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By Researcher's Name

Dong Sung An
Barbara Bates-Jensen
Mary-Lynn Brecht
Lynn Doering
Jo-Ann Eastwood
Karen Gylys
Nalo Hamilton
Felicia Hodge
Angela Hudson
Boyoung Hwang
Eufemia Jacob
Deborah Koniak-Griffin
Eunice Lee
Paul Macey
Sally Maliski
Adeline Nyamathi
Carol Pavlish
Linda Phillips
Wendie Robbins
Christian Roberts
Linda Sarna
Sophie Sokolow
Dorothy Wiley
Ann Williams
Marlyn Woo
Mary Woo

 

 

 

Dr. Dong Sung An

Title: GENETIC PROTECTION OF HEMATOPOIETIC STEM CELLS FOR STABLE HIV CONTROL
Agency: NIH National Institute of Allergy and Infectious Diseases, Project Number                                                                                                1R01AI100652-01A1 
          DESCRIPTION (provided by applicant): Hematopoietic stem/progenitor cell (HSPC) based gene therapy holds great promise to provide long-term control of HIV with a single treatment. Like HAART, it is essential to combine multiple drugs to effectively suppress HIV and prevent drug resistant HIV escape mutants. The overall hypothesis of this proposal is that stable introduction of highly potent combinations of anti-HIV genes capable of inhibiting multiple early and late steps of HIV viral lifecycle into HSPC will provide lifelong protection from HIV infection The safety and efficacy of anti-HIV HSPC gene therapy strategies, including inhibition of HIV, lowering of viral load and selective growth advantage of protected cells and prevention of resistance will be evaluated in the recently developed human bone marrow, liver and thymus (BLT) transplanted mouse model. Specific aims are 1) To develop novel multi-pronged anti-HIV gene therapeutic lentiviral vectors and characterize therapeutic reagents to inhibit HIV infection in HSPC and their progeny in vitro 2) To determine the long-term anti-gene expression and stable control of HIV through genetically engineered human HSPC transplant in the BLT mouse model. The approach is innovative because it focuses on novel HIV-1 target HSPC protection and the development of novel potent, broad-range early stage and late stage anti-HIV combinations, maximizing the potential to HIV replication not only in HSPC but also all potential target cells. The proposed research is significant because the results may ultimately lead to an innovative, more effective, more convenient, less toxic, safe and more cost effective way of controlling HIV infection than is currently available. The long-term goal is to advance HSPC based gene therapy research and make rapid progress towards providing a new therapy that leads to stable control of HIV by a single treatment. PUBLIC HEALTH RELEVANCE: Our proposed research will positively impact public health with the development of an anti-HIV gene therapy by blocking the multiple early and late stages of the HIV infection. Ultimately, HIV infection will be controlled with a single treatment by protecting the hematopoietic stem cells and their progeny. This research will provide significant knowledge towards the long-term goal of the NIH "HIV cure."

Title:  INVESTIGATE STABILITY OF RNA INTERFERENCE IN HUMAN LYMPHOCYTES
Agency: NIH National Heart, Lung, and Blood Institute, Project Number 3R01HL086409-03S1
          DESCRIPTION (provided by applicant): Our overall hypothesis is that RNA interference (RNAi) can be developed to reduce specific gene expression over long-term without toxic effects in human lymphocytes. RNAi using siRNA to inhibit specific gene expression is a powerful and promising technology for both basic research and therapeutic intervention. However, our results and several recent studies have shown unintended nonspecific cytotoxic effects associated with this technology in mammalian cells raising a concern for the long term use of the RNAi in therapeutic applications in humans. The cytotoxic effects were attributed at least in part to apoptosis, although other mechanisms are also possible. The cytotoxicity was associated with higher levels of shRNA expression. Based upon these results, we hypothesized that that the levels of shRNA are important for determining whether a given shRNA will be cytotoxic or not and that optimization of those levels can yield shRNAs that are both effective and not or minimally cytotoxic. We will also address whether the cell localization of the shRNA and/or its pathway for processing can affect the extent of cytotoxicity within cells. Through our proposed studies we will understand the effects of shRNA expression in mature lymphoid cells in vitro as well as the effects on the differentiation of the lymphocyte populations in an in vivo setting. We will minimize the cytotoxic effect and maximize stable and effective function of RNAi in primary T-lymphocytes. The relevance of this research to public health. RNA interference is a powerful and promising technology to inhibit specific gene expression for both basic research and therapeutic intervention. The inhibition of specific gene expression needs to be effective without unintended side effects. This proposal proposes to study the effects of RNAi in human T lymphocytes to maximize the RNAi effect and minimize side effects.

Title:  GENE AND CELL THERAPY CORE
Agency: NIH National Institute of Allergy and Infectious Diseases, Project Number 5P30AI028697-23
          DESCRIPTION (provided by applicant): The advent of highly active antiretroviral therapy has resulted in a decline in the incidence of opportunistic infections and prolonged survival in HIV-1 infected individuals. Obstacles towards virus erradication include the continued presence of an infected quiescent pool, drug resistance, toxicities, and lack of treatment adherence. The goal of genetic therapies is the replacement of the HIV-1-infected cell reservoir with cells that have been genetically engineered to resist HIV-1 replication. Unlike conventional drugs, it is possible to create a "single administration" reagent. However, successful gene therapy strategies require efficient gene delivery into hematopoietic stem cells and the presence and expression of the anti HIV genes in differentiated progenies that persist for years if not for the life of the individual. Thus, these current limitations must be investigated. A better understanding of the limitations of gene therapy techniques can lead to strategies to overcome such limitations as well as design potential clinical scenarios in which to test them. As possible alternatives or complements to antiretroviral therapy, stem cell gene therapy strategies are of interest to the scientific community, to the health policy community in particular and to the public at large. The overall goal of the Gene and Cellular Therapy Core (Core G) is to provide scientific and technical support for basic laboratory and clinical trial projects that require the use of purified CD34+ hematopoietic stem cells for HIV/AIDS gene therapy, hematopoiesis and pathogenesis of HIV.

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Dr. Barbara Bates-Jensen

Title: BIOPHYSICAL MEASURE TO PREDICT PRESSURE ULCERS IN NURSING HOME RESIDENTS
Agency: NIH National Institute of Nursing Research, Project Number 5R01NR010736-03
          DESCRIPTION (provided by applicant): This study will test the validity of a non-visual assessment strategy for stage I pressure ulcers (PUs) among nursing home (NH) residents with light or dark skin tones using a multi-site, longitudinal cohort design. PUs are common, often preventable, and costly; detection of early-stage PUs is important because intervention may prevent decline to more severe PUs. The standard method of detection, visual skin assessment for non- blanchable erythema, is somewhat reliable for individuals with light skin tones but detects changes after skin damage has already occurred. In addition, visual skin assessment fails to detect skin color changes in persons with darkly pigmented skin. Documented health disparities between African Americans and Caucasians for incidence of stage I PUs and prevention intervention may be related to deficiencies in detection. In our prior studies, we showed that a hand-held device that assesses sub-epidermal moisture (SEM), a measure of edema from inflammatory changes in the tissues, identified stage I PUs. Further, SEM was higher (e.g., increased edema and inflammation) when there was no visible skin damage at the time but a stage I PU was visible on the skin one week later; SEM values predicted 26 percent of the subsequent stage I PUs. Findings were similar in a small sub-sample of NH residents with dark skin tones. We propose to test the validity of this innovative approach to detecting PUs, particularly focusing on residents with dark skin tones; to test threshold SEM values for detecting stage I PUs and detecting progression of stage I PUs to stage II+ PUs. We will recruit 389 NH residents, 62 of whom will have dark skin tones, who are at risk for PU based on the Minimum Data Set Assessment from 24 NHs. Visual skin assessments and blinded SEM measures will be completed by research staff at least weekly for consented residents for 4 months. Skin tone of NH residents will be assessed using color tiles rather than by proxy measures of ethnicity as in previous research. In addition, participant demographics, MDS assessment data on functional level, and comorbid medical conditions will be obtained from medical record review. Risk assessments using the Braden Scale for Predicting Pressure Sores will be collected at baseline. Generalized ordered logistic modeling, appropriately modeling the repeated observations and time-dependent measures, will be used to evaluate the effectiveness of SEM measures to identify future skin damage. Measurement of SEM represents a potentially important tool for decreasing the disparity of prevention interventions between persons with different skin tones. PUBLIC HEALTH RELEVANCE: Statement to Public Health This project is the next step in the evaluation of a new assessment technique for bedsores, a common problem for nursing home residents. If this measurement can identify skin damage at an earlier stage to allow prompt intervention, evidence will be powerful for evaluating its use through a clinical trial. In addition, replacing methods of assessing skin damage that rely on skin color changes has the potential of reducing the severity of skin damage in persons with darkly pigmented skin, leading to reduction in observed health disparities and equalizing the chance of detecting damage at a point when prevention practices can be most effective.

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Dr. Lynn Brecht

Title: METHAMPHETAMINE ABUSE: LONG-TERM TRAJECTORIES, CORRELATES, TREATMENT EFFECTS
Agency: NIH National Institute on Drug Abuse, Project Number 5R01DA025113-03
          DESCRIPTION (provided by applicant): A decade and a half of rapidly increasing use of and geographic penetration of methamphetamine (MA) across the U.S. and the consequences of its use have generated concern and increasing efforts to improve interdiction, prevention, and treatment strategies, with a priority on research to inform these strategies. Limited information is available regarding the life course of MA abuse, particularly as MA users age. Further research is needed to provide empirical support for developing strategies to address issues specific to older users. The proposed project is a follow-up of 596 previously studied MA users, half recruited from drug treatment participation, half from the same communities but with no prior treatment for MA use at recruitment. The project will collect data using the Natural History Interview to add an average of 8 years of detailed histories on substance use, treatment, and criminal careers of these MA users; these new data combined with previously collected data will produce life course trajectories averaging at least 28 years in duration, covering teen and adult periods. Additional data will come from administrative records from several state agencies. The sample is 35% female/65% male, 33% Hispanic/38% non-Hispanic White/17% African- American/12% other ethnicity. Subjects will range in age from about 28 to 74 (average 42) at beginning of the follow-up study. Analyses will describe the current status and extended MA use histories, examining patterns of MA and other drug use, including escalation, deceleration, and possible cessation and recovery; examine drug treatment utilization patterns and relationship to MA use patterns; and determine health morbidity and mortality and assess differences between surviving and deceased users. The study will also assess the long-term outcomes (14 or more years) of a previously identified drug treatment episode (for the subsample recruited from treatment). In addition, the study will estimate cumulative social costs of MA abuse for the sample in terms of criminal activity, incarceration, drug treatment services, health and mental health services, and welfare system participation; and it will examine differences in costs related to distinctive patterns of MA use and user characteristics. Analysis methods will include growth models and growth mixture models to assess MA use trajectories and their relationships to services utilization, other events, and selected user characteristics. PUBLIC HEALTH RELEVANCE: Findings from this follow-up study will provide additional detail on the life course of methamphetamine (MA) use and an empirical basis for improving strategies for treatment outreach, engagement, service delivery, and continuing care. The accumulated knowledge will have implications for policy regarding the shift in clinical thinking to the long-term management of MA dependence as a chronic disease, the social and health burden of dependence, and importantly, the potential benefits of successful cessation of MA use.

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Dr. Lynn Doering

Title: HOME ECG MONITORING TO DETECT ALLOGRAFT REJECTION FOLLOWING HEART TRANSPLANTATION 
Agency: NIH National Institute of Nursing Research, Project Number 1R01NR012003-01A1 
          DESCRIPTION (provided by applicant): The long-term goal of this research is to apply novel technology for detection of donor organ (allograft) 3 rejection to improve patient outcomes following heart transplantation. The specific goal of this study is to 4 determine whether daily monitoring of the transplant recipient's electrocardiogram (ECG) using a simple home 5 device with transmission to an ECG Core Laboratory would provide an early biomarker for acute rejection. 6 Despite routine immunosuppressant drug therapy, acute rejection is common, especially within the first 6 7 months following transplant surgery. To detect rejection, frequent endomyocardial biopsies of heart tissue are 8 performed. An endomyocardial biopsy is a costly and invasive procedure performed in a hospital cardiac 9 catheterization laboratory that has associated risks. Recent evidence suggests that acute allograft rejection 10 causes delays in ventricular repolarization resulting in a longer QT interval on the ECG. The specific aims of 11 the study are to: 1) determine whether an increase in the QT interval during the first 6 months following heart 12 transplant is a sensitive and specific biomarker for acute rejection; and 2) determine the timing of QT interval 13 increases relative to biopsy-diagnosed stages of mild/moderate/severe rejection. Secondary aims are to: 3) 14 determine whether an increase in the QT interval predicts 1-year mortality; and 4) explore additional ECG 15 measurements that might predict rejection or death. 16 A prospective, double-blind, descriptive and correlational research design is planned. Investigators who 17 analyze ECG data will be blinded from biopsy results; healthcare providers will be blinded from QT 18 measurements. A sample of 325 adult heart transplant recipients will be recruited from 3 transplant centers: 19 Columbia University-New York Presbyterian Medical Center; University of California, Los Angeles and Cedars- 20 Sinai Medical Center, Los Angeles. Each subject will record a 30-second ECG daily using the HeartOneTM 21 device; the device will automatically transmit the ECG to an ECG Core Laboratory at the University of 22 California, San Francisco. For Primary Aim #1, a log regression analysis will be performed with the 23 independent variable being presence /absence of the ECG criteria ( QTC e25 milliseconds X 3 days) and the 24 dependent variable being presence /absence of acute allograft rejection. Odds ratios and confidence intervals 25 will be reported, as well as established evaluative criteria for new diagnostic instruments (sensitivity, specificity, 26 positive /negative predictive value, predictive accuracy). For Primary Aim #2, descriptive statistics will be used 27 to report the average time period between the development of the ECG criterion and biopsy evidence of 28 rejection. The potential benefit of finding a simple ECG biomarker of allograph rejection that could be 29 measured at home is that it might yield earlier detection of rejection, allow more timely therapy and reduce 30 mortality from acute allograft rejection. PUBLIC HEALTH RELEVANCE: The goal of this research is to identify changes in a heart transplant patient's electrocardiogram (ECG) that indicate donor organ rejection, a major cause of death in the first year. Patients will record their ECG daily using a simple home device combined with novel mobile phone technology that will automatically send their ECG to the researchers. The public health benefit of detecting a simple ECG marker of heart transplant rejection is that it might yield earlier detection, allow more timely initiation of medical therapy and reduce mortality from acute rejection.

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Dr. Jo-Ann Eastwood

Title: CARDIAC RISK REDUCTION INTERVENTION FOR AT RISK YOUNG BLACK WOMEN 
Agency: American Heart Association, Clinical Research Grant  
          DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the number one killer of women in the U.S. Morbidity and mortality rates are increasing in young women aged 25-45 years and are significantly higher in black women than white women. The higher prevalence of risk factors among young black women (YBW) may put them at a substantially higher risk for an earlier onset of CVD, or premature death due to heart disease or stroke. Thus, it is imperative that effective interventions be developed to reduce CVD risk factors in YBW. Interventions based on gender are limited and have been based commonly on studies where YBW were underrepresented or nonexistent. There is little evidence regarding targeted behavior change interventions and thus it is essential that we determine the best approach to CVD risk reduction specifically for this group. In this randomized control trial we propose to compare the effectiveness of a self-management risk reduction program combined with wireless coaching (SMP & WC) to usual care (UC) in order to determine effect sizes for the intervention. A survey will be administered to determine participants' views about the intervention and feedback about problematic areas and recommendations for change. Primary Specific Aim: To examine the short term effectiveness and describe effect sizes of the SMP+WC compared to UC on CVD risk behaviors (physical activity levels, and eating patterns) and biological outcomes (blood pressure, lipid profile, hsCRP, body mass index, waist circumference) in YBW living in Los Angeles County. Secondary Aim: To test the acceptability and feasibility (i.e. adherence to the intervention protocol; completion of the study by intervention and control patients) of the protocol. Impact: This study is important because it targets YBW, an extremely high risk group for whom CVD risk reduction interventions have not been developed. We will pilot test a highly effective program for self-management of CVD risk reduction from a white sample of predominately women, in a sample of urban, black women. Its novelty is twofold: 1) it will apply wireless technology to transfer patient data from the community to a nurse who will provide immediate assessment and feedback; and 2) it applies a delivery system (wireless technology) that is attractive, familiar and salient to its target population. The study findings will yield critical information regarding behavior change for YBW at risk for CVD and will provide extensive data for a large implementation study.

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Dr. Karen Gylys

Title: APOE AND CHOLESTEROL EFFECTS ON AMYLOID-BETA IN SYNAPTIC TERMINALS IN AD
Agency: NIH National Institute on Aging, Project Number 5R01AG027465-04
          DESCRIPTION (provided by applicant): A lack of disease-modifying treatment strategies for Alzheimer's disease (AD) results in part from an incomplete understanding of the earliest molecular changes, when there is opportunity for reversal. A body of evidence shows that synaptic dysfunction precedes amyloid-beta (AB) deposition, suggesting that the synaptic compartment is a key site of early pathology. Accurate localization of events to terminals is difficult; therefore, our laboratory has developed methods for flow cytometry analysis of synaptosomes prepared from cryopreserved human and rodent tissue. This technique allows 1) study of populations of individual terminals (5-10,000 particles/sample) and 2) absolute quantification of synaptic AB, phosphorylated tau (p-tau), and lipid and synaptic markers in postmortem human cases and in transgenic disease models. Flow cytometry results will be verified by biochemical assays and confocal and electron microscopy. Our first studies of postmortem AD synaptic terminals showed that ~50% of terminals in AD association cortex are strongly AB-positive. Subsequent experiments have shown that similar AB accumulations occur in the Tg2576 mouse model of AD, and that the AB buildup is accompanied by a significant increase in free cholesterol and GM1 ganglioside. Our general working hypothesis is that synaptic terminal AB accumulation is a key intermediate in synaptic dysfunction prior to loss, and a potential sources or seed for AB deposition in plaques. The specific hypothesis for this project is that cholesterol in lipid raft domains enhances processing of APP to AB; therefore manipulation of terminal cholesterol via ApoE genotype and drug treatment will alter the accumulation of AB and related lipids and peptides, and will affect synaptic function. In the first Specific Aim, our goal is to determine the relationship of synaptic terminal AB to regional AD pathology, disease stage, and apoE isotype in human samples and transgenic mouse models. In the second Specific Aim, we will use dual transgenic mice to determine the effect of apoE isotype on terminals levels of AB, cholesterol and related lipids, and on synaptic function. In addition, we will study the effect of hydrophobic vs. hydrophilic statins on terminal AB accumulation. The third Specific Aim has the goal of identifying the AB peptide species in terminals along with associated changes in signaling pathways, particularly integrin focal adhesion complexes and downstream deregulation of kinase/phosphatase activity. Development of therapeutic strategies for Alzheimer's disease requires a complete understanding of the earliest pathological changes when there is still opportunity for reversal. The present project has the long term goal of identifying potential drug targets and examines pathologic changes in synaptic terminals from Alzheimer's cases and mouse models that are treated with cholesterol lowering drugs. These experiments will help us to understand how cholesterol may contribute to Alzheimer's pathology.

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Dr. Nalo Hamilton

Title: Evaluating biological differences between breast cancer in African-American and Caucasian women to improve outcomes
Agency: Robert Wood Johnson Foundation
          DESCRIPTION (provided by applicant): The Robert Wood Johnson Foundation Nurse Faculty Scholars program was designed to increase the stature and academic standing of nursing faculty and draw more nurses to teaching careers by creating a cadre of national leaders in academic nursing through career development awards to outstanding junior nursing faculty. The purpose of this project is to assess the role of insulin-like growth factor-II (IGF-2) in the development of estrogen-independent breast cancer in African American (AA) and Caucasian (CA) women. This descriptive comparative study will evaluate the correlation between IGF-2 expression and ER localization in normal and malignant tissue of AA and CA breast cancer patients. These results will be compared with data obtained from in vitro studies using ethnic cell lines. The project will test the clinical utility of IGF-2 as a biomarker in predicting clinical outcome between AA and CA women with breast cancer.

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Dr. Felicia Hodge

Title: REDUCING SYMPTOM BARRIERS AMONG AMERICAN INDIANS
Agency: NIH National Cancer Institute, Project Number 5R01CA115358-06
          DESCRIPTION (provided by applicant): The long-range goal of this project is to reduce or overcome barriers to cancer-related symptom management among American Indians (AIs). Little is known about the phenomena of cancer-related symptoms, their management, and barriers to care, or about the barriers faced by AI patients needing and/or seeking symptom management. Such cancer-related symptoms as fatigue, depression, and pain experienced by this population require clearer understandings-in terms of definitions, cultural constructs of symptoms, decision-making strategies, barriers to care, provider referrals, and treatment for symptom management care. This is an innovative, interdisciplinary study to (a) clarify/define the cultural constructs of cancer-related symptoms, and (b) to develop and test a reproducible clinic-based, innovative, and culturally appropriate program to overcome barriers to care for AI symptom management. 1. To ascertain, through qualitative means, barriers to treatment and management that derive from AI cultural perspective. More specifically, this aims seeks: To gain an understanding of culturally-embedded meaning of cancer-related symptoms (pain, fatigue, depression), their conceptualization, cultural construct(s), patterns and strategies of their disclosure by AIs. To identify the pathways and mechanisms of communication and treatment-seeking that AIs use for management of cancer-related pain and symptoms. To identify symptom management decision-making strategies/barriers among AI cancer patients/providers. 2. To design culturally sensitive materials to be used in the intervention phase of the study. These tools will include educational and resource materials and culturally appropriate instruments for measuring symptoms intended to improve AI knowledge of and access to cancer symptom management services. 3. To develop and test a reproducible, clinicbased, culturally appropriate intervention designed to overcome barriers to the delivery of symptom management for AIs. This intervention will be cast in a Talking Circles format, a culturally meaningful vehicle that has proven effective in past studies.

Title: VULNERABLE POPULATIONS/HEALTH DISPARITIES RESEARCH
Agency: NIH National Institute of Nursing Research, Project Number 2T32NR007077-16
          DESCRIPTION (provided by applicant): This application is designed to continue our long trajectory of recruiting and training nurse scholars in pre- doctoral and postdoctoral education emphasizing methods and measures for ameliorating health disparities experienced by vulnerable populations (VPs). This training program began at the UCLA School of Nursing (SoN) in1994. Since then 23 pre-doctoral and 11 postdoctoral students were trained and supported in their VP- related research. Our program, VP/HD, is supported by the SoN's long history of working with VPs, expertise in research methods and measures, the SoN's research centers that includes research targeting the elderly, homeless, vulnerable and Indigenous populations, and a history of interdisciplinary faculty and community investigators. An improved curriculum targets methods and measures specific to vulnerable group research, as well as a summer Internship/immersion program that provides expanded experience in health disparities in rural and urban sites (such as among the homeless and Indian reservations). The strengths of this application are the long-term experience of the training program and the (1) Transition to new Program Director, (2) Significant numbers of new/continuing key faculty supporting trainee research, (3) Recruitment of trainees who reflect the ethnic make-up of the region, (4) A well-funded faculty research grant support program and research centers targeting VPs, (5) A well-designed curriculum on VP research methods and measures, and (6) a VP focused summer Internship/immersion program to provide pre-doctoral students with expanded hands-on experience in VP settings and healthcare nees..

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Dr. Angela Hudson


Title: Foster Youth stay smart with "Street Smart" (HIV & Pregnancy Prevention)
Agency: Robert Wood Johnson Foundation
          DESCRIPTION: Children in foster care are one of the most vulnerable groups in society1. Within the United States (U.S.), over 500,000 children live in foster care, and half of this population consists of adolescents. Children enter the foster care system as a result of sexual and physical abuse, or physical neglect and abandonment 2-4. These children are at increased risk for engagement in high-risk sexual behavior, substance abuse and early pregnancy 5-10. Multiple placements and interruptions in foster care placements are associated with depression, substance abuse, sexual promiscuity, unplanned pregnancy and early parenting outcomes 11-14.

Foster youth may benefit from specially designed HIV/Pregnancy prevention programs that have demonstrated effectiveness such as Street Smart, a Centers for Disease Control and Prevention (CDC)-endorsed model intervention designed for homeless and runaway youth 15, 16.

Specific aims:

  1. Using in-depth focus groups, I will conduct interviews with current foster youth (n = 20) to a) discuss the strength factors that are evident in preventing pregnancy and exposure to HIV; b) discuss content and schedule of Street Smart sessions and tailor to needs of current foster youth; c) review and culturally-tailor the Street Smart program by emphasizing the components that are relevant to enhancing the health of foster youth and decreasing risk-behaviors, and adding innovative enhancements such as incorporating use of phone text messaging (PTM) accessible to foster youth by mobile devices with an individual  coach.
  2. Conduct a randomized clinical pilot study to a) assess the feasibility of the culturally-tailored Street Smart for Foster Youth boosted with Phone Text Messaging (SS-FY + PTM) program; and b) estimate impact of the SS-FY + PTM compared to a UC group with 40 foster youth (20 foster youth per group) for selected outcomes, in terms of perceived susceptibility to HIV and barriers to condom use, decrease in depressive symptoms; pregnancy prevention; and taking an HIV test three months post intervention. 

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Dr. Boyoung Hwang

Title: STRESS AND HEALTH IN FAMILY CAREGIVERS OF PERSONS WITH HEART FAILURE
Agency: NIH National Institute of Nursing Research, Project Number 1K23NR013475-01A1
          DESCRIPTION (provided by applicant): The objective of this application for a K23 award is to provide additional training and mentored research experience for Dr. Boyoung Hwang to establish herself as an independent investigator in clinical research that is focused on the improvement of the health and well-being of caregivers of HF patients, and subsequently, of the HF patients themselves. The career development plan consists of obtaining training in design and implementation of randomized clinical trials, advanced biostatistical methods, cognitive behavioral interventions, and salivary biomarkers of stress. To achieve her training goals, Dr. Hwang has developed a focused research study and assembled an outstanding mentoring team comprised of a primary mentor, Dr. Lynn Doering, Professor of School of Nursing at UCLA, who is an expert in biobehavioral research in cardiovascular disease and cognitive behavioral therapy, and two co-mentors: Dr. Mary-Lynn Brecht, Biostatistician at UCLA, who has expertise in study design and complex biostatistical analysis; and Dr. Douglas A. Granger, Professor of Nursing, Public Health, and Medicine at the Johns Hopkins University, who is an expert in salivary biomarker research. Heart failure (HF) is a prevalent and debilitating disease. While support from family caregivers is crucial for better outcomes for HF patients, caring for a chronically ill family member can be challenging and stressful. It has been reported that HF caregivers are distressed and socially isolated due to their care responsibilities, perceive their health to be compromised, and suffer from poor quality of life. However, the literature lacks a comprehensive description of the health status of HF caregivers; no intervention study aimed at alleviating stress in HF caregivers has been reported to date. To fill these gaps, Dr. Hwang will conduct a pilot randomized clinical trial with 50 dyads of HF patients and their caregivers. The study will provide a comprehensive description of health problems and symptoms that caregivers experience (Aim 1) and evaluate the potential of a cognitive behavioral (CB) intervention designed to reduce stress and improve knowledge about HF care and perceived social support among caregivers. Using salivary cortisol measures, the study will examine how psychological benefits from the intervention lead to improvement in caregiver health. Specifically, the study will provide preliminary effect sizes of an 8-week CB caregiver intervention on psychological stress responses (i.e., perceived stress, caregiver stress, and depression), physiological stress responses (i.e., salivary cortisol), stress-related symptoms, health-related quality of life, and health care usage of caregivers. Clinical outcomes of HF patients will also be measured to determine the effects of this caregiver intervention on care recipients (Aim 2). Finally, the potential mediating effects of knowledge about HF care and perceived social support on changes in psychological stress responses and caregiver health will be examined (Aim 3). The study will provide critical pilot data to support an R01 application for a large randomized clinical trial. PUBLIC HEALTH RELEVANCE: Caregivers are vulnerable to health problems because of the stress and demands of their role as a caregiver. With the growing incidence of HF and the anticipated growth in the aging population, the number of HF caregivers is expected to rise. Therefore, the project will pilot test a cognitive behavioral intervention designed to reduce stres and improve knowledge about HF care and perceived social support among HF caregivers, which will ultimately contribute to promoting health and quality of life among HF caregivers and their loved ones with HF.

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Dr. Eufemia Jacob

Title: WIRELESS PAIN INTERVENTION PROGRAM FOR AT RISK YOUTHS WITH SICKLE CELL DISEASE
Agency: NIH National Heart, Lung, and Blood Institute, Project Number 5RC1HL100301-02
          DESCRIPTION (provided by applicant): This project addresses the broad challenge area (06): Enabling Technologies and the specific challenge topic (06-MD-101) Development of Telehealth Tools to Promote Health and Connect At-Risk Youth to the Health System via Low-Cost, Mobile, and Wireless Technologies. Sickle cell disease (SCD) is an inherited disorder that affects red blood cells, by causing them to form a sickle shape, blocking blood flow, and causing a tremendous amount of pain in times of physiological or psychosocial stress. Youths with SCD are at risk for pseudoaddiction. This phenomenon occurs when pain is poorly controlled, and their attempts to obtain medications are perceived by clinicians as drug seeking. Because SCD predominantly affects ethnic minorities, many believe that large proportions of youths with SCD are addicted, when in fact their pain is physiologically based. Most youths manage painful episodes at home and delay seeking treatments until pain becomes intolerable. The delay in treatment for pain leads to poor coping, interference with function, and sleep disturbance. Eventually, these youths are at risk for poor academic achievement, decrease in quality of life, and other negative outcomes that may interfere with overall health. Effective coping in youths with SCD pain will require different strategies that would encourage them to connect with the health care system in a timely manner. Advances in telehealth and internet technology are innovative approaches that may improve access to knowledgeable health care providers, and improve pain management through wireless communications. The handheld wireless technology and web-based applications may potentially minimize barriers that limit access to timely pain relief. We propose to test the effectiveness of an innovative wireless pain intervention program in sickle cell disease that utilizes 1) a cell phone/PDA with a program (e-Ouch) that has questions about pain; 2) a web link that will connect to resources including educational materials, a psychologist, and nurse practitioner, and 3) a peer social support network using cell phone/PDA. We will compare two groups of youths with SCD and randomly assign them to: 1) standard care, 2) standard care + wireless pain intervention program. Measurements will occur at baseline, then at 3 and 6 months following intervention. The youths (8 to 17 years old) in the standard care group will be asked to complete the paper diary three times a day on the days that they are having pain. The psychologist/youth counselor will explain the content in a booklet "Coping with Pain: Strategies that Help" during the orientation session. The 14-page booklet is a short summary of strategies that help cope with pain (deep breathing, muscle relaxation, information on pain and the five senses, imagery), distraction techniques, positive self-statements and positive thinking, trigger analyses and selfmonitoring, behavioral contracts, information on the emotion-pain connection, information on when counseling is needed, and resource/reading list. The youths in the intervention group will be instructed to use the cell phone/PDA to 1) answer questions on the e-Ouch(c) electronic diary three times a day on the days they are having pain, 2) link with the resources in the study web site, 3) connect with the psychologist/youth counselor who will be able to provide support and information about strategies for coping as needed, 4) connect with the nurse practitioner as needed who will be able to make an assessment, monitor, prescribe, and/or refer to other health care provider (pediatric pain specialist, hematologist), and 5) use the cell phone/PDA to connect with other youths with SCD, particularly the friendship network that will be connected via cell phone/PDA. We hypothesize that youths with SCD who participate in the wireless pain intervention program (WPIP) will have 1) increase pain coping; 2) decrease pain interference with daily activities; 3) improve sleep; 4) increase quality of life; and 5) decrease health care use related to pain. Future studies will more specifically examine the cost effectiveness of the WPIP and whether this pain intervention program will generalize to other childhood disorders that require pain management. The study will examine the effectiveness of the Wireless Pain Intervention Program. The program will consist of 1) a cell phone/PDAs with a program (e-Ouch) that has questions about pain; 2) a web link that will connect to resources including educational materials, a psychologist, and nurse practitioner, and 3) a peer social support network using cell phone/PDAs.

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Dr. Deborah Koniak-Griffin

Title: COMMUNITY-BASED LIFESTYLE PROMOTION WITH LATINO WOMEN
Agency: NIH National Heart, Lung, and Blood Institute, Project Number 5R01HL086931-02
          DESCRIPTION:  Overweight/obesity and physical inactivity are two significant predictors of morbidity and mortality from cardiovascular disease (CVD) and other chronic diseases (e.g., diabetes) in Latina adults. These risk factors are modifiable and amenable to lifestyle behavior prevention efforts that focus on promoting a healthy diet and increasing physical activity (PA). The overall goal of this experimental study is to evaluate the effects of a 6-month community-based healthy lifestyle behavior intervention (LSBI) provided by promotoras, designed to improve diet and PA of overweight/obese, middleage Latino women who are predominantly Spanish-speaking immigrants. The study builds upon formative and feasibility studies implemented using community-based participatory research methods and materials developed in a NHLBI CVD prevention initiative for Latinos. Participants (N=240), ranging in age from 35-64, will be randomly assigned to either the LSBI or a comparable length control condition (disaster preparedness and home safety program). The culturally sensitive LSBI includes 2 months of small group education (based upon Su Coraz¿n, Su Vida) and a walking club, followed by 4 months of individualized teaching and counseling (ITC). Strategies to promote behavior change, support healthy nutrition and weight loss, and increase PA will be incorporated into the ITC. Data will be collected at baseline, post intervention (6 months after intervention initiation) and at a 3- month follow-up using a combination of clinical and behavioral measures. The primary outcome to be evaluated is change in body mass index (BMI). Secondary outcomes include objective measures of PA (accelerometer readings), blood pressure, cholesterol, blood sugar, waist circumference and self-reported lifestyle behaviors. Selected mediating (stage of change) and moderating variables (social support), derived from the transtheoretical model of behavior change and social ecological model, will be examined in relation to the intervention and program outcomes. Findings will contribute to knowledge about effective communitybased CVD prevention for Latinas involving lifestyle intervention delivered at a grassroots level by promotoras, outside of clinical settings. Understanding also will be enhanced about the influence of interpersonal and environmental factors on adoption of healthy lifestyle behaviors of Latinas.

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Dr. Eunice Lee

Title: KOREAN IMMIGRANTS & MAMMOGRAPHY-CULTURE-SPECIFIC HEALTH INTERVENTION (KIM-CHI) 
Agency: NIH National Cancer Institute, Project Number 7R01CA127650-04
          DESCRIPTION (provided by applicant): Breast cancer is the most commonly occurring cancer and most common cause of cancer mortality among Korean American (KA) women, but mammography utilization among KA women remains suboptimal. Most breast cancer screening studies with KA women have been descriptive and correlational, but in this 4-year project we will test the effects of Korean Immigrants & Mammography-Culture-Specific Health Intervention (KIM-CHI) on adherence to recommended breast cancer screening protocols. The specific aims are to: (1) compare the group receiving KIM-CHI with an attention control group on mammogram attainment outcomes including number of mammograms obtained (0, 1, or 2) and if obtained, length of time to obtain the first mammogram, at 15 months using survival analysis; (2) compare the two groups on the mediating variables of health beliefs, knowledge, self-efficacy, spousal support and breast self-examination (BSE) practice at 2 weeks and 15 months using repeated measures multivariate analysis of variance; and (3) identify the mediating effects of health beliefs, knowledge, self-efficacy, spousal support, and BSE practice at 2 weeks on mammogram attainment outcomes at 15 months, using structural equation modeling. We have tested the feasibility of the KIM-CHI program targeting KA women by incorporating culture-specific strategies for changing (1) beliefs about breast cancer and screening, (2) knowledge of breast cancer and cancer screening, and (3) self-efficacy for obtaining a mammogram and requesting a referral for a mammogram from a physician. Using Korean churches randomly assigned to intervention or control conditions, a total sample of 400 KA women 40 years of age or older who have not had a mammogram within the past 2 years, along with their husbands in a separate group, will participate in a group session incorporating an educational DVD, BSE skill practice, peer discussion, and an assignment for the couple to have a discussion afterwards at home. Data on mammography attainment and the mediating variables will be collected at baseline and at 2-weeks and 15-months post-baseline. A strength of this proposal is the testing of a cost- conservative protocol with group delivery of consistent health behavior information using Korean role models, native Korean language, and male physician authentication as well inclusion of spouses for improving KA women's mammography attainment.

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Dr. Paul Macey

Title: GENDER DIFFERENCES IN NEURAL DEFICITS ASSOCIATED WITH OBSTRUCTIVE SLEEP APNEA
Agency: NIH National Institute of Nursing Research, Project Number 5R21NR011230-02
          DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) afflicts 20 million adults in the United States, and is associated with increased morbidity and mortality. Major male-female differences in the incidence and co-morbidities of the disorder are poorly understood. However, in preliminary studies, we found gender differences in the location and extend of neural injury associated with OSA. Since brain changes occurring with OSA may contribute to physiologic and neuropsychological characteristics, male-female differences could explain some of the gender differences in the disorder. Before attempting to related neural changes to comprehensive measures of health status, we aim to verify the gender differences in neural injury associated with OSA. We will assess 64 subjects with and without OSA, split evenly between males and females; all OSA subjects will be recently diagnosed and untreated for the sleep disorder. We will assess whole-brain structure with diffusion tensor imaging indices (fractional anisotropy and mean diffusivity), T2 relaxation time, and regional gray matter volume measures, modeled by gender and OSA status, and other potentially significant effects (sex, age, body mass index) and two-way interactions. We will additionally assess neural influences of depressive symptoms as measure by the Beck Depression Inventory-II, and OSA severity (apnea-hypopnea index). The findings will establish which brain areas show large male-female differences in neural injury associated with OSA; the functional roles of the particular structures affected will be used in future studies to select relevant health status measurements. For example, if depression-related regions are affected, follow-on studies will include comprehensive assessment of mental health status. Understanding the role of gender in brain injury occurring with OSA is important for understanding syndrome progression and development of co-morbidities, and for considering different treatment strategies for male and female patients. PUBLIC HEALTH RELEVANCE: This study will compare the brain damage between men and women with Obstructive Sleep Apnea (OSA), a sleep illness that leads to poor health and early death. We will use magnetic resonance imaging to see whether there is more or less brain injury in males than females. We will look at specific brain regions that are related to the problems that women but not men with OSA have, such as depression. If there are important differences between the sexes in the amount of damage, and places in the brain that are affected, our future studies will look to see if those brain changes explain the male-female health differences we see in OSA.

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Dr. Sally Maliski

Title: UNDESERVED MEN'S UNDERSTANDING OF ANDROGEN DEPRIVATION THERAPY RELATED RISKS
Agency: NIH National Institute of Nursing Research, Project Number 1R21NR012786-01
          DESCRIPTION (provided by applicant): Androgen deprivation therapy (ADT) is increasingly being used to treat prostate cancer in the neoadjuvant and adjuvant contexts with radiation therapy (RT), for recurrence following primary treatment with surgery or radiation, or when the prostate cancer is at an advanced stage such that local treatments, surgery or radiation, are no longer indicated. This is significant because prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. Of particular concern are underserved men. Latinos are the fastest growing minority in the United States (US) and have lower rates of health insurance coverage. African American (AA men) have almost twice the incidence as men of other ethnicities, and have advanced, aggressive disease. For purposes of this study, we will define underserved as low-income and uninsured or publically insured. Low-income will be household income 300% of the Federal Poverty Level (FPL) or less. Despite the proven survival benefit of ADT relative to prostate cancer, studies have shown that men on ADT are at increased risk for vasomotor symptoms, depression, fatigue, diminished healthrelated quality of life (HRQOL), decreased bone mineral density (BMD), sexual dysfunction, metabolic syndrome, increased fat mass, along with decreased lean muscle mass, increased serum lipids, and decreased arterial compliance all of which places them at higher risk for cardiovascular disease (CVD), osteoporosis, and type II diabetes. Both Latinos and AA more often have components of metabolic syndrome, obesity, dyslipidemia, low cardiovascular fitness, and diabetes placing them at higher risk for CVD. However, little is known about how these men understand ADT and its associated risks relative to their own health and well-being. Therefore, we aim to: 1. From previously collected data explore men's explanations of ADT, its purpose, effects, and risks among underserved men on ADT in order to develop interview guides focused on issues related to 2 Elicit in-depth narratives from underserved men on ADT focused on their understanding and experience of ADT and 3. Develop a descriptive framework of men's understanding of and response to ADT and its associated risks to guide development of interventions to decrease morbidity and mortality related to ADT-associated risks. We will use a two-stage qualitative approach to meet these aims. First we will conduct a new, in-depth analysis of existing qualitative data focused on men who were receiving ADT at the time of their interviews. From this analysis we will develop focused interview guides to more completely explore men's understanding and management of ADT-related with a new cohort of underserved men. This is necessary formative work to lay the foundation for the development and testing of interventions to minimize ADT-associated risks among highly vulnerable underserved men. These interventions have the potential to While androgen deprivation therapy (ADT) has survival benefit for men with recurrent of advanced prostate cancer, it has multiple associated risks related to cardiovascular disease, bone fraction, metabolic syndrome, and sexual dysfunction. Underserved men are at particular risk. Our goal is to understand how underserved men treated for prostate cancer with ADT understand their treatment and the risks associated with it. To do this, we will conduct the study in two phases. In the first phase we will use transcripts of interviews conducted with underserved men in two studies; one on the meaning of prostate cancer treatment-related incontinence and impotence among low-income African American and Latino men and the second on the impact for prostate cancer treatment-related symptoms on low income Latino couples. We will select the transcripts of the men who were on ADT and re-analyze them for understanding of ADT and its risks and for their management of related symptoms. We will use this to develop an interview guide to do in-depth interviews focused on ADT understanding and risks. We will use the analysis of this data to help develop interventions to minimize ADT-related risks.

Title: PROSTATE CANCER CLINICAL DECISION MAKING BY DIAGNOSED AND HIGH RISK LATINO MEN
Agency: NIH National Institute of Nursing Research, Project Number 5R21NR010383-02
          DESCRIPTION (provided by applicant): Prostate cancer is the most common noncutaneous cancer and second leading cause of death among men in the United States, and Latinos are the fastest growing minority in the United States. However, low income Latino men are more likely to be uninsured, have less education, and have lower incomes. Many do not speak English as their first language. For these men, much of the available information to help with informed decision-making is not accessible. Because of the lack of consensus on the benefits of screening on prostate cancer mortality or of superior survival benefit of any one treatment for early stage prostate cancer, men are faced with life-altering decisions regarding screening and treatment for those who are diagnosed. Furthermore, men with a first degree relative with prostate cancer are at increased risk. Yet, how the rapidly growing population of Latino men approaches the decision-making process in prostate cancer is virtually unknown. Therefore, the overall purpose of this study is to develop descriptive models of prostate cancer screening, treatment, and diagnosis disclosure decision-making from the perspective of Latino men to form an evidence base for the development of culturally appropriate intervention strategies to facilitate informed and confident decisionmaking. Specifically, we aim to: 1. Describe the process of deciding on treatment and disclosing diagnosis from the perspective of Latino men who have been treated for prostate cancer and 2. Describe the process of deciding to be screened or not screened for prostate cancer by brothers or sons of Latino men diagnosed with prostate cancer. We will use qualitative descriptive methods to understand prostate cancer treatment, disclosure, and screening decision-making processes from the perspective of Latino men. Both specific aims will be addressed with in-depth individual interviews exploring involvement in and comfort with treatment decision making process, influences on the decision, and disclosure of diagnosis by treated men. For high risk men we will explore risk perception, knowledge and beliefs about prostate cancer screening, sources of information, facilitators and barriers, and decision implementation. Analyses will result in clear, in-depth descriptions that will guide the future development of intervention strategies to facilitate informed decision-making regarding prostate cancer treatment, disclosure, and screening among Latino men facing prostate cancer decisions. PUBLIC HEALTH RELEVANCE: The relevance of this study to public health lies in the fact that Latinos are the fastest growing minority in the United States and Mexican/Mexican-Americans make up over 70% of this growing Latino population. Understanding how treatment, disclosure, and screening decisions are made by Mexican/Mexican-American men from this research will lay the foundation for culturally relevant interventions to assist these men as they face life-altering decisions. Potentially, informed, confident decision-making participation may contribute to better treatment outcomes and appropriate screening for this disadvantaged group of men.

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Dr. Adeline Nyamathi

Title:  HEALTH PROMOTION COACHING/VACCINE FOR HOMELESS PAROLEES
Agency: NIH National Institute on Drug Abuse, Project Number 5R01DA027213-03
          DESCRIPTION (provided by applicant): Homeless parolees are at high risk for Hepatitis B virus (HBV), Hepatitis C virus (HCV) and HIV infection due to high rates of injection drug use and unprotected sexual activity. Although HBV is a vaccine-preventable illness, 12% to 25% of formerly incarcerated individuals are infected with HBV. Homeless parolees pose a particular challenge for successful reentry as they have underlying mental health issues combined with substance use and abuse and must contend with unstable housing situations, disorganized lives, unemployment, and limited access to health care and social services. Generally about 50% of all parolees scheduled to enroll in community-based drug treatment fail to enroll and less than 10% of enrollees actually complete treatment. Not surprisingly, about two-thirds of all individuals on parole are rearrested and return to custody within three years of release from prison. Our recent data also revealed homeless persons least likely to complete a HAV/HBV vaccine series were young (< 40), and were men who had been discharged from prison. Therefore, it is critical to engage paroled adults in comprehensive intervention programs that not only protect them from HBV, but also reduce risky behavior, promote access to health care, social and employment services, and enable positive coping and communication skills. With advice from our community partners who have successfully treated parolees and our experience with hepatitis vaccination work, we propose to conduct a prospective, three-group study that randomly assigns 700 ready-for- discharge parolees, scheduled to enter a community residential drug treatment program, to enter one of three groups: 1) a PCPC (Parolee Comprehensive Care + Phone Coaching Program), which includes nurse case management and specialized hepatitis education sessions and referrals, the HAV/HBV vaccination series (to all eligible) and coach- facilitated mentoring (mostly by cell-phone); 2) a Parolee Brief Hepatitis Education + HBV vaccination + Phone Coaching (PBCP) Program, which includes brief hepatitis/HIV education, the HAV/HBV vaccination and coach-facilitated mentoring; or 3) a Usual Care (UC) control program, which includes brief general health information, and the HAV/HBV vaccine. For the randomized parolees, the primary aims will be to examine: reincarceration (any vs none), number of days to first reincarceration, completion of HAV/HBV vaccination (among those HBV-negative), and completion of six months of the Amity community-based residential drug treatment program. Secondary aims are to examine program- related differences in potential mediating variables, such as reduction in drug and alcohol use and sexual risk behaviors, visit to health care or social service providers, and improved knowledge of Hepatitis/HIV and communication skills, between 6 and 12 months or over the one-year study period, depending on the measure, and to assess the relative costs of the three programs. This study will advance our knowledge about drug treatment and HBV vaccine completion and recidivism among homeless parolees. Findings from this study can inform targeted interventions and lay the groundwork for health policy decisions that may impact hepatitis and HIV risk reduction and recidivism in this group who are a reservoir for these viruses in the general population, and are returning to prison at unprecedented numbers. PUBLIC HEALTH RELEVANCE: In this study, researchers from UCLA will partner with Amity Foundation and will work together in designing a program to engage soon-to-be discharged prisoners targeted to enter community-based residential drug treatment to receive a comprehensive program that not only protects them from hepatitis A and B infection by means of the hepatitis vaccination, but also reduces risky behaviors, helps them access health care, and social services, and help them to use more positive coping and communication skills. Using nurse case management strategies found successful with homeless adults, incorporating phone coaching, where a buddy who has successfully completed the drug treatment program supports the newly released parolee, we will evaluate the effectiveness of a Parolee Comprehensive Phone Coaching program compared to a less intense program or a usual care program. Findings from this study can inform targeted interventions and lay the groundwork for health policy decisions that may impact hepatitis and HIV risk reduction and rearrest and/or return to custody in this group who can spread hepatitis infection in the general population, and, are returning to prison at unprecedented numbers.

Title:  HBV PREVENTION FOR HOMELESS AT RISK FOR HBV/HCV/HIV
Agency: NIH National Institute on Drug Abuse, Project Number 5R01DA016147-08
          DESCRIPTION (provided by applicant): Homeless adults are at high risk for Hepatitis B virus (HBV), Hepatitis C virus (HCV) and HIV infection due to high rates of injection drug use and unprotected sexual activity. Our NIDA-funded RO1 award has enabled us to implement a successful intervention improve morbidity and mortality of underserved men on ADT thereby decreasing some of the health care and human costs that can be associated with ADT. PUBLIC HEALTH RELEVANCE: designed to evaluate the effectiveness of a HBV vaccination intervention with homeless adults. Our findings revealed that a greater percent of homeless adults randomized to the Nurse Case Managed Plus Incentive and Tracking group completed the HAV/HBV vaccine series compared to a Standard program without tracking. Homeless persons least likely to complete the vaccine series were young (<40), and were men having sex with men (MSM); a significant number of these young adults also reported methamphetamine (MA) and cocaine/crack use. Stimulants (SAs), including MA and cocaine/crack are commonly used by homeless MSM, who contend with disorganized lives, unemployment, and little access to health and social services; thus, HBV vaccination is particularly challenging in this population. HAV/HBV vaccination and effective behavioral treatment are two of the most important strategies for reducing HBV infection among this at-risk group of SA users. Based upon advice from our community partners who have successfully treated SA-using gay and bisexual men (GBM), we will incorporate contingency management into our vaccination completion program, which had lower completion rates among young adults and MSMs. Thus, in this competitive renewal, we propose a randomized, experimental, twogroup design to evaluate the effectiveness of a Nurse Case Managed Program, which includes specialized education and Contingency Management and Tracking (NCCMT), with a Standard Program, including brief education, Contingency Management and Tracking (SCMT) with 500 homeless, young (18-39), SA-using GBM, on completion of theTwinrixHAV/HBV vaccine and, secondarily, on reduction of risk for hepatitis and HIV. This study is innovative in that it will allow us to look at the effect of an enhanced case management and contingency management program versus a standard contingency management program. The proposed study combines optimal strategies to approach, engage and intervene with a hidden and high- risk population to assess the feasibility and efficacy of interventions that may prove beneficial in preventing HBV and HAV infections. We will also assess the relative cost of these programs in terms of completion of the HAV/HBV vaccination series. As use of SAs threatens to intensify homeless persons' risk of exposure to HAV and HBV, particularly among young users who may not yet be HBV-infected, research targeted to engage this group in treatment, until they are suitably protected from HBV, is critical. PUBLIC HEALTH RELEVANCE: In this study, researchers from UCLA and Friends Community Center will work together in designing a program to assist young homeless stimulant-using gay and bisexual homeless men to complete the hepatitis vaccine and in reducing drug and sexual activity. Using nurse case management strategies, found successful with homeless adults as well as contingency management strategies, found successful with gay and bisexual homeless adults by our community partners, we will evaluate the effectiveness of a program that combines both strategies. As Stimulant use threatens to increase homeless persons' risk of exposure to hepatitis A and B viruses, particularly among young users who may not yet be HBV-infected, this research is targeted to engage this group in treatment, until they are suitably protected from HBV, and hopefully reduce risk for HCV and HIV as well.

Title: ASHA HIV HEALTH PROMOTION INTERVENTION IN INDIA 
Agency: NIH National Institute of Mental Health, Project Number 5R34MH082662-03 
          DESCRIPTION (provided by applicant): In India, an estimated 5.7 million people are infected with HIV; of whom 2.5 million are women. While access to antiretroviral therapy (ART) is expanding for people living with AIDS, most of the treatment centers are located in urban areas. However, nearly half of the HIV infected population live in rural areas plagued with poor public health infrastructure. In India, rural women are the hardest hit by HIV/AIDS; they bear the brunt of stigma, have little autonomy or decision-making power, are illiterate, rarely employed, and lack basic knowledge of HIV transmission. These women living with HIV (WLH) face profound challenges in accessing and following treatment regimens, caring for family members, and maintaining positive mental health. Complicating the HIV/AIDS scenario is Mycobacterium Tuberculosis (TB). It is estimated that there are over 2 million cases of HIV/TB co-infection in India; over 60% of persons with AIDS have developed TB. To address the health needs of the rural population, the Government of India has promoted the ASHA (Accredited Social Health Activist); a health advocate who resides in rural communities and promotes the health of women and children in the areas of hygiene and nutrition. However, the expansion of the ASHAs' role to address the needs of a marginalized community of WLH is an innovative strategy that is timely and of societal relevance. A research team that possesses extensive experience in community-based qualitative and longitudinal HIV prevention and behavioral change research in the US and in India are well poised to design and pilot test a novel intervention for rural WLH to improve adherence behavior and enhance their mental health and social well-being. Along with US researchers, key HIV and TB researchers from the Indian Council for Medical Research and the All India Institute of Medical Sciences plan a descriptive Phase I followed by an exploratory randomized clinical trial pilot study in Phase II, to assess the acceptability and effectiveness of an intervention program, delivered by ASHAs, and focused on enhancing TB and/or HIV treatment and care, and promoting psychological adjustment to illness, and HIV-related social, cognitive, behavioral, psychological and treatment outcomes of WLH. Participants will be recruited from four high prevalent HIV/AIDS villages in rural Andhra Pradesh (AP), India, where ASHAs are providing general health services. Two of the four randomly selected villages will have ASHAs trained in the intervention strategies. The remaining two will be usual care. The planned program will be designed, in significant part, by our community partners composed of WLH, ASHAs, and health care experts. We anticipate this three- year study will lead to a culturally tailored intervention that will lead to a larger clinical trial.

Title: VULNERABLE POPULATIONS/HEALTH DISPARITIES RESEARCH
Agency: NIH National Institute on Drug Abuse, Project Number 5T32NR007077-14
          DESCRIPTION (provided by applicant): This revised competing continuation application requests 5 years of support for a pre and postdoctoral research training program to prepare nurse scholars to conduct and disseminate research in the area of health disparities (HD) among vulnerable populations (VPs) and to build nursing science in this area. 3 pre doctoral and 2 postdoctoral trainees will be supported by the grant in each of the 5 years. Specific objectives for trainees are: 1) plan, conduct, evaluate and disseminate culturally competent VP/HD research; 2) generate and test theory concerned with health disparities among VPs; 3) contribute to the development of science, both the knowledge base and methods, as a foundation for education and practice; 4) collaborate with research participants, clinicians, and other researchers in the design and conduct of VP/HD research and the development of science; 5) contribute to health and social policy and ethical decision-making as it affects VPs; and 6) develop skills to contribute as educators, mentors, and leaders in nursing and health care. 7) Post doctoral fellows will complete an extramural grant application to study health disparities in VPs. Training: Pre doc training is guided and directed by an individual faculty mentor (dissertation chair) and corresponding interdisciplinary team (dissertation committee). Training is provided through required coursework, seminars, research apprenticeships, scholarly writing and presentation requirements, involvement in the Vulnerable Populations Research Interest Group (VPRIG), enrollment in the Summer Institute on participatory research methods, and participation in VP/HD colloquia. Post docs will have individualized training programs based on their academic, research and methodologic needs provided under the guidance of two mentors, one in nursing and one in another discipline. Their training will include selected coursework as needed, seminars, participation in the VPRIG and the Summer Institute, and the other activities listed above. Trainee research will address VP/HD domains: resource availability, relative risk, and health status and involve the participation of one of the following groups: ethnic/racial minorities, people living in poverty, marginalized/stigmatized persons. Evaluation of the training program will be assessed by the progress of trainees toward designated benchmarks, increased faculty involvement in the training program, the development of science in VP/HD, and impact on curriculum and clinical practice.

Title: VULNERABLE POPULATIONS/HEALTH DISPARITIES RESEARCH
Agency: NIH National Institute of Nursing Research, Project Number 2T32NR007077-16 
          DESCRIPTION (provided by applicant): This application is designed to continue our long trajectory of recruiting and training nurse scholars in pre- doctoral and postdoctoral education emphasizing methods and measures for ameliorating health disparities experienced by vulnerable populations (VPs). This training program began at the UCLA School of Nursing (SoN) in1994. Since then 23 pre-doctoral and 11 postdoctoral students were trained and supported in their VP- related research. Our program, VP/HD, is supported by the SoN's long history of working with VPs, expertise in research methods and measures, the SoN's research centers that includes research targeting the elderly, homeless, vulnerable and Indigenous populations, and a history of interdisciplinary faculty and community investigators. An improved curriculum targets methods and measures specific to vulnerable group research, as well as a summer Internship/immersion program that provides expanded experience in health disparities in rural and urban sites (such as among the homeless and Indian reservations). The strengths of this application are the long-term experience of the training program and the (1) Transition to new Program Director, (2) Significant numbers of new/continuing key faculty supporting trainee research, (3) Recruitment of trainees who reflect the ethnic make-up of the region, (4) A well-funded faculty research grant support program and research centers targeting VPs, (5) A well-designed curriculum on VP research methods and measures, and (6) a VP focused summer Internship/immersion program to provide pre-doctoral students with expanded hands-on experience in VP settings and healthcare needs.

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Dr. Carol Pavlish

Title: SCREENING AND EARLY INTERVENTIONS FOR ETHICAL CONFLICTS AT THE END OF LIFE
Agency: Sigma Theta Tau
          DESCRIPTION: Ethical issues confront nurses in all work settings and frequently lead to ethical dilemmas and moral distress which can persist for years. Ethical issues are particularly relevant during end-of-life care. However, many nurses are unfamiliar with ethics terminology and what to do about moral distress. Furthermore, when nurses attempt moral actions grounded in their commitment to patient care, the healthcare systems in which they work frequently constrain such actions.
Being at the bedside and bearing witness to the human suffering that accompanies ethically difficult clinical situations, nurses are in a key position to assess early indicators of impending dilemmas and initiate early interventions to avoid further complications and accompanying moral distress. However, although much has been written about ethical dilemmas, the science behind risk factors, early indicators, and mitigation strategies is underdeveloped. This study intends to promote nurses' moral deliberation skills. Specifically, we aim to consult with ethics experts to develop an evidence-based Ethics Screening and Intervention at End of Life Toolkit and assess the toolkit's feasibility in two settings. The outcome will be an evidence-based ethics screening and early intervention tool that can be tested for its validity and effectiveness in additional settings.

Title: SILENT NO MORE, A FEASIBILITY STUDY ON WOMEN'S RIGHTS IN SUDAN
Agency: School of Nursing Intramural Grant
          DESCRIPTION: This community-based collaborative action research project aims to address gender-based violence (GBV) as a human rights violation among displaced women in the post-conflict setting of South Sudan.  Violence against women is most often associated with gender inequality and lack of respect for women's human rights; GBV most often results in physical, sexual, and psychological harm and is closely related to HIV infection in East African women.  A nurse, Dr. Carol Pavlish from the University of California Los Angeles and Dr. Anita Ho, a political philosopher and clinical ethicist from the University of British Columbia, Canada will travel to South Sudan and collaborate with local community health and development specialists for the American Refugee Committee (ARC) and their community partner, Raising Women's Hopes (RWH).  Based on past ethnographic and survey research projects in the region and preliminary planning with the local representative of ARC and RWH, this project includes the development of a human rights intervention with four media: fact sheet, posters, radio show, and docu-dramas with debriefing.  Local staff chose four human rights to focus on: right to non-discrimination, right to equal protection and justice under the law, freedom of expression, and freedom from degrading treatment. The overall goal is to collaboratively develop women's human rights materials that are respectful of local realities and observant of African-centered ethics and universal norms on human and people's rights as advanced by the African Union.  These materials will be tested in a feasibility study for their efficacy and effectiveness in transmitting information and changing attitudes about women's rights and violence against women.  Using a collaborative and participatory approach that engages community partners in the development and testing of human rights intervention is likely to result in culturally meaningful and acceptable messages.

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Dr. Linda Phillips

Title: UCLA/CDU PARTNERSHIP FOR ENHANCING DIVERSITY OF NURSES WITH RESEARCH CAREERS
Agency: NIH National Institute of General Medical Sciences, Project Number 1R25GM102777-01 
          DESCRIPTION (provided by applicant): Health disparities for individuals from under-represented minority groups (URMGs) continue to plague the US population. The roots of this problem are many and complex, but of great relevance is the dearth of individuals from URMGs in the health professions workforce, with serious disparities in the ethnic/racial composition of the workforce being particularly pronounced in nursing. The 2008 NSSRN survey showed 32.1% of Black/African American nurses and 39.4% of Latino nurses had baccalaureate degrees; for all racial/ethnic groups combined, only 11.4% had graduate degrees including PhDs. This state exists at a time when the US population is becoming older and more ethnically diverse. Given this dire state of affairs, we are proposing to enhance an existing relationship between the Schools of Nursing at the University of California, Los Angeles (UCLA) and Charles R. Drew University of Medicine and Science (CDU), an Historically Black Graduate Institution and Hispanic Serving Institution, for the purpose developing and implementing an integrated plan of individual and institutional activities to prepare masters students from URMGs to make a seamless transition to doctoral education. The long term goal of this project is to increase the ethnic/racial diversity of those prepared to pursue research careers in nursing focusing on research about aging adults (45+ years) by (1) increasing involvement of master's students and faculty at CDU SON in the scientific enterprise through structured development activities; (2) enriching the research course offerings and scientific environment at CDU SON to prepare master's students to seamlessly transition to doctoral education; and (3) facilitating student advancement to the UCLA SON via systems that facilitate student enrollment and scientific exchange between faculty at UCLA and CDU. PUBLIC HEALTH RELEVANCE: Health disparities persist despite efforts to curb them. Encouraging more diverse, underrepresented minority individuals to pursue doctoral education in the health care field, such as nursing, is one documented way to reduce health disparities. This application proposes collaboration between University of California Los Angeles and Charles Drew University to provide the supportive and educational activities required to prepare a more diverse nursing workforce at the doctoral level, who will ask the relevant research questions and develop the science that will ultimately reduce health disparities.

Title: PhD pathway to Culturally Competent Care of Older Adults
Agency: Department of Health and Human Services
          DESCRIPTION: The purpose of this one-year project is to collect and analyze data needed to design an emergency department (ED)-based intervention to improve the quality and safety of transitional care for vulnerable community-dwelling elders who seek and receive care in EDs and return, without a hospital admission, to their original places of residence.

The quality and safety of transitional care provided to vulnerable elders is of critical concern to health professionals and policymakers because of the relationships among poorly managed care transitions, premature mortality, cascading morbidity, poor quality of life, premature institutionalization and spiraling health care costs.  Some models have been developed and implemented to improve the quality and safety of care transitions within and between health care institutions and data shows progress is being made in that arena.  However, despite the facts that individuals 65+ are frequent uses of EDs, most elders seen in EDs are discharged to their original places of residence, and a high rate of adverse events occurs to elders following ED visits, very little research has focused on the characteristics of this group that might influence the quality and safety of care or on improving transitional care for this group. We believe the adverse events related to ED visits for older adults exist for the following reasons.

  • Even though the problems bringing elders to the ED may be considered by the health care providers as urgent rather than emergent, older adults can present in the ED with very complex needs.  Often they have symptoms that are vague and atypical.  At least some of ED visits are probably related to problems with managing geriatric syndromes and co-morbidities.
  • Some evidence suggests care at the ED may not be "geriatric focused" and geriatric syndromes and/or atypical presentations of illness may be undetected (yet related to the reason for the visit). 
  • Changes in treatment regimens may not be consistent with geriatric recommendations/ guidelines and may complicate already complex treatment regimens.  This may contribute to adverse events following discharge.
  • While ED staff prescribe new treatments, responsibility for implementing the treatments, monitoring the outcomes including assessing for incompatibilities with existing regimens and communicating the changes back to primary care providers fall squarely to elders themselves with or without the assistance of family caregivers. 
  • The ability of elders and caregivers to fulfill this responsibility successfully is intimately related to their abilities to understand information provided to them.  Many factors interfere with their clear understanding of instructions.
  • Few organizational structures exist for transfer of information or follow-up.

We believe there is a critical need to develop ED based transitional care models that take into account issues related to atypical presentations, geriatric syndromes and patterns of co-morbidity.  However, before such models can be developed, there is a need to better  describe the characteristics of elders who are discharged to home with regard to these three variables and the relationship between these variables and two trackable post-ED adverse events: (1) repeat ED visits and (2) admission to the hospital within 6 months.  These data will contribute to designing an ED-based transitional care intervention that is responsive to the complex needs of elders seen in the ED and targeted to elders who are at highest risk for adverse events. 

The project objectives are as follows:

  1. Using an existing database, describe the characteristics of vulnerable community-dwelling elders who seek and receive urgent care in a large, urban emergency department and return to their original places of residence without a hospital admission  with a focus on the frequency of atypical presentations, geriatric syndromes and patterns of co-morbidity.
  2. Using an existing database, describe the relationships among elder characteristics, atypical presentations, geriatric syndromes and patterns of co-morbidity and two trackable post-ED adverse events: (1) repeat ED visits and (2) admission to the hospital within 6 months. 

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Dr. Wendie Robbins

Title: EFFECT OF WALNUTS ON PROSTATE HEALTH
Agency: Walnut Commission
          DESCRIPTION: Having children is an important part of life, yet many couples struggle with this milestone due to infertility. Worldwide ~70 million couples suffer from infertility. In the USA infertility affects ~one in seven couples and has led to a steady increase in the number of couples seeking infertility services. In vitro fertilization and other assisted reproductive technologies now account for ~3 in every 100 live births. A more natural first step toward dealing with infertility would be to focus on factors we know are associated with good health, for example diet. As described below, walnuts provide a rich dietary source of nutrients needed for male reproductive health.

The male partner is responsible for about 30 - 50% of all cases of infertility. Although the underlying causes of most male infertility are not known, the clinical hallmark is poor semen quality (low sperm count, poor sperm motility, abnormally shaped sperm, fragmented sperm DNA). There are multiple reports of declining semen quality in specific geographic locations around the world, usually associated with industrialized nations. Some research suggests environmental pollutants and a trend toward a more Western diet (laden with saturated fats, refined sugars, low fruit and vegetable intake) are to blame.

It is logical to think that Western diets are not healthy for semen quality. Sperm need very flexible plasma membranes in order to swim and fuse with ova. Sperm require membranes that are highly enriched with beneficial polyunsaturated fatty acids. If polyunsaturated fatty acids are low in sperm, fertility is low. Decreasing the ratio of omega-3 to omega-6 polyunsaturated fatty acids in the diet has been shown to improve male fertility. Selenium is also critical to normal sperm development and function and if not adequate in the diet, sperm swim in circles and suffer damage to their membranes and DNA. A recent study has shown that increased folate in the diet reduces the number of sperm carrying too many or too few chromosomes. Sperm with an altered number of chromosomes can lead to disorders such as Down syndrome or spontaneous abortion. However, walnuts provide a rich dietary source of all the factors above needed for healthy semen quality. Walnuts contain beneficial lipids, selenium, folate, and antioxidants to protect sperm membranes and sperm DNA.  Walnuts have been shown repeatedly to improve lipid profiles in published dietary studies. Based on this, we propose a study to examine whether enriching the diet with walnuts might improve semen quality.
 
We will combine two respected research laboratories at UCLA to accomplish the research. One laboratory has a long history of conducting male reproductive health studies and the other a long history of conducting diet and nutrition research.

The plan is to enroll 120 men who habitually eat Western diets and then randomly assign half to eat their usual diet supplemented with walnuts (3 ounces per day) and the other half to eat their usual diet excluding nuts. At the beginning of the study we would collect full dietary histories, blood measures of omega-3 and omega-6 fatty acids, selenium, anti-oxidants and folate (the factors critical to sperm). We would also directly measure the semen quality including sperm count, motility, shape, chromosome number, and DNA fragmentation (the factors necessary to male fertility). After three months on the diets, we would collect the same measures again and look for changes in those measures. Throughout the study the research team would be available to monitor and assist study participants with the diets and other study procedures.

We have designed the study to be able to detect beneficial effects of walnuts on male reproductive health.  If couples planning pregnancies could enhance their fertility with a natural dietary source like walnuts, it would be preferable to taking supplements or rushing into in vitro technologies. Similar to the health information given on benefits of walnuts for cardiovascular health, information on benefits of walnuts for male reproductive health would be very beneficial to couples of reproductive age.

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Dr. Christian Roberts

Title: Effects of Resistance Training on Tobacco-Related CVD Risk
Agency: Tobacco-Related Disease Research Program (TRDRP)
          Overall Goal: There is an urgent public health need to identify novel strategies to prevent and treat tobacco-related cardiovascular disease in young adults.
          Aims: This project will determine if regular resistance training (RT) can ameliorate endothelial dysfunction, oxidative stress, inflammation and insulin resistance in smokers, with or without concomitant efforts to reduce smoking. The specific aims are to: 1) determine the effects of a 12-wk RT program on endothelial function and insulin sensitivity in smokers either attempting smoking cessation via counseling + nicotine patches or not attempting cessation; and 2) compare the effects of counseling + nicotine patches vs. RT vs. both on smoking cessation. I hypothesize that RT will improve cardiovascular function in smokers; however, the responses will be better in those who also stop smoking. In addition, resistance training will decrease smoking, however the effects of counseling + NRT alone or counseling + NRT in conjunction with RT will be better than RT alone.
          Design: Using randomized-controlled trial design, in a 2x2 factorial design, 100 young men and women (ages 18-35) will be assigned to either 3 days/wk resistance training for 12 wks or 12 wks of control and either counseling + nicotine replacement patches or no cessation intervention.
Dependent Variables: The methods selected for this project are gold-standard, sensitive techniques. Brachial artery ultrasound to determine flow-mediated dilation, arterial tonometry for arterial stiffness, endothelial progenitor cell number by fluorescence-activated cell sorting, plasma determinants of oxidative stress and inflammation (plasma oxLDL; C-reactive protein), and insulin sensitivity by a frequently-sampled intravenous glucose tolerance test.
          Significance: This project will determine if RT mitigates the endothelial dysfunction, its mediators, and insulin resistance commonly noted in smokers. In addition, this study will determine if RT can induce smoking cessation. If successful, greater emphasis may be placed on including resistance exercise in therapeutic interventions to reduce future tobacco-related cardiovascular disease in at-risk young adult smokers.

Title: VASCULAR FUNCTION, CARDIOVASCULAR DISEASE BIOMARKERS AND THE LATINO PARADOX
Agency: NIH National Heart, Lung, and Blood Institute, Project Number 5P50HL105188-02
          DESCRIPTION: The Latino health paradox intrigues researchers because it seems too good to be true: Better health outcomes for individuals with fewer resources. Why does acculturation to norms in the US, despite being accompanied by increased access to health resources and income, seem to contribute to worse health outcomes? To date, the study of acculturation and health risk has focused on behavioral factors, rather than on physiological phenotypes. There is an urgent public health need to gain insight into the cardiovascular health of Latinos, especially Mexican-Americans, an ethnic group increasingly prone to obesity-related comorbidities but understudied for cardiovascular risk factors. This interdisciplinary project will determine cardiovascular function in younger and older related adults varying in generational and immigrant status to increase understanding of the basis for the Latino acculturation paradox. 200 subjects from 100 families in East Los Angeles, including one family member from both an older and a younger generation will be enrolled. The project aims are to 1) Evaluate cardiovascular phenotypes, including arterial stiffness, endothelial function, cardiovascular risk factors and metabolic syndrome in Latino families; and 2) Evaluate the extent to which the Latino paradox holds within these families, based on their generational status and level of acculturation. Measurements will be determined at baseline and after 24 months follow-up. The primary outcome is arterial stiffness measured by applanation tonometry. Secondary outcomes include endothelial function via brachial artery flow-mediated dilation, cardiorespiratory fitness via incremental exercise test, and cardiovascular disease risk biomarkers including markers of endothelial dysfunction (soluble intracellular adhesion molecule-1 and E-selectin), oxidative stress (oxidized LDL and myeloperoxidase), systemic inflammation (C-reactive protein), and fibrinolysis. Other outcomes required to test the hypotheses include components of metabolic syndrome, diet, physical activity level and measures of acculturation. If our hypotheses are supported, more importance may be placed on taking acculturation into account when designing lifestyle change interventions designed to improve Latino cardiovascular health.

Title: GLYCEMIC LOAD AND RESISTANCE TRAINING ON ENDOTHELIAL FUNCTION AND INFLAMMATION
Agency: NIH National Institute of Diabetes and Digestive and Kidney Diseases, Project Number 1R01DK090406-01A1
          DESCRIPTION (provided by applicant): This project is prompted by the urgent public health need to find optimal nutrition and exercise prevention strategies to reduce future cardiovascular disease and type 2 diabetes risk in young adults. This project aims to investigate the efficacy of a low-glycemic load diet both alone, and in combination with resistance training, to ameliorate endothelial dysfunction, monocyte inflammation and 24-hr glycemic variations. 160 obese young adults will be randomly assigned to 1 of 4 groups for 12 weeks: 1) a control high-glycemic load diet; 2) a low- glycemic load diet; 3) a high-glycemic load diet + resistance training; or 4) low-glycemic load diet + resistance training. The aims are to determine if: 1) a low-GL diet improves endothelial function, monocyte inflammation and 24-hr glycemic variations compared to a standard high-glycemic load, Westernized diet and 2) a low-GL diet + RT has an additive effect with low-GL diet to improve endothelial function, monocyte inflammation and 24-hr glycemic variations. Dependent variables include endothelial function by brachial artery flow-mediated dilation (FMD), monocyte phenotyping by flow cytometry and PCR/protein analysis, 24-hr continuous glucose monitoring systems, insulin sensitivity by frequently sampled intravenous glucose tolerance test, whole body composition by DEXA, visceral and hepatic fat fraction by MRI, and acute responses to a high-glycemic index meal. The hypotheses are that a low-glycemic load diet will improve the above key cardiovascular risk related dependent variables and that the addition of resistance training will induce additive effects. This project will, for the first time, compare the isolated and combined effects of a low-glycemic load diet and/or resistance training on endothelial function, monocyte inflammation and 24-hr glycemic variations. If the hypotheses are upheld, new therapeutic options will become available to improve primary prevention of vascular dysfunction, chronic inflammation and insulin resistance, including in those young adults where alternative therapies may be less effective. PUBLIC HEALTH RELEVANCE: For the first time, a randomized controlled trial using a low glycemic-load diet and/or resistance training will be carried out in obese young men and women. This efficacy trial should have major public health implications to the tens of millions of Americans currently obese, presenting with less than optimal vascular function, chronic inflammatory status and insulin sensitivity, thus providing insight into novel preventive health strategies. Furthermore, due to individualized specificity of compliance issues for each patient, the arsenal of therapies for prescription needs to be large; the current proposal will potentially increase the range of therapies.

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Dr. Linda Sarna

Title: SMOKING CESSATION LEARNING FOR NURSES IN CHINA
Agency: Pfizer
Executive Summary:

  1. Health problem: The People's Republic of China (PRC) has the largest population of smokers in the world (350 million), but quitting is not common, few smokers receive help with cessation, and healthcare professionals and are not prepared to intervene. There have been limited efforts to educate the 1.65 million nurses about smoking cessation. The Chinese Registered Nurse-Helping Smokers Quit (CRN-HSQ) web-based program will be used to improve 1000 RNs' knowledge, skills and interventions with patients. Educated PRC RNs could have a significant impact on decreasing tobacco-related morbidity and mortality.
  2. Assessment of needs: Available evidence of needs will be supplemented by objective data. RNs' knowledge, skills, and delivery of smoking cessation interventions with patients will be evaluated using a Chinese translation of a web-based survey at baseline and at 3- and 6-months post-program. The Project team will meet with key nursing and health professional leaders in Beijing to discuss cultural appropriateness of the materials.
  3. Methods: The CRN-HSQ project, housed on the existing Tobacco Free Nurses website, includes downloadable materials and a 20 minute video-webcast, using Power Point slides adapted and translated into Chinese, based on the Rx for Change© validated curriculum.
  4. Outcome measures. Changes in RNs' knowledge, skills, and frequency of delivery of  cessation interventions at 3- and 6-month will be assessed using self-reports via web-based surveys with unique identifiers to link responses over time. Process measures to assess feasibility and acceptability of the educational program project will include the response rates, patterns of traffic on the project website, and specific questions on the 3 and 6 months surveys. Chinese nursing leaders will assess usefulness/ usability of the program and subjective outcomes related to content.
  5. Bias and conflict of interest:  We will have ongoing communication with our educational partner, ISNCC, and our colleagues in Beijing. No personnel supported or affiliated with the tobacco industry will be allowed to participate in this project.

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Dr. Sophie Sokolow

Title: Biochemical & functional analyses of the Na+/Ca2+ exchanger in AD pathology
Agency: Alzheimer's Association Grant
          DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is the most common form of dementia. Since there is no disease-modifying drug, the prevalence of AD is predicted to quadruple by 2050. Interventions that can prevent or delay AD onset will have a major impact on the health of seniors and on the economic toll this illness imposes on the US. AD is characterized by synapse loss, senile plaques and neurofibrillary tangles in the hippocampus and neocortex. The degree of clinical impairment strongly correlates to the decrease of electrophysiologically active synapses. Although the molecular triggers of AD are unknown, extensive studies indicate that the amyloid-beta (Aβ) protein plays a principal role in AD pathogenesis. New evidence suggests that presynaptic buildup of soluble Aβ is the proximal cause of synapse dysfunction in AD. Nonetheless, the direct link between presynaptic Aβ and the loss of synaptic function has yet to be established. Altered glutamate reuptake, postsynaptic decrease in glutamate receptor surface expression (Li et al., 2009) and disruption of calcium (Ca2+) homeostasis (Green and LaFerla, 2008; Kuchibhotla et al., 2008) are pathways by which soluble Aβ species alter synaptic function in different experimental models. Indirect evidence in AD models implies that elevated intracellular Ca2+ levels and Aβ buildup may be functionally associated with altered synaptic plasticity and synapse loss (Stutzmann, 2007; Kuchibhotla et al., 2008; Lopez et al., 2008). This leads to the hypothesis that Ca2+ overload might contribute to AD pathogenesis. The majority of publications on Ca2+ signaling in AD concern intracellular Ca2+ elevation resulting from i) impaired entry from the extracellular compartment (Demuro et al., 2005; Bezprozvanny and Mattson, 2008) or ii) abnormal release from the endoplasmic reticulum stores (Stutzmann et al., 2003; Stutzmann et al., 2007). The role of extrusion mechanisms regulating intracellular Ca2+ levels and their effects on glutamate release has not been thoroughly examined. The sodium-calcium exchanger (NCX) is a plasma membrane protein that plays an important role in maintaining Ca2+ homeostasis and protecting neurons from Ca2+overload and eventual death (Carafoli, 1991; Blaustein and Lederer, 1999). In its forward mode, NCX extrudes one Ca2+ against three entering sodium (Na+) (Philipson and Nicoll, 1992; Blaustein and Lederer, 1999). Three NCX isoforms have been identified (NCX1-3) and each NCX variant is expressed in mammalian brains (Minelli et al., 2007). Few investigations have addressed the role played by NCX in AD pathology (Colvin et al., 1994; Wu et al., 1997; Kim et al., 1999). Our recent study showed that NCX1-3 isoforms are co-localized with Aβ and specifically regulated in AD synaptosomes (Sokolow et al., 2011 in press).
The purpose of this proposal is i) to understand how intrasynaptic Aβ buildup affects NCX synaptic activity, NCX1-3 expression and glutamate release, in AD nerve terminals. Our overall hypothesis is that in a mouse model of AD (J20 line), NCX activity and protein expression will decrease in an age-dependent manner and as Aβ buildups in nerve terminals. We further hypothesize that this decline in NCX activity will impair presynaptic Ca2+ homeostasis and glutamate release.

 

 

 

Dr. Dorothy Wiley

Title: METHYLATION AND RELATED ANOGENITAL HPV CANCERS
Agency: NIH National Cancer Institute, Project Number 3R21CA124324-02S1
          DESCRIPTION:  Anal cancer is an emerging health crisis for homosexual men, especially within the context of human mmunodeficiency virus (HIV) infection. Like invasive cervical cancer, intra-anal cancers are largely attributable to chronic, high-risk human papillomavirus (HPV) infections. These infections and their associated low- and high-grade anal intraepithelial neoplasias (AIM) are common for men with a history of receptive anal intercourse. Though the prevalence of anal dysplasia is high, malignancy is a relatively rare occurrence. Domestically, there is no consensus for standards of care, and the outcome of treatment algorithms is largely unsatisfactory. There is an urgent need to identify key events in the underlying natural history of disease, which will enable clinicians to determine which individuals need immediate treatment or can remain under careful surveillance. More sensitive biomarkersthat can discriminate between men likely to progress from those that do not will allow better clinical algorithms to be tested. In the long term, these strategies will reduce morbidity and mortality and diminish the population's burden of disease. Methylation is an adaptive cellular process that hinders transcription of foreign DMA by making viral genomes less accessible to host-cell transcription factors and enzymes. Our recent studies suggest methylation of HPV genomes may be an epigenetic determinant, responsible for promoting latent infection and clinical disease progression. This investigation focuses on two aims using epidemiological methods and molecular biology techniques. First, we will determine whether previously observed relationships between methylation of HPV16 genomes and disease state are observable in 91 HIV/HPV16 coinfected men that have been evaluated for AIM. Second, using longitudinally-collected clinical samples and controlling for the effect of time-dependent covariates, we will determine whether particular baseline patterns of methylation in HPV16 genomes predict methylation patterns overtime in three high-risk HPVs. PUBLIC HEALTH STATEMENT: The findings from this study will improve the public's health by improving anal cancer screening accuracy through the identification of reliable biomarkers, to ultimately prevent premature death.

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Dr. Ann Williams

 

Title: ART Adherence Program in South East China
Agency: National Institute of Allergy and Infectious Diseases
          DESCRIPTION: This is a developmental project to design and test the feasibility and preliminary efficacy of a culturally appropriate intervention for supporting antiretroviral therapy (ART) adherence in South Central China, in a resource-constrained setting where the national CDC is presently scaling up ART-treatment. We will adapt a theoretically driven ART adherence intervention, which demonstrated efficacy in a randomized clinical trial conducted in the United States, to the Chinese cultural and social context. The adaptation will be informed by the results of our preliminary quantitative and qualitative work in this region of China and will be validated by patient, provider, and community review groups. We will conduct a randomized, controlled pilot study of the feasibility and acceptability of the intervention among 90 patients beginning ART through the China national ART program in Hunan Province and establish a preliminary effect size in anticipation of a full-scale clinical trial. We will also use Ultra Deep Sequencing technology to describe baseline prevalence and incidence of genotypic ART resistance and explore the relationship between adherence and ART resistance. Knowledge acquired from this study will contribute to successful treatment of HIV disease through increased understanding of factors associated with ART adherence and interventions to support or improve adherence and through increased understanding of the clinical significance of genotypic mutations, including low abundance species, and the value of genotypic testing as part of clinical care. These benefits will accrue to patients in both the developed and developing world. The opportunity to acquire this knowledge is unique and time-limited, because China is in the early stages of an ambitious and well-organized ART roll out.

 

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Dr. Kynna Wright

Title: DOCUMENTING THE CAPPR PROCESS IN THE L.A. SITE OF THE COMMUNITY CHILD HEALTH NETWORK STUDY
Agency: NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development, Project Number 5R03HD059584-02
          DESCRIPTION (provided by applicant): The proposed pilot study builds upon the Community Child Health Network Study (CCHN), an on-going NIH- funded multi-site research project that focuses on the reasons for disparities in maternal and child health development as well as the effect of paternal involvement on birth outcomes. In order to best research health disparities, this project will draw upon a community-based participatory research (CBPR) model. This current project, which focuses on the Los Angeles site of CCHN (CCHN-LA), is built upon a CBPR conceptual framework that was created by L. Jones, et al. and modified to include the concept of community-academic partnered participatory research (CAPPR). CAPPR are collaborative research projects conducted in a way that emphasizes equal partnership for community and academic entities, while building capacity for partnered planning and implementation of research informed programs. This framework will be the basis for achieving the following specific aims: (1) To systematically document the history of community-based participatory research in the CCHN-LA research study; (2) To identify the facilitators and the barriers to community-based participatory research in the CCHN-LA research study; (3) To develop measures of success for community- based participatory research; and (4) To disseminate the findings from this research study to a variety of relevant audiences, that is scientific, community/neighborhood, CCHH-LA study participants, and policymakers. The study uses both qualitative and quantitative analyses to achieve these specific aims. Key informant interviews with academic partners as well as dialogue sessions with community partners (members of the Healthy African American Families Preterm Workgroup) will be done at baseline and at 6 month intervals. This will provide the research study with a historical background of the CAPPPR process as well as information regarding ongoing activities that presumably engage the community and academic partners. In addition, the community partners will meet on a monthly basis and a participant survey will be obtained after each of the session. The survey is meant to elicit their perspectives on CAPPR at that point in time. At three time points in the study, the data from all research activities will be reported back to the community and academic partners for their feedback. By documenting the history and progression of the CAPPR process in a city-wide study, insight into the utilization of CAPPR as a quality improvement tool for health disparities research will be obtained. The proposed pilot study builds upon the Community Child Health Network Study (CCHN), an on-going NIH- funded multi-site research project that focuses on the reasons for disparities in maternal and child health development as well as the effect of paternal involvement on birth outcomes. This current project, which focuses on the Los Angeles site of CCHN (CCHN-LA), is built upon a community-based participatory research (CBPR) conceptual framework that has been changed to include the concept of community-academic partnered participatory research (CAPPR). This study will document the history and progression of the CAPPR process, identify ways that improve or hinder the process, and develop measures of success for CBPR within the CCHN-LA study.

Title: IMPACT OF A CBPR SCHOOL PROGRAM ON OBESITY-RELATED OUTCOMES IN UNDERSERVED YOUTH
Agency: NIH National Institute of Nursing Research, Project Number 1R01NR012676-01
          DESCRIPTION (provided by applicant): Over the past 20 years, obesity rates in U.S. children and youth have skyrocketed. National studies show that disparities exist where racial/ethnic minorities and those from a low-income are at higher risk for being overweight or obese. Design, implementation and dissemination of effective school-based prevention programs are critical to addressing these disparities in the obesity epidemic, however few successful models exist. Interventions that are both informed by community partners using a CBPR approach and are comprehensive, and those that include the integration of individual (physical activity behaviors), social (PE teacher curriculum training activities) and environmental (improved school PE equipment) factors have greater success in achieving long-term effects on children's obesity-related behaviors and cognitive performance, especially among medically underserved areas/populations (MUA/P). Resulting from a partnership with the UCLA School of Nursing, the Los Angeles Unified School District (LAUSD) we propose to assess the impact of a middle-school based environmental and curriculum intervention on physical activity and fitness behaviors and standardized achievement test scores among MUA/P youth. This research also examines whether the effects of the intervention vary by gender and ethnicity. The proposed environment and curriculum, coordinated school health program will consist of three components: (1) the SPARK Middle School Physical Education and Nutrition (M-SPAN) Program, 2) professional development (PD) and curriculum training for PE teachers; and 3) provision of quality PE equipment. This study uses a cluster randomized controlled trial design at 24 MUA/P middle schools in the LAUSD with repeated measures (pre-program, mid-program, immediate post-program) and random assignment to the intervention. M-SPAN is an evidenced-based program and is recommended by the CDC to decrease childhood obesity. In order to enhance M-SPAN, SPARK has created PE equipment to match the activities in M-SPAN. The curriculum intervention entails the combination of SPARK Active Recreation and LAUSD PE Standards curricula and will be delivered once a month over 11 months of each of the two intervention years (total 22 months). The project design will be implemented in two waves. Wave I (with 6 sites from each study condition) will run from Years 1-3 and Wave II (with 6 sites from each study condition); will run from Years 2-4. The study aims will be evaluated with objective and subjective activity measures including SOPLAY (System for Observing Plan and Leisure Activity in Youth), physical fitness via the FitnessGram assessment, measured by body composition (decreased BMI and skinfold thickness), aerobic fitness (one mile run), and muscular strength/endurance (curl-up and pull-up) as well as standardized achievement test scores. A small subsample of youth from intervention schools (n=3,960) will also be assessed for physical activity via a modified Youth Risk Behavior Survey (YRBSS), pre-intervention, mid- intervention and immediate post-intervention. For Wave I years 1, 2, and 3 and for Wave II, years 2, 3 and 4. PUBLIC HEALTH RELEVANCE: Childhood overweight and obesity have detrimental consequences in terms of physical and mental health for all children but especially youth from MUA/P. The outcome knowledge from this study will likely demonstrate the value of utilizing a culturally-sensitive, multi-component, collaborative intervention to decrease childhood obesity. Findings from this comprehensive study could impact future programs that aim to improve minority adolescent health and academic status and over the long term may result in a significant decrease in childhood obesity, especially among MUA/P.

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Dr. Marlyn Woo

 

Title: SLEEP DISORDERED BREATHING AND PASSIVE LIMB MOVEMENT IN CHILDREN WITH PARAPLEGIA
Agency: NIH National Institute on Nursing Research, Project Number 1R21NR012810-01A1
          DESCRIPTION (provided by applicant): Children and young adults with spinal cord injury (SCI) commonly show sleep-disordered breathing (SDB), which is associated with increased morbidity and mortality, with an incidence conservatively reported at over 30%. Current treatments for SDB have high non-compliance due to associated discomfort or lack of efficacy. The most common intervention, continuous positive airway pressure, poses special problems with children and young adolescents, since the necessary masks distort developing facial bone structure over time, often forcing surgical reconstruction, and are difficult to fit as the child grows. Passive limb movement, the rhythmic movement of extremities without voluntary effort, increases ventilation during sleep in subjects with intact spinal cords; the impact of this intervention in complete thoracic SCI (paraplegic) patients lacking sensory information from the lower limbs is unknown. We hypothesize that passive limb movement (PLM) in these SCI patients with intact spinal cords above the thoracic cord region will decrease SDB [decrease the Apnea- Hypopnea Index (AHI)] for both obstructive and central apnea events, improve ventilation and oxygenation, and do so without arousing subjects during the night.. Using a one-group, quasi-experimental, pre- and post- test design, we will perform overnight polysomnography on 26 pediatric and young adults with complete thoracic spinal cord injury (ASIA A paraplegia, age 12-25 years), earlier screened to show SDB, who will be randomized to undergo passive limb (hand) movement either during the first or last half of the night during overnight polysomnography. The specific aims for this study are to: 1) Determine whether PLM therapy in pediatric and young adults with complete thoracic SCI (complete paraplegia) with SDB will improve SDB (as indicated by apnea-hyperpnoea index), ventilation (end-tidal carbon dioxide), and oxygen saturation; and 2) Compare number of arousals in pediatric and young adults with complete thoracic SCI during baseline sleep and during sleep when they are receiving PLM therapy. The objective of this study is to determine whether a novel treatment, passive limb movement, will improve ventilation in complete thoracic SCI adolescents and young adults with SDB, and do so with minimal disturbance to sleep. If passive limb movement improves ventilation and is tolerable to SCI patients, the intervention will provide an inexpensive, non-invasive therapy that could change clinical practice and significantly improve quality of life and outcomes in this high risk patient population. PUBLIC HEALTH RELEVANCE: Sleep-disordered breathing is common in children and adult spinal cord injury patients, and is associated with increased risk for high blood pressure, learning disorders, anxiety, and depression. Current treatments for sleep-disordered breathing are associated with high non-compliance, ineffectiveness, and discomfort. Upper limb cyclic movement (passive limb movement) may assist breathing in patients with spinal cord lesions below the cervical vertebrae (paraplegia). Passive limb movement is an innovative treatment option for sleep- disordered breathing which has the potential to effectively treat both children and adults with paraplegia.

 

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Dr. Mary Woo

Title: CENTRAL AUTONOMIC NERVOUS SYSTEM REGULATION IN HEART FAILURE
Agency: CENTRAL AUTONOMIC NERVOUS SYSTEM REGULATION IN HEART FAILURE, Project Number 1R01NR013625-01A1  
          DESCRIPTION (provided by applicant): The objective is to determine how damaged brain autonomic nervous system (ANS) regulatory areas (hypothalamus, insula cortex, and cerebellum) respond to an ANS challenge, and to assess the laterality of functional responses to that challenge in heart failure (HF) subjects. Abnormal autonomic nervous system activity in HF is associated with increased morbidity and mortality. It is unclear if the structural damage seen in central ANS control regions reflects functional ANS abnormalities. Our preliminary studies found that injury in ANS control regions was accompanied by lateralized, altered (blunted, inverted, or time-delayed) functional deficits to ANS challenges in HF, and these changes preferentially occurred on the right side. The lateralization of damage and impaired functional responses on the right-side can increase risk for cardiac dysrhythmias and increase ANS abnormalities. However, responses of these damaged brain regions to ANS challenges are unclear, and the extent to which the lateralized injury contributes to abnormal ANS reactivity in HF has yet to be described. Therefore, using a two-group comparative design, we will examine the structural integrity in brain ANS control areas using diffusion tensor imaging procedures and functional responses and laterality of those signal changes to an ANS challenge using functional magnetic resonance imaging (MRI) procedures in 40 HF and 40 age- and gender-matched healthy controls. The specific aims are to:1) evaluate functional responses to an ANS challenge eliciting sequential sympathetic and parasympathetic actions (Valsalva maneuver) in a set of ANS regulatory brain regions (hypothalamus, insular cortices, and cerebellum) using functional MRI procedures in HF and healthy controls; 2) evaluate the relationships between structural integrity (using diffusion tensor imaging procedures) and functional activity (via functional MRI) of brain regions which regulate ANS tone in HF subjects. These studies will aid in the identification, development, and evaluation of new therapeutic strategies to protect and retrain central nervous system regions to restore ANS function, and improve survival and quality of life in this high risk patient population. Potential future interventions for these structural and functional ANS abnormalities could include peripheral or centrally-acting pharmacologic agents (such as statins or angiotensin-renin blockers), or neuroprotective interventions, including retraining/reorganization of alternative brain structures to restore ANS brain functions. PUBLIC HEALTH RELEVANCE: Heart failure patients show severe autonomic control irregularities, which are linked to increased morbidity and mortality, and may result from injury t autonomic regulatory brain sites. Determination of relationships between structural injury in autonomic control areas and aberrant functional responses to an autonomic challenge has the potential to disclose the processes contributing to abnormal autonomic control in the condition. [Understanding of the relationships between structural brain injury and functional consequences will assist in the identification of appropriate interventions to limit further brain injury, or reover brain functions which have the potential to impact morbidity and mortality and quality of life in this high risk patient population.

Title: SLEEP AND BRAIN STRUCTURE IN HEART FAILURE
Agency: NIH National Institute on Nursing Research, Project Number 5R01NR009116-06
          DESCRIPTION (provided by applicant): Heart failure (HF) patients show multiple neuropsychological and cardiovascular abnormalities which indicate changes in brain function. Brain injury, defined as loss of tissue and changes in tissue properties and function, occurs in areas which regulate mood, memory, blood pressure, heart rate, and breathing. All of these symptoms have been linked to increased morbidity and mortality in HF. However, the processes which elicit this brain injury are uncertain. Sleep-disordered breathing (SDB) characterized by repetitive hypoxia/reperfusion of oxygen and intermittent ischemia is common in HF, and may contribute significantly to brain damage found in the syndrome. However, the relationship between SDB and the extent and location of brain injury in HF patients is not established. We hypothesize that processes accompanying ischemia and hypoxia, and subsequent reperfusion associated with sleep-disordered breathing (SDB) in HF initiate and exacerbate the brain injury. We will 1) demonstrate that the extent of gray matter damage (assessed by structural magnetic resonance imaging, including mean diffusivity and fractional anisotropy) in HF depends on the presence of SDB (assessed via overnight polysomnography); 2) show that nerve fibers (white matter - evaluated via structural MRI and fiber tracking techniques) interconnecting major autonomic control structures are injured in HF patients with SDB; and 3) Determine whether the extent of brain injury (gray matter damage and white matter integrity) relates to aspects of deoxygenation/oxygen reperfusion during SDB, and whether such disordered breathing is more injurious during particular sleep states, or with more-frequent oxygen reperfusion. Using 2-group comparative and correlational designs, 80 subjects (30 HF subjects with SDB, 30 HF subjects without SDB, 20 healthy controls without SDB) will undergo structural MRI and overnight polysomnography studies. Inclusion criteria for all subjects will be age 40 - 65 yrs; HF will be systolic dilated, and LVEF < 0.40. Exclusion criteria for all subjects include claustrophobia, presence of loose metal (for example, pacemakers, braces, implanted hearing aids, or embolic coils). Statistical tests will consist of T-tests and Pearson's correlations with significance set at p < 0.05. The objective is to determine whether SDB is associated with alterations in brain structure in HF, and whether oxygenation/reperfusion processes accompanying apnea could lead to brain injuries in the syndrome. Determining the ongoing detrimental processes which cause brain damage in HF is essential to develop innovative treatments to reduce or prevent brain injury which can exacerbate the autonomic, cognitive, and mood deficits in this high-risk patient population. PUBLIC HEALTH RELEVANCE: Heart failure patients show multiple neuropsychological and cardiovascular abnormalities which indicate changes in brain function, and have been linked to increased morbidity and mortality in the syndrome. We reported brain injury, appearing as tissue loss or changes, and altered function in areas which regulate mood, memory, blood pressure, heart rate, and breathing; however, the processes underlying these brain alterations are uncertain. Sleep-disordered breathing imposes repetitive exposure to hypoxia and ischemia, is common in heart failure, and may contribute significantly to the brain damage. However, the relationship between sleep-disordered breathing and the extent and location of brain injury in heart failure patients is not established. Determining an association between sleep-disordered breathing components (such as the extent of decline in oxygen saturation, total duration of oxygen desaturation as reflected in apnea time, the number of oxygen reperfusions as indicated by number of arousals from apnea, and the patterns of sleep states) and extent of brain injury (evaluated by brain magnetic resonance imaging of gray and white matter) would allow health care providers to identify patients at increased risk for brain damage as well as to select and implement interventions which could alleviate the autonomic and neuropsychological impairment.

Title: MEMORY, THIAMINE LEVELS, AND BRAIN STRUCTURE IN HEART FAILURE
Agency: NIH National Institute of Nursing Research, Project Number 5R21NR011091-02
          DESCRIPTION (provided by applicant): Short-term memory is an important component of outpatient management of heart failure (HF). Many HF patients have short-term memory deficits, which can adversely impact management of their disease and dramatically increase morbidity and mortality. Injury in brain areas which control short-term memory have been reported in HF, with neural damage and symptoms (short-term memory loss, depression) similar to those seen in persons with thiamine deficiency. However, the associations between thiamine levels, brain injury (particularly of the mammillary bodies, which are important structures involved in short-term memory), and clinical measures of short-term memory have not been reported in HF. Therefore, the specific aims of this study are to: 1) Examine the associations between plasma thiamine levels, short-term memory (via the Digit Span Test), and mammillary body volumes (volumetric T1-weighted measures via magnetic resonance imaging [MRI]) in advanced (left ventricular ejection fraction [LVEF] < 0.40; systolic dysfunction; dilated cardiomyopathy) HF patients; 2) Examine the relationships between plasma thiamine levels, short-term memory, and mammillary body volumes and clinical characteristics (age, LVEF, body mass index, number of rehospitalizations for HF in 6 months). Using a one-group, correlational design, 26 HF subjects will undergo structural MRI (T1-weighted), have blood drawn for plasma thiamine analysis, and have their short-term memory evaluated using the Digit Span Test (auditory version). Inclusion criteria for all subjects will be age of 40 years to 65 years, systolic dilated HF, and LVEF < 0.40. Exclusion criteria for all subjects includes claustrophobia, presence of loose metal (for example, pacemakers, braces, implanted hearing aids, or embolic coils). MRI analysis will consist of volumetric measures (using T1) of the bilateral mammillary bodies of each HF subject. Statistical tests will consist of Pearson's correlations, Spearman's rho, and Chi-square with significance set at p < 0.05. In summary, the overall purpose of this study is to identify associations between mammilary body brain structure injury, thiamine levels, and clinical evaluation of short-term memory in HF patients. Information on the association among these factors has important clinical implications in HF. Evaluation of short-term memory is important for both patient education and self-management strategies, as well as for assessment of the impact of HF management treatments and potential identification of new treatment strategies in this high risk patient population. PUBLIC HEALTH RELEVANCE: Heart failure afflicts over 5 million persons in the United States, and many of these patients have significant problems with their memory, which diminishes their capacity to manage their disease and increases morbidity and mortality. Thiamine (B1) is a water-soluble vitamin which can induce both heart failure and brain damage (particularly in the mammillary bodies). Unfortunately, the links among these factors are not clear in heart failure. Identification of the relationship between memory, thiamine, and mammillary body brain injury will enable clinicians to better assess and evaluate heart failure patients and to identify patient education and health care resources to optimize heart failure management of this high risk group.

Title: PASSIVE FOOT MOVEMENT AND SLEEP-DISORDERED BREATHING IN HEART FAILURE
Agency: NIH National Institute of Nursing Research, Project Number 1R21NR012292-01
          DESCRIPTION (provided by applicant): Sleep-disordered breathing (SDB) is common in heart failure (HF) patients and associated with increased morbidity and mortality. Current treatments for SDB have not been shown to improve survival and often have high non-compliance, lack of efficacy in SDB alleviation, and/or associated with pain. Passive foot movement, the rhythmic movement of feet without voluntary effort, is known to increase ventilation but has not been examined in HF patients. We hypothesize that passive foot movement will decrease SDB (decrease in Apnea-Hypopnea Index [AHI]) with little or no impact on sleep state (fewer arousals during sleep), better sleep (measured by the Pittsburgh Sleep Quality Index Questionnaire) and greater preference for passive foot movement compared to continuous/biphasic positive airway pressure (CPAP/BiPAP - traditional SDB treatment methods). Using a one-group, quasi-experimental, pre- and post-test design, we will examine 26 subjects with advanced HF (left ventricular ejection fraction < 0.40, dilated systolic dysfunction, not in acute HF, age 40-65 years) and SDB (AHI > 5 via overnight polysomnography in the previous 6 months) who will be randomized to undergo passive foot movement either during the first or last half of the night during overnight polysomnography. The specific aims for this study are to: 1) Examine the association between SDB (as indicated by AHI), blood oxygen desaturation, carbon dioxide blood levels and passive foot movement; 2) Examine the association between passive foot movement and changes in sleep stage during an overnight sleep study (polysomnography) in HF patients with SDB; 3) Determine the impact of passive foot movement on subjective reports of sleep quality in HF patients with a history of SDB. The objective is of this study is to determine the relationships between a novel treatment option, passive foot movement, and SDB in HF patients. If passive foot movement decreases SDB and is tolerable to persons with HF, this intervention could have change clinical practice and improve outcomes in this high risk patient population. PUBLIC HEALTH RELEVANCE: Sleep-disordered breathing is common in heart failure and is associated with increased morbidity and mortality. Current treatments for sleep-disordered breathing have not demonstrated improvement in heart failure outcomes and often are associated with high non-compliance, ineffectiveness, and/or increased risk for pain. Passive foot movement is the rhythmic movement of the feet without voluntary effort, which results in increased ventilation. It is an innovative treatment option for sleep-disordered breathing which has the potential to effectively treat heart failure patients with dramatically decreased risk of adverse effects. If effective, passive foot movement could have important impact on heart failure disease progression and survival.

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