Palliative Care in the Neonatal Intensive Care Unit: An Evolutionary Concept Analysis of Uncertainty in Anticipated Loss.

BACKGROUND: Although the concepts of uncertainty and anticipated loss have been explored in a variety of contexts, advances in genetic testing and life-sustaining technology rendered changes in the care of medically complex infants. The separate concepts no longer have the descriptive power to clarify new phenomena endured by parents in the changing neonatal landscape. A current concept analysis examining uncertainty in anticipated loss is necessary to generate knowledge concurrently with deviations observed in the neonatal intensive care unit. PURPOSE: To explore the concept of uncertainty in anticipated loss among parents of infants with genetic disorders. METHODS: Following Rodgers' method of concept analysis, the concept was named, surrogate terms, antecedents, attributes, and consequences were identified from the literature, and a model case was constructed. The databases CINAHL, PubMed, and PsycINFO were used to conduct the literature search. RESULTS: Fifteen articles provided the data for this analysis. Uncertainty in anticipated loss is a complex, nonlinear, and multifaceted experience anteceded by an ultimately terminal diagnosis, an ambiguous prognosis, and a lack of clear knowledge to guide treatment. Its attributes include a loss of control, assumptive world remodeling, role/identity confusion, and prolonged emotional complexity that consequently leads to a cyclical pattern of positive and negative outcomes. IMPLICATIONS: This newly defined concept empowers neonatal nurses to provide care that includes a holistic understanding of the experience of uncertainty in anticipated loss . Nurses are ideally positioned and have the responsibility to utilize this concept to become better advocates for infants and facilitators of parental wellness.

Associations Between Estimates of Arterial Stiffness and Cognitive Functioning in Adults With HIV.

BACKGROUND: Vascular aging, a precursor of arterial stiffness, is associated with neurocognitive impairment (NCI) and cardiovascular disease. Although HIV is associated with rapid vascular aging, it is unknown whether arterial stiffness mediates changes in cognitive function. We explored whether estimated markers of vascular aging were associated with NCI indices in HIV-positive individuals. METHODS: This study was a secondary analysis of an observational study. Neurocognitive functioning was assessed using a battery of 7 domains (verbal fluency, executive functioning, speed of information processing, attention/working memory, memory [learning and delayed recall], and motor skills). Vascular aging was assessed using estimated markers of arterial stiffness (ie, estimated pulse wave velocity, pulse pressure, and vascular overload index). A multivariable regression adjusted for demographics, cardiovascular disease risk factors, and HIV clinical variables was used to examine the association between vascular aging and NCI outcomes. RESULTS: Among 165 people with HIV, the mean age was 51.5 ± 6.9 years (62% men and 83% African American/Black or Other). In fully adjusted models, an increase in estimated pulse wave velocity and pulse pressure was associated with lower T scores in learning (-2.95 [-5.13, -0.77]) and working memory (-2.37 [-4.36, -0.37]), respectively. An increase in vascular overload index was associated with lower T scores in working memory (-2.33 [-4.37, -0.29]) and learning (-1.85 [-3.49, -0.21]). CONCLUSIONS: Estimated markers of arterial stiffness were weakly associated with neurocognitive functioning, suggesting that vascular aging may have a role in cognitive decline among people with HIV.

A descriptive assessment of the informed consent document used by congenital cardiac surgery centres.

BACKGROUND: Informed consent for surgery is a complex process particularly in paediatrics. Complexity increases with procedures such as CHD surgery. Regulatory agencies outline informed consent contents for surgery. We assessed and described CHD surgical informed consent contents through survey dissemination to paediatric CHD centres across United States of America. METHODS: Publicly available email addresses for 125 paediatric cardiac clinicians at 70 CHD surgical centres were obtained. Nine-item de-identified survey assessing adherence to The Joint Commission informed consent standards was created and distributed via RedCap® 14 March, 2023. A follow-up email was sent 29 March, 2023. Survey link was closed 18 April, 2023. RESULTS: Thirty-seven surveys were completed. Results showed informed consent documents were available in both paper (25, 68%) and electronic (3, 8%) format. When both (9, 24%) formats were available, decision on which format to use was based on centre protocols (1, 11%), clinician personal preference (3, 33%), procedure being performed (1, 11%), or other (4, 45%). Five (13%) centres' informed consent documents were available only in English, with 32 (87%) centres also having a Spanish version. Review of informed consent documents demonstrated missing The Joint Commission elements including procedure specific risks, benefits, treatment alternatives, and expected outcomes. CONCLUSIONS: Informed consent for CHD surgery is a complex process with multiple factors involved. Majority of paediatric CHD surgical centres in the United States of America used a generic informed consent document which did not uniformly contain The Joint Commission specified information nor reflect time spent in discussion with families. Further research is needed on parental comprehension during the informed consent process.

Cognitive intra-individual variability in breast cancer survivors: A systematic review.

Subjective and objective cognitive impairments in Breast Cancer Survivors (BCS) often do not correlate. One important contribution to the reported disparities may be the reliance on mean-based cognitive performance. Cognitive intra-individual variability (IIV) may provide important insights into these reported disparities. Cognitive IIV refers to the fluctuation in performance for an individual on either one cognitive task across a trial or dispersed across tasks within a neuropsychological test battery. The purpose of this systematic review was to search for and examine the literature on cognitive IIV in BCS. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach was used to search for all articles related to cognitive IIV in BCS. MEDLINE (via PubMed), Embase, and Scopus databases were searched using detailed search terms and strategies. Initially, 164 articles were retrieved but only 4 articles met the criteria for this systematic review. BCS differed from healthy controls in similar ways across the four studies, generally demonstrating similar performance but showing increased cognitive IIV for the more difficult tasks. Differences were enhanced later during chemotherapy. The four studies provide support for cognitive IIV as a useful measure to detect the subtle objective cognitive change often reported by BCS but frequently not detected by standard normed-based cognitive testing. Unexpectedly, measures of cognitive IIV were not consistently associated with self-reported measures of cognition.

Health Literacy in Parents of Children Newly Diagnosed With Cancer and Comprehension of Key Concepts Related to Their Child's Care.

Background: There is a paucity of literature regarding health literacy in pediatric oncology. We sought to understand the relationship between health literacy and comprehension of key new diagnosis education concepts in parents of children newly diagnosed with cancer. Methods: Using data from a study evaluating a structured new diagnosis discharge teaching intervention, we performed a secondary analysis to understand the relationship between parental health literacy (Brief Health Literacy Screener: BHLS) and comprehension of six key concepts (child's diagnosis, primary oncologist, and treatment plan; seeking emergent care; fever definition; re-dosing medication). We also evaluated the association between parents self-reported sociodemographic characteristics, preferred learning style (one-item ordinal assessment) and health literacy. We tested relationships using Fisher's exact tests, independent samples t-tests, and Pearson correlations. Results: Fifty parents participated (age 35.4 ± 8.2 years [M ± SD]; 86% female; 60% non-Hispanic white; 24% with ≤high school education); nine parents (18%) scored in the BHLS low literacy range; 80% correctly responded to all six items on the key concepts questionnaire (100% comprehension). Health literacy was not significantly related to 100% comprehension or to individual key concept responses, with the exception of "child's treatment plan" (correct responses: 55.6% in low vs. 100% in adequate literacy groups; p < .001). Parental sociodemographic characteristics and preferred learning styles were not significantly related to health literacy. Discussion:Despite variability in health literacy levels, 80% of the parents comprehended all key concepts, suggesting that the intervention was effective for most parents, regardless of health literacy level.

Inflammatory and Cardiovascular Correlates of Physical Activity and Sedentary Behavior in Older Adults Living With HIV.

BACKGROUND: Inflammation is an indicator of oxidative stress that may contribute to cardiovascular diseases in older people living with HIV (OPWH). Physical activity (PA) may reduce these biomarkers in OPWH, but little is known about the association of PA with inflammatory and cardiovascular biomarkers. We sought to examine the inflammatory and cardiovascular biomarker correlates of PA and sedentary behavior in OPWH. METHODS: We included 101 OPWH with complete assessments of PA, sedentary behavior, and biomarker data to examine the association between the volume of PA and inflammatory and cardiovascular biomarkers. RESULTS: In this cohort of OPWH (mean age 55.9 y), 68% were male and 83% were African American/Black. Among OPWH, greater volume of PA (ie, walking, moderate, vigorous, and/or total) was associated with lower systolic (P < .05) and diastolic blood pressure (P < .05), pulse pressure (P < .05), and tumor necrosis factor-alpha (P < .05). Greater duration of sitting was associated with greater triglycerides, interleukin-6, and tumor necrosis factor-alpha (P < .05). CONCLUSIONS: Although adherence to regular PA among OPWH is low and sedentary behavior is high, the associations between biomarkers and PA suggest a greater volume of PA could attenuate the inflammatory and cardiovascular derangements experienced by OPWH.

Factors Associated With Health-Related Quality of Life 2 Years After Left Ventricular Assist Device Implantation: Insights From INTERMACS.

Background Factors related to health-related quality of life (HRQOL) 2 years after left ventricular assist device (LVAD) implantation are unknown. We sought to determine whether preimplant intended goal of LVAD therapy (heart transplant candidate [short-term group], uncertain heart transplant candidate [uncertain group], and heart transplant ineligible [long-term group]) and other variables were related to HRQOL 2 years after LVAD implantation. Methods and Results Our LVAD sample (n=1620) was from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Using the EuroQol-5 Dimension Questionnaire (EQ-5D-3L), a generic HRQOL measure, and the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a heart failure-specific HRQOL measure, multivariable linear regression modeling was conducted with the EQ-5D-3L Visual Analog Scale (VAS) score and KCCQ-12 overall summary score (OSS) as separate dependent variables. Two years after LVAD implant, the short-term group had a significantly higher mean VAS score versus the uncertain and long-term groups (short-term: 75.18 [SD, 20.62]; uncertain: 72.27 [SD, 20.33]; long-term: 70.87 [SD, 22.09], P=0.01); differences were not clinically meaningful. Two-year mean scores did not differ by group for the KCCQ-12 OSS (short-term, 67.85 [SD, 20.61]; uncertain, 67.79 [SD, 19.31]; long-term, 67.08 [SD, 21.49], P=0.80). Factors associated with a worse VAS score 2 years postoperatively (n=1205) included not working; not having a short-term LVAD; and postoperative neurological dysfunction, greater health-related stress, coping poorly, less VAD self-care confidence, and less satisfaction with VAD surgery, explaining 28% of variance (P<0.001). Factors associated with a worse KCCQ-12 OSS 2 years postoperatively (n=1250) included not working; history of high body mass index and diabetes mellitus; and postoperative renal dysfunction, greater health-related stress, coping poorly, less VAD self-care confidence, less satisfaction with VAD surgery, and regret regarding VAD implantation, accounting for 36% of variance (P<0.001). Conclusions Factors related to HRQOL 2 years after LVAD implantation include demographic, clinical, and psychological variables.

Description of the Nature of Musculoskeletal Shoulder Injuries in a Cohort of Commercial Truck Drivers: A Retrospective Cross-Sectional Study.

BACKGROUND: Commercial truck drivers (CTDs) are significantly affected by shoulder injuries; however, little is known about the unique mechanisms of injury (MOIs), specific injuries, or possible preventive measures among this group of workers. This study characterized the MOIs, musculoskeletal disorders (MSDs), and factors associated with MSDs of the shoulder among a group of CTDs. METHODS: A retrospective medical record review was conducted of CTDs between 21 and 65 years of age who were seen for MSDs of the shoulder between 2007 and 2015. RESULTS: A total of 130 CTDs were included, who were aged 21 to 65 years. Commercial truck drivers were most often injured during a fall (35%) or while using chains, tarps, or straps (31%). The two most common MSDs were unspecified sprains/strains (58%) and rotator cuff tears (24%). Age was found to be associated with all MSDs (p = .001) and an increased risk of developing rotator cuff tears (p =.005). Seventy-four percent of CTDs who experienced a rotator cuff tear were 46 years of age or older. CONCLUSION/APPLICATION TO PRACTICE: This study highlights the course of the injury in terms of diagnostics such as magnetic resonance imaging (MRI) and referral for surgery and describes the occupational activities associated with CTDs. These findings can inform employer injury prevention programs, patient and health care provider education, and future interventional research.

Targeting HIV-Related Neurocognitive Impairments with Cognitive Training Strategies: Insights from the Cognitive Aging Literature.

Approximately 50% of older adults with HIV meet the Frascati diagnostic criteria of HIV-associated neurocognitive disorders (HAND) which can interfere with everyday function such as medication adherence, employment, and driving ability, thus reducing quality of life. As the number of older adults with HIV continues to grow, many will become vulnerable to cognitive frailty, especially as they experience multimorbidities, polypharmacy, and geriatric syndromes. Healthcare professionals need strategies to prevent, remediate, and compensate for cognitive losses observed in memory, language, executive functioning, and speed of processing. Sadly, there are no standard protocols or accepted treatment/intervention guidelines to address HAND at this time. Fortunately, evidence from the cognitive aging literature indicates that cognitive training can protect and improve cognition in normal older adults and may even reduce the incidence of dementia/MCI. This article provides the scientific context in which computerized cognitive training approaches have been successfully used in older adults and provides examples of how these approaches have been translated to adults with HIV. Evidence from ongoing clinical trials are also presented that suggest that reversing a diagnosis of HAND may be possible. Recommendations for clinical practice and research are provided.

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.

Differences in health-related quality of life by implant strategy: Analyses from the Interagency Registry for Mechanically Assisted Circulatory Support.

BACKGROUND: Midterm change in health-related quality of life (HRQOL) by left ventricular assist device (LVAD) implant strategy is unknown. The purpose of this study was to examine HRQOL by pre-operative implant strategy from before to 2 years after surgery. METHODS: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support were stratified into 3 groups based on pre-implant device strategy: destination therapy (DT) (n = 2,901), bridge to transplant (BTT) (n = 2,209), and bridge to candidacy (BTC) (n = 3,076). HRQOL data were collected before and 2 years after surgery using the generic EQ-5D-3L survey and heart failure-specific Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Statistical analyses included chi-square tests, analysis of variance, paired t-tests, and general linear random effects models. RESULTS: Between April 1, 2008 and June 30, 2013, 4,422 patients and 1,660 patients (majority males and ≥50 years) who received primary continuous flow LVADs completed baseline EQ-5D-3L and KCCQ-12 questionnaires, respectively, whereas 1,615 and 1,408 patients completed EQ-5D-3L and KCCQ-12 questionnaires at 2 years, respectively. Although paired t-tests and general linear random effects models showed that both heart failure-specific and generic HRQOL improved for all groups across time (p-values <0.05), some differences in HRQOL were found by implant strategy at baseline and 2 years, with a pattern favoring better functioning for patients with BTT. The BTT group reported significantly higher overall HRQOL pre-implant using the KCCQ-12 (BTT = 37.09, BTC = 33.57, and DT = 33.56) and at 2 years using the EQ-5D-3L (BTT = 75.18, BTC = 72.27, and DT = 70.87) (p-values <0.05), although these differences were not clinically important differences. Differences in HRQOL domains were also found. CONCLUSIONS: Using generic and heart failure-specific instruments, overall HRQOL generally improved from before to 2 years after mechanical circulatory support implant regardless of implant strategy, although important domain-specific differences by group were identified.

Effects of a speed of processing training intervention on self-reported health outcomes in breast cancer survivors.

Purpose: Cognitive deficits are a concern for breast cancer survivors, as these effects are prevalent and impact daily functioning and quality of life (QoL). The purpose of this study was to examine the effects of a speed of processing (SOP) training intervention on secondary, self-reported health outcomes in this population. Methods: Sixty middle-aged and older adult women breast cancer survivors completed baseline assessments and were randomized to either a no-contact control group or an SOP training group, who completed 10 hrs of computerized SOP training online at home. Both conditions completed self-report surveys of sleep, QoL, cognitive difficulties, and depressive symptoms at six weeks and six months post study entry. Results: There were no significant effects of the SOP training on self-reported health outcomes. Conclusion: Future studies examining the effect of cognitive training on self-reported health outcomes are warranted that include individuals with baseline impairment in such indices in order to better determine efficacy, and longer follow-up time points may aid in examining the protective effects of this intervention in those without baseline impairment.

Positive Psychological Factors are Linked to Successful Cognitive Aging Among Older Persons Living with HIV/AIDS.

We aimed to characterize successful cognitive aging (SCA) among older HIV-infected (HIV+) and HIV-uninfected (HIV-) adults, and to determine associations with positive psychological factors and health-related quality of life (HRQoL). Ninety-nine HIV+ and 46 HIV- older adults (≥ 50 years) completed measures of neurocognition, positive psychological factors, and HRQoL. Using study-defined SCA criteria (i.e., no cognitive or everyday impairment or major depressive disorder), we compared positive psychological factors and HRQoL across four groups: HIV+/SCA+, HIV+/SCA-, HIV-/SCA+, HIV-/SCA-. SCA was identified in 29% of the HIV+ sample compared to 61% of the HIV- sample (p < 0.01). HIV+/SCA+ participants had higher scores on 8 of 10 measures of positive psychological factors as well as better HRQoL (ps < 0.05) as compared to the HIV+/SCA- group. Furthermore, the HIV+/SCA+ participants had comparable scores on these factors as HIV- adults. Fewer HIV+ than HIV- participants met SCA criteria; however, the level of positive psychological factors among the HIV+/SCA+ group was comparable to the HIV- sample. Our findings present opportunities for interventions to optimize positive psychological factors and potentially improve SCA among older HIV+ adults.

RESUMEN: Nuestro objetivo fue caracterizar el envejecimiento cognitivo exitoso (ECE) entre personas mayores VIH+ y VIH−, y determinar asociaciones con factores psicológicos positivos y con la calidad de vida relacionada a la salud (CVrS). Noventa y nueve personas mayores (de 50 años o más) VIH+ y 46 VIH− completaron indicadores de neurocognición, de factores psicológicos positivos y de CVrS. Mediante la utilización de criterios de ECE definidos por el presente estudio (p. ej. la ausencia de deterioro cognitivo, impedimentos en el funcionamiento cotidiano, o trastorno depresivo mayor) comparamos los factores psicológicos positivos y la CVrS entre cuatro grupos: VIH+/ECE+, VIH+/ECE−, VIH−/ECE+, VIH−/ECE−. El ECE fue identificado en 29% de la muestra de VIH+ comparado con 61% de la muestra de VIH− (p < 0,01). Los participantes VIH+/ECE+ obtuvieron puntuaciones más altas en 8 de los 10 indicadores de factores psicológicos positivos, así como mejor CVrS (ps < 0,05), comparado con el grupo VIH+/ECE−. Además, los participantes VIH+/ECE+ obtuvieron valores comparables a los de los adultos VIH− en estos factores. Una proporción menor de participantes VIH+ que VIH− cumplieron criterios de ECE; sin embargo, el nivel de los factores psicológicos positivos en el grupo VIH+/ECE+ fue comparable a la muestra de la población VIH−. Nuestros resultados presentan oportunidades de intervención para optimizar los factores psicológicos positivos y potencialmente mejorar el ECE entre los adultos mayores con VIH.

Feedback on a Multimodal Cognitive Intervention for Adults Aging With HIV: A Focus Group Study.

Nearly 50% of adult persons living with HIV (PLWH) experience HIV-associated neurocognitive disorder (HAND), which is associated with deteriorating brain health and cognitive functioning. Multimodal interventions that simultaneously improve physical activity, nutrition, and sleep hygiene may be of value for adult PLWH, especially as they age and become vulnerable to HAND. We used four focus groups of PLWH (N = 30; ages ≥ 50 years) to solicit feedback about Cognitive Prescriptions, a multimodal cognitive intervention. Lifestyle and health behaviors pertaining to Cognitive Prescriptions were assessed, including: (a) physical activity, (b) mental activity, (c) nutrition, (d) social engagement, (e) emotional health, (f) sleep hygiene, and (g) substance use. When presented a template of the intervention, participants expressed favorable opinions and remarked they would want to work with a clinician, paraprofessional, or peer to implement such a program into their own daily routines. From this, implications for practice and research are provided.

Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy.

BACKGROUND: HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. METHODS: To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected. RESULTS: HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (ß = 0.41, P < 0.01) and VEGF (ß = -0.43, P = 0.01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P < 0.01). In turn, PP demonstrated a quadratic association with neurocognitive function (ß = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. CONCLUSIONS: These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.

Higher Cystatin C Levels Are Associated With Neurocognitive Impairment in Older HIV+ Adults.

OBJECTIVE: The study aims to determine whether cystatin C is associated with HIV disease and HIV-associated neurocognitive impairment (NCI). METHODS: Participants included 124 (HIV+ n = 77; HIV- n = 47) older adults (age ≥ 50 years) examined at the University of California, San Diego HIV Neurobehavioral Research Program. Cystatin C, a biomarker of kidney functioning that has been linked to poor health outcomes, was measured in blood. Participants completed a comprehensive neurocognitive assessment that was used to define both global and domain NCI. RESULTS: The HIV+ group had significantly higher cystatin C concentrations than the HIV- group (d = 0.79 P < 0.001). Among HIV+ participants, those with NCI had higher cystatin C concentrations than those without NCI (d = 0.42, P = 0.055), particularly among participants taking tenofovir (d = 0.78, P = 0.004). A receiver-operator characteristic curve identified that cystatin C levels ≥0.75 mg/L were associated with NCI in the HIV+ group. Using this binary variable and including relevant covariates, multivariate modeling confirmed that NCI was associated with higher cystatin C levels (OR = 3.0; P = 0.03). CONCLUSIONS: Our results confirm that HIV+ older adults have higher cystatin C than HIV- older adults and further identify that cystatin C may be associated with NCI in this population, particularly if they use tenofovir. This blood biomarker may be a useful clinical tool to identify older HIV+ persons at greater risk for cognitive decline.

The Veterans Aging Cohort Study (VACS) Index and Neurocognitive Change: A Longitudinal Study.

BACKGROUND: The Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity among human immunodeficiency virus (HIV)-infected persons, has been associated with concurrent risk for neurocognitive impairment (NCI). The present study examined whether the VACS Index predicts longitudinal neurocognitive change. METHODS: Participants included 655 HIV-infected persons followed for up to 6 years in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (mean age at baseline, 42.5 years; 83% male; 60% white; AIDS in 67%; median current CD4(+) T-cell count, 346/µL; 61% receiving antiretroviral therapy). The VACS Index was calculated through standard methods. Participants completed a comprehensive neurocognitive battery. Neurocognitive status was plotted over time using demographically and practice-adjusted global and domain T scores. NCI was defined by global deficit scores derived from T scores. RESULTS: Baseline VACS Index scores were not predictive of changes in global T scores during the follow-up period (P = .14). However, in time-dependent analyses adjusting for covariates, higher VACS Index scores were significantly associated with worse global and domain neurocognitive performance (Ps < .01), as well as increased risk for developing NCI in a subgroup of persons who were neurocognitively normal at baseline (hazard ratio [HR], 1.17; P < .001). We categorized VACS Index scores by quartiles and found that the upper-quartile group was significantly more likely to develop NCI than the lower quartile (HR, 2.16; P < .01) and middle groups (HR, 1.76; P < .01). CONCLUSIONS: Changes in VACS Index scores correspond to changes in neurocognitive function. HIV-infected persons with high VACS Index scores are at increased risk for decline and incident NCI. The VACS Index shows promise as a tool for identifying HIV-infected persons at risk for NCI.

Complement Component 3 Is Associated with Metabolic Comorbidities in Older HIV-Positive Adults.

Our objective was to evaluate the association of plasma inflammatory biomarkers with MetS in an older population of treated HIV-infected (HIV(+)) as compared to age-matched HIV-negative (HIV(-)) adults. This was done in a retrospective observational study. Plasma concentrations of complement component 3 (C3), cystatin C, fibroblast growth factor 1, interleukin 6, oxidized LDL, soluble RAGE, soluble CD163, soluble CD14, and osteopontin were measured in 79 HIV(+) participants on combination antiretroviral treatment (cART) with a suppressed HIV viral load and 47 HIV(-) participants with a median age of 59 (range 50 to 79). Outcomes were individual MetS components (hypertension, type II diabetes, dyslipidemia, and obesity) and MetS. Covariates were screened for inclusion in multivariable models. Odds ratios are reported per 50 mg/dl increase in C3. In the HIV(+) group, higher C3 levels were associated with MetS (OR 3.19, p = 0.004), obesity (OR 2.02, p = 0.01), type II diabetes (OR 1.93, p = 0.02), and at a trend level with dyslipidemia (OR 1.87, p = 0.07) and hypertension (OR 1.66, p = 0.09). C3 levels were significantly higher in HIV(+) participants with MetS compared to those without MetS (p = 0.002). C3 was higher among HIV(+) patients with three or four MetS components as compared to those with one or two (p = 0.04) and those with none (p = 0.002). No associations were found between C3 and the outcomes for HIV(-) participants. C3 is strongly associated with both MetS and MetS components in an older HIV(+) sample on cART compared to HIV(-) controls. C3 warrants further investigation as a marker of cardiometabolic risk among persons aging with HIV.

Physical Activity is Associated with Better Neurocognitive and Everyday Functioning Among Older Adults with HIV Disease.

We examined the association between physical activity (PA), neurocognitive impairment (NCI), and instrumental activities of daily living (IADLs) among older HIV+ persons. One hundred older HIV+ adults completed the International Physical Activity Questionnaire, a neurocognitive battery, and IADL scale. Higher levels of moderate PA were associated with lower odds of NCI (p = 0.01), even when covariates were modeled. The association between moderate PA and NCI was driven by executive function (p = 0.04). Higher levels of moderate PA were also associated with lower odds of IADL Dependence (p = 0.03), although this fell to a trend (p = 0.08) when including covariates. Follow-up analysis showed those with both NCI and IADL Dependence had lower moderate PA than those with neither (p = 0.03). While these cross-sectional findings suggest PA is associated with better neurocognitive and everyday functioning in older HIV+ adults, longitudinal studies utilizing objective PA methods are needed to evaluate directionality and mechanisms.

The veterans aging cohort study index is associated with concurrent risk for neurocognitive impairment.

OBJECTIVE: The Veterans Aging Cohort Study (VACS) Index is predictive of mortality and combines age, traditional HIV biomarkers (HIV-1 plasma RNA and current CD4 count), and non-HIV biomarkers (indicators of renal and liver function, anemia, and hepatitis C coinfection). We examined the association between the VACS Index and HIV-associated neurocognitive impairment (NCI). DESIGN AND METHODS: Participants included 601 HIV-infected adults enrolled in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (ages: 18-76 years; 88% male; 63% white; median current CD4 = 364 cells/mm; 63% on antiretroviral therapy; AIDS = 64%). Biomarkers used in calculating the VACS Index were measured in prospectively collected blood samples using conventional laboratory methods. NCI was defined using global and seven domain deficit scores. RESULTS: Higher VACS Index scores were associated with concurrent risk for global NCI [P < 0.001; odds ratio = 1.21, confidence interval (CI): 1.12 to 1.32], even when adjusting for psychiatric comorbidities. This relation was statistically significant for most cognitive domains in adjusted models. Furthermore, the VACS Index predicted concurrent NCI beyond nadir CD4 and estimated duration of infection. Older age, lower hemoglobin, and lower CD4 counts were the VACS components most strongly linked to NCI. CONCLUSIONS: The findings extend previous research on the potential usefulness of the VACS Index in predicting HIV-associated outcomes to include NCI. Although the effect size was relatively small, our findings suggest that demographic information, HIV-disease factors, and common comorbidities might each play important roles in the clinical manifestation of cognitive impairment among HIV-infected individuals. Additional research is needed to determine if a more sensitive and specific index can be developed.