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Gabapentin is associated with dizziness, falls, and somnolence yet commonly prescribed to people with HIV (PWH) treated with chronic opioid therapy (COT). Physical function and cognition are understudied when prescribed together. Among PWH on COT, we evaluated whether co-prescribed gabapentin is associated with (a) functional impairment; (b) trouble thinking clearly; and (c) difficulty controlling drowsiness using logistic regression models adjusted for prescribed opioid dose, other (non-gabapentin) sedating medication, substance use disorder, and mental/physical health indicators in a cross-sectional study. Among 166 participants, 40% were prescribed gabapentin, 41% reported functional impairment, 41% trouble thinking clearly, and 38% difficulty controlling drowsiness. Gabapentin co-prescribed with COT was significantly associated with trouble thinking clearly but not with functional impairment or difficulty controlling drowsiness. Clinicians should be cognizant of potential problems with thinking clearly when co-prescribing gabapentin and opioid medication.

Background Measurement of waist circumference is used to assess abdominal fat and risk of heart disease, type 2 diabetes, cancer and stroke. It is performed in several clinical settings for health promotion and medical assessment purposes, including statutory medical assessments where results may influence decisions on fitness to work. Under the Diving at Work Regulations 1997, working divers must have an annual assessment of their fitness to dive performed by an approved medical examiner of divers (AMED), appointed by the Health and Safety Executive (HSE). The assessment includes measurement of height, weight and waist circumference, the latter used as an indicator of central adiposity and associated health risks. Aims To establish the practice of AMEDs in measuring waist circumference of working divers undergoing medical assessment to determine their fitness to dive. Methods Ninety-seven AMEDs were sent a questionnaire and asked to describe their current practice in measuring waist circumference. The response rate was 79%. The audit standard used was the consensus document published by the World Health Organization (WHO). Results Of the 77 responses, 76 were completed sufficiently to allow analysis. When the waist was measured, there was consistency in the diver’s level of clothing, stage of breathing and posture for the procedure but variability in the site of measurement. Only 7/76 (9%) respondents carried out waist measurement fully in line with WHO guidance. Conclusions The audit has identified that there is a need for guidance for AMEDs on measuring waist circumference in the statutory medical assessment of working divers.

Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections and child mortality. While RSV disease burden is highest in low- and middle-income countries, most knowledge about risk factors for fatal RSV disease comes from high-income settings. Methods Among infants aged 4 days to Results From 720 infant deaths, 6% (44) were RSV-positive, 70% were Conclusions Other than congenital cardiac conditions, we found a lack of association between RSV and underlying risk factors. This differs from high-income settings, where RSV mortality is concentrated among high-risk infants. In this population, birth-related outcomes are the highest mortality risk factors. Improved neonatal care remains crucial in the fight against neonatal mortality.

Background Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology in low- and middle-income countries is poorly understood. Risk factors associated with RSV-associated infant deaths that occur in community settings are incompletely known. Methods Community deaths for infants aged 4 days to 6 months were identified during a 3-year postmortem RSV prevalence study at the main city morgue in Lusaka, Zambia, where 80% of deaths are registered. This analysis focuses on the subset of deaths for which an abbreviated verbal autopsy was available and intended to sort deaths into respiratory or nonrespiratory causes by clinical adjudication. Posterior nasopharyngeal swab samples were collected within 48 hours of death and tested for RSV using quantitative reverse-transcription polymerase chain reaction. Associations between potential risk factors were determined as relative risks with 95% confidence intervals (CIs). Results We prospectively enrolled 798 community infant deaths with verbal autopsies and RSV laboratory results, of which 62 results were positive. The mean age of the infants was 10 weeks, and 41.4% of them were male. Of all deaths, 44% were attributed to respiratory causes. RSV was detected in 7.8% of the community infants and was significantly associated with respiratory deaths (risk ratio, 4.0 [95% CI, 2.2–7.1]). Compared with older infants, those aged 0–8 weeks had a 2.83 (95% CI, 1.30–6.15) increased risk of dying with RSV. The risk of RSV for the 0–8-week age group increased to 5.24 (1.56–33.14) with adjustment for demographics, parental education, and geography. RSV deaths were increased with domiciliary overcrowding and were concentrated in poor and dense neighborhoods in Lusaka (risk ratio, 2.00 [95% CI, 1.22–3.27]). Conclusion RSV is a significant contributor to community respiratory deaths in this population, particularly in the first 3 months of life and in the more poor and dense parts of Lusaka.

Aims Alcohol is hypothesized to have effects on the kynurenine pathway of tryptophan catabolism, a potential mechanism for alcohol-induced depression and aggression. A biomarker of this pathway, the plasma kynurenine to tryptophan ratio (K/T ratio), has been associated with HIV progression, mortality and depression. Our aim was to assess whether hazardous alcohol consumption is associated higher K/T ratio among people with HIV. Methods Participants were a subset of the Uganda Alcohol Research Collaboration on HIV/AIDS Cohort. Alcohol consumption was categorized (abstinent, moderate and hazardous alcohol use) using the Alcohol Use Disorders Identification Test—Consumption and phosphatidylethanol (PEth). K/T ratio was the primary outcome. We used linear regression adjusted for age, sex, FIB-4, hepatitis B surface antigen, log (HIV viral load) to estimate the association between alcohol consumption and K/T ratio. Results Compared to abstinent participants, hazardous drinkers and moderate drinkers had higher K/T ratio but these differences did not reach statistical significance. Conclusions Our results suggest that hazardous alcohol consumption, in the context of untreated HIV infection, may not significantly alter kynurenine to tryptophan ratio as a measure of activity of the kynurenine pathway of tryptophan metabolism.

Persons with HIV (PWH) experience chronic pain and Post-Traumatic Stress Disorder (PTSD) at higher rates than the general population, and more often receive opioid medications to treat chronic pain. A known association exists between PTSD and substance use disorders, but less is known about the relationship between PTSD and risky opioid use among PWH taking prescribed opioid medications. In this observational study of PWH on long-term opioid medications for pain we examined associations between PTSD symptom severity based on the Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5, response range 0–80) and the following outcomes : 1) risk for opioid misuse (COMM score ≥13); 2) risky alcohol use (AUDIT score ≥8); 3) concurrent benzodiazepine prescription; and 4) morphine equivalent dose. Among 166 patients, 38 (23%) had a PCL-5 score over 38, indicating high PTSD symptom burden. Higher PCL-5 score (per 10 point difference) was associated with increased odds of opioid misuse (aOR 1.55; 95%CI: 1.31–1.83) and risky drinking (aOR: 1.28;1.07–1.52). No significant association was observed between PCL-5 score and benzodiazepine prescriptions or morphine equivalent dose. These findings suggest that when addressing alcohol and opioid use in PWH on long term opioid therapy, attention to PTSD symptoms is especially important given the higher risk for risky alcohol and opioid use among patients with this common comorbid condition.

Background Chronic pain is prevalent among people living with human immunodeficiency virus (PLWH); managing pain with chronic opioid therapy (COT) is common. Human immunodeficiency virus (HIV) providers often diverge from prescribing guidelines. Methods This 2-arm, unblinded, cluster-randomized clinical trial assessed whether the Targeting Effective Analgesia in Clinics for HIV (TEACH) intervention improves guideline-concordant care compared to usual care for PLWH on COT. The trial was implemented from 2015 to 2018 with 12-month follow-up at safety-net hospital–based HIV clinics in Boston and Atlanta. We enrolled 41 providers and their 187 patients on COT. Prescribers were randomized 1:1 to either a 12-month intervention consisting of a nurse care manager with an interactive electronic registry, opioid education, academic detailing, and access to addiction specialists or a control condition consisting of usual care. Two primary outcomes were assessed through electronic medical records: ≥2 urine drug tests and any early COT refills by 12 months. Other outcomes included possible adverse consequences. Results At 12 months, the TEACH intervention arm had higher odds of ≥2 urine drug tests than the usual care arm (71% vs 20%; adjusted odds ratio [AOR], 13.38 [95% confidence interval {CI}, 5.85–30.60]; P < .0001). We did not detect a statistically significant difference in early refills (22% vs 30%; AOR, 0.55 [95% CI, .26–1.15]; P = .11), pain severity (6.30 vs 5.76; adjusted mean difference, 0.10 [95% CI, −1.56 to 1.75]; P = .91), or HIV viral load suppression (86.9% vs 82.1%; AOR, 1.21 [95% CI, .47–3.09]; P = .69). Conclusions TEACH is a promising intervention to improve adherence to COT guidelines without evident adverse consequences.

People living with HIV (PLWH) have high levels of functional impairment due to pain, also called pain interference. Long-term opioid therapy (LTOT) is commonly prescribed for chronic pain among PLWH. We sought to better understand the predictors of pain interference, measured with the Brief Pain Inventory Interference subscale (BPI-I), among PLWH with chronic pain on LTOT. Using a prospective cohort of PLWH on LTOT we developed a model to identify predictors of increased pain interference over 1 year of follow up. Participants (n=166) were 34% female, 72% African American with a median age of 55 years, and 40% had severe pain interference (BPI-I ≥7). In multivariable models, substance use disorder, depressive symptoms, PTSD symptoms, financial instability, and higher opioid doses were associated with increased pain interference. Measures of behavioral health and socioeconomic status had the most consistent association with pain interference. In contrast, the biomedical aspects of chronic pain and LTOT—comorbidities, duration of pain—were not predictive of pain interference. PLWH with chronic pain on LTOT with lower socioeconomic status and behavioral health symptoms have higher risk of pain interference. Addressing the social determinants of health and providing access to behavioral health services could improve patients’ pain-related functional status.

Consciousness is not explained by a single mechanism, rather it involves multiple specialized neural systems overlapping in space and time. We hypothesize that synergistic, large-scale subcortical and cortical attention and signal processing networks encode conscious experiences. To identify brain activity in conscious perception without overt report, we classified visual stimuli as perceived or not using eye measurements. Report-independent event-related potentials and functional magnetic resonance imaging (fMRI) signals both occurred at early times after stimuli. Direct recordings revealed a novel thalamic awareness potential linked to conscious visual perception based on report. fMRI showed thalamic and cortical detection, arousal, attentional salience, task-positive, and default mode networks were involved independent of overt report. These findings identify a specific sequence of neural mechanisms in human conscious visual perception.One-Sentence SummaryHuman conscious visual perception engages large-scale subcortical and cortical networks even without overt report.

HIV clinicians report low confidence and satisfaction prescribing chronic opioid therapy (COT). We hypothesized that the Targeting Effective Analgesia in Clinics for HIV (TEACH) intervention [a system-level improvement to increase guideline concordant care for COT] would improve satisfaction, confidence, and trust among PWH and their clinicians.We conducted a two-arm, unblinded cluster randomized controlled trial (RCT) to assess the TEACH intervention. Clinicians were randomized in a 1:1 ratio to receive either the TEACH intervention (an IT-enabled nurse care manager, opioid education, academic detailing, and access to addiction specialists) or usual care. Outcomes were the following: clinician satisfaction (primary); confidence prescribing COT; patient satisfaction with COT; and trust in clinician. Intention-to-treat analyses were conducted using linear and logistic regression models.Clinicians (n = 41) were randomized and their 114 patients assessed. At 12 months, the adjusted mean difference in satisfaction with COT was 1.11 points for intervention vs control clinicians (Scale 1-10; 95% confidence interval [CI]: -0.04 to 2.26, p = 0.06). The adjusted mean confidence with prescribing COT was 1.01 points higher among intervention clinicians (Scale 1-10; 95% CI: 0.05-1.96, p = 0.04). There were no significant differences in patient satisfaction with COT (adjusted odds ratio (AOR) 1.17, 95% CI: 0.50-2.76, p = 0.72) or trust in provider (AOR 1.63, 95% CI: 0.65-4.09, p = 0.30).TEACH did not significantly affect prescriber satisfaction, patient satisfaction with pain management or patient trust; however, it did improve prescriber confidence. TEACH is a promising strategy to improve provider prescribing of COT for PWH without adverse patient satisfaction or trust in provider.

OBJECTIVE: We examined whether gender is associated with heavy drinking in three cohorts of people living with HIV (PLWH) in Mbarara, Uganda; St. Petersburg, Russia; and Boston, Massachusetts. METHOD: We conducted secondary analyses of baseline data collected from three cohorts in the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) consortium. We used multiple logistic regression models to evaluate the association between gender and heavy drinking (defined in combination with self-report and phosphatidylethanol [PEth]) within each cohort. RESULTS: In unadjusted logistic regression models, we found no significant association between gender and heavy drinking in Russia or Boston. In Uganda, women were less likely than men to engage in heavy drinking (odds ratio = 0.38, 95% CI [0.26, 0.58], p < .01). These findings were invariant to adjustment for covariates. CONCLUSIONS: We did not detect associations between gender and heavy drinking in cohorts of PLWH in Russia or Boston, suggesting that heavy drinking may be as common in women living with HIV as in men living with HIV in these locations. Although these cohorts were enriched with heavy drinking participants, which limits broad extrapolation to PLWH in those settings, nonetheless the findings are concerning given the significant morbidity associated with alcohol use among PLWH and women in particular.

BACKGROUND Medical marijuana is legal in 29 US states and the District of Columbia: both HIV and chronic pain are "approved conditions" for receipt. Chronic pain is common among people living with HIV (PLWH). We anticipate PLWH will question their providers about medical marijuana for chronic pain. We examined marijuana use and its associations with pain, opioid dose, and HIV viral suppression among PLWH receiving chronic opioid therapy. METHODS PLWH prescribed chronic opioid therapy were recruited into the Targeting Effective Analgesia in Clinics for HIV cohort. The main exposure variable was any past 12-month marijuana use. The primary outcomes were (1) opioid misuse (≥9 on the Current Opioid Misuse Measure) and (2) opioid dose (morphine equivalent daily dose). HIV viral load (VL) suppression (

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Objectives In the late 1990s, when the current Russian opioid epidemic began, illicit opioids used in Russia consisted almost exclusively of heroin. The type of opioids used has evolved in the early 21st Century. The objective of this study was to describe the evolution of illicit opioid use among people living with HIV (PLWH) reporting recent opioid use in St Petersburg, Russia. Methods We examined baseline data from four research studies conducted in the period 2004-2015 that included PLWH who used opioids [Partnership to Reduce the Epidemic Via Engagement in Narcology Treatment (PREVENT; 2004-2005; n = 17), HIV Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic (HERMITAGE; 2007-2010; n = 281), Linking Infectious and Narcology Care (LINC; 2013-2014; n = 119) and Russia Alcohol Research Collaboration on HIV/AIDS (Russia ARCH; 2012-2015; n = 121)] and reported recent use of heroin and other opioids. Results Although these studies spanned more than a decade, the participants represented similar birth cohorts; the mean age was 24.5 years in 2004 and 33.3 years in 2014. The use of opioid types, however, evolved across cohorts, with the use of any illicit drug other than heroin increasing from 6% [95% confidence interval (CI) 000.2, 29%] in PREVENT (2004-2005) to 30% (95% CI 25, 36%) in HERMITAGE (2007-2010) to 70% (95% CI 61, 78%) in LINC (2013-2014) to 77% (95% CI 68, 84%) in ARCH (2012-2015). Any heroin use consistently decreased over the 10-year period in the cohorts, from 100% (95% CI 80, 100%) in 2004-2005 to 54% (95% CI 44, 63%) in 2012-2015. Conclusions Among PLWH who use opioids in St Petersburg, Russia, illicit use of opioids other than heroin appears to be more common than heroin use.

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ) peptides and is considered a potential treatment target for Alzheimer's disease (AD). To support Japan's participation in the global clinical development program, we characterized the safety, pharmacokinetics (PKs), and pharmacodynamics of the BACE1 inhibitor verubecestat (MK-8931) in 24 healthy Japanese adults in a two-part, single-center, randomized, placebo-controlled phase I trial (protocol MK-8931-007) and compared the results with historical data from non-Japanese subjects. Both single (20, 100, and 450 mg) and multiple (80 and 150 mg once daily for 14 days) doses of verubecestat were well tolerated. Verubecestat's PK profile was similar in Japanese and non-Japanese subjects. Verubecestat also reduced mean cerebrospinal fluid concentrations of the Aβ proteins Aβ40, Aβ42, and soluble β fragment of amyloid precursor protein; the level of reduction was comparable between Japanese and non-Japanese subjects. These results support the continued global development of verubecestat as a potential disease-modifying agent for Japanese and non-Japanese subjects who are at risk for developing AD.

Background Alcohol use is common among persons living with HIV (PLWH), who often experience chronic pain, yet its impact on pain and opioid misuse is not fully characterized. Methods We assessed associations between hazardous alcohol use and pain interference, defined as the self-reported impact of pain on daily living, pain severity, and risk for opioid misuse among PLWH who were on long-term opioid therapy (LTOT). A cohort was recruited as part of the “Targeting Effective Analgesia in Clinics for HIV” (TEACH) study, a randomized controlled trial to improve LTOT in HIV clinics. The Alcohol Use Disorders Test (AUDIT), Brief Pain Inventory (BPI) and the Current Opioid Misuse Measure (COMM) were administered at both baseline and 12-months. Linear mixed and generalized estimating equation models, incorporating data from both time points, evaluated associations between hazardous alcohol use (AUDIT ≥8) and: pain interference (0–10), pain severity (0–10), and opioid misuse risk (COMM ≥13), adjusting for age, gender, depressive symptoms, use of non-alcohol substances, time-point, and study-arm. Results The sample was comprised of 166 participants, of which 31 (19%) reported hazardous alcohol use. The majority were male (65%), black (72%), and the mean age was 54 (range: 29–77). Hazardous alcohol use was significantly associated with higher pain interference (adjusted mean difference [AMD]: 1.02; 95% CI: 0.08, 1.96) and higher odds of opioid misuse risk (AOR: 3.73, 95% CI: 1.88–7.39), but not pain severity (AMD: 0.47, 95% CI: − 0.35, 1.29). Conclusions Hazardous alcohol use was associated with greater functional impairment in daily living from their pain and higher odds for prescription opioid misuse in this study of PLWH on LTOT. Providers should be attentive to alcohol use among PLWH who are prescribed opioids given associations with pain and opioid misuse. Trial registration ClinicalTrials.govNCT02564341 (Intervention, September 30, 2015) and NCT02525731 (Patient Cohort, August 17, 2015). Both prospectively registered.

This cross-sectional study describes naloxone rescue kit receipt among people with HIV (PWH) on chronic opioid therapy (COT) and HIV clinician opioid overdose prevention care in two clinics between 2015 and 2017. Naloxone rescue kit receipt was uncommon. History of overdose was associated with receiving naloxone but having a clinician who reported providing overdose prevention care was not. This study suggests that clinicians prescribing COT to PWH should improve overdose prevention care, including naloxone co-prescribing.

ObjectivesLimited SARS CoV 2 testing in many African countries has constrained availability of data on the impact of COVID-19 (CV19). To address this gap, we conducted a systematic post-mortem surveillance study to directly measure the fatal impact of CV19 in an urban African population.DesignWe enrolled deceased individuals at the University Teaching Hospital (UTH) Morgue in Lusaka, Zambia. We obtained nasopharyngeal swabs for testing via reverse-transcriptase quantitative PCR (RT-qPCR) against the SARS-2 Coronavirus. We stratified deaths by CV19 status, by location, age, sex, and underlying risk factors.SettingUTH is Zambia’s largest tertiary care referral hospital and its morgue registers ∼80% of Lusaka’s deaths.ParticipantsParticipants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent.ResultsWe enrolled 372 participants between June and September 2020, and had PCR results for 364 (99.5%). CV19 was detected in 70/364 (19.2%). The median age for CV19+ deaths was 48 years (IQR 36-72 years) and 70% were male. Most CV19+ deaths (51/70, 72.8%) occurred in the community; none had been tested for CV19 antemortem. Among the 19/70 facility deaths, six were tested antemortem. Among the 52/70 CV19 deaths with symptoms data, 44/52 had typical symptoms of CV19 (cough, fever, shortness of breath), of whom only five were tested antemortem. We identified CV19 among seven children; only one had been tested antemortem. The proportion of CV19+ deaths increased with age, but 75.7% of CV19+ deaths were aged ConclusionsContrary to expectations, CV19+ deaths were common in Lusaka. The majority occurred in the community where testing capacity is lacking. Yet few who died at facilities were tested, despite presenting with typical symptoms of CV19. Therefore, CV19 cases were under reported because testing was rarely done, not because CV19 was rare. If our data are generalizable, the impact of CV19 in Africa has been vastly underestimated.

INTRODUCTION: Management of chronic pain is an essential aspect of HIV primary care. Previous literature in the general population has elucidated racial disparities in the evaluation and treatment of pain. This study examined racial/ethnic differences in patient satisfaction and barriers to pain management among a cohort of PWH receiving LTOT. MATERIALS AND METHODS: Patient-reported survey and EMR data were compared between non-white (n=135; 81.3%) and white (n=31; 18.7%) patients in a cohort of 166 PWH receiving LTOT in two clinics in Atlanta and Boston. Quantile and linear regression were used to evaluate the association between race and pain management outcomes: 1) satisfaction with pain management (0–10) and −2) patient-related barriers to pain management, including patient perceptions of pain medications, fatalism, and communication about pain. Models were adjusted for sex, age, clinical site, and baseline general health. RESULTS: Non-white participants were noted to receive chronic opioids for a shorter mean duration of time than white participants (6.0 versus 11.0 years, p

This study evaluated the impact of human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) on immune activation during pregnancy in a Zambian cohort of HIV-exposed but uninfected children followed up from birth. Activated CD8+ T cells (CD38+ and HLA-DR+) were compared among HIV-uninfected (n = 95), cART experienced HIV-infected (n = 111), and cART-naive HIV-infected (n = 21) pregnant women. Immune activation was highest among HIV-infected/cART-naive women but decreased during pregnancy. Immune activation HIV-infected women who started cART during pregnancy was reduced but not to levels similar to those in HIV-uninfected women. The effects of elevated maternal immune activation in pregnancy on subsequent infant health and immunity remain to be determined.

Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

18F-MK-6240 (18F-labeled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine) is a highly selective, subnanomolar-affinity PET tracer for imaging neurofibrillary tangles (NFTs). Plasma kinetics, brain uptake, and preliminary quantitative analysis of 18F-MK-6240 in healthy elderly (HE) subjects, subjects with clinically probable Alzheimer disease (AD), and subjects with amnestic mild cognitive impairment were characterized in a study that is, to our knowledge, the first to be performed on humans. Methods: Dynamic PET scans of up to 150 min were performed on 4 cognitively normal HE subjects, 4 AD subjects, and 2 amnestic mild cognitive impairment subjects after a bolus injection of 152–169 MBq of 18F-MK-6240 to evaluate tracer kinetics and distribution in brain. Regional SUV ratio (SUVR) and distribution volume ratio were determined using the cerebellar cortex as a reference region. Total distribution volume was assessed by compartmental modeling using radiometabolite-corrected input function in a subgroup of 6 subjects. Results:18F-MK-6240 had rapid brain uptake with a peak SUV of 3–5, followed by a uniformly quick washout from all brain regions in HE subjects; slower clearance was observed in regions commonly associated with NFT deposition in AD subjects. In AD subjects, SUVR between 60 and 90 min after injection was high (approximately 2–4) in regions associated with NFT deposition, whereas in HE subjects, SUVR was approximately 1 across all brain regions, suggesting high tracer selectivity for binding NFTs in vivo. 18F-MK-6240 total distribution volume was approximately 2- to 3-fold higher in neocortical and medial temporal brain regions of AD subjects than in HE subjects and stabilized by 60 min in both groups. Distribution volume ratio estimated by the Logan reference tissue model or compartmental modeling correlated well (R2 > 0.9) to SUVR from 60 to 90 min for AD subjects. Conclusion:18F-MK-6240 exhibited favorable kinetics and high binding levels to brain regions with a plausible pattern for NFT deposition in AD subjects. In comparison, negligible tracer binding was observed in HE subjects. This pilot study suggests that simplified ratio methods such as SUVR can be used to quantify NFT binding. These results support further clinical development of 18F-MK-6240 for potential application in longitudinal studies.

Background Chronic opioid therapy (COT) is common in people living with human immunodeficiency virus (PLHIV), but is not well studied. We assessed opioid risk behaviors, perceptions of risk, opioid monitoring, and associated Current Opioid Misuse Measure (COMM) scores of PLHIV on COT. Methods COT was defined as ≥3 opioid prescriptions ≥21 days apart in the past 6 months. Demographics, substance use, COMM score, and perceptions of and satisfaction with COT monitoring were assessed among PLHIV on COT from 2 HIV clinics. Results Among participants (N = 165) on COT, 66% were male and 72% were black, with a median age of 55 (standard deviation, 8) years. Alcohol and drug use disorders were present in 17% and 19%, respectively. In 43%, the COMM score, a measure of potential opioid misuse, was high. Thirty percent had an opioid treatment agreement, 66% a urine drug test (UDT), and 12% a pill count. Ninety percent acknowledged opioids' addictive potential. Median (interquartile range) satisfaction levels (1-10 [10 = highest]) were 10 (7-10) for opioid treatment agreements, 9.5 (6-10) for pill counts, and 10 (8-10) for UDT. No association was found between higher COMM score and receipt of or satisfaction with COT monitoring. Conclusions Among PLHIV on COT, opioid misuse and awareness of the addictive potential of COT are common, yet COT monitoring practices were not guideline concordant. Patients who received monitoring practices reported high satisfaction. Patient attitudes suggest high acceptance of guideline concordant care for PLHIV on COT when it occurs.

Reproducible outcomes in clinical trials depend on adherence to study protocol. Short message service (also known as text message) reminders have been shown to improve clinical trial adherence in the United States and elsewhere. However, due to systematic differences in mobile data plans, languages, and technology, these systems are not easily translated to international settings.To gauge technical capabilities for international projects, we developed SMSMessenger, an automated Android application that uses a US server to send medication reminders to participants in a clinical trial in St. Petersburg, Russia (Zinc for HIV disease among alcohol users-a randomized controlled trial in the Russia Alcohol Research Collaboration on HIV/AIDS cohort). The application is downloaded once onto an Android study phone. When it is time for the text message reminders to be sent, study personnel access the application on a local phone, which in turn accesses the existing clinical trial database hosted on a US web server. The application retrieves a list of participants with the following information: phone number, whether a message should be received at that time, and the appropriate text of the message. The application is capable of storing multiple outgoing messages. With a few clicks, text messages are sent to study participants who can reply directly to the message. Study staff can check the local phone for incoming messages. The SMSMessenger application uses an existing clinical trial database and is able to receive real-time updates. All communications between the application and server are encrypted, and phone numbers are stored in a secure database behind a firewall. No sensitive data are stored on the phone, as outgoing messages are sent through the application and not by messaging features on the phone itself. Messages are sent simultaneously to study participants, which reduces the burden on local study staff. Costs and setup are minimal. The only local requirements are an Android phone and data plan.The SMSMessenger technology could be modified to be applied anywhere in the world, in any language, script, or alphabet, and for many different purposes. The novel application of this existing low-cost technology can improve the usefulness of text messaging in advancing the goals of international clinical trials.

Introduction and Aims. The Massachusetts Department of Public Health Overdose Education and Naloxone Distribution Program provides overdose education and naloxone rescue kits to people at risk for overdose and bystanders, including family members. Using Massachusetts Department of Public Health data, the aims are to: (i) describe characteristics of family members who receive naloxone; (ii) identify where family members obtain naloxone; and (iii) describe characteristics of rescues by family members. Design and Methods. We conducted a retrospective review using program enrollee information collected on a standardised form between 2008 and 2015. We calculated descriptive statistics, including demographics, current substance use, enrolment location, history of witnessed overdoses and rescue attempt characteristics. We conducted a stratified analysis comparing family members who used drugs with those who did not. Results. Family members were 27% of total program enrollees (n = 10 883/40 801). Family members who reported substance use (n = 4679) were 35.6 years (mean), 50.6% female, 76.3% non-Hispanic white, 75.6% had witnessed an overdose, and they obtained naloxone most frequently at HIV prevention programs. Family members who did not report substance use (n = 6148) were 49.2 years (mean), 73.8% female, 87.9% non-Hispanic white, 35.3% had witnessed an overdose, and they obtained naloxone most frequently at community meetings. Family members were responsible for 20% (n = 860/4373) of the total rescue attempts. Discussion and Conclusions. The Massachusetts experience demonstrates that family members can be active participants in responding to the overdose epidemic by rescuing family members and others. Targeted intervention strategies for families should be included in efforts to expand overdose education and naloxone in Massachusetts. [Bagley SM, Forman LS, Ruiz S, Cranston K, Walley AY. Expanding access to naloxone for family members: The Massachusetts experience. Drug Alcohol Rev 2017;00:000-000]

BACKGROUND: People living with HIV (PLWH) frequently experience chronic pain and receive long-term opioid therapy (LTOT). Adherence to opioid prescribing guidelines among their providers is suboptimal. OBJECTIVE: This paper describes the protocol of a cluster randomized trial, Targeting Effective Analgesia in Clinics for HIV (TEACH), which tested a collaborative care intervention to increase guideline-concordant care for LTOT among PLWH. METHODS: HIV physicians and advanced practice providers (n=41) were recruited from September 2015 – December 2016 from two HIV clinics in Boston and Atlanta. Patients receiving LTOT from participating providers were enrolled through a waiver of informed consent (n=187). After baseline assessment, providers were randomized to the control group or the year-long TEACH intervention involving: 1) a nurse care manager and electronic registry to assist with patient management; 2) opioid education and academic detailing; and 3) facilitated access to addiction specialists. Randomization was stratified by site and LTOT patient volume. Primary outcomes (≥2 urine drug tests, early refills, provider satisfaction) were collected at 12-months. In parallel, PLWH receiving LTOT (n=170) were recruited into a longitudinal cohort at both clinics and underwent baseline and 12-month assessments. Secondary outcomes were obtained through patient self-report among participants enrolled in both the cohort and the RCT (n=117). CONCLUSION: TEACH will report the effects of an intervention on opioid prescribing for chronic pain on both provider and patient-level outcomes. The results may inform delivery of care for PLWH on LTOT for chronic pain at a time when opioid practices are being questioned in the US.

Summary Background ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways. Objectives The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate‐to‐severe AD. Methods A total of 36 patients with moderate‐to‐severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28‑day period (20 mg, 40 mg and 80 mg once daily). Results ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg −1·3 ± 2·1, P = 0·81; 40 mg −3·1 ± 2·7, P = 0·27; 80 mg −4·7 ± 2·1, P = 0·01; placebo −1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose‐dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis‐associated biomarker E selectin/SELE. Conclusions In patients with moderate‐to‐severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation., What's already known about this topic? Currently available therapeutic options for atopic dermatitis (AD) include topical corticosteroids, calcineurin inhibitors, crisaborole, dupilumab, ciclosporin and phototherapy. However, few oral treatments are available and those are associated with safety concerns. What does this study add? ASN002, an oral, dual Janus kinase and spleen tyrosine kinase inhibitor, was well tolerated and showed promising efficacy and rapid onset of action in patients with moderate‐to‐severe AD at daily doses of 40 mg and 80 mg.The encouraging efficacy, safety and tolerability profile of ASN002 warrant further investigation of ASN002 in patients with moderate‐to‐severe AD. Linked Comment: https://doi.org/10.1111/bjd.18349. https://doi.org/10.1111/bjd.18398 available online https://www.bjdonline.com/article/the-oral-janus-kinasespleen-tyrosine-kinase-inhibitor-asn-002-demonstrates-efficacy-and-improves-associated-systemic-inflammation-in-patients-with-moderate-to-severe-atopic-dermatiti/

Introduction Despite the high prevalence and significant health risks of substance use disorders (SUDs), a minority of individuals with SUDs receive treatment of any kind. The aims of this study are to describe inpatients with an SUD who receive an addiction consult at a large urban safety net hospital and explore characteristics associated with receiving an addiction consult. Methods This is a retrospective cohort study of all adult patients with a discharge diagnosis of an SUD from July 2015 to July 2016. A generalized estimating equation (GEE) logistic regression model was used to explore patient factors associated with receipt of an addiction consult, such as demographics, social, medical, and SUD characteristics. Results A total of 3905 patients with SUD diagnoses with 5979 hospitalization encounters were included in this study. There were 694 addiction consults (11.6%, 95% CI: 10.71% to 12.5%) across all of the encounters and 576 unique patients that received consults. Patients with opioid use disorder had higher odds of receiving a consult (Adjusted Odds Ratio: 6.39, 95% CI 5.14–7.94), as did patients with acute complications from their substance use (AOR: 1.64, 95% CI 1.34–2.02), patients with human immunodeficiency virus (HIV) (AOR: 2.06, 95% CI 1.59–2.67), and homeless patients (AOR: 1.31, 95% CI 1.08–1.59). Patients with a psychiatry consult had higher odds of receiving an addiction consult (AOR: 1.75, 95% CI 1.37–2.23), and so did patients receiving benzodiazepines and/or phenobarbital (AOR: 1.88, 95% CI 1.55–2.28). Older patients (AOR: 0.82, 95% CI 0.76–0.88 per 10 year increase) had lower odds of receiving a consult, as did patients with an overdose diagnosis (AOR: 0.71, 95% CI 0.53–0.96). Conclusion A minority of inpatients with SUD received an addiction consult, however, inpatients with opioid use disorder, acute complications (medical, mental health) and homelessness had higher odds of receiving an addiction consult. Patients surviving overdose, a severe acute complication of substance use, had lower odds of receiving a consult and, thus, warrant development of care pathways to provide overdose prevention and addiction treatment engagement.