for auditory impairment in Caucasian children (p < 0.0005). Therefore, while overall long-term quality of life is not significantly altered for children born with gastroschisis, the previously unreported increased risk for learning disabilities and possible association with hearing impairment are important findings that should be conveyed to prospective parents.

Patients' preferences for a prostate cancer consultation, a discrete choice experiment

Four basic medical decision making models are commonly discussed in the literature in reference to physician-patient interactions. All fall short in their attempt to capture the nuances of physician-patient interactions, and none satisfactorily address patients' preferences for communication and other attributes of care. Prostate cancer consultations are one setting where preferences matter and are likely to vary among patients. Fortunately, discrete choice experiments are capable of casting light on patients' preferences for communication and other attributes of value that make up a consultation before the consultation occurs, which is crucial if patients are to derive the most utility from the process of reaching a decision as well as the decision itself. The results of my dissertation provide strong support to the notion that patients, at least in the hypothetical setting of a DCE, have identifiable preferences for the attributes of a prostate cancer consultation and that those preferences are capable of being elicited before a consultation takes place. Further, patients' willingness-to-pay for the non-cost attributes of the consultation is surprisingly robust to a variety of individual level variables of interest. ^

Infant breastfeeding patterns by sex: Do males feed more?

Background: Most studies have looked at breastfeeding practices from the point of view of the maternal behavior only, however in counseling women who choose to breastfeed it is important to be aware of general infant feeding patterns in order to adequately provide information about what to expect. Available literature on the differences in infant breastfeeding behavior by sex is minimal and therefore requires further investigation. Objectives: This study determined if at the age of 2 months there were differences in the amount of breast milk consumed, duration of breastfeeding, and infant satiety by infant sex. It also assessed whether infant sex is an independent predictor of initiation of breastfeeding. Methods: This is a secondary analysis of data obtained from the Infant Feeding Practices Survey II (IFPS II) which was a longitudinal study carried out from May 2005 through June 2007 by the Food and Drug Administration and the Centers for Disease Control and Prevention. The questionnaires asked about demography, prenatal care, mode of delivery, birth weight, infant sex, and breastfeeding patterns. A total of 3,033 and 2,552 mothers completed the neonatal and post-neonatal questionnaires respectively. ^ Results: There was no significant difference in the initiation of breastfeeding by infant sex. About 85% of the male infants initiated breastfeeding compared with 84% of female infants. The odds ratio of ever initiating breastfeeding by male infants was 0.93 but the difference was not significant with a p-value of 0.49. None of the other infant feeding patterns differed by infant gender. ^ Conclusion: This study found no evidence that male infants feed more or that their mothers are more likely to initiate breastfeeding. Each baby is an individual and therefore will have a unique feeding pattern. Based on these findings, the major determining factors for breastfeeding continue to be maternal factors therefore more effort should be invested in promoting breastfeeding among mothers of all ethnic groups and social classes.^

THE NATURAL AND ORTHOGONAL INTERACTION (NOIA) MODELS FOR QUANTITATIVE TRAITS (QTs) AND COMPLEX DISEASES

My dissertation focuses on developing methods for gene-gene/environment interactions and imprinting effect detections for human complex diseases and quantitative traits. It includes three sections: (1) generalizing the Natural and Orthogonal interaction (NOIA) model for the coding technique originally developed for gene-gene (GxG) interaction and also to reduced models; (2) developing a novel statistical approach that allows for modeling gene-environment (GxE) interactions influencing disease risk, and (3) developing a statistical approach for modeling genetic variants displaying parent-of-origin effects (POEs), such as imprinting. In the past decade, genetic researchers have identified a large number of causal variants for human genetic diseases and traits by single-locus analysis, and interaction has now become a hot topic in the effort to search for the complex network between multiple genes or environmental exposures contributing to the outcome. Epistasis, also known as gene-gene interaction is the departure from additive genetic effects from several genes to a trait, which means that the same alleles of one gene could display different genetic effects under different genetic backgrounds. In this study, we propose to implement the NOIA model for association studies along with interaction for human complex traits and diseases. We compare the performance of the new statistical models we developed and the usual functional model by both simulation study and real data analysis. Both simulation and real data analysis revealed higher power of the NOIA GxG interaction model for detecting both main genetic effects and interaction effects. Through application on a melanoma dataset, we confirmed the previously identified significant regions for melanoma risk at 15q13.1, 16q24.3 and 9p21.3. We also identified potential interactions with these significant regions that contribute to melanoma risk. Based on the NOIA model, we developed a novel statistical approach that allows us to model effects from a genetic factor and binary environmental exposure that are jointly influencing disease risk. Both simulation and real data analyses revealed higher power of the NOIA model for detecting both main genetic effects and interaction effects for both quantitative and binary traits. We also found that estimates of the parameters from logistic regression for binary traits are no longer statistically uncorrelated under the alternative model when there is an association. Applying our novel approach to a lung cancer dataset, we confirmed four SNPs in 5p15 and 15q25 region to be significantly associated with lung cancer risk in Caucasians population: rs2736100, rs402710, rs16969968 and rs8034191. We also validated that rs16969968 and rs8034191 in 15q25 region are significantly interacting with smoking in Caucasian population. Our approach identified the potential interactions of SNP rs2256543 in 6p21 with smoking on contributing to lung cancer risk. Genetic imprinting is the most well-known cause for parent-of-origin effect (POE) whereby a gene is differentially expressed depending on the parental origin of the same alleles. Genetic imprinting affects several human disorders, including diabetes, breast cancer, alcoholism, and obesity. This phenomenon has been shown to be important for normal embryonic development in mammals. Traditional association approaches ignore this important genetic phenomenon. In this study, we propose a NOIA framework for a single locus association study that estimates both main allelic effects and POEs. We develop statistical (Stat-POE) and functional (Func-POE) models, and demonstrate conditions for orthogonality of the Stat-POE model. We conducted simulations for both quantitative and qualitative traits to evaluate the performance of the statistical and functional models with different levels of POEs. Our results showed that the newly proposed Stat-POE model, which ensures orthogonality of variance components if Hardy-Weinberg Equilibrium (HWE) or equal minor and major allele frequencies is satisfied, had greater power for detecting the main allelic additive effect than a Func-POE model, which codes according to allelic substitutions, for both quantitative and qualitative traits. The power for detecting the POE was the same for the Stat-POE and Func-POE models under HWE for quantitative traits.

THE IMPACT OF FAMILY HISTORY ON MEDULLARY THYROID CANCER IN MEN2A PATIENTS

The American Thyroid Association recently classified all MEN2A-associated codons into increasing risk levels A-C and stated that some patients may delay prophylactic thyroidectomy if certain criteria are met. One criterion is a less aggressive family history of MTC but whether families with the same mutated codon have variable MTC aggressiveness is not well described. We developed several novel measures of MTC aggressiveness and compared families with the same mutated codon to determine if there is significant inter-familial variability. Pedigrees of families with MEN2A were reviewed for codon mutated and proportion of RET mutation carriers with MTC. Individuals with MTC were classified as having local or distant MTC and whether they had progressive MTC. MTC status and age were assessed at diagnosis and most advanced MTC stage. For those without MTC, age was recorded at prophylactic thyroidectomy or last follow-up if the patient did not have a thyroidectomy. For each pedigree, the mean age of members without MTC, with MTC, and the proportion of RET mutation carriers with local or distant and progressive MTC were calculated. We assessed differences in these variables using ANOVA and the Fisher’s exact test. Sufficient data for analysis were available for families with mutated codons 609 (92 patients from 13 families), 618 (41 patients from 7 families), and 634 (152 patients from 13 families). The only significant differences found were the mean age of patients without MTC between families with codon 609 and 618 mutations even after accounting for prophylactic thyroidectomy (p=0.006 and 0.001, respectively), and in the mean age of MTC diagnosis between families with codon 618 and 634 mutations even after accounting for symptomatic presentation (p=0.023 and 0.014, respectively). However, these differences may be explained by generational differences in ascertainment of RET carriers and the availability of genetic testing when the proband initially presented.

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due to Lynch Syndrome?

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS. HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients. METHODS: 253 individuals with an MMRD CRC or EC who underwent genetic counseling at one institution were included in analysis in 1 of 4 groups: LS, MMRD+/germline-, MMRD+/VUS, sporadic MSI-H (MMRD tumor with MLH1 promoter hypermethylation or BRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM1,2,6. Kruskal-Wallis tests were used to compare family history scores. Logistic regression was used to determine what factors were predictive of LS. RESULTS: MMRD+/germline- individuals had significantly lower median family history scores (PREMM1,2,6=7.3, MMRpro=8.1) than LS individuals (PREMM1,2,6=26.1, MMRpro=89.8, p CONCLUSION: MMRD+/germline- individuals have less suggestive family histories of LS than individuals with LS, but more suggestive family histories than sporadic MSI-H individuals. CRC and/or EC patients with abnormal tumor studies are more likely to have a germline LS mutation if they have a family history suggestive of hereditary cancer. These results imply that the MMRD+/germline- group may not all have LS. This finding highlights the need to determine other somatic, epigenetic or germline causes of MMRD tumors so that these patients and their families can be accurately counseled regarding screening and management.

ATTITUDES AND PRACTICES OF GENETIC COUNSELORS IN PROVIDING PREDICTIVE TESTING TO MINORS AT RISK FOR LI-FRAUMENI SYNDROME

Li- Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome caused by mutations in the TP53 gene that predisposes individuals to a wide variety of cancers, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, and adrenocortical carcinomas. Individuals found to carry germline mutations in TP53 have a 90% lifetime cancer risk, with a 20% chance to develop cancer under the age of 20. Despite the significant risk of childhood cancer, predictive testing for unaffected minors at risk for LFS historically has not been recommended, largely due to the lack of available and effective screening for the types of cancers involved. A recently developed screening protocol suggests an advantage to identifying and screening children at risk for LFS and we therefore hypothesized that this alongside with the availability of new screening modalities may substantiate a shift in recommendations for predictive genetic testing in minors at risk for LFS. We aimed to describe current screening recommendations that genetic counselors provide to this population as well as explore factors that may have influenced genetic counselors attitude and practice in regards to this issue. An online survey was emailed to members of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC). Of an estimated 1000 eligible participants, 172 completed surveys that were analyzed. Genetic counselors in this study were more likely to support predictive genetic testing for this population as the minor aged (p

Baseline quality of life as a predictor of exercise intervention adherence among endometrial cancer survivors

Background: The objective of this analysis is to test whether baseline quality of life (QOL) measurements, body mass index (BMI) and prior exercise behavior are significantly associated with (1) telephone counseling adherence, and (2) activity at the final assessment, in a physical activity promoting intervention among endometrial cancer survivors.^ Methods: One hundred endometrial cancer survivors not currently meeting physical activity guidelines completed baseline QOL and anthropometric assessments to measure general physical and mental health [Medical Outcomes Survey (SF-36)], sleep patterns and sleep quality [Pittsburgh Sleep Quality Index (PSQI)], perceived stress [Perceived Stress Scale (PSS)], cancer-specific concerns of long-term survivors [Quality of Life in Adult Cancer Survivors (QLACS)], and psychological distress [Brief Symptom Inventory-18 (BSI-18)]. Survivors were counseled by telephone during the 6-month intervention and their completion rate determined their adherence. The primary variables of interest included age, baseline BMI, baseline activity level, time since diagnosis, education, treatment received, and the SF-36 physical and mental component scores.^ Results: Final activity was most closely linked with baseline activity (p<.001) and less invasive surgery, being leaner and older, and experiencing less pain and more vitality. Telephone counseling was also predicted well by baseline activity, working less and having better overall cancer-related functioning.^ Conclusion: Above and beyond the QOL measures, baseline activity was the strongest predictor of both final activity and telephone counseling adherence. While education, surgery treatment type and bodily pain were important predictors for final exercise and employment status and cancer-related quality of life were important predictors for telephone counseling adherence, considering adaptive exercise interventions that focus heavily on engaging inactive participants may be a way to produce better exercise-related outcomes in the endometrial cancer survivor population.^

The effects of adequacy and content of prenatal care on birth outcomes in a high -risk Missouri population

The purpose of this observational study was investigation of the relationship between quantitative adequacy of prenatal care, specific prenatal care content and pregnancy outcome in a high risk Missouri population. A sample of 1484 women from three Missouri regions known to have high rates of low birth weight, infant mortality, and inadequate prenatal care rates participated in structured post-partum interviews. Approximately one-half of the sample had received adequate prenatal care and the other half inadequate prenatal care as determined by an index utilized by the Missouri Department of Health.^ Prenatal care content was assessed by reports of prenatal education in six different areas: Diet, smoking, alcohol, drug, preterm labor counseling, and advice on when to call the health provider if preterm labor was suspected by the woman. Low birth weight, in both term and preterm infants, were the two birth outcomes examined. A variety of maternal socio-demographic variables were also considered.^ The results of this study suggest that specific educational content, delivered during prenatal care, may have lessen the risk of giving birth to a preterm-low birth weight infant. Prenatal education for recognition of preterm labor, and advice on when to call the health provider if preterm labor was suspected were found to be associated with a decreased risk of preterm delivery. Specific educational content was not, however, associated with risk of term-low weight birth nor was quantitative adequacy of care associated with the risk of either term- or preterm-low birth weight.^ These findings reinforce a body of literature which stresses the importance of appropriate prenatal care in preventing preterm low birth weight. Additionally, the findings suggest interventions that may be specifically effective for prematurity prevention. ^

Cost -effectiveness of services and treatments for ambulatory dually diagnosed CMHC clients: Implications for managed care

This paper reports a cost-effectiveness analysis of standard therapeutic interventions received by ambulatory dually diagnosed clients of a Community Mental Health Center (CMHC). For the purposes of this study dually diagnosed was defined as a DSM-III-R or IV diagnosis of a major mental disorder and a concomitant substance abuse disorder. The prevalence of dually diagnosed people among the mentally ill and their unique and problematic nature continues to challenge and encumber CMHCs and poses grave public health risks. An absence of research on these clients in community-based settings and the cost-effectiveness of their standard CMHC care has hindered the development of effective community-based intervention strategies. This exploratory and descriptive effort is a first step toward providing information on which to base programmatic management decisions.^ Data for this study were derived from electronic client records of a CMHC located in a large Southwestern, Sun-belt metropolitan area. A total of 220 records were collected on clients consecutively admitted during a two-and-one-half year period. Information was gathered profiling the clients' background characteristics, receipt of standard services and treatments, costs of the care they received, and length of CMHC enrollment and subsequent psychiatric hospitalizations. The services and treatments were compared with regard to their costs and predicted contributions toward maintaining clients in the community and out of public psychiatric hospitals.^ This study investigated: (1) the study groups' background, mental illness, and substance abuse characteristics; (2) types, extent, and patterns of their receipt of standard services and treatments; (3) associations between the receipt of services and treatments, community tenure, and risk of psychiatric hospitalization; and, (4) comparisons of average costs for services and treatments in terms of their contributions toward maintaining the clients in the community.^ The results suggest that substance abuse and other lifestyle factors were related to the dually diagnosed clients' admissions to the CMHC. The dually diagnosed clients' receipt of care was associated strongly with their insurability and global functioning. Medication Services were the most expensive yet effective service or treatment. Supported Education was the third most expensive and second most effective. Psychosocial Services, the second most expensive, were only effective in terms of maintaining clients in the community. Group Counseling, the fourth most expensive, had no effect on community maintenance and increased the risk of hospitalization when accompanied by Medication Services. Individual Counseling, the least expensive, had no effect on community maintenance. But it reduced the risk of hospitalization when accompanied by Medication Services. Networking/Referral, the fifth most expensive service or treatment, was ineffective.^ The study compared the results with findings in the literature. Implications are discussed regarding further research, study limitations, practical applications and benefits, and improvements to theoretical understandings, in particular, concepts underscoring Managed Care. ^

Planning, implementation, and evaluation of an HIV -screening program for pregnant women

The purpose of this study was to evaluate the effectiveness of an HIV-screening program at a private health-care institution where the providers were trained to counsel pregnant women about the HIV-antibody test according to the latest recommendations made by the U.S. Public Health Service (PHS) and the Texas legislature. A before-and-after study design was selected for the study. The participants were OB/GYN nurses who attended an educational program and the patients they counseled about the HIV test. Training improved the nurses' overall knowledge about the content of the program and nurses were more likely to offer the HIV test to all pregnant women regardless of their risk of infection. Still, contrary to what was predicted, the nurses did not give more information to increase the knowledge pregnant women had about HIV infection, transmission, and available treatments. Consequently, many women were not given the chance to correctly assess their risk during the counseling session and there was no evidence that knowledge would reduce the propensity of many women to deny being at risk for HIV. On the other hand, pregnant women who received prenatal care after the implementation of the HIV-screening program were more likely to be tested than women who received prenatal care before its implementation (96% vs. 48%); in turn, the likelihood that more high-risk women would be tested for HIV also increased (94% vs. 60%). There was no evidence that mandatory testing with right of refusal would deter women from being tested for HIV. When the moment comes for a woman to make her decision, other concerns are more important to her than whether the option to be tested is mandatory or not. The majority of pregnant women indicated that their main reasons for being tested were: (a) the recommendation of their health-care provider; and (b) concern about the risks to their babies. Recommending that all pregnant women be tested regardless of their risk of infection, together with making the HIV test readily available to all women, are probably the two best ways of increasing the patients' participation in an HIV-screening program for pregnant women. ^

Evaluación de conductas adictivas en personal médico y no médico en un hospital de agudos : estudio comparativo

Objetivo: Identificar abuso, dependencia, adicciones (tabaquismo, problemas con alcohol y alimentación) y automedicación en el personal de la salud de un Hospital de agudos.- Material y Métodos: Estudio protocolizado y observacional mediante. encuesta estructurada, autoadministrada y anónima. Se realizó el análisis en 4 grupos: Médicos (M) (MS: Staff y MF: en formación), NO M: enfermeros (E) y otros (O: administración, laboratorio, farmacia, servicios generales). Se realizó un estudio comparativo con una población encuestada en el año 2004. Resultados: Se incluyeron 373 personas: 195 M (73 MS y 122 MF), 83 E y 92 O; 225 mujeres (60,3%); edad promedio grupal: 36.1 años (DS± 9.98). El 77.5% con pareja estable, el 98.1% heterosexuales y 67,3% universitarios. El 67.3% se automedicaba, el 35.1% eran tabaquistas activos; el 28.4% presentaba problemas con el alcohol y el 36.2% con la alimentación. El tabaquismo fue más frecuente entre 40-50 años (42,5%) y en E: 56.6%; MS: 21,9%; MF: 27% y O: 36.9%(p<0.05). Se incrementó la intención de abandonar el cigarrillo comparado con el año 2004 (74.6 vs 56.3%)(p<0.05). Los problemas con el alcohol fueron frecuentes entre 20 y 30 años (47.2%), en personas con pareja inestable (73.6%), sin diferencias entre los grupos y en 51.8% coexistía con tabaquismo. Los problemas de alimentación ocurrieron significativamente en MF (46,9%) comparados con MS (22.5%) (p<0.05). Se detectó automedicación en el 68.3 del Grupo O y en 48.1% del Grupo M (p<0.05). Al comparar la automedicación en las encuestas del año 2004 y 2007, se comprobó una reducción en E (87.8 vs 52.4%) y en O (77.5 vs 48.1%)(p<0.05).- Conclusiones: Se detectó elevada prevalencia de tabaquismo, problemas con el alcohol, alimentación y automedicación en todo el personal hospitalario. El tabaquismo predominó en enfermeros, los trastornos alimentarios en médicos en formación y el alcoholismo en solteros con pareja inestable.