Improving the health and well-being of women at risk for neural tube defect recurrence

There is growing interest in providing women with internatal care, a package of healthcare and ancillary services that can improve their health during the period after the termination of one pregnancy but before the conception of the next pregnancy. Women who have had a pregnancy affected by a neural tube defect can especially benefit from internatal care because they are at increased risk for recurrence and improvements to their health during the inter-pregnancy period can prevent future negative birth outcomes. The dissertation provides three papers that inform the content of internatal care for women at risk for recurrence by examining descriptive epidemiology to develop an accurate risk profile of the population, assessing whether women at risk for recurrence would benefit from a psychosocial intervention, and determining how to improve health promotion efforts targeting folic acid use.^ Paper one identifies information relevant for developing risk profiles and conducting risk assessments. A number of investigations have found that the risk for neural tube defects differs between non-Hispanic Whites and Hispanics. To understand the risk difference, the descriptive epidemiology of spina bifida and anencephaly was examined for Hispanics and non-Hispanic Whites based on data from the Texas Birth Defects Registry for the years 1999 through 2004. Crude and adjusted birth prevalence ratios and corresponding 95% confidence intervals were calculated between descriptive epidemiologic characteristics and anencephaly and spina bifida for non-Hispanic Whites and for Hispanics. In both race/ethnic groups, anencephaly expressed an inverse relationship with maternal age and a positive linear relationship with parity. Both relationships were stronger in non-Hispanic Whites. Female infants had a higher risk for anencephaly in non-Hispanic Whites. Lower maternal education was associated with increased risk for spina bifida in Hispanics.^ Paper two assesses the need for a psychosocial intervention. For mothers who have children with spina bifida, the transition to motherhood can be stressful. This qualitative study explored the process of becoming a mother to a child with spina bifida focusing particularly on stress and coping in the immediate postnatal environment. Semi-structured interviews were conducted with six mothers who have children with spina bifida. Mothers were asked about their initial emotional and problem-based coping efforts, the quality and kind of support provided by health providers, and the characteristics of their meaning-based coping efforts; questions matched Transactional Model of Stress and Coping (TMSC) constructs. Analysis of the responses revealed a number of modifiable stress and coping transactions, the most salient being: health providers are in a position to address beliefs about self-causality and prevent mothers from experiencing the repercussions that stem from maintaining these beliefs. ^ Paper three identifies considerations when creating health promotion materials targeting folic acid use. A brochure was designed using concepts from the Precaution Adoption Process Model (PAPM). Three focus groups comprising 26 mothers of children with spina bifida evaluated the brochure. One focus group was conducted in Spanish-only, the other two focus groups were conducted in English and Spanish combined. Qualitative analysis of coded transcripts revealed that a brochure is a helpful adjunct. Questions about folic acid support the inclusion of an insert with basic information. There may be a need to develop different educational material for Hispanics so the importance of folic acid is provided in a situational context. Some participants blamed themselves for their pregnancy outcome which may affect their receptivity to messages in the brochure. The women's desire for photographs that affect their perception of threat and their identification with the second role model indicate they belong to PAPM Stage 2 and 3. Participants preferred colorful envelopes, high quality paper, intimidating photographs, simple words, conversational style sentences, and positive messages.^ These papers develop the content of risk assessment, psychosocial intervention, and health promotion components of internatal care as they apply to women at risk for recurrence. The findings provided evidence for considering parity and maternal age when assessing nutritional risk. The two dissimilarities between the two race/ethnic groups, infant sex and maternal education lent support to creating separate risk profiles. Interviews with mothers of children with spina bifida revealed the existence of unmet needs-suggesting that a psychosocial intervention provided as part of internatal care can strengthen and support women's well-being. Segmenting the audience according to race/ethnicity and PAPM stage can improve the relevance of print materials promoting folic acid use.^

Enlarged tracheoesophageal puncture: A systematic review and retrospective analysis

Background. An enlarged tracheoesophageal puncture (TEP) results in aspiration around the voice prosthesis (VP) and may lead to pneumonia. The aims of this research were: (1) to conduct a systematic review and meta-analysis on enlarged TEP; (2) to analyze preoperative, perioperative, and postoperative risk factors for enlarged TEP; and (3) to evaluate control of leakage around the VP using conservative treatments and adverse events in patients with enlarged TEP.^ Methods. A systematic review was conducted (1978-2008). A summary risk estimate was calculated using a random-effects meta-analysis model. A retrospective cohort study was completed. Patients who underwent total laryngectomy and TEP at The University of Texas M. D. Anderson Cancer Center (MDACC) were included. Multiple logistic regression methods were used to assess risk factors for enlargement. Descriptive and bivariate statistics were calculated to evaluate outcomes and adverse events. Results: Twenty-seven manuscripts were included in the systematic review. The summary risk estimate of enlarged TEP/leakage around the VP was 7.2% (95% CI: 4.8%-9.6%). Temporary VP removal and TEP-site injections were the most commonly reported treatments. Neither prosthetic diameter (p=0.076) nor timing of TEP (p=0.297) significantly increased risk of enlargement per stratified analyses of published outcomes. The cumulative incidence of enlarged TEP was 18.6% (36/194, 95% CI: 13.0%-24.1%) in the MDACC cohort. Enlarged TEP occurred exclusively in irradiated patients. Adjusting for length of follow-up and timing of TEP, advanced nodal disease (ORadjusted: 4.3, 95% CI: 1.0-19.1), stricture (ORadjusted : 3.2, 95% CI: 1.2-8.6), and locoregional recurrence/distant metastasis after laryngectomy (ORadjusted: 6.2, 95% CI: 2.3-16.4) increased risk of enlarged TEP. At last follow-up, conservative methods controlled leakage around the VP in 81% (29/36) of patients. Unresolved leakage was associated with recurrent cancer (p=0.081) and TEP-site irregularity (p=0.003). Relative to those without enlargement, enlarged TEP patients had significantly higher risk of pneumonia (RR: 3.4, 95% CI: 1.9-6.2).^ Conclusions. These data establish that enlarged TEP poses serious health risks, and provide insight into medical and oncologic factors that may contribute to development of this complication. In addition, this research supports the use of conservative treatments to address leakage after enlarged TEP in lieu of complete TEP closure.^

Factors governing late-recurrence of disease in a cohort of early-stage breast cancer survivors

Purpose. To determine the risk of late breast cancer recurrence (5 years after treatment) in a population of women diagnosed with early-stage breast cancer at The University of Texas M.D. Anderson Cancer Center (MDACC) between 1985-2000 and to examine the effect of this population’s BMI, smoking history, reproductive history, hormone use, and alcohol intake at the time of diagnosis on risk of late recurrence.^ Methods. Patients included 1,913 members of the Early Stage Breast Cancer Repository recruited at MDACC who had survived without a recurrence for at least five years after their initial diagnosis of early stage breast cancer. Clinical and epidemiological information was ascertained twice on participants during the study—first by medical record abstraction then by patient interview at least five years after receipt of adjuvant treatment. A total of 223 late breast cancer recurrences were captured, with an average follow-up of 10.6 years. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). ^

A comprehensive review of the environmental impacts and human health risks associated with the occurrence of waste pharmaceuticals in water sources of the United States, and policy implications

The occurrence of waste pharmaceuticals has been identified and well documented in water sources throughout North America and Europe. Many studies have been conducted which identify the occurrence of various pharmaceutical compounds in these waters. This project is an extensive review of the documented evidence of this occurrence published in the scientific literature. This review was performed to determine if this occurrence has a significant impact on the environment and public health. This project and review found that pharmaceuticals such as sex hormone drugs, antibiotic drugs and antineoplastic/cytostatic agents as well as their metabolites have been found to occur in water sources throughout the United States at levels high enough to have noticeable impacts on human health and the environment. It was determined that the primary sources of this occurrence of pharmaceuticals were waste water effluent and solid wastes from sewage treatment plants, pharmaceutical manufacturing plants, healthcare and biomedical research facilities, as well as runoff from veterinary medicine applications (including aquaculture). ^ In addition, current public policies of US governmental agencies such as the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Drug Enforcement Agency (DEA) have been evaluated to see if they are doing a sufficient job at controlling this issue. Specific recommendations for developing these EPA, FDA, and DEA policies have been made to mitigate, prevent, or eliminate this issue.^ Other possible interventions such as implementing engineering controls were also evaluated in order to mitigate, prevent and eliminate this issue. These engineering controls include implementing improved current treatment technologies such as the advancement and improvement of waste water treatment processes utilized by conventional sewage treatment and pharmaceutical manufacturing plants. In addition, administrative controls such as the use of “green chemistry” in drug synthesis and design were also explored and evaluated as possible alternatives to mitigate, prevent, or eliminate this issue. Specific recommendations for incorporating these engineering and administrative controls into the applicable EPA, FDA, and DEA policies have also been made.^

Information bias and lifetime mortality risks of radiation-induced cancer

Additive and multiplicative models of relative risk were used to measure the effect of cancer misclassification and DS86 random errors on lifetime risk projections in the Life Span Study (LSS) of Hiroshima and Nagasaki atomic bomb survivors. The true number of cancer deaths in each stratum of the cancer mortality cross-classification was estimated using sufficient statistics from the EM algorithm. Average survivor doses in the strata were corrected for DS86 random error ($\sigma$ = 0.45) by use of reduction factors. Poisson regression was used to model the corrected and uncorrected mortality rates with covariates for age at-time-of-bombing, age at-time-of-death and gender. Excess risks were in good agreement with risks in RERF Report 11 (Part 2) and the BEIR-V report. Bias due to DS86 random error typically ranged from $-$15% to $-$30% for both sexes, and all sites and models. The total bias, including diagnostic misclassification, of excess risk of nonleukemia for exposure to 1 Sv from age 18 to 65 under the non-constant relative projection model was $-$37.1% for males and $-$23.3% for females. Total excess risks of leukemia under the relative projection model were biased $-$27.1% for males and $-$43.4% for females. Thus, nonleukemia risks for 1 Sv from ages 18 to 85 (DRREF = 2) increased from 1.91%/Sv to 2.68%/Sv among males and from 3.23%/Sv to 4.02%/Sv among females. Leukemia excess risks increased from 0.87%/Sv to 1.10%/Sv among males and from 0.73%/Sv to 1.04%/Sv among females. Bias was dependent on the gender, site, correction method, exposure profile and projection model considered. Future studies that use LSS data for U.S. nuclear workers may be downwardly biased if lifetime risk projections are not adjusted for random and systematic errors. (Supported by U.S. NRC Grant NRC-04-091-02.) ^

Anesthetic choices and breast cancer recurrence: A retrospective cohort study of risk factors

Background: The impact of anesthetic techniques for breast cancer surgery traditionally has been centered on the incidence of acute pain syndromes and complications immediately after surgery. Evaluating anesthesia management beyond short-term effects is an emerging science. Several animal studies have concluded that regional anesthesia independently reduces cancer recurrence and metastasis. A small number of retrospective clinical studies indicate that reductions in cancer recurrence are attributable to anesthesia technique; however, individual risk factors need to be taken into consideration. ^ Purpose: The aims were to: 1) investigate differences in patient, disease and treatment factors between women who received surgical treatment for breast cancer with paravertebral regional and general anesthesia compared to women who received general anesthesia alone; 2) explore patient, disease and treatment factors associated with recurrence of breast cancer; and 3) test the association between type of anesthesia and breast cancer recurrence and survival over 22–46 months following surgery. ^ Methods: This retrospective cohort study included 358 patients with stage 0-III disease who received a partial or total mastectomy without axillary node dissection between October 2006 and October 2008 at a large academic cancer center. Follow-up ended in August 2010 with a median follow-up time of 28.8 months. ^ Results: The patient demographics were equally represented across anesthesia groups. Mean BMI (kg/m2) was greater for the patients who received general anesthesia (GA) alone (29±6.8) compared to those that received paravertebral regional block (PVB) with GA (28±5.1), p=0.001. The PVB with GA group had more advanced stages of disease (p=0.01) and longer surgeries (p=0.01) than the GA only group. Breast cancer recurrence was detected in only 1.7% of the study population. The mean age was 51±18 in those who had a recurrence compared to 58±11 in the non-recurrent group (p=0.06). Overall, no association between anesthesia type and recurrence was found (p=0.53), with an unadjusted estimated hazard ratio of 1.84 (95% CI 0.34–10.08). ^ Conclusions: In contrast to previous retrospective studies in cancer patients receiving surgical and anesthesia treatment, this study was unable to detect a difference in relating type of anesthesia with decreased breast cancer recurrence. Nonetheless, a significant association between BMI and type of anesthesia was observed and should be taken into account in future studies. Because the overall rate of recurrence was very small in this population, a larger study would be needed to detect any differences in rates of recurrence attributable to type of anesthesia. ^

Risk factors of pneumonia in traumatic spinal-cord-injured patients

Pneumonia is a well-documented and common respiratory infection in patients with acute traumatic spinal cord injuries, and may recur during the course of acute care. Using data from the North American Clinical Trials Network (NACTN) for Spinal Cord Injury, the incidence, timing, and recurrence of pneumonia were analyzed. The two main objectives were (1) to investigate the time and potential risk factors for the first occurrence of pneumonia using the Cox Proportional Hazards model, and (2) to investigate pneumonia recurrence and its risk factors using a Counting Process model that is a generalization of the Cox Proportional Hazards model. The results from survival analysis suggested that surgery, intubation, American Spinal Injury Association (ASIA) grade, direct admission to a NACTN site and age (older than 65 or not) were significant risks for first event of pneumonia and multiple events of pneumonia. The significance of this research is that it has the potential to identify patients at the time of admission who are at high risk for the incidence and recurrence of pneumonia. Knowledge and the time of occurrence of pneumonias are important factors for the development of prevention strategies and may also provide some insights into the selection of emerging therapies that compromise the immune system. ^

Venous thromboembolism in patients with acute leukemia: Prevalence, incidence, recurrence of thrombosis, risk factors, and impact on survival

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most preventable cardiovascular disease and a growing public health problem in the United States. The incidence of VTE remains high with an annual estimate of more than 600,000 symptomatic events. DVT affects an estimated 2 million American each year with a death toll of 300,000 persons per year from DVT-related PE. Leukemia patients are at high risk for both hemorrhage and thrombosis; however, little is known about thrombosis among acute leukemia patients. The ultimate goal of this dissertation was to obtain deep understanding of thrombotic issue among acute leukemia patients. The dissertation was presented in a format of three papers. First paper mainly looked at distribution and risk factors associated with development of VTE among patients with acute leukemia prior to leukemia treatment. Second paper looked at incidence, risk factors, and impact of VTE on survival of patients with acute lymphoblastic leukemia during treatment. Third paper looked at recurrence and risk factors for VTE recurrence among acute leukemia patients with an initial episode of VTE. Descriptive statistics, Chi-squared or Fisher's exact test, median test, Mann-Whitney test, logistic regression analysis, Nonparametric Estimation Kaplan-Meier with a log-rank test or Cox model were used when appropriate. Results from analyses indicated that acute leukemia patients had a high prevalence, incidence, and recurrent rate of VTE. Prior history of VTE, obesity, older age, low platelet account, presence of Philadelphia positive ALL, use of oral contraceptives or hormone replacement therapy, presence of malignancies, and co-morbidities may place leukemia patients at an increased risk for VTE development or recurrence. Interestingly, development of VTE was not associated with a higher risk of death among hospitalized acute leukemia patients.^

Correlates of post-diagnosis weight management among female breast cancer survivors: An Internet survey

Objective. Weight gain after cancer treatment is associated with breast cancer recurrence. In order to prolong cancer-free survivorship, interventions to manage post-diagnosis weight are sometimes conducted. However, little is known about what factors are associated with weight management behaviors among cancer survivors. In this study, we examined associations of demographic, clinical, and psychosocial variables with weight management behaviors in female breast cancer survivors. We also examined whether knowledge about post-diagnosis weight gain and its risk is associated with weight management behaviors. ^ Methods. 251 female breast cancer survivors completed an internet survey. They reported current performance of three weight management behaviors (general weight management, physical activity, and healthy diet). We also measured attitude, elf-efficacy, knowledge and social support regarding these behaviors along with demographic and clinical characteristics. ^ Results. Multiple regression models for the weight management behaviors explained 17% of the variance in general weight management, 45% in physical activity and 34% in healthy dieting. The models had 9–14 predictor variables which differed in each model. The variables associated with all three behaviors were social support and self-efficacy. Self-efficacy showed the strongest contribution in all models. The knowledge about weight gain and its risks was not associated with any weight management behaviors. However, women who obtained the knowledge during cancer treatment were more likely to engage in physical activity and healthy dieting. ^ Conclusions. The findings suggest that an intervention designed to increase their self-efficacy to manage weight, to be physically active, to eat healthy will effectively promote survivors to engage in these behaviors. Knowledge may motivate women to manage post-diagnosis weight about risk if information is provided during cancer treatment.^

Is H. pylori infection associated with diarrhea in a cohort of 3- to 8-year-old Colombian children?

The Estudio Comunitario sobre la Salud del Niño cohort study followed 326 3- to 8-year-old Colombian children for 4 years to observe the natural history of Helicobacter pylori infection and identify risk factors for acquisition, recurrence and persistence. Acute H. pylori infection during childhood may predispose to other enteric infections and therefore increase the risk of diarrheal disease. This dissertation aimed to estimate the effect of H. pylori infection on the occurrence of diarrhea and parasitic co-infections. The analysis used Generalized Estimating Equations to obtain odds ratios to estimate relative risks for diarrhea and the Zhang-Yu algorithm to estimate relative risks for on parasitic infections. Andersen-Gill models were used to estimate rate ratios for the effect of H. pylori status on the recurrence of parasitic infections. H. pylori status was classified for the entire follow-up duration in 1 of 3 categories: persistently positive, intermittently positive, and persistently negative. Multivariable models included child’s sex, age, symptoms, medication use, and socio-environmental factors. H. pylori infection was weakly and imprecisely associated with diarrheal disease, which occurred at an unexpectedly low frequency in this study. Persistently H. pylori-positive children had a somewhat higher incidence of reported diarrhea than intermittently positive or persistently negative children. Stratified analysis revealed that the presence of specific helminthes modified the effect of persistent H. pylori infection on diarrhea. The incidence of any parasitic infections was higher in children with persistent H. pylori infection relative to those with intermittent or persistently negative status, but this association did not hold when adjusted for the full set of selected covariates. The effects of H. pylori persistent status were similar for the occurrence or recurrence of Giardia duodenalis, Entamoeba histolytica, and Ascaris lumbricoides. These results show that H. pylori frequently co-exists with other parasites in Andean children and suggest that intermittently H. pylori–positive children might be at a lower risk of parasitic infections than persistently positive children. The relationship of H. pylori infection, helminthic infection and diarrheal disease should be further explored in studies that devote more intensive resources to accurate ascertainment of diarrhea.^

Population-level risks of physical activity: Saving bones and screening hearts

Documented risks of physical activity include reduced bone mineral density at high activity volume, and sudden cardiac death among adults and adolescents. Further illumination of these risks is needed to inform future public health guidelines. The present research seeks to 1) quantify the association between physical activity and bone mineral density (BMD) across a broad range of activity volume, 2) assess the utility of an existing pre-screening questionnaire among US adults, and 3) determine if pre-screening risk stratification by questionnaire predicts referral to physician among Texas adolescents. ^ Among 9,468 adults 20 years of age or older in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, linear regression analyses revealed generally higher BMD at the lumbar spine and proximal femur with greater reported activity volume. Only lumbar BMD in women was unassociated with activity volume. Among men, BMD was similar at activity beyond four times the minimum volume recommended in the Physical Activity Guidelines. These results suggest that the range of activity reported by US adults is not associated with low BMD at either site. ^ The American Heart Association / American College of Sports Medicine Preparticipation Questionnaire (AAPQ) was applied to 6,661 adults 40 years of age or older from NHANES 2001-2004 by using NHANES responses to complete AAPQ items. Following AAPQ referral criteria, 95.5% of women and 93.5% of men would be referred to a physician before exercise initiation, suggesting little utility for the AAPQ among adults aged 40 years or older. Unnecessary referral before exercise initiation may present a barrier to exercise adoption and may strain an already stressed healthcare infrastructure. ^ Among 3181 athletes in the Texas Adolescent Athlete Heart Screening Registry, 55.2% of boys and 62.2% of girls were classified as high-risk based on questionnaire answers. Using sex-stratified contingency table analyses, risk categories were not significantly associated with referral to physician based on electrocardiogram or echocardiogram, nor were they associated with confirmed diagnoses on follow-up. Additional research is needed to identify which symptoms are most closely related to sudden cardiac death, and determine the best methods for rapid and reliable assessment. ^ In conclusion, this research suggests that the volume of activity reported by US adults is not associated with low BMD at two clinically relevant sites, casts doubts on the utility of two existing cardiac screening tools, and raises concern about barriers to activity erected through ineffective screening. These findings augment existing research in this area that may inform revisions to the Physical Activity Guidelines regarding risk mitigation.^

Advanced methodologies for the dendrogeomorphic analysis of past floods and related risks

This communication presents an overview of their first results and innovate methodologies, focused in their possibilities and limitations for the reconstruction of recent floods and paleofloods over the World.

Economic analysis of drought risks: an application to irrigated agriculture in Spain

Abstract This paper describes a two-part methodology for managing the risk posed by water supply variability to irrigated agriculture. First, an econometric model is used to explain the variation in the production value of irrigated agriculture. The explanatory variables include an index of irrigation water availability (surface storage levels), a price index representative of the crops grown in each geographical unit, and a time variable. The model corrects for autocorrelation and it is applied to 16 representative Spanish provinces in terms of irrigated agriculture. In the second part, the fitted models are used for the economic evaluation of drought risk. In flow variability in the hydrological system servicing each province is used to perform ex-ante evaluations of economic output for the upcoming irrigation season. The model?s error and the probability distribution functions (PDFs) of the reservoirs? storage variations are used to generate Monte Carlo (Latin Hypercube) simulations of agricultural output 7 and 3 months prior to the irrigation season. The results of these simulations illustrate the different risk profiles of each management unit, which depend on farm productivity and on the probability distribution function of water in flow to reservoirs. The potential for ex-ante drought impact assessments is demonstrated. By complementing hydrological models, this method can assist water managers and decisionmakers in managing reservoirs.

Assessment of self-combustion risks for solid fuels (POSTER)

Every solid fuel has a tendency to react with oxygen, a fact that constitutes the basis of their ability to oxidation and energy intake for combustion, but that poses a risk when it occurs in an uncontrolled manner. When the slow oxidation phenomenon produces more heat than can be evacuated, the result is a heating process, which promotes combustion reactions, primarily fuel oxidation, and a progressive increase in temperature.