Anya Umlauf

Objective: This study examined associations of days of methamphetamine (METH) abstinence with neurocognitive functioning and whether age moderates this relationship in people with HIV (PWH). Methods: Retrospective data from 122 PWH with lifetime METH use disorder (MUD) were analyzed. Linear, piecewise, and curvilinear models were compared to characterize the association between length of METH abstinence and Global neuropsychological test T-scores. An interaction term between METH Abstinence Days and Age Group (49) was added to the best model to test moderation both globally and by domain. Results: A curvilinear model with log-transformed METH Abstinence Days provided the best model fit, with higher METH Abstinence Days associated with higher Global T-scores and a decreasing positive slope over time. Age Group did not moderate Global T-scores. At the domain level, Age Group moderated associations between METH Abstinence Days and Information Processing Speed, with steepest slopes in the youngest age group. Conclusions: Length of METH abstinence is curvilinearly associated with neurocognitive functioning, with the steepest associations occurring in early abstinence, and is largely independent of age. These results emphasize that most neurocognitive recovery in domains impacted by MUD occurs during early abstinence across age groups and may inform the timing of neurocognitive assessment and intervention.

Background: A digital health technology’s success or failure depends on how it is received by users. Objectives: We conducted a user experience (UX) evaluation among persons who used the Food and Drug Administration–approved Digital Health Feedback System incorporating ingestible sensors (ISs) to capture medication adherence, after they were prescribed oral pre-exposure prophylaxis (PrEP) to prevent HIV infection. We performed an association analysis with baseline participant characteristics, to see if “personas” associated with positive or negative UX emerged. Methods: UX data were collected upon exit from a prospective intervention study of adults who were HIV negative, prescribed oral PrEP, and used the Digital Health Feedback System with IS-enabled tenofovir disoproxil fumarate plus emtricitabine (IS-Truvada). Baseline demographics; urine toxicology; and self-report questionnaires evaluating sleep (Pittsburgh Sleep Quality Index), self-efficacy, habitual self-control, HIV risk perception (Perceived Risk of HIV Scale 8-item), and depressive symptoms (Patient Health Questionnaire–8) were collected. Participants with ≥28 days in the study completed a Likert-scale UX questionnaire of 27 questions grouped into 4 domain categories: overall experience, ease of use, intention of future use, and perceived utility. Means and IQRs were computed for participant total and domain subscores, and linear regressions modeled baseline participant characteristics associated with UX responses. Demographic characteristics of responders versus nonresponders were compared using the Fisher exact and Wilcoxon rank-sum tests. Results: Overall, 71 participants were enrolled (age: mean 37.6, range 18-69 years; n=64, 90% male; n=55, 77% White; n=24, 34% Hispanic; n=68, 96% housed; and n=53, 75% employed). No demographic differences were observed in the 63 participants who used the intervention for ≥28 days. Participants who completed the questionnaire were more likely to be housed (52/53, 98% vs 8/10, 80%; P=.06) and less likely to have a positive urine toxicology (18/51, 35% vs 7/10, 70%; P=.08), particularly methamphetamine (4/51, 8% vs 4/10, 40%; P=.02), than noncompleters. Based on IQR values, ≥75% of participants had a favorable UX based on the total score (median 3.78, IQR 3.17-4.20), overall experience (median 4.00, IQR 3.50-4.50), ease of use (median 3.72, IQR 3.33-4.22), and perceived utility (median 3.72, IQR 3.22-4.25), and ≥50% had favorable intention of future use (median 3.80, IQR 2.80-4.40). Following multipredictor modeling, self-efficacy was significantly associated with the total score (0.822, 95% CI 0.405-1.240; P<.001) and all subscores (all P<.05). Persons with more depressive symptoms reported better perceived utility (P=.01). Poor sleep was associated with a worse overall experience (−0.07, 95% CI −0.133 to −0.006; P=.03). Conclusions: The UX among persons using IS-enabled PrEP (IS-Truvada) to prevent HIV infection was positive. Association analysis of baseline participant characteristics linked higher self-efficacy with positive UX, more depressive symptoms with higher perceived utility, and poor sleep with negative UX.

Objective: Many persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood. Method and participants: Study participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time. Results: HPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14. Conclusions: Worsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

Background: HIV is a chronic illness that impacts the lives of more than 1 million people in the United States. As persons living with HIV (PWH) are living longer, it is important to understand the influence that religiosity/spirituality has among middle-aged and older PWH. Objective: Compare the degree of religiosity/spirituality among middle-aged and older PWH and HIV-negative individuals, and to identify demographic, clinical, and psychosocial factors associated with religiosity/spirituality among PWH. Method: Baseline data on 122 PWH and 92 HIV-negative individuals (ages 36-65 years; 61.1% Non-Hispanic White) from a longitudinal study were analyzed for the current study. Recruitment occurred through HIV treatment clinics and community organizations in San Diego. Participants completed questionnaires on religiosity, spirituality, and psychosocial functioning. Independent samples t-tests, Pearson correlations, and multiple linear regression analyses were conducted to test the study objective. Results: No significant differences in religiosity/spirituality were found between PWH and HIV-negative individuals. Demographic and psychosocial variables were unrelated to religiously/spirituality among HIV-negative individuals. Among PWH, multiple linear regression models indicated higher daily spirituality was significantly associated with racial/ethnic minority membership (Hispanic/Latino, African American/Black, or Other), fewer years of estimated duration of HIV, greater social support, and higher grit. Greater engagement in private religious practices was significantly associated with racial/ethnic minority membership and higher social support. Conclusions: For PWH, being a racial/ethnic minority and having higher social support was associated with greater engagement in religious/spiritual practices. Future longitudinal studies should examine whether religion/spirituality impacts well-being across the lifespan among racial/ethnic minority groups of PWH.

Colorectal cancer (CRC) is a leading cause of international morbidity and is the second highest cause of cancer-related mortality in the world. The purpose of this study was to investigate the relationship between international health care spending on CRC mortality over time. This is a retrospective study using a publicly available data from the WHO Global Health Observatory database. General estimating equations were used to analyze the relationship between total health care expenditure per capita (THEpc) and CRC mortality at the country level. The primary predictors of interest were quartiles of THEpc. Other exposure variables included gross domestic product per capita (GDPpc), smoking (% of adult population smoking), physician density (per 10,000), and time. Mortality decreased significantly from 2000 to 2016 (coefficient [95% CI], −2.2 [−3.3 to −1.1]; P < .001). THEpc, GDPpc, time, and percentage of adult population smoking were significant predictors of CRC mortality. Patients in the top two quartiles of THEpc had 3% higher rates of CRC mortality compared with countries in Q1 THEpc (Q3: 3.4 [1.9-4.8], P < .001; Q4: 3.2 [1.4-5.0], P = .001). Similar trends were seen in GDPpc (Q4: 3.2 [1.4-5.0], P = .001; Q3: 3.4 [1.9-4.8], P < .001; Q2: 1.7 [0.7-2.6], P < .001; Q1: reference). Overall, mortality decreased significantly over the study period. Countries with higher health expenditures and higher gross domestic products experienced higher rates of CRC mortality. Further research will be necessary to determine the cause for this, but we postulate that it may be a result of more robust diagnostic and follow-up methods in countries with more resources.

Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆⁹-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids’ concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by liquid chromatography with tandem mass spectrometry for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent compared to occasional users, whereas there were no significant differences in OF Cmax. Blood THC remained detectable (≥5 ng/mL) at the final sample collection for 14% of individuals who smoked either the 5.9 or 13.4% THC cigarette, whereas 54% had detectable THC in OF when applying the same cutoff. Occasional and frequent cannabis users’ profiles were compared, THC was detectable for significantly longer duration in blood and OF from frequent users. Detection rates between frequent and occasional users at multiple per se cutoffs showed larger differences in blood versus OF. Understanding cannabinoid profiles of frequent and occasional users and the subsequent impact on detectability with current drug per se driving limits is important to support forensic interpretations and the development of scientifically supported driving under the influence of cannabis laws.

HIV-associated neurocognitive disorders (HAND) are frequently associated with impaired executive function and verbal fluency. Given limited knowledge concerning HAND in Sub-Saharan-Africa and lack of Cameroonian adult neuropsychological (NP) test norms, we administered four executive function [Halstead Category Test (HCT), Wisconsin Card Sorting Test (WCST), Color Trails-II (CTT2), and Stroop Color-Word-Interference (SCWT)] and three verbal fluency (Category, Action, and Letter Fluency) tests to 742 adult Cameroonians (395 HIV−, 347 HIV+). We developed demographically-corrected NP test norms and examined the effects of HIV and related variables on subjects’ executive function and verbal fluency. HIV+ subjects had significantly lower T-scores on CTT2 (P = 0.005), HCT (P = 0.032), WCST (P < 0.001); lower executive function composite (P = 0.002) and Action Fluency (P = 0.03) T-scores. ART, viremia, and CD4 counts did not affect T-scores. Compared to cases harboring other viral subtypes, subjects harboring HIV-1 CRF02_AG had marginally higher CTT2 T-scores, significantly higher SCWT (P = 0.015) and executive function (P = 0.018) T-scores. Thus, HIV-1 infection in Cameroon is associated with impaired executive function and some aspects of verbal fluency, and viral genotype influenced executive function. We report the first normative data for assessing executive function and verbal fluency in adult Cameroonians and provide regression-based formulas for computing demographically-adjusted T-scores. These norms will be useful for investigating HIV/AIDS and other diseases affecting cognitive functioning in Cameroon.