Bayesian dual threshold design with Dirichlet distribution: An alternative way to frequentist multi-stage phase II designs in oncology

Many phase II clinical studies in oncology use two-stage frequentist design such as Simon's optimal design. However, they have a common logistical problem regarding the patient accrual at the interim. Strictly speaking, patient accrual at the end of the first stage may have to be suspended until all patients have events, success or failure. For example, when the study endpoint is six-month progression free survival, patient accrual has to be stopped until all outcomes from stage I is observed. However, study investigators may have concern when accrual is suspended after the first stage due to the loss of accrual momentum during this hiatus. We propose a two-stage phase II design that resolves the patient accrual problem due to an interim analysis, and it can be used as an alternative way to frequentist two-stage phase II studies in oncology. ^

Assessing childhood difficulties: Comparing the SDQ and the BASC-2

This study of the Behavior Assessment System for Children, Second Edition (BASC-2), had two objectives. First, was to compare the Strengths and Difficulties Questionnaire (SDQ) and the BASC-2. Participants were students from SBISD, identified as having difficulties, assessed with the BASC-2 and completed the SDQ. Based on the small sample (N=8), scores from the SDQ and the BASC-2 were found to correlate highly with one another on most conceptually similar scales. With both Parent and Teacher raters, diagnostic concordance was high for nearly all behavior and emotional problem scales. While the diagnostic concordance of the SDQ and BASC-2 looks promising, results need to be replicated with a larger sample. ^ The second objective was to assess the BASC-2 inter-informant concordance (parent, teacher and child). Participants were 145 students, 3-17 years, 78.6% male, 28% Hispanic, 37% White, 34% Black, and 64% were economically disadvantaged. Of the four dyads, teacher-teacher pairs had the highest correlations and agreement levels, especially on externalizing scale items, regardless of the subjects' age group, gender or ethnicity. ^ Overall, parent-teacher pairs had low to moderate concordance for most scale items, with slightly higher agreement for externalizing problems, with better concordance for preschool children, very low correlations with girls' ratings, but moderate correlations with boy ratings. Correlational results were generally moderate for teachers and parents of White children and low for teachers and parents of Hispanic and Black children. ^ Parent-child self-reports had low concordance for nearly all scale items evaluated, particularly with girl self-raters, but moderate with the boys. Conversely, Teacher-Girl pairs had larger correlations than with Boy. Parents reported substantially higher frequency of disorder endorsement than reported by the children, regardless of the child's ethnicity or gender. While generally low, Teachers and Black students had higher concordance on internalizing measures than Hispanic or White students. Parents of Black students had higher frequency of disorder endorsements than other ethnicities. ^ The difference in format and lack of externalizing measures on the self-report version (SRP) hinders inter-rater comparisons. Future studies using the revised, BASC-2 with children in a school-based setting are needed to assess further its rater reliability. ^

Diffusely adherent Escherichia coli (DAEC) as a cause of acute diarrhea

Acute diarrhea is the most common medical problem in the developing countries. Infectious agents are responsible for a majority of cases of acute diarrhea. Knowing the cause of acute diarrhea is important to developing plans for disease prevention, control and therapy. Acute diarrhea is caused by many viruses, bacteria and parasites. ^ Travelers to developing countries of the world commonly develop diarrhea as a result of eating contaminated food or drinking contaminated water. About 30-50% of travelers who travel from industrialized countries like United States to the developing countries are at risk of developing diarrhea. High risk areas for travelers' diarrhea are Mexico, Latin America and Southeast Asia. Public restaurants are the common sites for exposure to this type of food-borne infectious disease in travelers. Food becomes contaminated when they are handled by people with fecal content on their hands. ^ The importance of Diffusely Adherent Escherichia Coli (DAEC) in travelers to these areas has not been well studied. Some of the studies looking at DAEC have shown the organism to be present in children without symptoms. Other studies have shown a relationship between DAEC infection and presence of symptoms. I have selected this topic because the patho-physiological processes in DAEC infection that allow intestinal and extra-intestinal infections to develop are not fully understood. DAEC related acute diarrhea is a relatively new topic of public health significance. There is a limited number of studies regarding the virulence and pathogenic mechanisms of DAEC. The presumed virulence factor of the organism is diffuse attachment to the intestinal lining of the infected host. However more research needs to be done to identify the pathogenic mechanisms and virulence factors associated with DAEC infection for better treatment planning and diarrhea prevention. ^

Mechanisms of liposomal all-{\it trans\/} retinoic acid and vitamin D3 induced inhibition of cell proliferation and stimulation of apoptosis in aggressive B-cell non-Hodgkin's lymphoma

The Non-Hodgkin's Lymphoma (NHLs) are neoplasms of the immune system. Currently, less than 1% of the etiology of the 22,000 newly diagnosed lymphoma cases in the U.S.A. every year is known. This disease has a significant prevalence and high mortality rate. Cell growth in lymphomas has been shown to be an important parameter in aggressive NHL when establishing prognosis, as well as an integral part in the pathophysiology of the disease process. While many aggressive B cell NHLs respond initially to chemotherapeutic regimens such as CHOP-bleo (adriamycin, vincristine and bleomycin) etc., relapse is common, and the patient is then often refractory to further salvage treatment regimens.^ To assess their potential to inhibit aggressive B cell NHLs and induce apoptosis (also referred to as programmed cell death (PCD)), it was proposed to utilize the following biological agents-liposomal all-trans retinoic acid (L-ATRA) which is a derivative of Vitamin A in liposomes and Vitamin D3. Preliminary evidence indicates that L-ATRA may inhibit cell growth in these cells and may induce PCD as well. Detailed studies were performed to understand the above phenomena by L-ATRA and Vitamin D3 in recently established NHL-B cell lines and primary cell cultures. The gene regulation involved in the case of L-ATRA was also delineated. ^

Factors affecting the symptom burden in chronic heart failure

Background. Heart failure (HF) is a health problem of epidemic proportions and a clinical syndrome that leads to progressively severe symptoms, which contribute significantly to the burden of the disease. Several factors may affect the symptom burden of patients with HF, including physiological, psychological, and spiritual factors. This study was designed to examine the inter-relationship of physiological, psychological, and spiritual factors affecting symptoms for patients with HF. ^ Objectives. The aims of this study were to examine symptom burden of heart failure patients related to: (1) the physiological factor of brain natriuretic peptide (BNP); (2) the psychological factor of depression; (3) the spiritual factors of self transcendence and purpose in life; and (4) combined effects of physiological, psychological and spiritual factors. One additional aim was to describe symptom intensity related to symptom burden. ^ Methods. A cross-sectional non-experimental correlational design was used to examine factors affecting symptom burden in 105 patients with HF from a southwestern medical center outpatient heart failure clinic. Both men and women were included; average age was 56.6 (SD = 16.86). All measures except BNP were obtained by patient self-report. ^ Results. The mean number of symptoms present was 8.17 (SD = 3.34) with the three most common symptoms being shortness of breath on exertion, fatigue, and weakness. The mean symptom intensity was 365.66 (SD = 199.50) on a summative scale of visual analogue reports for 13 symptoms. The mean BNP level was 292.64 pg/ml (SD = 57 1.11). The prevalence rate for depression was 43.6% with a mean score of 3.48 (SD = 2.75) on the Center for Epidemiological Studies - Depression scale (CES-D 10) scale. In a multivariate analysis, depression was the only significant predictor of symptom burden (r = .474; P < .001), accounting for 18% of the variance. Spirituality had an interaction effect with depression (P ≤ .001), serving as a moderator between depression and symptom burden. ^ Conclusion. HF is a chronic and progressive syndrome characterized by severe symptoms, hospitalizations and disability. Depression is significantly related to symptom burden and this relationship is moderated by spirituality. ^

The School Sealant Program: An evaluation of the oral health education component

Dental caries is a common preventable childhood disease leading to severe physical, mental and economic repercussions for children and their families if left untreated. A needs assessment in Harris County reported that 45.9% of second graders had untreated dental caries. In order to address this growing problem, the School Sealant Program (SSP), a primary preventive initiative, was launched by the Houston Department of Health and Human Services (HDHHS) to provide oral health education, and underutilized dental preventive services to second grade children from participating Local School Districts (LSDs). ^ To determine the effectiveness and efficiency of the SSP, a program evaluation was conducted by the HDHHS between September 2007 and June 2008 for the Oral Health Education (OHE) component of the SSP. The objective of the evaluation was to assess short term changes in oral health knowledge of the participants and determine if these changes, if any, were due to the OHE sessions. An 8-item multiple choice pre/post test was developed for this purpose and administered to the participants before and immediately after the OHE sessions. ^ The present project analyzed pre and post test data of 1,088 second graders from 22 participating schools. Changes in overall and topic-specific knowledge of the program participants before and after the OHE sessions were analyzed using the Wilcoxon's signed rank test. ^ Results. The overall knowledge assessment showed a statistically significant (p <0.001) increase in the dental health knowledge of the participants after the oral health education sessions. Participants in the higher scoring category (7-8 correct responses) increased from 9.5% at baseline to 60.8% after the education sessions. Overall knowledge increased in all school regions with the highest knowledge gains seen in the Central and South regions. Males and females had similar knowledge gains. Significant knowledge differences were also found for each of the topic specific categories (functions of teeth, healthy diet, healthy habits, dental sealants; p<0.001) indicating an increase in topic specific knowledge of the participants post-health education sessions. ^ Conclusions. The OHE sessions were successful in increasing the short term oral health knowledge of the participants. ^

Foodborne illness - An age old problem requiring contemporary solutions

Foodborne illness has always been with us, and food safety is an increasingly important public health issue affecting populations worldwide. In the United States of America, foodborne illness strikes millions of people and kills thousands annually, costing our economy billions of dollars in medical care expense and lost productivity. The nature of food and foodborne illness has changed dramatically in the last century. The regulatory systems have evolved to better assure a safe food supply. The food production industry has invested heavily to meet regulatory requirement and to improve the safety of their products. Educational efforts have increased public awareness of safe food handling practices, empowering consumers to fulfill their food safety role. Despite the advances made, none of the Healthy People 2010 targets for reduction of foodborne pathogens has been reached. There is no single solution to eliminating pathogen contamination from all classes of food products. However, irradiation seems especially suited for certain higher-risk foods such as meat and poultry and its use should advance the goal of reducing foodborne illness by minimizing the presence of pathogenic organisms in the food supply. This technology has been studied extensively for over 50 years. The Food and Drug Administration has determined that food irradiation is safe for use as approved by the Agency. It is time to take action to educate consumers about the benefits of food irradiation. Consumer demand will compel industry to meet demand by investing in facilities and processes to assure a consistent supply of irradiated food products. ^

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

Statistical Methods for Differential Expressions of Genes Detected in Multiple-Condition Experiment of Microarray

Most studies of differential gene-expressions have been conducted between two given conditions. The two-condition experimental (TCE) approach is simple in that all genes detected display a common differential expression pattern responsive to a common two-condition difference. Therefore, the genes that are differentially expressed under the other conditions other than the given two conditions are undetectable with the TCE approach. In order to address the problem, we propose a new approach called multiple-condition experiment (MCE) without replication and develop corresponding statistical methods including inference of pairs of conditions for genes, new t-statistics, and a generalized multiple-testing method for any multiple-testing procedure via a control parameter C. We applied these statistical methods to analyze our real MCE data from breast cancer cell lines and found that 85 percent of gene-expression variations were caused by genotypic effects and genotype-ANAX1 overexpression interactions, which agrees well with our expected results. We also applied our methods to the adenoma dataset of Notterman et al. and identified 93 differentially expressed genes that could not be found in TCE. The MCE approach is a conceptual breakthrough in many aspects: (a) many conditions of interests can be conducted simultaneously; (b) study of association between differential expressions of genes and conditions becomes easy; (c) it can provide more precise information for molecular classification and diagnosis of tumors; (d) it can save lot of experimental resources and time for investigators.^

U.S. school based sealant programs: Review of their most common characteristics

In the United States, dental caries is the most common chronic illness in children, occurring five to eight times as frequently as asthma. 11 Dental caries is an unmet health need, disproportionately affecting minority groups and individuals with low socio-economic status.15,34,36 School-Based Sealant Programs were developed to target children at risk, to provide dental services in a closer geographic area, to offer low cost preventive dental services, and to educate families about oral health and prevention.1 There is scientific, evidence based literature that shows the effectiveness of dental sealants preventing dental decay. 13^ Currently, there is no central source for cataloging School-Based Sealant Programs (SBSPs). Information is scattered around publications and documents. For instance, the National Health and Nutrition Examination Survey (NHANES) does not have information about all the existing SBSPs. ^ This literature review determined which are the most common characteristics of SBSPs in the U.S. and determined the extent to which these programs provide sealants to children of low socio-economic status. The method utilized was an electronic database search. Pubmed and EBESCO host databases were searched with Mesh terms like “dental school sealant programs”, “community dentistry”, “school based sealant programs” and “oral preventive programs”. Results were organized in terms of location, population served, providers, funding source and data shared. ^ The searches produced 77 studies, from which 40 were included in this work. Only 18 U.S. states were represented in the results; however these findings are very consistent with the Best Practice Approach – School Based Sealant Programs3. Most of the SBSPs provide their services to children from low income families, and utilized the lower labor cost providers permitted by their state regulations. The author intends that this thesis work will become an aide in the development of future programs, and as evidence for the sustainability of these programs.^