Pilot Feasibility Study of a Video Intervention to Educate Patients with Breast Cancer About Clinical Trials.

The purpose of this project was to develop and test the feasibility and preliminary efficacy of a video about cancer clinical trials (CCTs) developed for breast cancer patients. We developed 2 brief 7-min videos that focused on breast cancer patients describing their experiences participating in CCTs, supplemented with doctors and research staff explaining key research concepts. One video was culturally tailored to Black patients and the other to White patients. To assess feasibility study, participants and their care providers completed a survey to evaluate their satisfaction with the video. Eligibility criteria for the study included ≥ 21 years of age, English-speaking, no prior experience participating in a CCT, and being potentially eligible for breast CCT enrollment. Preliminary efficacy was evaluated with a pretest-posttest design using a single item asking about intent to enroll in a clinical trial. The mean age of the patient sample (n = 50) was 53.0 years, and 50.0% were Black. Participants reported that the video was in the right length, useful, and easy to understand. Providers' evaluation (n = 5) revealed that viewing the video helped prepare patients for further CCT discussion. Preliminary efficacy showed no statistically significant difference in participant interest in CCT enrollment pre- and post-video. Changes in patients' intent in enrollment were associated with age and education. Culturally adapted video interventions can be helpful in supporting both patients and providers throughout the CCT education process but additional work is needed to improve enrollment into clinical trials.

A comprehensive data-driven analysis framework for detecting impairments in brain function networks with resting state fMRI in HIV-infected individuals on cART.

Central nervous system (CNS) sequelae continue to be common in HIV-infected individuals despite combination antiretroviral therapy (cART). These sequelae include HIV-associated neurocognitive disorder (HAND) and virologic persistence in the CNS. Resting state functional magnetic resonance imaging (rsfMRI) is a widely used tool to examine the integrity of brain function and pathology. In this study, we examined 16 HIV-positive (HIV+) subjects and 12 age, sex, and race matched HIV seronegative controls (HIV-) whole-brain high-resolution rsfMRI along with a battery of neurocognitive tests. A comprehensive data-driven analysis of rsfMRI revealed impaired functional connectivity, with very large effect sizes in executive function, language, and multisensory processing networks in HIV+ subjects. These results indicate the potential of high-resolution rsfMRI in combination with advanced data analysis techniques to yield biomarkers of neural impairment in HIV.

Predictors of disparities in retention in care among African Americans living with HIV.

Limited health literacy may contribute to racial disparities in retention in HIV care. The purpose of this study was to evaluate the effects of health literacy and patient and social-level factors on retention in care among African Americans living with HIV. This study included 699 participants recruited from outpatient HIV clinics and retention in care was defined as visit adherence. Multivariable logistic regression models were used to assess predictors of visit adherence among persons with 100% visit adherence compared to less than 100% visit adherence. Controlling for demographic factors, the odds of 100% visit adherence was greater among non-African Americans compared to African Americans. In models that included health literacy, race was no longer significant and health literacy was a significant predictor of 100% visit adherence. Among participants with less than 100% visit adherence, health literacy was not a significant predictor of visit adherence; however, age, marital status, and patient attitudes towards the health care provider were significant predictors. Findings suggest that health literacy may mediate the relationship between race and visit adherence. Future studies should further examine these relationships and develop interventions that target modifiable factors, with a goal of improving health equity and minimizing disparities.

Is Social Isolation Related to Emotion Dysregulation and Retention in Care Among Older Persons Living with HIV?

Retention in care is important in managing HIV among older persons living with HIV (PLWH). We used Theory of Loneliness-loneliness affects emotion-regulatory processes which lead to dysfunctional health behaviors-to test whether social isolation is related to retention in care either directly or indirectly through emotion dysregulation in older PLWH (≥ 50 years of age; N = 144). Retention in care was defined as the proportion of attended scheduled medical visits; visit data were collected prospectively over 12 months from electronic medical records. Self-reported social isolation, emotion dysregulation, and covariates were assessed cross-sectionally at baseline. Most participants were male (60%), African American/Black (86%), and single (59%); 56% were optimally retained in care. Retention was related to monthly income, CD4 + T cell count, and drug use with no direct or indirect effects of social isolation on retention in care. Socioeconomic and behavioral vulnerabilities are closely related to retention in care among older PLWH.

RESUMEN: Retención en atención médica es importante para el manejo de VIH con personas mayores que viven con VIH (PMVV). Nosotros usamos la Teoría de Soledad- soledad afecta los procesos que regulan emociones y crea comportamientos de salud disfuncionales- para probar si aislamiento social está asociado directamente o indirectamente con la retención en atención médica por desregular emociones en PMVV (≥ 50 años de edad; N = 144). Retención en atención médica fue definido por la proporción de visitas médicas programadas y atendidas; y los datos de visitas atendidas que fueron programadas fueron recopilados prospectivamente por 12 meses de archivos médicos electrónicos. Aislamiento social auto-reportado, desregulación emocional, y covariables fueron evaluados transversalmente de la línea de base. La mayoría de los participantes fueron masculinos (60%), negros/americanos africanos (86%) y solteros (59%); 56% de nuestra muestra fueron retenidos optimamente en atención médica. Retención en atención médica fue asociada con ingresos mensuales, el conteo de linfocitos cd4 + , y el consumo de drogas ilegales; no encontramos efectos directos ni indirectos del aislamiento social a la retención en atención médica. Vulnerabilidades socioeconómicas y de comportamiento están vinculados estrechamente a la retención en atención médica para PMVV.

Adherence trajectories in oral therapy for chronic myeloid leukemia: Overview of a research protocol.

Over a quarter of chemotherapy regimens now include oral agents. Individuals living with cancer are now responsible for administering this lifesaving therapy at home by taking every dose as prescribed. One type of oral chemotherapy, tyrosine kinase inhibitors (TKIs), is the current recommended treatment for chronic myeloid leukemia. This targeted therapy has markedly improved survival but comes with significant side effects and financial costs. In the study described in this protocol, the investigators seek to understand the dynamic nature of TKI adherence experienced by individuals diagnosed with CML. Using a mixed-method approach in this prospective observational study, funded by the National Cancer Institute, we seek to describe subjects' adherence trajectories over 1 year. We aim to characterize adherence trajectories in individuals taking TKIs using model-based cluster analysis. Next, we will determine how side effects and financial toxicity influence adherence trajectories. Then we will examine the influence of TKI adherence trajectories on disease outcomes. Additionally, we will explore the experience of patients taking TKIs by interviewing a subset of participants in different adherence trajectories. The projected sample includes 120 individuals taking TKIs who we will assess monthly for 12 months, measuring adherence with an objective measure (Medication Event Monitoring System). Identifying differential trajectories of adherence for TKIs is important for detecting subgroups at the highest risk of nonadherence and will support designing targeted interventions. Results from this study can potentially translate to other oral agents to improve care across different types of cancer.

Distinct cellular immune properties in cerebrospinal fluid are associated with cognition in HIV-infected individuals initiating antiretroviral therapy.

We examined the relationship between CSF immune cells and neurocognition and neuronal damage in HIV+ individuals before and after initiating antiretroviral therapy. Multivariate analysis at baseline indicated that greater CD4+ T cell abundance was associated with better cognition (p = .017), while higher CSF HIV RNA was associated with increased neuronal damage (p = .014). Following 24 weeks of antiretroviral therapy, CD8+ T cells, HLA-DR expressing CD4+ and CD8+ T cells, B cells, NK cells, and non-classical monocyte percentage decreased in CSF. Female gender was negatively associated with cognitive performance over time, as was higher percentage of HLA-DR expressing CD8+ T cells at baseline.

Neurocognitive Functioning is Associated with Self-Reported and Performance-Based Treatment Management Abilities in People Living with HIV with Low Health Literacy.

OBJECTIVE: People living with HIV (PLWH) are at higher risk for poorer neurocognitive functioning and health literacy than uninfected persons, which are associated with worse medical outcomes. Aging research suggests that the effect of neurocognitive functioning on health outcomes may be more pronounced in those with low health literacy. We aimed to determine whether low health literacy might amplify the adverse effects of neurocognitive functioning on treatment management outcomes in 171 PLWH aged 40+. METHOD: In this cross-sectional, observational study, participants completed a well-validated battery of neurocognitive, health literacy, and treatment management measures. A binary health literacy variable (low vs. adequate) was determined via established cut points on the well-validated health literacy tests. Treatment management outcomes included biomarkers of HIV (i.e., CD4 counts and viral load), self-management of HIV disease (i.e., self-reported medication adherence and self-efficacy for HIV disease management), and performance-based health-related decision-making. RESULTS: Forty-seven percent of the sample met the criteria for low health literacy. Multivariable regressions adjusting for clinicodemographic (e.g., race, socioeconomic status) covariates revealed significant interactions for self-efficacy for HIV disease management and health-related decision-making, such that neurocognitive functioning was associated with these outcomes among those with low, but not adequate health literacy. CONCLUSIONS: Findings suggest that low health literacy may increase the vulnerability of PLWH to the adverse effects of neurocognitive impairment on health outcomes, or conversely that adequate health literacy may provide a buffer against the health risks associated neurocognitive impairment. Interventions targeting health literacy in PLWH may mitigate the effects of neurocognitive impairment on health outcomes.

Psychosocial Resources and Emotions in Women Living With HIV Who Have Cognitive Impairment: Applying the Socio-Emotional Adaptation Theory.

Decreased cognitive function is related to undesirable psychological outcomes such as greater emotional distress and lower quality of life, particularly among women living with HIV who experience cognitive impairment (WLWH-CI). Yet, few studies have examined the psychosocial resources that may attenuate these negative emotional outcomes. The current study sought to identify the interrelated contributions of social relationships and psychological resources in 399 WLWH-CI by applying Socio-Emotional Adaptation (SEA) theory using data from the Women's Interagency HIV Study (WIHS). Cognitive impairment (CI) was defined as impairment on two or more cognitive domains. Logistic regression models were used to estimate the odds of experiencing specific emotions due to a combination of four psychosocial resources. Emotions (i.e., depression, apathy, fear, anger, and acceptance) were related to a combination of binary (positive/negative) psychosocial resources including relationship with an informal support partner, relationship with a formal caregiver, coping, and perceived control. Understanding the conditions that may influence emotions in WLWH-CI is important for identifying and appropriately addressing the needs of this population. As CI increases, these individuals experience increasing challenges with articulating their care needs and having their needs met. As such, it becomes increasingly important to identify possible triggers for emotional responses to best address these underlying challenges.

An Exploratory Study of Correlates of Allostatic Load in Older People Living With HIV.

BACKGROUND: Older people living with HIV (PLWH) experience poorer outcomes than seronegative counterparts. Allostatic load (AL) markers have shown utility as indicators of cumulative wear-and-tear of stress on biological systems. However, little is known about correlates of AL in PLWH. METHODS: Ninety-six PLWH aged 50+ completed a comprehensive neurobehavioral assessment and blood draw. Select AL markers (ie, 10 blood markers) were available for a subset (n = 75) of seronegative controls. AL was operationalized as a sum of markers in the highest risk quartile for: cortisol, DHEA, IL-6, TNF-alpha, C-reactive protein, glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, albumin, systolic and diastolic blood pressure, and body mass index. RESULTS: PLWH had higher risk levels than seronegatives with small-medium effect sizes for several biomarkers. Among HIV+ African Americans (84% of PLWH), higher AL was associated with lower psychological resilience (rho = -0.27, P = 0.02), less physical activity (rho = -0.29, P < 0.01), poorer neurocognitive functioning (rho = -0.26, P = 0.02), greater basic activity of daily living complaints (P < 0.01), and diabetes (P < 0.01). Multivariable regressions within African American PLWH for significant AL-outcome associations (ie, neurocognitive function, basic activity of daily living complaints, diabetes) showed that associations with AL remained significant when adjusting for relevant covariates. Mediation analysis suggested that the association between socioeconomic status and neurocognitive function was mediated by AL. CONCLUSIONS: These exploratory findings are consistent with the larger aging literature, suggesting that lower AL may serve as a pathway to better health and functional outcomes, particularly in African American PLWH. Furthermore, resilience and physical activity may reduce AL in this population.

Disparities in Retention in Care Among Adults Living with HIV/AIDS: A Systematic Review.

As national HIV prevention goals aim to increase the proportion of persons living with HIV, determining existing disparities in retention in care will allow for targeted intervention. The purpose of this systematic review was to identify existing disparities in retention in care. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 guided this systematic review. Electronic databases, including PubMed/MEDLINE, CINAHL, Sociological Collection, PsychInfo, and Cab Direct/Global Health, were systematically searched and twenty studies were included. This review identified disparities in retention in care that have been documented by race, gender, age, HIV exposure, incarceration history, place of birth, and U.S. geographic location. Research is necessary to further identify existing disparities in retention in care and to better understand determinants of health disparities. Additionally, interventions must be tailored to meet the needs of health disparate populations and should be assessed to determine their effectiveness in reducing health disparities.

Correlates of loneliness in older persons living with HIV.

Loneliness poses a significant risk for morbidity and mortality in the context of older adulthood. Research shows that older persons living with HIV (PLWH) often face increased and complex vulnerability in terms of physical and psychosocial needs which may promote loneliness. The current study sought to identify correlates of loneliness in a sample of 146 older PLWH (age ≥50) recruited from an outpatient HIV clinic in Atlanta, GA. Participants completed a survey on loneliness, depression, HIV-related stigma, social network size, HIV-disclosure status, disease burden, and demographics. HIV biomarkers were abstracted from electronic medical records. Participants were predominantly male (60%) and African American (86%). Twelve percent (n = 17) reported past homelessness/unstable housing. Multivariable modeling revealed that depression and HIV-related stigma explained 41% of the variance in loneliness, above and beyond the effects of past homelessness/unstable housing and disease burden (R2 = 0.41, F(7, 138) = 13.76, p < .001). Findings suggest that targeting HIV-related stigma and depression may reduce loneliness in older PLWH, but more studies are needed to elucidate causal pathways. A greater understanding of the mechanisms by which loneliness affects health among older PLWH could help better inform efforts to improve health in this patient population.

A Path Analysis of Patient and Social-Level Factors on Health Literacy and Retention in Care Among African Americans Living with HIV.

Low health literacy and poor retention in care may contribute to HIV health disparities among African Americans, but causal pathways have not been examined. We utilized an adapted health literacy model to examine the role of health literacy on racial disparities in retention in care. Retention in care for 699 participants was assessed 24-months post survey and operationalized as 100% visit adherence versus less than 100% visit adherence. Most participants were African American (60%) and virally suppressed (93%). Results from a path analysis revealed that non-African American race was related to greater health literacy (p = .023) and to 100% visit adherence (p = .024). Greater health literacy was associated with 100% visit adherence (p = .008), which was in turn related to viral suppression (p < .001). Findings indicate that health literacy partially mediates the relationship between race and retention in care and are among the first to suggest these causal pathways.

Same-Day Associations Between Substance Use and Medication Nonadherence Among Persons Living with HIV.

OBJECTIVES: To examine the same-day associations between substance use and objectively measured antiretroviral therapy (ART) nonadherence among persons living with HIV (PLWH). METHODS: PLWH (N = 53) were given an electronic pill box (EPB), and their ART adherence was monitored for 14 days. During a follow-up interview, participants were asked about any alcohol or drug use that occurred during those same 14 days. RESULTS: Daily heavy drinking (⩾5 drinks for males and ⩾4 drinks for females) was associated with a nearly five times greater likelihood of same-day ART nonadherence (OR = 4.90, 95% CI = 1.79-13.36, P = .002). Further, drug use was associated with a nearly two times greater likelihood of ART nonadherence on the same day (OR = 1.80, 95% CI = 1.14-2.85, P = .012). CONCLUSIONS: These results highlight the importance of continuing to pursue interventions to effectively address heavy drinking and drug use among PLWH in order to improve ART adherence.

Enhancing the Impact of Mobile Health Literacy Interventions to Reduce Health Disparities.

Health literacy is a key factor in health outcomes that should be considered when creating mobile health promotion apps. In this paper, we detail our work over the past 10 years in developing the theory and practice of targeting the content of mobile apps at a level appropriate for the intended audience. We include a review of our theory of health literacy as expertise, the ASK model, and integrate it with the Theory of Planned Behavior. We then provide data that support both the model and its use. More recently, we have developed a predictive analytic model that uses demographic information and patient performance on a 10-item screening measure to determine patient level of health literacy at a high level of accuracy. The predictive model will enable apps to automatically provide content to users at an appropriate level of health literacy. This strategy, along with other aspects of tailoring, will allow apps to be more personally relevant to users, enhancing their effects in promoting health behavior change.

Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.

HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer's disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181 and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181 to characterize HAND.

Relationship Between Depressive Symptoms and Engagement With the Health Care Provider in People Living With HIV: A Two-Wave Cross-Lag Model.

Depressive symptoms in persons living with HIV (PLWH) negatively affect retention in care, antiretroviral therapy adherence, and health outcomes. Patient-provider relationships and depressive symptoms are associated, but less is known regarding their bidirectional relationship. We assessed whether depressive symptoms in PLWH are a risk factor or a consequence of the patient-provider relationship or both. We used a two-wave cross-lag model to test the prospective and reciprocal relationship between depressive symptoms and the patient-provider relationship, from baseline to 28-week follow-up. The findings from our study found no causal association between depressive symptoms and the patient-provider relationship. Specifically, findings revealed that available social support and HIV stigma weaken the effect of the baseline patient-provider relationship on later depressive symptoms. Findings from our study suggest that although the patient-provider relationship is beneficial for mental health outcomes in PLWH, addressing sociodemographic factors may be of greater importance.

Picture Pill Count: An Innovative, Reliable, Valid and Feasible Method to Measure Adherence to ART.

We report the reliability, validity, and feasibility of self-performed picture pill count (PPC) as an adherence measure that was used in a randomized trial with HIV positive people living in rural Georgia. The first 61 (of 149) participants conducted an additional PPC 1-2 days after baseline. Reliability, measured by a PPC scoring instrument, analyzed participants' ability to reproduce high quality pill count photographs free from artifact or blurring that could hamper accurate visualization of the pills and bottle labels. Except for label blur, baseline photographs (performed with coaching by study staff) and independently performed post-baseline photographs were rated as acceptable quality (> 93%). Label blur significantly worsened between the baseline and post-baseline scoring (93% vs 80%, p = 0.039), possibly indicating that participants required more education to ensure readability. Validity was determined by comparing the number of pills entered into the PC survey with the number of pills in the texted PPC; 77.5% of participants had perfectly matched pill counts (r = 0.690, p < 0.001). We found PCC to be a reliable and valid method of measuring adherence. The high rate of participant satisfaction underscores its feasibility. It provides an innovative alternative to other more invasive and labor intensive methods of measuring adherence using pill counts.

Exercise and Cognitive Training as a Strategy to Improve Neurocognitive Outcomes in Heart Failure: A Pilot Study.

OBJECTIVE: Mild cognitive impairment, especially memory loss, is prevalent in patients with heart failure (HF) and contributes to poor clinical outcomes and higher mortality. METHODS: This study evaluated a combined aerobic exercise and cognitive training (EX/CT) program on memory, executive function, attention, processing speed and reaction time compared to exercise only or a usual care attention control (UCAC) stretching and flexibility program. Participants completed a standardized neurocognitive battery at baseline, 3 months, and 6 months along with demographic, clinical, and functional capacity (6-minute walk test). A linear mixed model analysis was used with comorbidity as a covariate. RESULTS: Sixty-nine participants were enrolled, the mean age was 61 ± 10 years, 54% were women, 55% were African American, and the mean left ventricular ejection fraction percentage was 35 ± 15. A significant group by time interaction for verbal memory was found at 3 months (F [2, 53] = 4.3, p = 0.018) but was not sustained at 6 months in the EX/CT group. Processing speed/attention differed across treatment groups between baseline and 6 months, but improvement occurred among UCAC participants. There were also significant group differences in the 6MWT distance occurring at 3 months (F [2, 52] = 3.5, p = 0.036); however, significant improvement was observed within the EX/CT group only. There were no significant differences in 6MWT in the other groups at 3 or 6 months. CONCLUSION: An EX/CT intervention was associated with improved memory in persons with HF and warrants further investigation in a larger trial. The relationship between functional capacity and cognitive function also needs further study.

A mixed analysis approach to elucidate the multiple chronic condition experience of English- and Spanish-speaking older adults.

BACKGROUND: Having multiple chronic conditions (MCCs) is the most common health condition in older adults. The management of each condition presents many challenges. A key factor in patients' ability to manage their own health care is their level of health literacy. PURPOSE: The purpose of this mixed analysis study was to elucidate the experience of older adults living with MCCs and identify associations among the experiences to determine targets for future mobile health (mHealth) interventions focused on MCCs and health literacy. PARTICIPANTS AND METHODS: Using the Abilities, Skills, and Knowledge Model as a framework, semi-structured interviews were completed with 25 older adults in English and Spanish. Interviews were analyzed using inductive thematic analysis and hierarchical cluster analysis. RESULTS: The main themes from these results included 1) Reflections of chronic disease; 2) Emotional aspects of chronic disease; 3) Physical barriers to well-being; 4) Quality-of-care factors; and 5) Cognitive strategies for self-management. Qualitative results highlighted the importance of a multi-targeted approach to chronic disease self-management (CDSM). Cluster analysis identified associations within the qualitative data, revealing the importance of the subthemes related to coping with pain and the impact of the patient-provider relationship on treatment adherence. CONCLUSION: Results support the utility of mHealth interventions to improve health literacy and promote CDSM.

HIV-1 Infection, Injecting Drug Use, and Neuroendocrine Response to Psychological Stress.

BACKGROUND: Previous studies have suggested that HIV-1 infection is associated with neuroendocrine abnormalities including alterations in autonomic nervous system (ANS) activity. The norepinephrine (NE) response to cold pressor stress, an α-adrenergic challenge, is blunted in HIV-1 infection. Given the relation of ANS activity to the function of the hypothalamic-pituitary-adrenal (HPA) axis and its role in cognitive functioning, changes in response to stress may be a factor in HIV-related cognitive dysfunction. OBJECTIVE: In this study, we evaluated the NE and cortisol response of persons in three groups. DESIGN/PARTICIPANTS: We studied stress response in three groups: (1) those with HIV-1 infection and a history of injecting drug use (IDU), those with HIV-1 infection but no IDU, and a control group of uninfected individuals without a history of IDU. Stress was induced by administering a neuropsychological test known to induce an immediate increase in NE, the Stroop Color-Word Test. Blood samples were obtained immediately before and after participants completed the Stroop and then at two intervals over the next 20 minutes. Data were analyzed using mixed-effects repeated measures models. MAIN MEASURES: Serum norepinephrine, epinephrine, and cortisol. RESULTS: Analyses showed that those with both HIV-1 infection and history of IDU had a significantly greater NE response to stress that did not return to baseline over 20 minutes compared to those without infection or IDU history. Epinephrine and cortisol responses followed similar patterns, but between-group differences were not statistically significant. CONCLUSIONS: The combination of history of IDU and HIV infection may produce an exaggerated neuroendocrine response that does not quickly return to baseline levels. Given the potential impact of these on cognitive and physical function in affected these individuals, implementing stress management techniques with them may be important.