Evaluation of the city of Houston HIV/STD prevention program in Houston Independent School District (HISD) high schools

This cross-sectional study was undertaken to evaluate the impact in terms of HIV/STD knowledge and sexual behavior that the City of Houston HIV/STD prevention program in HISD high schools has had on students who have participated in it by comparing them with their peers who have not, based on self reports. The study further evaluated the program cost-effectiveness for averting future HIV infections by computing Cost-Utility Ratios based on reported sexual behavior. ^ Mixed results were obtained, indicating a statistically significant difference in knowledge with the intervention group having scored higher (p-value 0.001) but not for any of the behaviors assessed. The knowledge score outcome's overall p-value after adjusting for each stratifying variable (age, grade, gender and ethnicity) was statistically significant. The Odds Ratio of intervention group participants aged 15 years or more scoring 70% or higher was 1.86 times; that of intervention group female participants was 2.29 times; and that of intervention group Black/African American participants was 2.47 times relative to their comparison group counterparts. The knowledge score results remained statistically significant in the logistic regression model, which controlled for age, grade level, gender and ethnicity. The Odds Ratio in this case was 1.74. ^ Three scenarios based on the difference in the risk of HIV infection between the intervention and comparison group were used for computation of Cost-Utility Ratios: Base, worst and best-case scenario. The best-case scenario yielded cost-effective results for male participants and cost-saving results for female participants when using ethnicity-adjusted HIV prevalence. The scenario remained cost-effective for female participants when using the unadjusted HIV prevalence. ^ The challenge to the program is to devise approaches that can enhance benefits for male participants. If it is a threshold problem implying that male participants require more intensive programs for behavioral change, then programs should first be piloted among boys before being implemented across the board. If it is a reflection of gender differences, then we might have to go back to the drawing board and engage boys in focus group discussions that will help formulate more effective programs. Gender-blind approaches currently in vogue do not seem to be working. ^

Data quality in trauma transfusion studies and the impact of missing data on predicting massive transfusion

Maximizing data quality may be especially difficult in trauma-related clinical research. Strategies are needed to improve data quality and assess the impact of data quality on clinical predictive models. This study had two objectives. The first was to compare missing data between two multi-center trauma transfusion studies: a retrospective study (RS) using medical chart data with minimal data quality review and the PRospective Observational Multi-center Major Trauma Transfusion (PROMMTT) study with standardized quality assurance. The second objective was to assess the impact of missing data on clinical prediction algorithms by evaluating blood transfusion prediction models using PROMMTT data. RS (2005-06) and PROMMTT (2009-10) investigated trauma patients receiving ≥ 1 unit of red blood cells (RBC) from ten Level I trauma centers. Missing data were compared for 33 variables collected in both studies using mixed effects logistic regression (including random intercepts for study site). Massive transfusion (MT) patients received ≥ 10 RBC units within 24h of admission. Correct classification percentages for three MT prediction models were evaluated using complete case analysis and multiple imputation based on the multivariate normal distribution. A sensitivity analysis for missing data was conducted to estimate the upper and lower bounds of correct classification using assumptions about missing data under best and worst case scenarios. Most variables (17/33=52%) had <1% missing data in RS and PROMMTT. Of the remaining variables, 50% demonstrated less missingness in PROMMTT, 25% had less missingness in RS, and 25% were similar between studies. Missing percentages for MT prediction variables in PROMMTT ranged from 2.2% (heart rate) to 45% (respiratory rate). For variables missing >1%, study site was associated with missingness (all p≤0.021). Survival time predicted missingness for 50% of RS and 60% of PROMMTT variables. MT models complete case proportions ranged from 41% to 88%. Complete case analysis and multiple imputation demonstrated similar correct classification results. Sensitivity analysis upper-lower bound ranges for the three MT models were 59-63%, 36-46%, and 46-58%. Prospective collection of ten-fold more variables with data quality assurance reduced overall missing data. Study site and patient survival were associated with missingness, suggesting that data were not missing completely at random, and complete case analysis may lead to biased results. Evaluating clinical prediction model accuracy may be misleading in the presence of missing data, especially with many predictor variables. The proposed sensitivity analysis estimating correct classification under upper (best case scenario)/lower (worst case scenario) bounds may be more informative than multiple imputation, which provided results similar to complete case analysis.^

An ordinal logistic regression model with misclassification of the outcome variable and categorical covariate

Ordinal outcomes are frequently employed in diagnosis and clinical trials. Clinical trials of Alzheimer's disease (AD) treatments are a case in point using the status of mild, moderate or severe disease as outcome measures. As in many other outcome oriented studies, the disease status may be misclassified. This study estimates the extent of misclassification in an ordinal outcome such as disease status. Also, this study estimates the extent of misclassification of a predictor variable such as genotype status. An ordinal logistic regression model is commonly used to model the relationship between disease status, the effect of treatment, and other predictive factors. A simulation study was done. First, data based on a set of hypothetical parameters and hypothetical rates of misclassification was created. Next, the maximum likelihood method was employed to generate likelihood equations accounting for misclassification. The Nelder-Mead Simplex method was used to solve for the misclassification and model parameters. Finally, this method was applied to an AD dataset to detect the amount of misclassification present. The estimates of the ordinal regression model parameters were close to the hypothetical parameters. β1 was hypothesized at 0.50 and the mean estimate was 0.488, β2 was hypothesized at 0.04 and the mean of the estimates was 0.04. Although the estimates for the rates of misclassification of X1 were not as close as β1 and β2, they validate this method. X 1 0-1 misclassification was hypothesized as 2.98% and the mean of the simulated estimates was 1.54% and, in the best case, the misclassification of k from high to medium was hypothesized at 4.87% and had a sample mean of 3.62%. In the AD dataset, the estimate for the odds ratio of X 1 of having both copies of the APOE 4 allele changed from an estimate of 1.377 to an estimate 1.418, demonstrating that the estimates of the odds ratio changed when the analysis includes adjustment for misclassification. ^

DEVELOPMENT OF A BEAM-SPECIFIC PLANNING TARGET VOLUME AND A ROBUST PLAN ANALYSIS TOOL FOR PROTON THERAPY

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of this dissertation research was to develop a treatment planning method and a planevaluation method that address proton-specific issues regarding setup and range uncertainties. Treatment plan designing method adapted to proton therapy: Currently, for proton therapy using a scanning beam delivery system, setup uncertainties are largely accounted for by geometrically expanding a clinical target volume (CTV) to a planning target volume (PTV). However, a PTV alone cannot adequately account for range uncertainties coupled to misaligned patient anatomy in the beam path since it does not account for the change in tissue density. In order to remedy this problem, we proposed a beam-specific PTV (bsPTV) that accounts for the change in tissue density along the beam path due to the uncertainties. Our proposed method was successfully implemented, and its superiority over the conventional PTV was shown through a controlled experiment.. Furthermore, we have shown that the bsPTV concept can be incorporated into beam angle optimization for better target coverage and normal tissue sparing for a selected lung cancer patient. Treatment plan evaluation method adapted to proton therapy: The dose-volume histogram of the clinical target volume (CTV) or any other volumes of interest at the time of planning does not represent the most probable dosimetric outcome of a given plan as it does not include the uncertainties mentioned earlier. Currently, the PTV is used as a surrogate of the CTV’s worst case scenario for target dose estimation. However, because proton dose distributions are subject to change under these uncertainties, the validity of the PTV analysis method is questionable. In order to remedy this problem, we proposed the use of statistical parameters to quantify uncertainties on both the dose-volume histogram and dose distribution directly. The robust plan analysis tool was successfully implemented to compute both the expectation value and its standard deviation of dosimetric parameters of a treatment plan under the uncertainties. For 15 lung cancer patients, the proposed method was used to quantify the dosimetric difference between the nominal situation and its expected value under the uncertainties.

Improving Cervical Cancer Nodal Boost Radiation Therapy by Quantifying Uncertainties and Exploring Advanced Radiation Therapy Modalities

Radiation therapy for patients with intact cervical cancer is frequently delivered using primary external beam radiation therapy (EBRT) followed by two fractions of intracavitary brachytherapy (ICBT). Although the tumor is the primary radiation target, controlling microscopic disease in the lymph nodes is just as critical to patient treatment outcome. In patients where gross lymphadenopathy is discovered, an extra EBRT boost course is delivered between the two ICBT fractions. Since the nodal boost is an addendum to primary EBRT and ICBT, the prescription and delivery must be performed considering previously delivered dose. This project aims to address the major issues of this complex process for the purpose of improving treatment accuracy while increasing dose sparing to the surrounding normal tissues. Because external beam boosts to involved lymph nodes are given prior to the completion of ICBT, assumptions must be made about dose to positive lymph nodes from future implants. The first aim of this project was to quantify differences in nodal dose contribution between independent ICBT fractions. We retrospectively evaluated differences in the ICBT dose contribution to positive pelvic nodes for ten patients who had previously received external beam nodal boost. Our results indicate that the mean dose to the pelvic nodes differed by up to 1.9 Gy between independent ICBT fractions. The second aim is to develop and validate a volumetric method for summing dose of the normal tissues during prescription of nodal boost. The traditional method of dose summation uses the maximum point dose from each modality, which often only represents the worst case scenario. However, the worst case is often an exaggeration when highly conformal therapy methods such as intensity modulated radiation therapy (IMRT) are used. We used deformable image registration algorithms to volumetrically sum dose for the bladder and rectum and created a voxel-by-voxel validation method. The mean error in deformable image registration results of all voxels within the bladder and rectum were 5 and 6 mm, respectively. Finally, the third aim explored the potential use of proton therapy to reduce normal tissue dose. A major physical advantage of protons over photons is that protons stop after delivering dose in the tumor. Although theoretically superior to photons, proton beams are more sensitive to uncertainties caused by interfractional anatomical variations, and must be accounted for during treatment planning to ensure complete target coverage. We have demonstrated a systematic approach to determine population-based anatomical margin requirements for proton therapy. The observed optimal treatment angles for common iliac nodes were 90° (left lateral) and 180° (posterior-anterior [PA]) with additional 0.8 cm and 0.9 cm margins, respectively. For external iliac nodes, lateral and PA beams required additional 0.4 cm and 0.9 cm margins, respectively. Through this project, we have provided radiation oncologists with additional information about potential differences in nodal dose between independent ICBT insertions and volumetric total dose distribution in the bladder and rectum. We have also determined the margins needed for safe delivery of proton therapy when delivering nodal boosts to patients with cervical cancer.

The emergence of the social determinants of health on the policy agenda in Britain: A case study, 1980--2003

Numerous theories have been advanced in the effort to explain how a given policy issue manages to take root in the public sphere and subsequently move forward on the public legislative agenda—or not. This study examined how the social determinants of health (SDOH) came to be part of the legislative policy agenda in Britain from 1980 to 2003. ^ The specific objectives of the research were: (1) to conduct a sociopolitical analysis grounded in alternative agenda-setting theories to identify the factors responsible for moving the social determinants health perspective onto the British policy agenda; and (2) to determine which of the theories and related dimensions best accounted for the emergence of this perspective. ^ A triangulated content and context analysis of British news articles, historical accounts, and research commentaries of the SDOH movement was conducted guided by relevant agenda-setting theories set within a social movement framework to chronicle the emergence of the SDOH as a significant policy issue in Britain. ^ The most influential social movement and agenda setting elements in the emergence of the SDOH in Britain were issue generation tactics, framing efforts, mobilizing structures, and political opportunities grounded in social movement and agenda setting theories. Policy content or the details of the policy had comparatively little impact on the successful emergence of the SDOH. Despite resistance by the government, from 1980 to 1996 interest groups created a political understanding of the SDOH utilizing a framing package encompassing notions of inequality, fairness, and justice. This frame transmitted a powerful idea connected to a core set of British values and beliefs. After 1996, a shift in political opportunities cemented the institutional arrangements needed to sustain an environment conducive to the development and implementation of SDOH policies and programs. ^ This research demonstrates that the U.S. emergence of the SDOH on the policy agenda will depend upon: (1) U.S. ideals and values regarding poverty, inequality, race, health, and health care that will determine issue framing; (2) political opportunities that will emerge—or not—to advance the SDOH policy agenda; and (3) the mobilizing structures that support or oppose the issue. ^

Issues related to HIV stigma: An embedded case study of PLHAS and community in Nepal

Little is known about HIV stigma in Nepal. Findings from other parts of the world suggest that HIV related stigma acts as a limiting factor for People Living with HIV & AIDS (PLHAs) from accessing needed health care and the subsequent psychological outcomes make PLHAs and their immediate family members more vulnerable. The purpose of this study is to understand and describe Nepalese PLHA's and community peoples' experiences regarding sources, types, causes and mechanism of HIV-associated stigma. This study aimed to best utilize the existing data. Study participants were recruited through local Community Based Organizations working in the field of HIV. The data, collected in the form of focus group discussions in workshop settings, were coded and analyzed. Study has revealed key issues related to HIV stigma in Nepal: hierarchy of stigma, denial and rejection, death as a form of punishment and Mumbaiya disease. A conceptual model was developed to explain the HIV stigma in Nepal. Our hope is that this finding, stigma being a contextual variable, will be helpful in triggering a novel public health discourse in the field of HIV stigma in Nepal, which will eventually be helpful for developing policies and interventions to eliminate HIV-associated stigma.^

Seroprevalence of toxoplasmosis and current thinking regarding screening in pregnancy: A review of the literature and case study discussion

The approach to the diagnosis and treatment of congenital toxoplasmosis has been one of flux and debate, fueled by lack of knowledge, lack of consensus, different methods of screening and different national policies for screening in different parts of the world. Countries with higher prevalence of disease such as in Europe and South America have a heightened awareness of the need to screen and treat for this parasitic infection during pregnancy. In contrast, in the United States, it is a condition scarcely discussed and has been largely ignored except in some large centers and by a few researchers. Policies and research strategies for any condition should start with obtaining good data. The aims of this thesis included a review of prevalence studies conducted in the United States, focused on the past 20 years, combined with a description of original research conducted by the author several years ago. The latter was a cross-sectional study performed in Houston, one of the largest American cities with a great ethnic mix. The study analyzed prevalence rates of Toxoplasma gondii IgG antibody in sera of women of reproductive age. Overall seroprevalence was 12.3%. In keeping with other studies, higher prevalence correlated with lower socioeconomic status, Black and Hispanic and Asian ethnicities, and increasing age. A literature search revealed only three prevalence studies performed in the United States over the past 20 years, with another four studies only referred to as personal communications or within a textbook, without further study detail available. The literature review also revealed a lack of consensus on whether or not to screen for toxoplasmosis in pregnancy, and even whether or not treatment in utero is worthwhile.^ Proponents of screening and treatment in pregnancy site studies both in the United States and France, emphasize that treatment reduces disease manifestations in infants. Opponents cite other studies that show only marginal benefits, together with potential side effects of medication regimens and generation of anxiety in parents. What is agreed on so far is the value of educating pregnant women on how to avoid contracting toxoplasmosis, and educating physicians on making the best use of reference laboratories before major treatment decisions are made. Further research to reevaluate the literature critically, review new treatment regimens and examine costs and benefits of screening and treatment of toxoplasmosis in pregnancy, bringing together European and American researchers, is needed.^

An evaluation of Employee Assistance Programs: An overview and case study

Methodologies for the analysis and cross-evaluations of Employee Assistance Programs (EAPs) are necessary to indicate program weaknesses and strengths for both present and future EAP services.^ As EAPs have matured from simplistic industrial alcoholism programs to all problem-encompassing, complex programs, an aggressive group of entrepreneurs has developed. Business and industrial managements need established criteria to select the most suitable professional services for their needs, as well as the best investment value for cost containments.^ Four major EAPs were compared to determine critical areas necessary for cross evaluation. Future standardization of terminology and definitions of services will facilitate both the evaluation of a specific program and its comparison to problems or successes of other EAPs.^ Past evaluation difficulties have been caused by the lack of EAP program accreditations and professional personnel licensure requirements. The Association of Labor Management Administrators and Consultants on Alcoholism (ALMACA) has recently set certification criteria for personnel, which will enhance the professional standards for EAPs. ^

Planning and implementation efficacy as a determinant of health risk communication outcomes: Case studies of the U.S. Public Health Service (PHS)

This study was conducted under the auspices of the Subcommittee on Risk Communication and Education of the Committee to Coordinate Environmental Health and Related Programs (CCEHRP) to determine how Public Health Service (PHS) agencies are communicating information about health risk, what factors contributed to effective communication efforts, and what specific principles, strategies, and practices best promote more effective health risk communication outcomes.^ Member agencies of the Subcommittee submitted examples of health risk communication activities or decisions they perceived to be effective and some examples of cases they thought had not been as effective as desired. Of the 10 case studies received, 7 were submitted as examples of effective health risk communication, and 3, as examples of less effective communication.^ Information contained in the 10 case studies describing the respective agencies' health risk communication strategies and practices was compared with EPA's Seven Cardinal Rules of Risk Communication, since similar rules were not found in any PHS agency. EPA's rules are: (1) Accept and involve the public as a legitimate partner. (2) Plan carefully and evaluate your efforts. (3) Listen to the public's specific concerns. (4) Be honest, frank, and open. (5) Coordinate and collaborate with other credible sources. (6) Meet the needs of the media. (7) Speak clearly and with compassion.^ On the basis of case studies analysis, the Subcommittee, in their attempts to design and implement effective health risk communication campaigns, identified a number of areas for improvement among the agencies. First, PHS agencies should consider developing a focus specific to health risk communication (i.e., office or specialty resource). Second, create a set of generally accepted practices and guidelines for effective implementation and evaluation of PHS health risk communication activities and products. Third, organize interagency initiatives aimed at increasing awareness and visibility of health risk communication issues and trends within and between PHS agencies.^ PHS agencies identified some specific implementation strategies the CCEHRP might consider pursuing to address the major recommendations. Implementation strategies common to PHS agencies emerged in the following five areas: (1) program development, (2) building partnerships, (3) developing training, (4) expanding information technologies, and (5) conducting research and evaluation. ^