Impact and correlates of sub-optimal social support among patients in HIV care.

Social support (SS) predicts health outcomes among patients living with HIV. We administered a brief, validated measure of SS, the Multifactoral Assessment of Perceived Social Support, within a patient-reported outcomes assessment of health domains in HIV care at 4 U.S. clinics in English and Spanish (n = 708). In univariate analysis, low SS was associated with poorer engagement in care, antiretroviral adherence, and health-related quality of life; current methamphetamine/crystal use, depression, anxiety, and HIV stigma (all p < 0.001); any use of either methamphetamines/crystal, illicit opioids, or cocaine/crack (p = 0.001), current marijuana use (p = 0.012), nicotine use (p = 0.005), and concern for sexually transmitted infection exposure (p = 0.001). High SS was associated with undetectable viral load (p = 0.031). Multivariate analyses found low SS independently associated with depression (risk ratio (RR) 3.72, 95% CI 2.93-4.72), lower adherence (RR 0.76, 95% CI 0.64-0.89), poor engagement in care (RR 2.05, 95% CI 1.44-2.96), and having more symptoms (RR 2.29, 95% CI 1.92-2.75). Medium SS was independently associated with depression (RR 2.59, 95% CI 2.00-3.36), poor engagement in care (RR 1.62, 95% CI 1.15-2.29) and having more symptoms (RR 1.75, 95% CI 1.44-2.13). SS assessment may help identify patients at risk for these outcomes.

Patient acceptability and usability of a self-administered electronic patient-reported outcome assessment in HIV care: relationship with health behaviors and outcomes.

We assessed acceptability/usability of tablet-based patient-reported outcome (PRO) assessments among patients in HIV care, and relationships with health outcomes using a modified Acceptability E-Scale (AES) within a self-administered PRO assessment. Using multivariable linear regression, we measured associations between patient characteristics and continuous combined AES score. Among 786 patients (median age=48; 91% male; 49% white; 17% Spanish-speaking) overall mean score was 26/30 points (SD: 4.4). Mean scores per dimension (max 5, 1=lowest acceptability, 5=highest): ease of use 4.7, understandability 4.7, time burden 4.3, overall satisfaction 4.3, helpfulness describing symptoms/behaviors 4.2, and enjoyability 3.8. Higher overall score was associated with race/ethnicity (+1.3 points/African-American patients (95%CI:0.3-2.3); +1.6 points/Latino patients (95%CI:0.9-2.3) compared to white patients). Patients completing PROs in Spanish scored +2.4 points on average (95%CI:1.6-3.3). Higher acceptability was associated with better quality of life (0.3 points (95%CI:0.2-0.5)) and adherence (0.4 points (95%CI:0.2-0.6)). Lower acceptability was associated with: higher depression symptoms (-0.9 points (95%CI:-1.4 to -0.4)); recent illicit opioid use (-2.0 points (95%CI:-3.9 to -0.2)); multiple recent sex partners (-0.8 points (95%CI:-1.5 to -0.1)). While patients endorsing depression symptoms, recent opioid use, condomless sex, or multiple sex partners found PROs less acceptable, overall, patients found the assessments highly acceptable and easy to use.

Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies.

Tauopathies, including Alzheimer's disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFTs). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, P=3.8 × 10-8) in 909 prospective autopsies. The association is replicated in an independent data set of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology. In contrast, we found that the ZCWPW1 AD susceptibility variant influences NFT accumulation and that this effect is mediated by an accumulation of amyloid ß plaques. We also performed complementary analyses to identify common pathways that influence multiple neuropathologies that coexist with NFT and found suggestive evidence that certain loci may influence multiple different neuropathological traits, including tau, amyloid ß plaques, vascular injury and Lewy bodies. Overall, these analyses offer an evaluation of genetic susceptibility to NFT, a common end point for multiple different pathologic processes.

Circumstances Surrounding High-risk Sexual Experiences Among Primary Care Patients Living With and Without HIV.

INTRODUCTION: Rates of sexually transmitted infection (STI) are rising in the USA, yet STI risk remains under-addressed by providers, even in HIV care, and with high-risk patients. We interviewed primary care patients living with and without HIV regarding circumstances surrounding sexual risk behavior to identify opportunities for providers to address and reduce STI risk. METHODS: We conducted semi-structured 1:1 interviews with patients living with and without HIV reporting ≥ 1 sex partner and varying STI exposure risk in the past 12 months from four geographically diverse US HIV and primary care clinics. We audio-recorded, transcribed, and coded interviews by circumstance type, using double-coding to ensure inter-coder reliability. We used Fisher's exact and T tests to determine associations with demographic/risk factors. RESULTS: Patients (n = 91) identified a mean of 3 of 11 circumstances. These included substance use (54%), desire for physical/emotional intimacy (48%), lack of HIV/STI status disclosure (44%), psychological drivers (i.e., coping, depression; 38%), personal dislike of condoms (22%), partner condom dislike/refusal (19%), receiving payment for sex (13%), and condom unavailability (9%). Higher proportions of those who were high STI-exposure risk patients, defined as those with ≥ 2 sex partners in the past 3 months reporting never or sometimes using condoms, reported disliking condoms (p = .006); higher proportions of the high-risk and moderate-risk (≥ 2 partners and condom use "most of the time") groups reported substance use as a circumstance (p = .04). CONCLUSION: Circumstances surrounding perceived STI exposure risk were diverse, often overlapping, and dependent on internal, environmental, and partner-related factors and inadequate communication. Meaningful care-based interventions regarding HIV/STI transmission behavior must address the diversity and interplay of these factors.

A Comparison of Adherence Timeframes Using Missed Dose Items and Their Associations with Viral Load in Routine Clinical Care: Is Longer Better?

Questions remain regarding optimal timeframes for asking about adherence in clinical care. We compared 4-, 7-, 14-, 30-, and 60-day timeframe missed dose items with viral load levels among 1099 patients on antiretroviral therapy in routine care. We conducted logistic and linear regression analyses examining associations between different timeframes and viral load using Bayesian model averaging (BMA). We conducted sensitivity analyses with subgroups at increased risk for suboptimal adherence (e.g. patients with depression, substance use). The 14-day timeframe had the largest mean difference in adherence levels among those with detectable and undetectable viral loads. BMA estimates suggested the 14-day timeframe was strongest overall and for most subgroups although findings differed somewhat for hazardous alcohol users and those with current depression. Adherence measured by all missed dose timeframes correlated with viral load. Adherence calculated from intermediate timeframes (e.g. 14-day) appeared best able to capture adherence behavior as measured by viral load.

Validity assessment of the PROMIS fatigue domain among people living with HIV.

PURPOSE: To evaluate psychometric characteristics and cross-sectional and longitudinal validity of the 7-item PROMIS® Fatigue Short Form and additional fatigue items among people living with HIV (PLWH) in a nationally distributed network of clinics collecting patient reported data at the time of routine clinical care. METHODS: Cross-sectional and longitudinal fatigue data were collected from September 2012 through April 2013 across clinics participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We analyzed data regarding psychometric characteristics including simulated computerized adaptive testing and differential item functioning, and regarding associations with clinical characteristics. RESULTS: We analyzed data from 1597 PLWH. Fatigue was common in this cohort. Scores from the PROMIS® Fatigue Short Form and from the item bank had acceptable psychometric characteristics and strong evidence for validity, but neither performed better than shorter instruments already integrated in CNICS. CONCLUSIONS: The PROMIS® Fatigue Item Bank is a valid approach to measuring fatigue in clinical care settings among PLWH, but in our analyses did not perform better than instruments associated with less respondent burden.

Provider perceptions of the value of same-day, electronic patient-reported measures for use in clinical HIV care.

Strong evidence suggests that patient-reported outcomes (PROs) aid in managing chronic conditions, reduce omissions in care, and improve patient-provider communication. However, provider acceptability of PROs and their use in clinical HIV care is not well known. We interviewed providers (n = 27) from four geographically diverse HIV and community care clinics in the US that have integrated PROs into routine HIV care, querying perceived value, challenges, and use of PRO data. Perceived benefits included the ability of PROs to identify less-observable behaviors and conditions, particularly suicidal ideation, depression, and substance use; usefulness in agenda setting prior to a visit; and reduction of social desirability bias in patient-provider communication. Challenges included initial flow integration issues and ease of interpretation of PRO feedback. Providers value same-day, electronic patient-reported measures for use in clinical HIV care with the condition that PROs are (1) tailored to be the most clinically relevant to their population; (2) well integrated into clinic flow; and (3) easy to interpret, highlighting chief patient concerns and changes over time.

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Unannounced telephone-based pill counts: a valid and feasible method for monitoring adherence.

Phone-based unannounced pill counts to measure medication adherence are much more practical and less expensive than home-based unannounced pill counts, but their validity has not been widely assessed. We examined the validity of phone versus home-based pill counts using a simplified protocol streamlined for studies embedded in clinical care settings. A total of 100 paired counts were used to compare concordance between unannounced phone and home-based pill counts using interclass correlations. Discrepancy analyses using χ(2) tests compared demographic and clinical characteristics across patients who were concordant between phone and home-based pill counts and patients who were not concordant. Concordance was high for phone-based and home-based unannounced total pill counts, as well as individual medication counts and calculated adherence. This study demonstrates that a simplified phone-based pill count protocol can be implemented among patients from a routine clinical care setting and is a feasible means of monitoring medication adherence.

Evaluation of the single-item self-rating adherence scale for use in routine clinical care of people living with HIV.

The self-rating scale item (SRSI) is a single-item self-report adherence measure that uses adjectives in a 5-point Likert scale, from "very poor" to "excellent," to describe medication adherence over the past 4 weeks. This study investigated the SRSI in 2,399 HIV-infected patients in routine care at two outpatient primary HIV clinics. Correlations between the SRSI and four commonly used adherence items ranged from 0.37 to 0.64. Correlations of adherence barriers, such as depression and substance use, were comparable across all adherence items. General estimating equations suggested the SRSI is as good as or better than other adherence items (p's <0.001 vs. <0.001-0.99) at predicting adherence-related clinical outcomes, such as HIV viral load and CD4(+) cell count. These results and the SRSI's low patient burden suggest its routine use could be helpful for assessing adherence in clinical care and should be more widespread, particularly where more complex instruments may be impractical.

Measuring depression levels in HIV-infected patients as part of routine clinical care using the nine-item Patient Health Questionnaire (PHQ-9).

Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the nine-item Patient Health Questionnaire (PHQ-9) from the PRIME-MD. The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex; and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework.

Development and content validation of measures assessing adherence barriers and behaviors for use in clinical care.

BACKGROUND: Providers are often unaware of poor adherence to prescribed medications for their patients with chronic diseases. OBJECTIVE: To develop brief, computer-administered patient-reported measures in English and Spanish assessing adherence behaviors and barriers. Design, Participants, and Main Measures: Item pools were constructed from existing measures of medication adherence behaviors and barriers, which informed development of a patient concept elicitation interview guide to identify medication adherence behavior and barrier-related concepts. Two hundred six patients either living with HIV (PLWH) or without were interviewed. Interviews were coded, concepts matched to item pool content, and new items were developed for novel concepts. A provider/investigator team highlighted clinically relevant items. Cognitive interviews were conducted with patients on final candidate items (n = 37). The instruments were administered to 2081 PLWH. KEY RESULTS: Behavioral themes from concept elicitation interviews included routines incorporating time of day, placement, visual cues, and intentionality to miss or skip doses. Barrier themes included health-related (e.g. depressed mood, feeling ill), attitudes/beliefs (e.g., need for medication), access (e.g., cost/insurance problems), and circumstantial barriers (e.g., lack of privacy, disruption of daily routine). The final instruments included 6 behavior items, and 1 barrier item with up to 23 response options. PLWH endorsed a mean (SD) of 3.5 (1.1) behaviors. The 201 PLWH who missed ≥2 doses in the previous week endorsed a mean (SD) of 3.1 (2.5) barriers. The intraclass correlation coefficient (ICC) for the numbers of behaviors endorsed in 61 PLWH after 4-16 days was 0.54 and for the number of barriers for the 20 PLWH with ≥2 missed doses the ICC was 0.89, representing fair and excellent test-retest reliability. CONCLUSION: Measures of medication adherence behaviors and barriers were developed for use with patients living with chronic diseases focusing on clinical relevance, brevity, and content validity for use in clinical care.

Medication understanding among patients living with multiple chronic conditions: Implications for patient-reported measures of adherence.

BACKGROUND: Low health literacy is associated with poor medication adherence and poor health outcomes. Limited understanding of prescribed medications may decrease validity of patient-reported adherence measures. OBJECTIVES: To assess knowledge of names and purposes of prescribed medications among patients with multiple chronic conditions. METHODS: Individual interviews were conducted with a convenience sample of patients from six U.S. primary care clinics. Participants (n = 57) were English and/or Spanish-speaking patients prescribed 3+ medications for chronic conditions, for which non-adherence may lead to disability or death. In individual interviews, patients were asked to name their medications, explain the purpose of each, and to explain how they distinguish them from one another. Interviews were audio recorded, transcribed, and coded; coded content was quantified by 1) whether or not the patient could name medications; 2) method of categorizing medications; 3) whether or not the purpose of the medication was understood. Descriptive statistics were compiled using Fisher's exact test to determine the relationship between patient knowledge and medication characteristics. RESULTS: Thirty percent of patients could not name at least one of their medications; 19% did not know their purpose; 30% held misconceptions about the purpose of one or more medications. There was no significant difference in ability to name medications or state their medication's purpose between patients using medi-sets, pre-packaged rolls, or blister packs, and patients who stored pills in their original containers (p = 0.56 and p = 0.73, respectively), or across demographic groups (p = 0.085 to 0.767). CONCLUSIONS: Many patients demonstrated difficulty identifying the name and purpose of prescribed medications; this did not differ by demographic group or medication storage type. Patients may benefit from routine review of medications with their provider in order to improve health literacy, outcomes, and patient-reported adherence measurement.

Integrating a web-based, patient-administered assessment into primary care for HIV-infected adults.

Providers routinely under diagnose at risk behaviors and outcomes, including depression, suicidal ideation, substance abuse, and poor medication adherence. To address this, we developed a web-based, self-administered patient-reported assessment tool and integrated it into routine primary care for HIV-infected adults. Printed results were delivered to providers and social workers immediately prior to patient appointments. The assessment included brief, validated instruments measuring clinically relevant domains including depression, substance use, medication adherence, and HIV transmission risk behaviors. Utilizing the Institute for Healthcare Improvement's Plan-Do-Study-Act (PDSA) approach to quality improvement, we addressed issues with clinic flow, technology, scheduling, and delivery of assessment results with the support of all levels of clinic staff. We found web-based patient-reported assessments to be a feasible tool that can be integrated into a busy multi-provider HIV primary care clinic. These assessments may improve provider recognition of key patient behaviors and outcomes. Critical factors for successful integration of such assessments into clinical care include: strong top-level /ort from clinic management, provider understanding of patient-reported assessments as a valuable clinical tool, tailoring the assessment to meet provider needs, communication among clinic staff to address flow issues, timeliness of delivery, and sound technological resources.

Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques.

OBJECTIVES: Observational and experimental studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD); however, clinical trials and other observational studies, including the Adult Changes in Thought (ACT) study, show no protection or promotion of AD. The objective of this study is to determine the relationship between common dementia-associated pathologies and mid- to late-life NSAID exposure. METHODS: We examined the association of mid- to late-life NSAID use with neuropathologic findings on 257 autopsies from ACT, a population-based study of brain aging and incident dementia. Cumulative standard daily doses (SDD) of nonselective NSAIDs were determined from ≥10 years of computerized pharmacy dispensing data. Analyses were adjusted for selection bias to broaden generalizability of results to 3,026 eligible participants in the ACT cohort. Seven pathologic indices were evaluated: intermediate or frequent score for neuritic plaques, Braak stages V or VI for neurofibrillary tangles, >2 cerebral microinfarcts, the presence of any neocortical Lewy bodies, any macroscopic infarcts, any amyloid angiopathy, and moderate or severe atherosclerosis. RESULTS: Of the neuropathologic indices evaluated, only neuritic plaque score was significantly increased in participants with greater use of nonselective NSAIDs (p = 0.065), specifically in those with high levels of cumulative use: 1,000-2,000 SDD (adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.02-4.25, compared to light/nonuse [<60 SDD]) and >2,000 SDD (adjusted RR 2.37, 95% CI 1.24-4.67). CONCLUSIONS: Increased neuritic plaque accumulation may explain the association between heavy use of nonselective NSAIDs and increased risk of dementia among ACT participants.

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD). METHODS: We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged > or = 65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500 + SDD), with some analyses also adding consecutive biennial self-reports of NSAID use. RESULTS: Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24-2.24) and 1.57 (95% confidence interval, 1.10-2.23). Addition of self-reported exposure data did not alter these results. CONCLUSIONS: These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation.

Judgment in older adults: development and psychometric evaluation of the Test of Practical Judgment (TOP-J).

This article reports on the development and validation of a novel, objective test of judgment for use with older adults. The Test of Practical Judgment (TOP-J) is an open-ended measure that evaluates judgment related to safety, medical, social/ethical, and financial issues. Psychometric features were examined in a sample of 134 euthymic individuals with mild Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), or cognitive complaints but intact neuropsychological performance (CC), and demographically-matched healthy controls (HC). Measures of reliability were adequate to high, and TOP-J scores correlated with select measures of executive functioning, language, and memory. AD participants obtained impaired TOP-J scores relative to HCs, while MCI and CC participants showed an intermediate level of performance. Confirmatory factor analyses were consistent with a unidimensional structure. Results encourage further development of the TOP-J as an indicator of practical judgment skills in clinical and research settings. Longitudinal assessments are being performed to examine predictive validity of the TOP-J for cognitive progression in our clinical groups.