Effects of Combined Bevacizumab and Paclitaxel on Tumor Interstitial Fluid Pressure in a Preclinical Breast Cancer Model

Effects of Combined Bevacizumab and Paclitaxel on Tumor Interstitial Fluid Pressure in a Preclinical Breast Cancer Model by Ricardo H. Alvarez Several mechanisms of cell resistance are often accountable for unsuccessful chemotherapy against cancer. Another reason, which has received increased attention, is the inefficient transport of anticancer drugs into tumor tissue. These impaired transports of chemotherapy into the tumor have been attributed to abnormal microvasculature and to pathologically increased tumor hypertension also called: interstitial fluid pressure (IFP). The pathophysiological processes leading to elevated tumor IFP are poorly understood. Here, in a preclinical breast cancer model, it is argued that a condition of raised IFP is a major factor in preventing optimal access of systemically administered chemotherapy agents. In our experimental model, we used a GILM2 human breast cancer in xenografts; mice were treated with different doses of paclitaxel –a widely used antimicrotubular agent, and bevacizumab –monoclonal antibody against vascular endothelial growth factor (VEGF). The proposed research project is designed to test the hypothesis that paclitaxel in combination with bevacizumab decreases the tumor IPF by restoring tumor permeability and increasing chemotherapy delivery. We demonstrated that the combination of paclitaxel and bevacizumab produced greater tumor control than either agent given alone and this combination reduced the IFP, producing an increment of 75% of apoptosis compared with the control arm. In addition, the intra-tumor paclitaxel quantification by liquid chromatography/Mass Spectrometry (LC/MS) demonstrated that lower dose of both agents showed a synergistic effect compared with high dose of treatment, where there is no significantly increase of paclitaxel into the tumor. These preclinical results are likely to have broad implications for the utility of anti-angiogenic therapies alone and in combination with chemotherapeutic agents.

Development of a Bayesian Joint Logistic Model to Better Study the Association between Haplotypes and Disease

In 2011, there will be an estimated 1,596,670 new cancer cases and 571,950 cancer-related deaths in the US. With the ever-increasing applications of cancer genetics in epidemiology, there is great potential to identify genetic risk factors that would help identify individuals with increased genetic susceptibility to cancer, which could be used to develop interventions or targeted therapies that could hopefully reduce cancer risk and mortality. In this dissertation, I propose to develop a new statistical method to evaluate the role of haplotypes in cancer susceptibility and development. This model will be flexible enough to handle not only haplotypes of any size, but also a variety of covariates. I will then apply this method to three cancer-related data sets (Hodgkin Disease, Glioma, and Lung Cancer). I hypothesize that there is substantial improvement in the estimation of association between haplotypes and disease, with the use of a Bayesian mathematical method to infer haplotypes that uses prior information from known genetics sources. Analysis based on haplotypes using information from publically available genetic sources generally show increased odds ratios and smaller p-values in both the Hodgkin, Glioma, and Lung data sets. For instance, the Bayesian Joint Logistic Model (BJLM) inferred haplotype TC had a substantially higher estimated effect size (OR=12.16, 95% CI = 2.47-90.1 vs. 9.24, 95% CI = 1.81-47.2) and more significant p-value (0.00044 vs. 0.008) for Hodgkin Disease compared to a traditional logistic regression approach. Also, the effect sizes of haplotypes modeled with recessive genetic effects were higher (and had more significant p-values) when analyzed with the BJLM. Full genetic models with haplotype information developed with the BJLM resulted in significantly higher discriminatory power and a significantly higher Net Reclassification Index compared to those developed with haplo.stats for lung cancer. Future analysis for this work could be to incorporate the 1000 Genomes project, which offers a larger selection of SNPs can be incorporated into the information from known genetic sources as well. Other future analysis include testing non-binary outcomes, like the levels of biomarkers that are present in lung cancer (NNK), and extending this analysis to full GWAS studies.

Left ventricular growth from age 8 to 18 and its anthropometric determinants: Longitudinal results from Project Heartbeat!

Left ventricular mass (LVM) is a strong predictor of cardiovascular disease (CVD) in adults. However, normal growth of LVM in healthy children is not well understood, and previous results on independent effects of body size and body fatness on LVM have been inconsistent. The purpose of this study was (1) to establish the normal growth curve of LVM from age 8 to age 18, and evaluate the determinants of change in LVM with age, and (2) to assess the independent effects of body size and body fatness on LVM.^ In Project HeartBeat!, 678 healthy children aged 8, 11 and 14 years at baseline were enrolled and examined at 4-monthly intervals for up to 4 years. A synthetic cohort with continuous observations from age 8 to 18 years was constructed. A total of 4608 LVM measurements was made from M-mode echocardiography. The multilevel linear model was used for analysis.^ Sex-specific trajectories of normal growth of LVM from age 8 to 18 was displayed. On average, LVM was 15 g higher in males than females. Average LVM increased linearly in males from 78 g at age 8 to 145 g at age 18. For females, the trajectory was curvilinear, nearly constant after age 14. No significant racial differences were found. After adjustment for the effects of body size and body fatness, average LVM decreased slightly from age 8 to 18, and sex differences in changes of LVM remained constant.^ The impact of body size on LVM was examined by adding to a basic LVM-sex-age model one of 9 body size indicators. The impact of body fatness was tested by further introducing into each of the 9 LVM models (with one or another of the body size indicators) one of 4 body fatness indicators, yielding 36 models with different body size and body fatness combinations. The results indicated that effects of body size on LVM can be distinguished between fat-free body mass and fat body mass, both being independent, positive predictors. The former is the stronger determinant. When a non-fat-free body size indicator is used as predictor, the estimated residual effect of body fatness on LVM becomes negative. ^

Project Alpha: A culturally appropriate approach to adolescent male sex education

In the United States today, adolescents face unacceptably high rates of mortality and morbidity due to the contraction of HIV/AIDS, sexually transmitted diseases and teenage pregnancy. In view of these rates, there is a need for applied preventive interventions to delay adolescent sexual behavior until adulthood. Project Alpha was a school-adopted, quasi-experimental program for adolescent male students attending Sharpstown High School in Houston, Texas. This intervention used student newsletters to provide specific role-model stories on community and student role models who have changed attitudes or improved efficacy to abstain from sexual behavior until adulthood. It was hypothesized that teenagers exposed to the intervention would show improvements in knowledge, beliefs, avoidance skills, perceived norms, intentions and self-efficacy to delay sexual behavior compared to no-treatment reference teenagers in the same school.^ In total, the Project Alpha program had a significant effect on student knowledge, beliefs (towards abstinence and having sex with multiple partners), perceived risk (HIV/STD testing), self-efficacy (could avoid sex with attractive girl who wants to have sex), perceived social norms (friends believing in sexual abstinence) and sexual intentions. However, no significant intervention effects were found in student's beliefs (that it was OK to have sex with girlfriend), perceived risk of HIV/STD, self-efficacy (to avoid sex with girlfriend) and social norms (friends believe it is OK to have sex with a girlfriend and multiple partners in the same month). ^

A longitudinal comparison of cardiovascular disease risk factors among children and adolescents in the U.S. and Japan: Project HeartBeat!

Blood cholesterol and blood pressure development in childhood and adolescence have important impact on the future adult level of cholesterol and blood pressure, and on increased risk of cardiovascular diseases. The U.S. has higher mortality rates of coronary heart diseases than Japan. A longitudinal comparison in children of risk factor development in the two countries provides more understanding about the causes of cardiovascular disease and its prevention. Such comparisons have not been reported in the past. ^ In Project HeartBeat!, 506 non-Hispanic white, 136 black and 369 Japanese children participated in the study in the U.S. and Japan from 1991 to 1995. A synthetic cohort of ages 8 to 18 years was composed by three cohorts with starting ages at 8, 11, and 14. A multilevel regression model was used for data analysis. ^ The study revealed that the Japanese children had significantly higher slopes of mean total cholesterol (TC) and high density lipoprotein (HDL) cholesterol levels than the U.S. children after adjusting for age and sex. The mean TC level of Japanese children was not significantly different from white and black children. The mean HDL level of Japanese children was significantly higher than white and black children after adjusting for age and sex. The ratio of HDL/TC in Japanese children was significantly higher than in U.S. whites, but not significantly different from the black children. The Japanese group had significantly lower mean diastolic blood pressure phase IV (DBP4) and phase V (DBP5) than the two U.S. groups. The Japanese group also showed significantly higher slopes in systolic blood pressure, DBP5 and DBP4 during the study period than both U.S. groups. The differences were independent from height and body mass index. ^ The study provided the first longitudinal comparison of blood cholesterol and blood pressure between the U.S. and Japanese children and adolescents. It revealed the dynamic process of these factors in the three ethnic groups. ^

Enhanced in vivo angiogenesis within a model tissue engineered construct using biodegradable microspheres containing encapsulated VEGF

Introduction. Tissue engineering techniques offer a potential means to develop a tissue engineered construct (TEC) for the treatment of tissue and organ deficiencies. However, a lack of adequate vascularization is a limiting factor in the development of most viable engineered tissues. Vascular endothelial growth factor (VEGF) could aid in the development of a viable vascular network within TECs. The long-term goals of this research are to develop clinically relevant, appropriately vascularized TECs for use in humans. This project tested the hypothesis that the delivery of VEGF via controlled release from biodegradable microspheres would increase the vascular density and rate of angiogenesis within a model TEC. ^ Materials and methods. Biodegradable VEGF-encapsulated microspheres were manufactured using a novel method entitled the Solid Encapsulation/Single Emulsion/Solvent Extraction technique. Using a PLGA/PEG polymer blend, microspheres were manufactured and characterized in vitro. A model TEC using fibrin was designed for in vivo tissue engineering experimentation. At the appropriate timepoint, the TECs were explanted, and stained and quantified for CD31 using a novel semi-automated thresholding technique. ^ Results. In vitro results show the microspheres could be manufactured, stored, degrade, and release biologically active VEGF. The in vivo investigations revealed that skeletal muscle was the optimal implantation site as compared to dermis. In addition, the TECs containing fibrin with VEGF demonstrated significantly more angiogenesis than the controls. The TECs containing VEGF microspheres displayed a significant increase in vascular density by day 10. Furthermore, TECs containing VEGF microspheres had a significantly increased relative rate of angiogenesis from implantation day 5 to day 10. ^ Conclusions. A novel technique for producing microspheres loaded with biologically active proteins was developed. A defined concentration of microspheres can deliver a quantifiable level of VEGF with known release kinetics. A novel model TEC for in vivo tissue engineering investigations was developed. VEGF and VEGF microspheres stimulate angiogenesis within the model TEC. This investigation determined that biodegradable rhVEGF 165-encapsulated microspheres increased the vascular density and relative rate of angiogenesis within a model TEC. Future applications could include the incorporation of microvascular fragments into the model TEC and the incorporation of specific tissues, such as fat or bone. ^

CATCH across Texas: Building a model for the diffusion of effective school-based health promotion programs

The impact of health promotion programs is related to both program effectiveness and the extent to which the program is implemented among the target population. The purpose of this dissertation was to describe the development and evaluation of a school-based program diffusion intervention designed to increase the rate of dissemination and adoption of the Child and Adolescent Trial for Cardiovascular Health, or CATCH program (recently renamed the Coordinated Approach to Child Health). ^ The first study described the process by which schools across the state of Texas spontaneously began to adopt the CATCH program after it was tested and proven effective in a multi-site randomized efficacy trial. A survey of teachers and administrator representatives of all schools on record that purchased the CATCH program, but were not involved in the efficacy trial, was used to find out who brought CATCH into the schools, how they garnered support for its adoption, why they decided to adopt the program, and what was involved in deciding to adopt. ^ The second study described how the Intervention Mapping framework guided the planning, development and implementation of a program for the diffusion of CATCH. An iterative process was used to integrate theory, literature, the experience of project staff and data from the target population into a meaningful set of program determinants and performance objectives. Proximal program objectives were specified and translated into both media and interpersonal communication strategies for program diffusion. ^ The third study assessed the effectiveness of the diffusion program in a case-comparison design. Three of the twenty Education Service Center regions in Texas were chosen, selected based on similar demographic criteria, and were followed for adoption of the CATCH curriculum. One of these regions received the full media and interpersonal channel intervention; a second received a reduced media-only intervention, and a third received no intervention. Results suggested the use of the interpersonal channels with media follow-up is an effective means to facilitate program dissemination and adoption. The media-alone condition was not effective in facilitating program adoption. ^

Comparison of a traditional and a multilevel Cox Proportional Hazards model

Hierarchically clustered populations are often encountered in public health research, but the traditional methods used in analyzing this type of data are not always adequate. In the case of survival time data, more appropriate methods have only begun to surface in the last couple of decades. Such methods include multilevel statistical techniques which, although more complicated to implement than traditional methods, are more appropriate. ^ One population that is known to exhibit a hierarchical structure is that of patients who utilize the health care system of the Department of Veterans Affairs where patients are grouped not only by hospital, but also by geographic network (VISN). This project analyzes survival time data sets housed at the Houston Veterans Affairs Medical Center Research Department using two different Cox Proportional Hazards regression models, a traditional model and a multilevel model. VISNs that exhibit significantly higher or lower survival rates than the rest are identified separately for each model. ^ In this particular case, although there are differences in the results of the two models, it is not enough to warrant using the more complex multilevel technique. This is shown by the small estimates of variance associated with levels two and three in the multilevel Cox analysis. Much of the differences that are exhibited in identification of VISNs with high or low survival rates is attributable to computer hardware difficulties rather than to any significant improvements in the model. ^

Tracking of plasma lipids and lipoproteins, within-person and year-to-year variability in plasma cholesterol levels among participants from age 8 to 18 in Project HeartBeat!

Coronary heart disease remains the leading cause of death in the United States and increased blood cholesterol level has been found to be a major risk factor with roots in childhood. Tracking of cholesterol, i.e., the tendency to maintain a particular cholesterol level relative to the rest of the population, and variability in blood lipid levels with increase in age have implications for cholesterol screening and assessment of lipid levels in children for possible prevention of further rise to prevent adulthood heart disease. In this study the pattern of change in plasma lipids, over time, and their tracking were investigated. Also, within-person variance and retest reliability defined as the square root of within-person variance for plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides and their relation to age, sex and body mass index among participants from age 8 to 18 years were investigated. ^ In Project HeartBeat!, 678 healthy children aged 8, 11 and 14 years at baseline were enrolled and examined at 4-monthly intervals for up to 4 years. We examined the relationship between repeated observations by Pearson's correlations. Age- and sex-specific quintiles were calculated and the probability of participants to remain in the uppermost quintile of their respective distribution was evaluated with life table methods. Plasma total cholesterol, HDL-C and LDL-C at baseline were strongly and significantly correlated with measurements at subsequent visits across the sex and age groups. Plasma triglyceride at baseline was also significantly correlated with subsequent measurements but less strongly than was the case for other plasma lipids. The probability to remain in the upper quintile was also high (60 to 70%) for plasma total cholesterol, HDL-C and LDL-C. ^ We used a mixed longitudinal, or synthetic cohort design with continuous observations from age 8 to 18 years to estimate within person variance of plasma total cholesterol, HDL-C, LDL-C and triglycerides. A total of 5809 measurements were available for both cholesterol and triglycerides. A multilevel linear model was used. Within-person variance among repeated measures over up to four years of follow-up was estimated for total cholesterol, HDL-C, LDL-C and triglycerides separately. The relationship of within-person and inter-individual variance with age, sex, and body mass index was evaluated. Likelihood ratio tests were conducted by calculating the deviation of −2log (likelihood) within the basic model and alternative models. The square root of within-person variance provided the retest reliability (within person standard deviation) for plasma total cholesterol, HDL-C, LDL-C and triglycerides. We found 13.6 percent retest reliability for plasma cholesterol, 6.1 percent for HDL-cholesterol, 11.9 percent for LDL-cholesterol and 32.4 percent for triglycerides. Retest reliability of plasma lipids was significantly related with age and body mass index. It increased with increase in body mass index and age. These findings have implications for screening guidelines, as participants in the uppermost quintile tended to maintain their status in each of the age groups during a four-year follow-up. The magnitude of within-person variability of plasma lipids influences the ability to classify children into risk categories recommended by the National Cholesterol Education Program. ^

Comparing the factorial structure, invariance, and predictive validity of transtheoretical model constructs for alcohol use across restricted and unrestricted settings

With substance abuse treatment expanding in prisons and jails, understanding how behavior change interacts with a restricted setting becomes more essential. The Transtheoretical Model (TTM) has been used to understand intentional behavior change in unrestricted settings, however, evidence indicates restrictive settings can affect the measurement and structure of the TTM constructs. The present study examined data from problem drinkers at baseline and end-of-treatment from three studies: (1) Project CARE (n = 187) recruited inmates from a large county jail; (2) Project Check-In (n = 116) recruited inmates from a state prison; (3) Project MATCH, a large multi-site alcohol study had two recruitment arms, aftercare (n = 724 pre-treatment and 650 post-treatment) and outpatient (n = 912 pre-treatment and 844 post-treatment). The analyses were conducted using cross-sectional data to test for non-invariance of measures of the TTM constructs: readiness, confidence, temptation, and processes of change (Structural Equation Modeling, SEM) across restricted and unrestricted settings. Two restricted (jail and aftercare) and one unrestricted group (outpatient) entering treatment and one restricted (prison) and two unrestricted groups (aftercare and outpatient) at end-of-treatment were contrasted. In addition TTM end-of-treatment profiles were tested as predictors of 12 month drinking outcomes (Profile Analysis). Although SEM did not indicate structural differences in the overall TTM construct model across setting types, there were factor structure differences on the confidence and temptation constructs at pre-treatment and in the factor structure of the behavioral processes at the end-of-treatment. For pre-treatment temptation and confidence, differences were found in the social situations factor loadings and in the variance for the confidence and temptation latent factors. For the end-of-treatment behavioral processes, differences across the restricted and unrestricted settings were identified in the counter-conditioning and stimulus control factor loadings. The TTM end-of-treatment profiles were not predictive of drinking outcomes in the prison sample. Both pre and post-treatment differences in structure across setting types involved constructs operationalized with behaviors that are limited for those in restricted settings. These studies suggest the TTM is a viable model for explicating addictive behavior change in restricted settings but calls for modification of subscale items that refer to specific behaviors and caution in interpreting the mean differences across setting types for problem drinkers. ^

A model for use by local public health departments to evaluate pandemic influenza plans

The events of the 1990's and early 2000's demonstrated the need for effective planning and response to natural and man-made disasters. One of those potential natural disasters is pandemic flu. Once defined, the CDC stated that program, or plan, effectiveness is improved through the process of program evaluation. (Centers for Disease Control and Prevention, 1999) Program evaluation should be accomplished not only periodically, but in the course of routine administration of the program. (Centers for Disease Control and Prevention, 1999) Accomplishing this task for a "rare, but significant event" is challenging. (Herbold, John R., PhD., 2008) To address this challenge, the RAND Corporation (under contract to the CDC) developed the "Facilitated Look-Backs" approach that was tested and validated at the state level. (Aledort et al., 2006).^ Nevertheless, no comprehensive and generally applicable pandemic influenza program evaluation tool or model is readily found for use at the local public health department level. This project developed such a model based on the "Facilitated Look-Backs" approach developed by RAND Corporation. (Aledort et al., 2006) Modifications to the RAND model included stakeholder additions, inclusion of all six CDC program evaluation steps, and suggestions for incorporating pandemic flu response plans in seasonal flu management implementation. Feedback on the model was then obtained from three LPHD's—one rural, one suburban, and one urban. These recommendations were incorporated into the final model. Feedback from the sites also supported the assumption that this model promotes the effective and efficient evaluation of both pandemic flu and seasonal flu response by reducing redundant evaluations of pandemic flu plans, seasonal flu plans, and funding requirement accountability. Site feedback also demonstrated that the model is comprehensive and flexible, so it can be adapted and applied to different LPHD needs and settings. It also stimulates evaluation of the major issues associated with pandemic flu planning. ^ The next phase in evaluating this model should be to apply it in a program evaluation of one or more LPHD's seasonal flu response that incorporates pandemic flu response plans.^

A project to improve the information seeking skills and increase the use of evidence-based research in public health practice

The ability of public health practitioners (PHPs) to work efficiently and effectively is negatively impacted by their lack of knowledge of the broad range of evidence-based practice information resources and tools that can be utilized to guide them in their development of health policies and programs. This project, a three-hour continuing education hands-on workshop with supporting resources, was designed to increase knowledge and skills of these resources. The workshop was presented as a pre-conference continuing education program for the Texas Public Health Association (TPHA) 2008 Annual Conference. Topics included: identification of evidence-based practice resources to aid in the development of policies and programs; identification of sources of publicly available data; utilization of data for community assessments; and accessing and searching the literature through a collection of databases available to all citizens of Texas. Supplemental resources included a blog that served as a gateway to the resources explored during the presentation, a community assessment workbook that incorporates both Healthy People 2010 objectives and links to reliable sources of data, and handouts providing additional instruction on the use of the resources covered during the workshop.^ Before- and after-workshop surveys based on Kirkpatrick's 4-level model of evaluation and the Theory of Planned Behavior were administered. Of the questions related to the trainer, the workshop, and the usefulness of the workshop, participants gave "Good" to "Excellent" responses to all one question. Confidence levels overall increased a statistically significant amount; measurements of attitude, social norms, and control showed no significant differences before and after the workshop. Lastly, participants indicated they were likely to use resources shown during the workshop within a one to three month time period on average. ^ The workshop and creation of supplemental resources served as a pilot for a funded project that will be continued with the development and delivery of four 4-week long webinar-based training sessions to be completed by December 2008. ^

Homeless access to dental health care: Creation of a dental service model

This project involved developing a model for planning a dental emergency treatment center that could function as an embedded component of a shelter for the homeless population. The dental services provided by such a clinic should include treatment for tooth pain, dental caries or cavities, chipped or broken teeth, broken partials, abscessed teeth, emergency cleanings, periodontal disease or gum disease and fillings. These are the dental services that are most often sought by homeless people in hospital emergency rooms.^ The underlying assumption for this project was that the oral health needs of the homeless community can most effectively be addressed by implementing small dental clinics in existing facilities that provide shelter and other services for this population. The model described in this project identifies oral health care services that would be provided by the clinic, facility (physical plant) requirements and associated infrastructure to operate an embedded dental clinic, methods for obtaining funding, strategies of recruiting dental professionals to staff the facility, and methods to assess the outcomes of the embedded clinic strategy. As an example, this project describes a strategy for developing such an embedded clinic at San Antonio Metropolitan Ministries SAMM shelter based on recommendations from community health care leaders, managers of homeless shelters, members of the homeless community and dental professionals^

Concomitant Mycobacterium tuberculosis infection and type 2 diabetes: A descriptive model with global health implications

The type 2 diabetes (diabetes) pandemic is recognized as a threat to tuberculosis (TB) control worldwide. This secondary data analysis project estimated the contribution of diabetes to TB in a binational community on the Texas-Mexico border where both diseases occur. Newly-diagnosed TB patients > 20 years of age were prospectively enrolled at Texas-Mexico border clinics between January 2006 and November 2008. Upon enrollment, information regarding social, demographic, and medical risks for TB was collected at interview, including self-reported diabetes. In addition, self-reported diabetes was supported by blood-confirmation according to guidelines published by the American Diabetes Association (ADA). For this project, data was compared to existing statistics for TB incidence and diabetes prevalence from the corresponding general populations of each study site to estimate the relative and attributable risks of diabetes to TB. In concordance with historical sociodemographic data provided for TB patients with self-reported diabetes, our TB patients with diabetes also lacked the risk factors traditionally associated with TB (alcohol abuse, drug abuse, history of incarceration, and HIV infection); instead, the majority of our TB patients with diabetes were characterized by overweight/obesity, chronic hyperglycemia, and older median age. In addition, diabetes prevalence among our TB patients was significantly higher than in the corresponding general populations. Findings of this study will help accurately characterize TB patients with diabetes, thus aiding in the timely recognition and diagnosis of TB in a population not traditionally viewed as at-risk. We provide epidemiological and biological evidence that diabetes continues to be an increasingly important risk factor for TB.^

COSTS AND EFFECTS OF ARKANSAS' LONG-TERM CARE DEMONSTRATION PROJECT (MEDICAID, CHANELLING, COMMUNITY ASSESSMENT)

The purpose of this study was to assess the impact of the Arkansas Long-Term Care Demonstration Project upon Arkansas' Medicaid expenditures and upon the clients it serves. A Retrospective Medicaid expenditure study component used analyses of variance techniques to test for the Project's effects upon aggregated expenditures for 28 demonstration and control counties representing 25 percent of the State's population over four years, 1979-1982.^ A second approach to the study question utilized a 1982 prospective sample of 458 demonstration and control clients from the same 28 counties. The disability level or need for care of each patient was established a priori. The extent to which an individual's variation in Medicaid utilization and costs was explained by patient need, presence or absence of the channeling project's placement decision or some other patient characteristic was examined by multiple regression analysis. Long-term and acute care Medicaid, Medicare, third party, self-pay and the grand total of all Medicaid claims were analyzed for project effects and explanatory relationships.^ The main project effect was to increase personal care costs without reducing nursing home or acute care costs (Prospective Study). Expansion of clients appeared to occur in personal care (Prospective Study) and minimum care nursing home (Retrospective Study) for the project areas. Cost-shifting between Medicaid and Medicare in the project areas and two different patterns of utilization in the North and South projects tended to offset each other such that no differences in total costs between the project areas and demonstration areas occurred. The project was significant ((beta) = .22, p < .001) only for personal care costs. The explanatory power of this personal care regression model (R('2) = .36) was comparable to other reported health services utilization models. Other variables (Medicare buy-in, level of disability, Social Security Supplemental Income (SSI), net monthly income, North/South areas and age) explained more variation in the other twelve cost regression models. ^