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1.  Physician Characteristics and the Reported Effect of Evidence-Based Practice Guidelines 
Health Services Research  2008;43(2):569-581.
To explore characteristics that may contribute to the effect practice guidelines have on the practice of medicine.
Data Sources
From the third round of the Community Tracking Study, Physician Survey, 2000–2001.
Study Design
An ordinal logistic regression model was estimated to capture the full range of responses.
Principal Findings
Recent medical school graduates, women, minorities, ob-gyn specialists, physicians who use computers for information in their practices, and physicians in nonsolo practice types were significantly more likely to state practice guidelines had an effect on their practice.
Many barriers have prevented wide acceptance of practice guidelines among the medical community. Our findings suggest there will be positive results on guideline effects as recent graduates, women, and minorities enter the physician workforce.
PMCID: PMC2442364  PMID: 18484106
Evidence-based practice guidelines; physician characteristics
2.  A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression 
Nanoparticle (NP)-enabled near infrared (NIR) photothermal therapy has realized limited success in in vivo studies as a potential localized cancer therapy. This is primarily due to a lack of successful methods that can prevent NP uptake by the reticuloendothelial system, especially the liver and kidney, and deliver sufficient quantities of intravenously injected NPs to the tumor site. Histological evaluation of photothermal therapy-induced tumor regression is also neglected in the current literature. This report demonstrates and histologically evaluates the in vivo potential of NIR photothermal therapy by circumventing the challenges of intravenous NP delivery and tumor targeting found in other photothermal therapy studies.
Subcutaneous Cal 27 squamous cell carcinoma xenografts received photothermal nanotherapy treatments, radial injections of polyethylene glycol (PEG)-ylated gold nanorods and one NIR 785 nm laser irradiation for 10 minutes at 9.5 W/cm2. Tumor response was measured for 10–15 days, gross changes in tumor size were evaluated, and the remaining tumors or scar tissues were excised and histologically analyzed.
The single treatment of intratumoral nanorod injections followed by a 10 minute NIR laser treatment also known as photothermal nanotherapy, resulted in ~100% tumor regression in ~90% of treated tumors, which was statistically significant in a comparison to the average of all three control groups over time (P<0.01).
Photothermal nanotherapy, or intratumoral nanorod injections followed by NIR laser irradiation of tumors and tumor margins, demonstrate the potential of NIR photothermal therapy as a viable localized treatment approach for primary and early stage tumors, and prevents NP uptake by the reticuloendothelial system.
PMCID: PMC4227627  PMID: 25395847
photothermal cancer therapy; malignancy; cancer treatment; intratumoral; gold nanorods; nanoparticles; PEGylation; laser therapy
3.  MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and neck squamous cell carcinoma 
Oncoscience  2014;1(11):725-737.
Little is known about the molecular pathways regulating poor differentiation and invasion of head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to determine the role of MDA-9/Syntenin, a metastasis associated molecule in HNSCC tumorigenesis. Elevated MDA-9/Syntenin expression was evident in 67% (54/81) primary HNSCC tumors (p=0.001-0.002) and 69% (9/13) pre-neoplastic tissues (p=0.02-0.03). MDA-9/Syntenin overexpression was associated with the stage (p=0.001), grade (p=0.001) and lymph node metastasis (p=0.0001). Silencing of MDA-9/Syntenin in 3 poorly differentiated HNSCC cell lines induced squamous epithelial cell differentiation, disrupted angiogenesis and reduced tumor growth in vitro and in vivo. We confirmed SPRR1B and VEGFR1 as the key molecular targets of MDA-9/Syntenin on influencing HNSCC differentiation and angiogenesis respectively. MDA-9/Syntenin disrupted SPRR1B expression interacting through its PDZ1 domain and altered VEGFR1 expression in vitro and in vivo. VEGFR1 co-localized with MDA-9/Syntenin in HNSCC cell lines and primary tumor. Downregulation of growth regulatory molecules CyclinD1, CDK4, STAT3, PI3K and CTNNB1 was also evident in the MDA-9/Syntenin depleted cells, which was reversed following over-expression of MDA-9/Syntenin in immortalized oral epithelial cells. Our results suggest that early induction of MDA-9/Syntenin expression influences HNSCC progression and should be further evaluated for potential biomarker development.
PMCID: PMC4278274  PMID: 25593999
Head and neck suqamous cell carcinoma; MDA-9/Syntenin; differentiation; SPRR1B; VEGFR1
4.  Disparities in Cervical Cancer Mortality Rates as Determined by the Longitudinal Hyperbolastic Mixed-Effects Type II Model 
PLoS ONE  2014;9(9):e107242.
The main purpose of this study was to model and analyze the dynamics of cervical cancer mortality rates for African American (Black) and White women residing in 13 states located in the eastern half of the United States of America from 1975 through 2010.
The cervical cancer mortality rates of the Surveillance, Epidemiology, and End Results (SEER) were used to model and analyze the dynamics of cervical cancer mortality. A longitudinal hyperbolastic mixed-effects type II model was used to model the cervical cancer mortality data and SAS PROC NLMIXED and Mathematica were utilized to perform the computations.
Despite decreasing trends in cervical cancer mortality rates for both races, racial disparities in mortality rates still exist. In all 13 states, Black women had higher mortality rates at all times. The degree of disparities and pace of decline in mortality rates over time differed among these states. Determining the paces of decline over 36 years showed that Tennessee had the most rapid decline in cervical cancer mortality for Black women, and Mississippi had the most rapid decline for White Women. In contrast, slow declines in cervical cancer mortality were noted for Black women in Florida and for White women in Maryland.
In all 13 states, cervical cancer mortality rates for both racial groups have fallen. Disparities in the pace of decline in mortality rates in these states may be due to differences in the rates of screening for cervical cancers. Of note, the gap in cervical cancer mortality rates between Black women and White women is narrowing.
PMCID: PMC4167327  PMID: 25226583
5.  GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft 
Cancer letters  2012;330(1):22-32.
Multiple lines of evidence suggest that the Sonic Hedgehog (Shh) signaling pathway is aberrantly reactivated in pancreatic cancer stem cells (CSCs). The objectives of this study were to examine the molecular mechanisms by which GANT-61 (Gli transcription factor inhibitor) regulates stem cell characteristics and tumor growth. Effects of GANT-61 on CSC’s viability, spheroid formation, apoptosis, DNA-binding and transcriptional activities, and epithelial-mesenchymal transition (EMT) were measured. Humanized NOD/SCID/IL2Rgammanull mice were used to examine the effects of GANT-61 on CSC’s tumor growth. GANT-61 inhibited cell viability, spheroid formation, and Gli-DNA binding and transcriptional activities, and induced apoptosis by activation of caspase-3 and cleavage of Poly-ADP ribose Polymerase (PARP). GANT-61 increased the expression of TRAIL-R1/DR4, TRAIL-R2/DR5 and Fas, and decreased expression of PDGFRα and Bcl-2. GANT-61 also suppressed EMT by up-regulating E-cadherin and inhibiting N-cadherin and transcription factors Snail, Slug and Zeb1. In addition, GANT-61 inhibited pluripotency maintaining factors Nanog, Oct4, Sox-2 and cMyc. Suppression of both Gli1 plus Gli2 by shRNA mimicked the changes in cell viability, spheroid formation, apoptosis and gene expression observed in GANT-61-treated pancreatic CSCs. Furthermore, GANT-61 inhibited CSC tumor growth which was associated with up-regulation of DR4 and DR5 expression, and suppression of Gli1, Gli2, Bcl-2, CCND2 and Zeb1 expression in tumor tissues derived from NOD/SCID IL2Rγ null mice. Our data highlight the importance of Shh pathway for self-renewal and metastasis of pancreatic CSCs, and also suggest Gli as a therapeutic target for pancreatic cancer in eliminating CSCs.
PMCID: PMC4153855  PMID: 23200667
Pancreatic cancer stem cells; GANT-61; Sonic hedgehog; Gli transcription factor
6.  A Phase I Clinical Trial of Ad5/3-Δ24, a Novel Serotype-Chimeric, Infectivity-Enhanced, Conditionally-Replicative Adenovirus (CRAd), in Patients with Recurrent Ovarian Cancer 
Gynecologic oncology  2013;130(3):518-524.
The conditionally replicative adenovirus Ad5/3-Δ24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Δ24 achieves significant oncolysis and antitumor activity in ovarian cancer models. The purpose of this study was to evaluate in a Phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Δ24 in recurrent ovarian cancer patients.
Eligible patients were treated with IP Ad5/3-Δ24 for 3 consecutive days in one of three dose cohorts ranging 1 × 1010–1 × 1012 vp. Toxicity was assessed utilizing CTC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response.
Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grade 1–2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased CA-125 from pretreatment levels one month after treatment. Ancillary biologic studies indicated Ad5/3-Δ24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody effect.
This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Δ24, as a potential therapeutic option for recurrent ovarian cancer patients.
PMCID: PMC3748258  PMID: 23756180
CRAd; gene therapy; infectivity-enhanced adenoviral vectors; ovarian cancer
7.  microRNA-29 negatively regulates EMT regulator N-myc interactor in breast cancer 
Molecular Cancer  2014;13(1):200.
N-Myc Interactor is an inducible protein whose expression is compromised in advanced stage breast cancer. Downregulation of NMI, a gatekeeper of epithelial phenotype, in breast tumors promotes mesenchymal, invasive and metastatic phenotype of the cancer cells. Thus the mechanisms that regulate expression of NMI are of potential interest for understanding the etiology of breast tumor progression and metastasis.
Web based prediction algorithms were used to identify miRNAs that potentially target the NMI transcript. Luciferase reporter assays and western blot analysis were used to confirm the ability of miR-29 to target NMI. Quantitive-RT-PCRs were used to examine levels of miR29 and NMI from cell line and patient specimen derived RNA. The functional impact of miR-29 on EMT phenotype was evaluated using transwell migration as well as monitoring 3D matrigel growth morphology. Anti-miRs were used to examine effects of reducing miR-29 levels from cells. Western blots were used to examine changes in GSK3β phosphorylation status. The impact on molecular attributes of EMT was evaluated using immunocytochemistry, qRT-PCRs as well as Western blot analyses.
Invasive, mesenchymal-like breast cancer cell lines showed increased levels of miR-29. Introduction of miR-29 into breast cancer cells (with robust level of NMI) resulted in decreased NMI expression and increased invasion, whereas treatment of cells with high miR-29 and low NMI levels with miR-29 antagonists increased NMI expression and decreased invasion. Assessment of 2D and 3D growth morphologies revealed an EMT promoting effect of miR-29. Analysis of mRNA of NMI and miR-29 from patient derived breast cancer tumors showed a strong, inverse relationship between the expression of NMI and the miR-29. Our studies also revealed that in the absence of NMI, miR-29 expression is upregulated due to unrestricted Wnt/β-catenin signaling resulting from inactivation of GSK3β.
Aberrant miR-29 expression may account for reduced NMI expression in breast tumors and mesenchymal phenotype of cancer cells that promotes invasive growth. Reduction in NMI levels has a feed-forward impact on miR-29 levels.
PMCID: PMC4169820  PMID: 25174825
N-Myc interactor; EMT; Breast cancer; miR-29
8.  Rural-Urban Disparities in Quality of Life Among Patients With COPD 
Limited evidence in the US suggests that among patients with chronic obstructive pulmonary disease (COPD), rural residence is associated with higher hospitalization rates and increased mortality. However, little is known about the reasons for these disparities. This study’s purpose was to describe the health status of rural vs urban residence among patients with COPD and to examine factors associated with differences between these 2 locations.
This was a cross-sectional study of baseline data from a representative sample of patients with COPD enrolled in a clinical trial. Rural-urban residence was determined from zip code. Health status was measured using the SF-12 and health care utilization. Independent sample t-tests, chi-square tests, and multiple linear and logistic regressions were performed to examine differences between rural and urban patients.
Rural residence was associated with poorer health status and higher health care utilization. Among rural patients unadjusted physical functioning scores were lower on the SF-12 (30.22 vs 33.49; P = .005) that persisted after adjustment for potential confounders (β = -2.35; P = .04). However, after further adjustment for social and psychological factors only the Body-Mass index, Airflow obstruction, Dyspnea, and Exercise (BODE) Index was significantly associated with health status.
In this representative sample of patients with COPD rural residence was associated with worse health status, primarily associated with greater impairment as measured by BODE index. While rural patients reported a higher dose of smoking, a number of other unmeasured factors associated with rural residence may contribute to these disparities.
PMCID: PMC3752695  PMID: 23944281
COPD; health disparities; health-related quality of life; rural; utilization of health services
9.  The Prognostic Value of microRNAs Varies with Patient Race/Ethnicity and Stage of Colorectal Cancer 
MicroRNAs (miRNAs) have potential prognostic value for colorectal cancers (CRCs); however, their value based on patient race/ethnicity and pathologic stage has not been determined. The goal was to ascertain the prognostic value of 5 miRNAs with increased expression in CRCs of African American (Black) and non-Hispanic Caucasian (White) patients.
Experimental Design
TaqMan® qRT-PCR was used to quantify expression of miR-20a, miR-21, miR-106a, miR-181b, and miR-203 in paired normal and tumor CRC archival tissues collected from 106 Black and 239 White patients. The results were correlated with overall survival based on patient race/ethnicity and pathologic stage. Since decisions regarding adjuvant therapy are important for Stage III CRCs, and since miR-181b appeared to have prognostic value only for Stage III Black patients, we assessed its prognostic value in a separate cohort of Stage III CRCs of Blacks.
All 5 miRNAs had higher expression in CRCs (>1.0-fold) than in corresponding normal tissues. High expression of miR-203 was associated with poor survival of Whites with Stage IV CRCs (HR=3.00, 95% CI=1.29–7.53), but in Blacks it was an indicator of poor survival of patients with Stage I and II CRCs (HR=5.63, 95% CI=1.03–30.64). Increased miR-21 expression correlated with poor prognosis for White Stage IV patients (HR=2.50, 95% CI=1.07–5.83). In both test and validation cohorts, high miR-181b expression correlated with poor survival of only Black patients with Stage III CRCs (HR=1.94, 95% CI=1.03–3.67).
These preliminary findings suggest that the prognostic value of miRNAs in CRCs varies with patient race/ethnicity and stage of disease.
PMCID: PMC3746330  PMID: 23719259
Race; miRNAs; prognosis; stage; colorectal cancer
10.  Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial (COPD-SMART): Design and Methods 
Contemporary clinical trials  2013;35(2):77-86.
Treatment of COPD requires multiple pharmacological and non-pharmacological intervention strategies. One target is physical inactivity because it leads to disability and contributes to poor physical and mental health. Unfortunately, less than one percent of eligible patients have access to gold-standard pulmonary rehabilitation.
A single-site parallel group randomized trial was designed to determine if a self-management lifestyle physical activity intervention would improve physical functioning and dyspnea. During the first six weeks after enrollment patients receive COPD self-management education delivered by a health coach using a workbook and weekly telephone calls. Patients are then randomized to usual care or the physical activity intervention. The 20 week physical activity intervention is delivered by the health coach using a workbook supported by alternating one-on-one telephone counseling and computer assisted telephone calls. Theoretical foundations include social cognitive theory and the transtheoretical model.
Primary outcomes include change in Chronic Respiratory Questionnaire (CRQ) dyspnea domain and 6-minute walk distance measured at 6-, 12-, and 18-months after randomization. Secondary outcomes include other CRQ domains (fatigue, emotion, and mastery), SF-12, and health care utilization. Other measures include process outcomes and clinical characteristics.
This theory driven self-management lifestyle physical activity intervention is designed to reach patients unable to complete center-based pulmonary rehabilitation. Results will advance knowledge and methods for dissemination of a potentially cost-effective program for patients with COPD.
PMCID: PMC3703772  PMID: 23680985
chronic obstructive pulmonary disease; self-management; physical activity; lifestyle; pulmonary rehabilitation; randomized trial
11.  Impact of a Community Based Implementation of REACH II Program for Caregivers of Alzheimer's Patients 
PLoS ONE  2014;9(2):e89290.
In 2009 an estimated 5.3 million people in the United States were afflicted with Alzheimer's disease, a degenerative form of dementia. The impact of this disease is not limited to the patient but also has significant impact on the lives and health of their family caregivers. The Resources for Enhancing Alzheimer's Caregiver Health (REACH II) program was developed and tested in clinical studies. The REACH II program is now being delivered by community agencies in several locations. This study examines the impact of the REACH II program on caregiver lives and health in a city in north Texas.
Study design
Family caregivers of Alzheimer's patients were assessed using an instrument covering the multi-item domains of Caregiver Burden, Depression, Self-Care, and Social Support upon enrollment in the program and at the completion of the 6 month intervention. The domain scores were analyzed using a multivariate paired t-test and Bonferroni confidence interval for the differences in pre- and post-service domain scores.
A total of 494 families were enrolled in the program during the period January 1, 2011 through June 30, 2012. Of these families 177 completed the 6 month program and have pre – and post service domain scores. The median age for the caregivers was 62 years. The domain scores for Depression and Caregiver Burden demonstrated statistically significant improvements upon program completion.
The REACH II intervention was successfully implemented by a community agency with comparable impacts to those of the clinical trial warranting wider scale implementation.
PMCID: PMC3937331  PMID: 24586664
12.  Health information technology capacity at federally qualified health centers: a mechanism for improving quality of care 
The adoption of health information technology has been recommended as a viable mechanism for improving quality of care and patient health outcomes. However, the capacity of health information technology (i.e., availability and use of multiple and advanced functionalities), particularly in federally qualified health centers (FQHCs) on improving quality of care is not well understood. We examined associations between health information technology (HIT) capacity at FQHCs and quality of care, measured by the receipt of discharge summary, frequency of patients receiving reminders/notifications for preventive care/follow-up care, and timely appointment for specialty care.
The analyses used 2009 data from the National Survey of Federally Qualified Health Centers. The study included 776 of the FQHCs that participated in the survey. We examined the extent of HIT use and tested the hypothesis that level of HIT capacity is associated with quality of care. Multivariable logistic regressions, reporting unadjusted and adjusted odds ratios, were used to examine whether ‘FQHCs’ HIT capacity’ is associated with the outcome measures.
The results showed a positive association between health information technology capacity and quality of care. FQHCs with higher HIT capacity were significantly more likely to have improved quality of care, measured by the receipt of discharge summaries (OR=1.43; CI=1.01, 2.40), the use of a patient notification system for preventive and follow-up care (OR=1.74; CI=1.23, 2.45), and timely appointment for specialty care (OR=1.77; CI=1.24, 2.53).
Our findings highlight the promise of HIT in improving quality of care, particularly for vulnerable populations who seek care at FQHCs. The results also show that FQHCs may not be maximizing the benefits of HIT. Efforts to implement HIT must include strategies that facilitate the implementation of comprehensive and advanced functionalities, as well as promote meaningful use of these systems. Further examination of the role of health information systems in clinical decision-making and improvements in patient outcomes are needed to better understand the benefits of HIT in improving overall quality of care.
PMCID: PMC3570359  PMID: 23363660
Health information technology; Federally qualified health centers; Electronic medical records; Quality of care; Patient reminder/notification; Adoption of technology; Meaningful use; Care coordination
13.  Clinical and multiple gene expression variables in survival analysis of breast cancer: Analysis with the hypertabastic survival model 
BMC Medical Genomics  2012;5:63.
We explore the benefits of applying a new proportional hazard model to analyze survival of breast cancer patients. As a parametric model, the hypertabastic survival model offers a closer fit to experimental data than Cox regression, and furthermore provides explicit survival and hazard functions which can be used as additional tools in the survival analysis. In addition, one of our main concerns is utilization of multiple gene expression variables. Our analysis treats the important issue of interaction of different gene signatures in the survival analysis.
The hypertabastic proportional hazards model was applied in survival analysis of breast cancer patients. This model was compared, using statistical measures of goodness of fit, with models based on the semi-parametric Cox proportional hazards model and the parametric log-logistic and Weibull models. The explicit functions for hazard and survival were then used to analyze the dynamic behavior of hazard and survival functions.
The hypertabastic model provided the best fit among all the models considered. Use of multiple gene expression variables also provided a considerable improvement in the goodness of fit of the model, as compared to use of only one. By utilizing the explicit survival and hazard functions provided by the model, we were able to determine the magnitude of the maximum rate of increase in hazard, and the maximum rate of decrease in survival, as well as the times when these occurred. We explore the influence of each gene expression variable on these extrema. Furthermore, in the cases of continuous gene expression variables, represented by a measure of correlation, we were able to investigate the dynamics with respect to changes in gene expression.
We observed that use of three different gene signatures in the model provided a greater combined effect and allowed us to assess the relative importance of each in determination of outcome in this data set. These results point to the potential to combine gene signatures to a greater effect in cases where each gene signature represents some distinct aspect of the cancer biology. Furthermore we conclude that the hypertabastic survival models can be an effective survival analysis tool for breast cancer patients.
PMCID: PMC3548720  PMID: 23241496
Hypertabastic survival models; Gene expression variables; Breast cancer biomarkers; Seventy gene signature; ErbB2 overexpression; Fibroblast core serum response
14.  Factors associated with attention deficit/hyperactivity disorder among US children: Results from a national survey 
BMC Pediatrics  2012;12:50.
The purpose of this study was to investigate the association between Attention Deficit/Hyperactivity Disorder (ADHD) and various factors using a representative sample of US children in a comprehensive manner. This includes variables that have not been previously studied such as watching TV/playing video games, computer usage, family member’s smoking, and participation in sports.
This was a cross-sectional study of 68,634 children, 5–17 years old, from the National Survey of Children’s Health (NSCH, 2007–2008). We performed bivariate and multivariate logistic regression analyses with ADHD classification as the response variable and the following explanatory variables: sex, race, depression, anxiety, body mass index, healthcare coverage, family structure, socio-economic status, family members’ smoking status, education, computer usage, watching television (TV)/playing video games, participation in sports, and participation in clubs/organizations.
Approximately 10% of the sample was classified as having ADHD. We found depression, anxiety, healthcare coverage, and male sex of child to have increased odds of being diagnosed with ADHD. One of the salient features of this study was observing a significant association between ADHD and variables such as TV usage, participation in sports, two-parent family structure, and family members’ smoking status. Obesity was not found to be significantly associated with ADHD, contrary to some previous studies.
The current study uncovered several factors associated with ADHD at the national level, including some that have not been studied earlier in such a setting. However, we caution that due to the cross-sectional and observational nature of the data, a cause and effect relationship between ADHD and the associated factors can not be deduced from this study. Future research on ADHD should take into consideration these factors, preferably through a longitudinal study design.
PMCID: PMC3502478  PMID: 22583686
National Survey of Children’s Health; Neurobehavioral disorder; Obesity; Depression; Medication; TV usage; Participation in sports; Smoking status
Respiratory medicine  2011;105(5):734-739.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality caused by cigarette smoking and other environmental exposures. While variation in exposures may affect COPD morbidity and mortality, little is known about geographic variation, a surrogate of exposures. The objective of this manuscript is to explore the geographic variation in COPD hospitalization rates among the Texas population in 2006.
The study population consisted of all Texas residents with COPD hospitalizations in the 2006 Texas Health Care Information Council (THCIC) data. County population estimates stratified by race, age, gender were linked to THCIC data to calculate county level COPD hospitalization rates per 100,000 admissions. The data were merged with Urban Influence Codes by county, and metropolitan status was determined by United States Department of Agriculture (USDA) criteria. Variation in COPD hospitalization rates were analyzed using Poisson Regression.
Overall, non-Hispanic (NH) Whites had the highest rate of hospitalization, followed by NH Blacks (rate ratio=0.42) and Hispanics (RR=0.17), the 65+ age category had the highest rates of hospitalization. In the metropolitan counties COPD hospitalization rates are lower than non metropolitan counties, however in metropolitan counties the rates of hospitalization are significantly higher (p<0.0001) in females compared to males. The rates were significantly higher in males in public health regions 10 and 11, which are predominantly non-metropolitan counties.
In Texas there is substantial geographic variation in hospitalization rates associated with gender and race/ethnicity. Other factors that may contribute to the variation and require further investigation include differences in smoking and exposure to other environmental risk factors, access to primary care, medical practice patterns, and coding practices.
PMCID: PMC3064740  PMID: 21255991
16.  Safety-net facilities and hospitalization rates of chronic obstructive pulmonary disease: a cross-sectional analysis of the 2007 Texas Health Care Information Council inpatient data 
Geographic disparities in hospitalization rates for chronic obstructive pulmonary disease (COPD) have been observed in Texas. However, little is known about the sources of these variations. The purpose of this manuscript is to further explore the geographic disparity of COPD hospitalization rates in Texas by examining county-level factors affecting access to care.
Patients and methods
The study is a cross-sectional analysis of the 2007 Texas Health Care Information Council, Texas, demographer population projections and the 2009 Area Resource File (ARF). The unit of analysis was county-specific hospitalization rate, calculated as the number of discharges of county residents divided by county-level population estimates. Indicators of access to care included: type of safety-net facility and number of pulmonary specialists in a county. Safety-net facilities of interest were federally qualified health centers (FQHCs) and rural health clinics (RHCs).
There was a significant difference (P < 0.05) in hospitalization rates according to health center presence. Counties with only FQHCs had the lowest COPD hospitalization rate (132 per 100,000 observations), and counties with only RHCs had the highest hospitalization rate (229 per 100,000 observations). The presence of a pulmonary specialist was associated with a significant decrease (25%) in hospitalization rates among counties with only FQHCs.
In Texas, counties with only FQHCs were associated with lower COPD hospitalization rates. The presence of a RHC alone may be insufficient to decrease hospitalizations from COPD. There are a number of factors that may contribute to these variations in hospitalization rates, such as racial/ethnic distribution, types and quality of services provided, and the level of rurality, which creates greater distances to care and lower concentration of hospitals and pulmonary specialists.
PMCID: PMC3224651  PMID: 22135489
health centers; COPD; health disparities
17.  Sociodemographic and geographic characteristics associated with patient visits to osteopathic physicians for primary care 
Health care reform promises to dramatically increase the number of Americans covered by health insurance. Osteopathic physicians (DOs) are recognized for primary care, including a "hands-on" style with an emphasis on patient-centered care. Thus, DOs may be well positioned to deliver primary care in this emerging health care environment.
We used data from the National Ambulatory Medical Care Survey (2002-2006) to study sociodemographic and geographic characteristics associated with patient visits to DOs for primary care. Descriptive analyses were initially performed to derive national population estimates (NPEs) for overall patient visits, primary care patient visits, and patient visits according to specialty status. Osteopathic and allopathic physician (MD) patient visits were compared using cross-tabulations and multiple logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for DO patient visits. The latter analyses were also conducted separately for each geographic characteristic to assess the potential for effect modification based on these factors.
Overall, 134,369 ambulatory medical care visits were surveyed, representing 4.6 billion (NPE) ± 220 million (SE) patient visits when patient visit weights were applied. Osteopathic physicians provided 336 million ± 30 million (7%) of these patient visits. Osteopathic physicians provided 217 million ± 21 million (10%) patient visits for primary care services; including 180 million ± 17 million (12%) primary care visits for adults (21 years of age or older) and 37 million ± 5 million (5%) primary care visits for minors. Osteopathic physicians were more likely than MDs to provide primary care visits in family and general medicine (OR, 6.03; 95% CI, 4.67-7.78), but were less likely to provide visits in internal medicine (OR, 0.37; 95% CI, 0.24-0.58) or pediatrics (OR, 0.21; 95% CI, 0.11-0.40). Overall, patients in the pediatric and geriatric ages, Blacks, Hispanics, and persons in the South and West were less likely to utilize DOs, although there was some evidence of effect modification according to United States Census region.
Health care reform provides unprecedented opportunities for DOs to reach historically underserved populations and to overcome the "pediatric primary-care paradox."
PMCID: PMC3238348  PMID: 22053988
18.  Random Regression Models Based On The Skew Elliptically Contoured Distribution Assumptions With Applications To Longitudinal Data * 
Bartolucci et al.(2003) extended the distribution assumption from the normal (Lyles et al., 2000) to the elliptical contoured distribution (ECD) for random regression models used in analysis of longitudinal data accounting for both undetectable values and informative drop-outs. In this paper, the random regression models are constructed on the multivariate skew ECD. A real data set is used to illustrate that the skew ECDs can fit some unimodal continuous data better than the Gaussian distributions or more general continuous symmetric distributions when the symmetric distribution assumption is violated. Also, a simulation study is done for illustrating the model fitness from a variety of skew ECDs. The software we used is SAS/STAT, V. 9.13.
PMCID: PMC3104683  PMID: 21637734
Multivariate analysis; skew elliptically contoured distributions; skew power exponential distributions; gamma distributions; maximum likelihood functions; censoring; informative drop-outs; undetectable
19.  Resveratrol Enhances Antitumor Activity of TRAIL in Prostate Cancer Xenografts through Activation of FOXO Transcription Factor 
PLoS ONE  2010;5(12):e15627.
Resveratrol (3, 4′, 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer.
Methodology/Principal Findings
Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27/K IP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity.
These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.
PMCID: PMC3011015  PMID: 21209944
20.  Resveratrol Induces Growth Arrest and Apoptosis through Activation of FOXO Transcription Factors in Prostate Cancer Cells 
PLoS ONE  2010;5(12):e15288.
Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Although resveratrol possesses chemopreventive properties against several cancers, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. The present study was carried out to examine whether PI3K/AKT/FOXO pathway mediates the biological effects of resveratrol.
Methodology/Principal Findings
Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors (LY294002 and Wortmannin) and AKT inhibitor alone slightly induced apoptosis in LNCaP cells. These inhibitors further enhanced the apoptosis-inducing potential of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis. Wild type PTEN and PTEN-G129E enhanced resveratrol-induced apoptosis, whereas PTEN-G129R had no effect on proapoptotic effects of resveratrol. Furthermore, apoptosis-inducing potential of resveratrol was enhanced by dominant negative AKT, and inhibited by wild-type AKT and constitutively active AKT. Resveratrol has no effect on the expression of FKHR, FKHRL1 and AFX genes. The inhibition of FOXO phosphorylation by resveratrol resulted in its nuclear translocation, DNA binding and transcriptional activity. The inhibition of PI3K/AKT pathway induced FOXO transcriptional activity resulting in induction of Bim, TRAIL, p27/KIP1, DR4 and DR5, and inhibition of cyclin D1. Similarly, resveratrol-induced FOXO transcriptional activity was further enhanced when activation of PI3K/AKT pathway was blocked. Over-expression of phosphorylation deficient mutants of FOXO proteins (FOXO1-TM, FOXO3A-TM and FOXO4-TM) induced FOXO transcriptional activity, which was further enhanced by resveratrol. Inhibition of FOXO transcription factors by shRNA blocked resveratrol-induced upregulation of Bim, TRAIL, DR4, DR5, p27/KIP1 and apoptosis, and inhibition of cyclin D1 by resveratrol.
These data suggest that FOXO transcription factors mediate anti-proliferative and pro-apoptotic effects of resveratrol, in part due to activation of extrinsic apoptosis pathway.
PMCID: PMC3001855  PMID: 21179458
21.  Text and Structural Data Mining of Influenza Mentions in Web and Social Media 
Text and structural data mining of web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5 October 2008 to 21 March 2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.
PMCID: PMC2872292  PMID: 20616993
disease surveillance; public health epidemiology; health informatics; graph-based data mining; web and social media; social network analysis
22.  Differences in risk factors for children with special health care needs (CSHCN) receiving needed specialty care by socioeconomic status 
BMC Pediatrics  2009;9:48.
The purpose of this study is to identify factors affecting CSHCN's receiving needed specialty care among different socioeconomic levels. Previous literature has shown that Socioeconomic Status (SES) is a significant factor in CHSHCN receiving access to healthcare. Other literature has shown that factors of insurance, family size, race/ethnicity and sex also have effects on these children's receipt of care. However, this literature does not address whether other factors such as maternal education, geographic location, age, insurance type, severity of condition, or race/ethnicity have different effects on receiving needed specialty care for children in each SES level.
Data were obtained from the National Survey of Children with Special Health Care Needs, 2000–2002. The study analyzed the survey which studies whether CHSCN who needed specialty care received it. The analysis included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for SES levels defined by federal poverty level: < 199%; 200–299%; ≥ 300%.
For the poorest children (,199% FPL) being uninsured had a strong negative effect on receiving all needed specialty care. Being Hispanic was a protective factor. Having more than one adult in the household had a positive impact on receipt of needed specialty care but a larger number of children in the family had a negative impact. For the middle income group of children (200–299% of FPL severity of condition had a strong negative association with receipt of needed specialty care.
Children in highest income group (> 300% FPL) were positively impacted by living in the Midwest and were negatively impacted by the mother having only some college compared to a four-year degree.
Factors affecting CSHCN receiving all needed specialty care differed among socioeconomic groups. These differences should be addressed in policy and practice. Future research should explore the CSHCN population by income groups to better serve this population
PMCID: PMC2729735  PMID: 19646227
23.  Hypertabastic survival model 
A new two-parameter probability distribution called hypertabastic is introduced to model the survival or time-to-event data. A simulation study was carried out to evaluate the performance of the hypertabastic distribution in comparison with popular distributions. We then demonstrate the application of the hypertabastic survival model by applying it to data from two motivating studies. The first one demonstrates the proportional hazards version of the model by applying it to a data set from multiple myeloma study. The second one demonstrates an accelerated failure time version of the model by applying it to data from a randomized study of glioma patients who underwent radiotherapy treatment with and without radiosensitizer misonidazole. Based on the results from the simulation study and two applications, the proposed model shows to be a flexible and promising alternative to practitioners in this field.
PMCID: PMC2169222  PMID: 17963492
24.  High blood pressure in school children: prevalence and risk factors 
BMC Pediatrics  2006;6:32.
The purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age.
Elementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95th percentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association.
Females, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85th percentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors.
Twenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children.
PMCID: PMC1657006  PMID: 17109750
25.  Using GIS technology to identify areas of tuberculosis transmission and incidence 
Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where on-going tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance.
This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering.
Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of on-going transmission. Based on this evidence we plan to perform geographically based screening and treatment programs.
Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction.
PMCID: PMC529461  PMID: 15479478

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