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The diagnosis of meralgia paresthetica, while based on clinical suspicion, can be confirmed via electrophysiological testing. Previous testing of the sensory conduction of the lateral femoral cutaneous nerve placed the stimulating electrode one centimeter medial to the anterior superior iliac spine (ASIS). This position is both uncomfortable for the patient and difficult for the operator to perform. The following article suggests an alternate position for the stimulating electrode, four centimeters distal to the ASIS. Twenty subjects served as their own controls and both the old technique and the new technique were performed. Using the old technique, the response rate was 35% (7 out of 20 subjects). Using the new technique, the response rate was 90% (18 out of 20 subjects). These results indicate a significantly higher response rate when the only variable altered is the electrode placement. This simple change in technique requires no more effort, cost, or training on the part of the operator yet produces a much higher percentage of responses. [ABSTRACT FROM AUTHOR]

Background and Aims: People with HIV (PWH) whose disease is controlled on anti-retroviral regimens remain at an increased risk for coronary artery disease (CAD). Traditional cardiovascular risk factors do not fully explain the residual risk in PWH suggesting contributions from nontraditional factors. Homocysteine (Hcy) may be one of these as prior work in adults without HIV demonstrate that Hcy may impair endothelial function by decreasing the availability of nitric oxide, promoting the development of atherosclerosis. In addition, plasma Hcy levels are higher in PWH than in individuals living without HIV. The aim of this study was to investigate whether Hcy levels influence the association between HIV and coronary stenosis in an inner city African American population., Methods: African Americans from the Heart Study in Baltimore, with and without HIV, recruited from inner-city Baltimore between June 2004 and February 2015, were included in this analysis. Participants underwent coronary CT angiography to evaluate the presence of coronary stenosis, defined as luminal stenosis >10%. Hcy was measured from stored serum samples., Results: In this analysis, the median [IQR] age of the 664 participants was 56 [50-66] years; 68.1% were living with HIV and 43.1% were women. Elevated Hcy (>15 µmol/L) was more prevalent in those with coronary stenosis (23.3%, 95% CI: 18.4%-28.2%) than in those without coronary stenosis (13.1%, 95% CI: 9.7%-16.5%) ( p = 0.0007), and HIV was associated with coronary stenosis in those participants with an elevated Hcy (Prevalence Ratio: 1.94, 95% CI: 1.04-3.64, p = 0.0038) and not in those with a Hcy ≤15 µmol/L (Prevalence Ratio: 1.02, 95% CI: 0.83-1.25, p = 0.87)., Conclusions: Our data suggest an association between elevated Hcy levels (>15 µmol/L) and the prevalence of coronary stenosis in PWH from this inner city African American population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association. Methods: We analyzed data from 788 adults (≥45 years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain during causal mediation analysis. Results: Overall, HIV was not associated with NCI presence. However, HIV was associated with NCI among individuals with homocysteine >14 μmol/L. Furthermore, HIV was both directly and indirectly associated with NCI in DCCS test scores. Notably, the mediating role of elevated homocysteine in DCCS scores was only observable among individuals who had never used cocaine or had used it for ≤ 10 years, suggesting that extended cocaine use may have a substantial influence on cognitive performance. Conclusions: The findings from this study suggest elevated homocysteine levels may moderate and mediate the association between HIV and neurocognitive impairment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The HIV/AIDS epidemic remains a major public health concern since the 1980s; untreated HIV infection has numerous consequences on quality of life. To optimize patients' health outcomes and to reduce HIV transmission, this study focused on vulnerable populations of people living with HIV (PLWH) and compared different predictive strategies for viral suppression using longitudinal or repeated measures. The four methods of predicting viral suppression are (1) including the repeated measures of each feature as predictors, (2) utilizing only the initial (baseline) value of the feature as predictor, (3) using the last observed value as the predictors and (4) using a growth curve estimated from the features to create individual-specific prediction of growth curves as features. This study suggested the individual-specific prediction of the growth curve performed the best in terms of lowest error rate on an independent set of test data., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77-1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population.

Objectives: To develop a general framework to assess temporal changes in lesion morphology on radiological images beyond volumetric changes and to test whether cocaine abstinence changes coronary plaque structure on serial coronary CT angiography (CTA)., Methods: Chronic cocaine users with human immunodeficiency virus (HIV) infection were prospectively enrolled to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CTA at baseline and 6 and 12 months following recruitment. We segmented all coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features (named as different colors) and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes and whether serum biomarkers causally mediate these changes. Furthermore, we used Bayesian hidden Markov network changepoint analysis to assess the potential rewiring of the radiomic network., Results: Sixty-nine PLWH (median age 55 IQR: 52-59 years, 19% female) completed the study, of whom 26 achieved total abstinence. Twenty consensus eigen radiomic features were derived. Cocaine abstinence significantly affected the pink and cyan eigen features (-0.04 CI: [-0.06; -0.02], p = 0.0009; 0.03 CI: [0.001; 0.04], p = 0.0017, respectively). These effects were mediated through changes in endothelin-1 levels. In abstinent individuals, we observed significant rewiring of the latent radiomic signature network., Conclusions: Using our proposed framework, we found 1 year of cocaine abstinence to significantly change specific latent coronary plaque morphological features and rewire the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics., Key Points: • We propose a general methodology to decompose the latent morphology of lesions on radiological images using a radiomics-based systems biology approach. • As a proof-of-principle, we show that 1 year of cocaine abstinence results in significant changes in specific latent coronary plaque morphologic features and rewiring of the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. • We found endothelin-1 levels to mediate these structural changes providing potential pathological pathways warranting further investigation., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: Determine if cocaine use impacts gut permeability, promotes microbial translocation and immune activation in people living with HIV (PLWH) using effective antiretroviral therapy (ART)., Methods: Cross-sectional analysis of 100 PLWH (ART ≥6 months, HIV-RNA <200 copies/mL) from the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was assessed by self-report, urine screen, and blood benzoylecgonine (BE). Blood samples were collected to assess gut permeability (intestinal fatty acid-binding protein, I-FABP), microbial translocation (lipopolysaccharide, LPS), immune activation (sCD14, sCD27, and sCD163) and markers of inflammation (hs-CRP, TNF-α and IL-6). Multiple linear regression models were used to analyze the relationships of cocaine use., Results: A total of 37 cocaine users and 63 cocaine non-users were evaluated. Cocaine users had higher levels of I-FABP (7.92±0.35 vs. 7.69±0.56 pg/mL, P = 0.029) and LPS (0.76±0.24 vs. 0.54±0.27 EU/mL, P<0.001) than cocaine non-users. Cocaine use was also associated with the levels of LPS (P<0.001), I-FABP (P = 0.033), and sCD163 (P = 0.010) after adjusting for covariates. Cocaine users had 5.15 times higher odds to exhibit higher LPS levels than non-users (OR: 5.15 95% CI: 1.89-13.9; P<0.001). Blood levels of BE were directly correlated with LPS (rho = 0.276, P = 0.028), sCD14 (rho = 0.274, P = 0.031), and sCD163 (rho = 0.250, P = 0.049)., Conclusions: Cocaine use was associated with markers of gut permeability, microbial translocation, and immune activation in virally suppressed PLWH. Mitigation of cocaine use may prevent further gastrointestinal damage and immune activation in PLWH., Competing Interests: The authors have declared that no competing interests exist. Dr. RN Mandler, an employee of the National Institute on Drug Abuse, is an author and did review and approve the manuscript as a part of his authorship role as a Scientific Official. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The simultaneous consumption of cocaine and alcohol results in the production of cocaethylene (CE) in the liver, a highly toxic metabolite. Prior research suggests that cocaine use contributes to liver disease and its concomitant use with alcohol may increase its hepatotoxicity, but studies in humans are lacking. We evaluated the role of cocaine, its simultaneous use with alcohol, and CE on liver fibrosis., Methods: We performed a cross-sectional analysis of the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was determined via self-report, urine screen, and blood metabolites, using liquid chromatography with tandem mass spectrometry. Hazardous drinking was determined with the AUDIT-C and liver fibrosis with the Fibrosis-4 Index (FIB-4)., Results: Out of 649 participants included in this analysis, 281 (43.3%) used cocaine; of those, 78 (27.8%) had CE in blood. Cocaine users with CE had higher concentrations of cocaine metabolites in blood and were more likely to drink hazardously than cocaine users without CE and cocaine non-users. Overall, cocaine use was associated with liver fibrosis. CE in blood was associated with 3.17 (95% CI: 1.61, 6.23; p = 0.0008) times the odds of liver fibrosis compared to cocaine non-users, adjusting for covariates including HIV and HCV infection. The effect of CE on liver fibrosis was significantly greater than that of cocaine or alcohol alone., Conclusions: CE is a reliable marker of simultaneous use of cocaine and alcohol that may help identify individuals at risk of liver disease and aid in the prevention of its development or progression., (Copyright © 2022. Published by Elsevier B.V.)

Objective: The COVID-19 pandemic has dramatically impacted mental health, increasing rates of substance misuse. Resilience is a positive adaptation to stress that may act as a buffer against adverse mental health outcomes. Based on prior knowledge, we hypothesized that PLWH would display higher resilience than HIV-uninfected peers, and that high resilience would be associated with lower risk of substance misuse., Methods: This analysis of the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) included data from six USA cohorts that administered a COVID-19-related survey with a 3-month follow-up during May 2020 and March 2021. All data was self-reported. The Brief Resilience Scale and General Anxiety Disorder-7 were utilized. Primary analyses consisted of multivariate generalized linear mixed models with random intercepts using binary logistic regression., Results: A total of 1430 participants completed both surveys, of whom 670 (46.9%) were PLWH. PLWH had lower odds of anxiety (OR=0.67, 95% CI: 0.51-0.89) and higher odds of high resilience (OR=1.21, 95% CI: 1.02-1.44) than HIV-uninfected participants, adjusted for covariates. The presence of anxiety was associated with higher risk of misuse of all substances. High resilience was associated with lower risk of anxiety and misuse of substances, adjusted for covariates., Conclusions: Psychological resilience was associated with lower risk of anxiety and substance misuse, potentially serving as a buffer against poor mental and behavioral health during the COVID-19 pandemic. Further research is needed to identify pathways of resilience in the context of substance misuse and comprehensive resilience-focused interventions., (Copyright © 2022. Published by Elsevier B.V.)

Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indirectly promotes the progression of clinical characteristics of coronary artery disease (CAD). 300 African Americans with asymptomatic CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV-infected) who underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years) were randomly selected from 1429 participants of a prospective epidemiological study between May 2004 and August 2015. We calculated Agatston-scores, number of coronary plaques and segment stenosis score (SSS). Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use on CAD. There was no significant difference in annual progression rates between HIV-infected and-uninfected regarding Agatston-scores (10.8 ± 25.1/year vs. 7.2 ± 17.8/year, p = 0.17), the number of plaques (0.2 ± 0.3/year vs. 0.3 ± 0.5/year, p = 0.11) or SSS (0.5 ± 0.8/year vs. 0.5 ± 1.3/year, p = 0.96). Multivariately, HIV-infection was not associated with Agatston-scores (8.3, CI: [- 37.2-53.7], p = 0.72), the number of coronary plaques (- 0.1, CI: [- 0.5-0.4], p = 0.73) or SSS (- 0.1, CI: [- 1.0-0.8], p = 0.84). ASCVD risk scores and years of cocaine-use significantly increased all CAD outcomes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-medications were associated with any of the CAD outcomes. HIV-infection is not directly associated with CAD and therefore HIV-infected are not destined to have worse CAD profiles. However, HIV-infection may indirectly promote CAD progression as risk factors may have a more prominent role in the acceleration of CAD in these patients., (© 2021. The Author(s).)

Background: Socioeconomic disadvantages and potential immunocompromise raise particular concerns for people living with HIV (PLWH) and other marginalized communities during the COVID-19 pandemic. In this study, we explored COVID-19 testing and the impact of the pandemic among participants from the Miami Adult Studies on HIV cohort, predominantly composed of low-income minorities living with and without HIV., Methods: Between July and August 2020, a telephone survey was administered to 299 Miami Adult Studies on HIV participants to assess COVID-19 testing, prevention behaviors, and psychosocial stressors. Health care utilization, antiretroviral adherence, food insecurity, and substance use during the pandemic were compared with those of their last cohort visit (7.8 ± 2.9 months earlier)., Results: Half of surveyed participants had been tested for COVID-19, 8 had tested positive and 2 had been hospitalized. PLWH (n = 183) were 42% times less likely than HIV-uninfected participants to have been tested. However, after adjustment for age, employment, COVID-19 symptoms, mental health care, and substance use, the effect of HIV status was no longer significant. PLWH were more likely to have seen a health care provider, use face coverings, and avoid public transportation and less likely to be food insecure and drink hazardously. There were significant changes in substance use patterns during the pandemic when compared with those before., Conclusion: PLWH, compared with their HIV-uninfected peers, were more likely to engage in preventive measures and health care during the pandemic, potentially reducing their exposure to COVID-19. There were no reported changes in antiretroviral adherence or health care utilization, but there were changes in substance use; these need to be monitored as this crisis progresses., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cognitive impairment is common in people living with HIV (PLWH). Opioid drugs exert direct and indirect effects on cognitive processes, which may contribute to cognitive dysfunction among PLWH. This study was designed to determine if opioid use is associated with cognitive impairment and whether the effect differs between PLWH and HIV-uninfected adults. Other neuropsychiatric symptoms, such as depression and apathy, were also examined. We conducted a cross-sectional analysis of 265 PLWH and 284 HIV-uninfected participants from the Miami Adult Studies on HIV (MASH) cohort. The Mini-Mental State Examination (MMSE) was used to assess cognitive impairment. Substance use was self-reported. Overall, 26.8% of PLWH and 15.1% of HIV-uninfected used opioids. Cognitive impairment was more frequent among people who used heroin and/or fentanyl than those who misused prescription opioids (31.6% vs. 10.5%, p = .005). The use of heroin/fentanyl was associated with increased odds for cognitive impairment (adjusted OR: 2.21, 95% CI 1.05-4.64, p = .036). Among PLWH only, the misuse of opioids was associated with a higher frequency of neuropsychiatric symptoms such as depression and apathy. A higher risk for cognitive impairment was seen among people who used heroin and fentanyl. PLWH who misuse opioids may be at an increased risk for neuropathology, but elucidation of mechanisms for opioid-induced cognitive deficits is needed.

Objectives: To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans., Methods: We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: -100-350HU), low-attenuation noncalcified (LA-NCP: -100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes., Results: There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0-19.4] mm 3 /year vs. 4.9 [IQR: 1.5-18.3] mm 3 /year, p = 0.14), LA-NCP (0.2 [IQR: 0.0-1.6] mm 3 /year vs. 0.2 [IQR: 0.0-0.9] mm 3 /year, p = 0.07) or CP volumes (0.3 [IQR: 0.0-3.4] mm 3 /year vs. 0.1 [IQR: 0.0-3.2] mm 3 /year, p = 0.30). Multivariately, HIV infection was not associated with NCP (-6.9mm 3 , CI: [-32.8-19.0], p = 0.60), LA-NCP (-0.1mm 3 , CI: [-2.6-2.4], p = 0.92), or CP volumes (-0.3mm 3 , CI: [-9.3-8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all)., Conclusions: The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume., Key Points: • Human immunodeficiency virus-infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.

Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) ( P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the United States. Food-insecure individuals often depend on low-cost, energy-dense but nutritionally poor foods, resulting in obesity and chronic diseases related to NAFLD., Objectives: To determine whether food insecurity is associated with NAFLD in a cohort of HIV and hepatitis C virus (HCV) infected and uninfected adults., Methods: We conducted a cross-sectional analysis of low-income, middle-aged adults from the Miami Adult Studies on HIV (MASH) cohort without a history of excessive alcohol consumption. Food security was assessed with the USDA's Household Food Security Survey. MRIs were used to assess liver steatosis and fibrosis. Metabolic parameters were assessed from fasting blood, anthropometrics, and vitals., Results: Of the total 603 participants, 32.0% reported food insecurity. The prevalences of NAFLD, fibrosis, and advanced fibrosis were 16.1%, 15.1%, and 4.6%, respectively. For every 5 kg/m2 increase in BMI, the odds of NAFLD increased by a factor of 3.83 (95% CI, 2.37-6.19) in food-insecure participants compared to 1.32 (95% CI, 1.04-1.67) in food-secure participants. Food insecurity was associated with increased odds for any liver fibrosis (OR, 1.65; 95% CI, 1.01-2.72) and advanced liver fibrosis (OR, 2.82; 95% CI, 1.22-6.54), adjusted for confounders. HIV and HCV infections were associated with increased risks for fibrosis, but the relationship between food insecurity and liver fibrosis did not differ between infected and uninfected participants., Conclusions: Among low-income, middle-aged adults, food insecurity exacerbated the risk for NAFLD associated with a higher BMI and independently increased the risk for advanced liver fibrosis. People who experience food insecurity, particularly those vulnerable to chronic diseases and viral infections, may be at increased risk for liver-related morbidity and mortality. Improving access to adequate nutrition and preventing obesity among low-income groups may lessen the growing burden of NAFLD and other chronic diseases., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: People who use opioids and people living with HIV (PLWH) are at increased risk for liver-related morbidity and mortality. Although animal models suggest that chronic opioid use may cause liver damage, research in humans is limited. We aimed to determine whether opioid use, particularly heroin, was associated with liver fibrosis., Methods: Cross-sectional analysis of 679 participants (295 HIV/HCV uninfected, 218 HIV mono-infected, 87 HCV mono-infected, 79 HIV/HCV coinfected) from the Miami Adult Studies on HIV (MASH) cohort. Liver fibrosis was assessed via magnetic resonance elastography (MRE) on a 3 T Siemens MAGNETOM Prisma scanner., Results: A total of 120 (17.7 %) participants used opioids. Liver fibrosis was present in 99 (14.6 %) participants and advanced liver fibrosis in 31 (4.6 %). Heroin use (N = 46, 6.8 %) was associated with HCV-seropositivity, smoking, misuse of prescription opioids, and polysubstance use. The use of heroin, but not misuse of prescription opioids, was significantly associated with liver fibrosis (OR = 2.77, 95 % CI: 1.18-6.50) compared to heroin non-users, after adjustment for confounders including excessive alcohol consumption, polysubstance use and HIV and HCV infections. Both HIV and HCV infections were associated with liver fibrosis, whether virally suppressed/undetectable or viremic., Conclusions: Heroin use was independently associated with increased risk for liver fibrosis irrespective of the use of other substances and HIV or HCV infections. Both HIV and HCV were associated with higher risk for liver fibrosis, even among those with suppressed or undetectable viral loads. The exact mechanisms for opioid-induced liver fibrosis remain to be fully elucidated., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is growing public health concern around the potential impact of the opioid crisis on efforts to eradicate HIV. This secondary analysis seeks to determine if those who report opioids as their primary problem drug compared to those who report other drugs and/or alcohol differ in engagement in HIV primary care among a sample of hospitalized people with HIV (PWH) who use drugs and/or alcohol, a traditionally marginalized and difficult to engage population key to ending the HIV epidemic., Setting and Participants: A total of 801 participants (67% male; 75% Black, non-Hispanic; mean age 44.2) with uncontrolled HIV and reported drug and/or alcohol use were recruited from 11 hospitals around the U.S. in cities with high HIV prevalence from 2012 to 2014 for a multisite clinical trial to improve HIV viral suppression., Methods: A generalized linear model compared those who reported opioids as their primary problem drug to those who reported other problem drugs and/or alcohol on their previous engagement in HIV primary care, controlling for age, sex, race, education, income, any previous drug and/or alcohol treatment, length of time since diagnosis, and study site., Results: A total of 95 (11.9%) participants reported opioids as their primary problem drug. In adjusted models, those who reported opioids were significantly less likely to have ever engaged in HIV primary care than those who reported no problem drug use (adjusted risk ratio, ARR = 0.84, 95% Confidence Interval, CI 0.73, 0.98), stimulants (ARR = 0.84, 95% CI 0.74, 0.95), and polydrug use but no alcohol (ARR = 0.79, 95% CI 0.68, 0.93). While not statistically significant, the trend in the estimates of the remaining drug and/or alcohol categories (alcohol, cannabis, polydrug use with alcohol, and [but excluding the estimate for] other), point to a similar phenomena-those who identify opioids as their primary problem drug are engaging in HIV primary care less., Conclusions: These findings suggest that for hospitalized PWH who use drugs and/or alcohol, tailored and expanded efforts are especially needed to link those who report problem opioid use to HIV primary care. Trial registration This study was funded by National Institutes of Health (NIH) grant: U10-DA01372011 (Project HOPE-Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users; Metsch); which is also a registered clinical trial under the Clinical Trials Network (CTN-0049). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Background: Substance use can reduce care engagement for individuals with HIV. However, little is known as to whether heavy drinkers differ from drug users. This study compares heavy drinkers, drug users, and those drinking heavily and using drugs on their HIV care engagement., Methods: HIV-infected adult inpatients (n = 801; 67% male; 78% Black) from 11 urban hospitals across the United States participated in a multisite clinical trial to improve patient engagement in HIV care and virologic outcomes. All participants drank heavily and/or used drugs, and had poorly controlled HIV. Participants reported care history at baseline. We compared heavy drinkers, drug users, and those both drinking heavily and using drugs (reference group) on their engagement in care., Results: Heavy drinkers reported lowest rates of lifetime HIV care, AOR = 0.59 (95% CI = 0.36, 0.97). Groups did not differ in recent care, prescription of HIV medication, medical mistrust, or patient-provider relationship. Drug users evidenced the best medication adherence, AOR = 2.38 (95% CI = 1.33, 4.23). Exploratory analyses indicated that drinkers had lower initial care engagement, but that it increased more rapidly with duration of known HIV infection, with similar rates of recent care. Drinkers had the lowest CD4 counts (B=-0.28, p < 0.0001), but no difference in viral load., Conclusions: Heavy drinkers were least likely to have ever been in HIV care. More research is needed to determine why heavy drinkers evidence the lowest initial care engagement and current CD4 counts, and whether drinking intervention early in infection may increase HIV care engagement., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Using baseline data from the NIDA Clinical Trials Network 0049 study (Project HOPE), we performed latent class analyses (LCA) to identify discrete classes, or clusters, of people living with HIV (PLWH) based on their past year substance use behaviors and lifetime arrest history. We also performed multinomial logistic regressions to identify key characteristics associated with class membership. We identified 5 classes of substance users (minimal drug users, cocaine users, substantial cocaine/hazardous alcohol users, problem polysubstance users, substantial cocaine/heroin users) and 3 classes of arrest history (minimal arrests, non-drug arrests, drug-related arrests). While several demographic variables such as age and being Black or Hispanic were associated with class membership for some of the latent classes, participation in substance use treatment was the only covariate that was significantly associated with membership in all classes in both substance use and arrest history LCA models. Our analyses reveal complex patterns of behaviors among substance using PLWH and suggest that HIV intervention strategies may need to take into consideration such nuanced differences to better inform future studies and program implementation.

Background and Aims: HIV-infected people with substance use disorders are least likely to benefit from advances in HIV treatment. Integration of extended-release naltrexone (XR-NTX) into HIV clinics may increase engagement in the HIV care continuum by decreasing substance use. We aimed to compare (1) XR-NTX treatment initiation, (2) retention and (3) safety of XR-NTX versus treatment as usual (TAU) for treating opioid use disorder (OUD) and/or alcohol use disorder (AUD) in HIV clinics., Design: Non-blinded randomized trial of XR-NTX versus pharmacotherapy TAU., Setting: HIV primary care clinics in Vancouver, BC, Canada and Chicago, IL, USA., Participants: Fifty-one HIV-infected patients seeking treatment for OUD (n = 16), AUD (n = 27) or both OUD and AUD (n = 8)., Measurements: Primary outcomes were XR-NTX initiation (receipt of first injection within 4 weeks of randomization) and retention at 16 weeks. Secondary outcomes generated point estimates for change in substance use, HIV viral suppression [HIV RNA polymerase chain reaction (pcr) < 200 copies/ml] and safety., Findings: Two-thirds (68%) of participants assigned to XR-NTX initiated treatment, and 88% of these were retained on XR-NTX at 16 weeks. In comparison, 96% of TAU participants initiated treatment, but only 50% were retained on medication at 16 weeks. Mean days of opioid use in past 30 days decreased from 17.3 to 4.1 for TAU and from 20.3 to 7.7 for XR-NTX. Mean heavy drinking days decreased from 15.6 to 5.7 for TAU and 12.5 to 2.8 for XR-NTX. Among those with OUD, HIV suppression improved from 67 to 80% for XR-NTX and 58 to 75% for TAU. XR-NTX was well tolerated, with no precipitated withdrawals and one serious injection-site reaction., Conclusions: Extended-release naltrexone (XR-NTX) is feasible and safe for treatment of opioid use disorder and alcohol use disorder in HIV clinics. Treatment initiation appears to be lower and retention greater for XR-NTX compared with treatment as usual (clinicaltrials.gov NCT01908062)., (© 2017 Society for the Study of Addiction.)

Objectives: Sexually transmitted infections (STIs) are significant public health and financial burdens in the United States. This manuscript examines the relationship between substance use and prevalent and incident STIs in HIV-negative adult patients at STI clinics., Methods: A secondary analysis of Project AWARE was performed based on 5012 patients from 9 STI clinics. STIs were assessed by laboratory assay and substance use by self-report. Patterns of substance use were assessed using latent class analysis. The relationship of latent class to STI rates was investigated using Poisson regression by population groups at high risk for STIs defined by participant's and partner's gender., Results: Drug use patterns differed by risk group and substance use was related to STI rates with the relationships varying by risk behavior group. Substance use treatment participation was associated with increased STI rates., Conclusions: Substance use focused interventions may be useful in STI clinics to reduce morbidity associated with substance use. Conversely, gender-specific sexual health interventions may be useful in substance use treatment., Competing Interests: None of the authors have declared any conflict of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

HIV counseling with testing has been part of HIV prevention in the U.S. since the 1980s. Despite the long-standing history of HIV testing with prevention counseling, the CDC released HIV testing recommendations for health care settings contesting benefits of prevention counseling with testing in reducing sexual risk behaviors among HIV-negatives in 2006. Efficacy of brief HIV risk-reduction counseling (RRC) in decreasing sexual risk among subgroups of substance use treatment clients was examined using multi-site RCT data. Interaction tests between RRC and subgroups were performed; multivariable regression evaluated the relationship between RRC (with rapid testing) and sex risk. Subgroups were defined by demographics, risk type and level, attitudes/perceptions, and behavioral history. There was an effect (p < .0028) of counseling on number of sex partners among some subgroups. Certain subgroups may benefit from HIV RRC; this should be examined in studies with larger sample sizes, designed to assess the specific subgroup(s).

Importance: Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes. Patient navigation (care coordination with case management) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care, but there is little evidence for their efficacy in improving HIV-1 viral suppression rates., Objective: To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital inpatients., Design, Setting, and Participants: From July 2012 through January 2014, 801 patients with HIV infection and substance use from 11 hospitals across the United States were randomly assigned to receive patient navigation alone (n = 266), patient navigation plus financial incentives (n = 271), or treatment as usual (n = 264). HIV-1 plasma viral load was measured at baseline and at 6 and 12 months., Interventions: Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months. Financial incentives (up to $1160) were provided for achieving targeted behaviors aimed at reducing substance use, increasing engagement in HIV care, and improving HIV outcomes. Treatment as usual was the standard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment., Main Outcomes and Measures: The primary outcome was HIV viral suppression (≤200 copies/mL) relative to viral nonsuppression or death at the 12-month follow-up., Results: Of 801 patients randomized, 261 (32.6%) were women (mean [SD] age, 44.6 years [10.0 years]). There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months. Eighty-five of 249 patients (34.1%) in the usual-treatment group experienced treatment success compared with 89 of 249 patients (35.7%) in the navigation-only group for a treatment difference of 1.6% (95% CI, -6.8% to 10.0%; P = .80) and compared with 98 of 254 patients (38.6%) in the navigation-plus-incentives group for a treatment difference of 4.5% (95% CI -4.0% to 12.8%; P = .68). The treatment difference between the navigation-only and the navigation-plus-incentives group was -2.8% (95% CI, -11.3% to 5.6%; P = .68)., Conclusions and Relevance: Among hospitalized patients with HIV infection and substance use, patient navigation with or without financial incentives did not have a beneficial effect on HIV viral suppression relative to nonsuppression or death at 12 months vs treatment as usual. These findings do not support these interventions in this setting., Trial Registration: clinicaltrials.gov Identifier: NCT01612169.

Increasing rates of HIV testing within substance use disorder (SUD) treatment clients is an important public health strategy for reducing HIV transmission rates. The present study examined uptake of HIV testing among 1,224 clients in five SUD treatment units that offered on-site testing in Florida, New York, and California. Nearly one-third (30 %) of the participants, who had not previously tested positive, reported not having been tested for HIV within the past 12 months. Women, African Americans, and injection drug users had a higher likelihood of having been tested within the past 12 months. The SUD treatment program was the most frequently identified location of participants' last HIV test. Despite the availability of free, on-site testing, a substantial proportion of clients were not tested, suggesting that strategies to increase uptake of testing should include addressing barriers not limited to location and cost.

Importance: Medical treatment settings such as emergency departments (EDs) present important opportunities to address problematic substance use. Currently, EDs do not typically intervene beyond acute medical stabilization., Objective: To contrast the effects of a brief intervention with telephone boosters (BI-B) with those of screening, assessment, and referral to treatment (SAR) and minimal screening only (MSO) among drug-using ED patients., Design, Setting, and Participants: Between October 2010 and February 2012, 1285 adult ED patients from 6 US academic hospitals, who scored 3 or greater on the 10-item Drug Abuse Screening Test (indicating moderate to severe problems related to drug use) and who were currently using drugs, were randomized to MSO (n = 431), SAR (n = 427), or BI-B (n = 427). Follow-up assessments were conducted at 3, 6, and 12 months by blinded interviewers., Interventions: Following screening, MSO participants received only an informational pamphlet. The SAR participants received assessment plus referral to addiction treatment if indicated, and the BI-B participants received assessment and referral as in SAR, plus a manual-guided counseling session based on motivational interviewing principles and up to 2 "booster" sessions by telephone during the month following the ED visit., Main Outcomes and Measures: Outcomes evaluated at follow-up visits included self-reported days using the patient-defined primary problem drug, days using any drug, days of heavy drinking, and drug use based on analysis of hair samples. The primary outcome was self-reported days of use of the patient-defined primary problem drug during the 30-day period preceding the 3-month follow-up., Results: Follow-up rates were 89%, 86%, and 81% at 3, 6, and 12 months, respectively. For the primary outcome, estimated differences in number of days of use (95% CI) were as follows: MSO vs BI-B, 0.72 (-0.80 to 2.24), P (adjusted) = .57; SAR vs BI-B, 0.70 (-0.83 to 2.23), P (adjusted) = .57; SAR vs MSO, -0.02 (-1.53 to 1.50), P (adjusted) = .98. There were no significant differences between groups in self-reported days using the primary drug, days using any drug, or heavy drinking days at 3, 6, or 12 months. At the 3-month follow-up, participants in the SAR group had a higher rate of hair samples positive for their primary drug of abuse (265 of 280 [95%]) than did participants in the MSO group (253 of 287 [88%]) or the BI-B group (244 of 275 [89%]). Hair analysis differences between groups at other time points were not significant., Conclusions and Relevance: In this sample of drug users seeking emergency medical treatment, a relatively robust brief intervention did not improve substance use outcomes. More work is needed to determine how drug use disorders may be addressed effectively in the ED., Trial Registration: clinicaltrials.gov Identifier:NCT01207791.

Study Objective: Drug-related emergency department (ED) visits have steadily increased, with substance users relying heavily on the ED for medical care. The present study aims to identify clinical correlates of problematic drug use that would facilitate identification of ED patients in need of substance use treatment., Methods: Using previously validated tests, 15,224 adult ED patients across 6 academic institutions were prescreened for drug use as part of a large randomized prospective trial. Data for 3,240 participants who reported drug use in the past 30 days were included. Self-reported variables related to demographics, substance use, and ED visit were examined to determine their correlative value for problematic drug use., Results: Of the 3,240 patients, 2,084 (64.3%) met criteria for problematic drug use (Drug Abuse Screening Test score ≥ 3). Age greater than or equal to 30 years, tobacco smoking, daily or binge alcohol drinking, daily drug use, primary noncannabis drug use, resource-intense ED triage level, and perceived drug-relatedness of ED visit were highly correlated with problematic drug use. Among primary cannabis users, correlates of problematic drug use were age younger than 30 years, tobacco smoking, binge drinking, daily drug use, and perceived relatedness of the ED visit to drug use., Conclusion: Clinical correlates of drug use problems may assist the identification of ED patients who would benefit from comprehensive screening, intervention, and referral to treatment. A clinical decision rule is proposed. The correlation between problematic drug use and resource-intense ED triage levels suggests that ED-based efforts to reduce the unmet need for substance use treatment may help decrease overall health care costs., (Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of alcohol, tobacco, and other drug (ATOD) use among emergency department (ED) patients is high and many of these patients have unrecognized and unmet substance use treatment needs. Identification of patients in the ED with problem substance use is not routine at this time., Methods: We examined screening data, including standardized measures of ATOD use (HSI, AUDIT-C, DAST-10), from 14,866 ED patients in six hospitals across the United States. We expected younger age, male gender, higher triage acuity, and other substance use severity (ATOD) to be associated both with use versus abstinence and with severity of each substance use type. We used negative binomial hurdle models to examine the association between covariates and (1) substance use versus abstinence (logistic submodel) and with (2) severity among those who used substances (count submodel)., Results: Rates of use and problem use in our sample were similar to or higher than other ED samples. Younger patients and males were more likely to use ATOD, but the association of age and gender with severity varied across substances. Triage level was a poor predictor of substance use severity. Alcohol, tobacco, and drug use were significantly associated with using other substances and severity of other substance use., Conclusion: Better understanding of the demographic correlates of ATOD use and severity and the patterns of comorbidity among classes of substance can inform the design of optimal screening and brief intervention procedures addressing ATOD use among ED patients. Tobacco may be an especially useful predictor., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Importance: To increase human immunodeficiency virus (HIV) testing rates, many institutions and jurisdictions have revised policies to make the testing process rapid, simple, and routine. A major issue for testing scale-up efforts is the effectiveness of HIV risk-reduction counseling, which has historically been an integral part of the HIV testing process., Objective: To assess the effect of brief patient-centered risk-reduction counseling at the time of a rapid HIV test on the subsequent acquisition of sexually transmitted infections (STIs)., Design, Setting, and Participants: From April to December 2010, Project AWARE randomized 5012 patients from 9 sexually transmitted disease (STD) clinics in the United States to receive either brief patient-centered HIV risk-reduction counseling with a rapid HIV test or the rapid HIV test with information only. Participants were assessed for multiple STIs at both baseline and 6-month follow-up., Interventions: Participants randomized to counseling received individual patient-centered risk-reduction counseling based on an evidence-based model. The core elements included a focus on the patient's specific HIV/STI risk behavior and negotiation of realistic and achievable risk-reduction steps. All participants received a rapid HIV test., Main Outcomes and Measures: The prespecified outcome was a composite end point of cumulative incidence of any of the measured STIs over 6 months. All participants were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (syphilis), herpes simplex virus 2, and HIV. Women were also tested for Trichomonas vaginalis., Results: There was no significant difference in 6-month composite STI incidence by study group (adjusted risk ratio, 1.12; 95% CI, 0.94-1.33). There were 250 of 2039 incident cases (12.3%) in the counseling group and 226 of 2032 (11.1%) in the information-only group., Conclusion and Relevance: Risk-reduction counseling in conjunction with a rapid HIV test did not significantly affect STI acquisition among STD clinic patients, suggesting no added benefit from brief patient-centered risk-reduction counseling., Trial Registration: clinicaltrials.gov Identifier: NCT01154296.

Objectives: We examined the effectiveness of risk reduction counseling and the role of on-site HIV testing in drug treatment., Methods: Between January and May 2009, we randomized 1281 HIV-negative (or status unknown) adults who reported no past-year HIV testing to (1) referral for off-site HIV testing, (2) HIV risk-reduction counseling with on-site rapid HIV testing, or (3) verbal information about testing only with on-site rapid HIV testing., Results: We defined 2 primary self-reported outcomes a priori: receipt of HIV test results and unprotected anal or vaginal intercourse episodes at 6-month follow-up. The combined on-site rapid testing participants received more HIV test results than off-site testing referral participants (P<.001; Mantel-Haenszel risk ratio=4.52; 97.5% confidence interval [CI]=3.57, 5.72). At 6 months, there were no significant differences in unprotected intercourse episodes between the combined on-site testing arms and the referral arm (P=.39; incidence rate ratio [IRR]=1.04; 97.5% CI=0.95, 1.14) or the 2 on-site testing arms (P=.81; IRR=1.03; 97.5% CI=0.84, 1.26)., Conclusions: This study demonstrated on-site rapid HIV testing's value in drug treatment centers and found no additional benefit from HIV sexual risk-reduction counseling.

Background: Injection drug use (IDU) is a primary vector for blood-borne infections. Awareness of Hepatitis C virus (HCV) infection status may affect risky injection behaviors. This study determines the prevalence of risky injection practices and examines associations between awareness of positive HCV status and risky injection behaviors., Methods: We surveyed individuals seeking treatment for substance use at 12 community treatment programs as part of a national HIV screening trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants reported socio-demographic characteristics, substance use, risk behaviors, and HCV status. We used multivariable logistic regression to test associations between participant characteristics and syringe/needle sharing., Results: The 1281 participants included 244 (19.0%) individuals who reported injecting drugs in the past 6 months and 37.7% of IDUs reported being HCV positive. During the six months preceding baseline assessment, the majority of IDUs reported obtaining sterile syringes from pharmacies (51.6%) or syringe exchange programs (25.0%), but fewer than half of IDUs always used a sterile syringe (46.9%). More than one-third (38.5%) shared syringe/needles with another injector in the past 6 months. Awareness of positive HCV vs. negative/unknown status was associated with increased recent syringe/needle sharing (aOR 2.37, 95% CI 1.15, 4.88) in multivariable analysis., Conclusions: Risky injection behaviors remain prevalent and awareness of HCV infection was associated with increased risky injection behaviors. New approaches are needed to broadly implement HCV prevention interventions for IDUs seeking addiction treatment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background/objectives: HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years., Results: While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs., Conclusion/significance: While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.

Background: Medical settings such as emergency departments (EDs) present an opportunity to identify and provide services for individuals with substance use problems who might otherwise never receive any form of assessment, referral, or intervention. Although screening, brief intervention, and referral to treatment models have been extensively studied and are considered effective for individuals with alcohol problems presenting in EDs and other medical settings, the efficacy of such interventions has not been established for drug users presenting in EDs., Objectives: This article describes the design of a NIDA Clinical Trials Network protocol testing the efficacy of an screening, brief intervention, and referral to treatment model in medical EDs, highlighting considerations that are pertinent to the design of other studies targeting substance use behaviors in medical treatment settings., Methods: The protocol is described, and critical design decisions are discussed., Results: Design challenges included defining treatment conditions, study population, and site characteristics; developing the screening process; choosing the primary outcome; balancing brevity and comprehensiveness of assessment; and selecting the strategy for statistical analysis., Conclusion: Many of the issues arising in the design of this study will be relevant to future studies of interventions for addictions in medical settings., Scientific Significance: Optimal trial design is critical to determining how best to integrate substance abuse interventions into medical care.

This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months; interventions added to standard treatment offered no improvement in risk behavior outcomes.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that typically affects optic nerves and spinal cord. Its pathogenic relationship to multiple sclerosis (MS) is uncertain. Unlike MS, NMO lesions are characterized by deposits of IgG and IgM co-localizing with products of complement activation in a vasculocentric pattern around thickened hyalinized blood vessels, suggesting a pathogenic role for humoral immunity targeting an antigen in the perivascular space. A recently identified specific serum autoantibody biomarker, NMO-IgG, targets aquaporin-4 (AQP4), the most abundant water channel protein in the CNS, which is highly concentrated in astrocytic foot processes. We analysed and compared patterns of AQP4 immunoreactivity in CNS tissues of nine patients with NMO, 13 with MS, nine with infarcts and five normal controls. In normal brain, optic nerve and spinal cord, the distribution of AQP4 expression resembles the vasculocentric pattern of immune complex deposition observed in NMO lesions. In contrast to MS lesions, which exhibit stage-dependent loss of AQP4, all NMO lesions demonstrate a striking loss of AQP4 regardless of the stage of demyelinating activity, extent of tissue necrosis, or site of CNS involvement. We identified a novel NMO lesion in the spinal cord and medullary tegmentum extending into the area postrema, characterized by AQP4 loss in foci that were inflammatory and oedematous, but neither demyelinated nor necrotic. Foci of AQP4 loss coincided with sites of intense vasculocentric immune complex deposition. These findings strongly support a role for a complement activating AQP4-specific autoantibody as the initiator of the NMO lesion, and further distinguish NMO from MS.

Neuromyelitis optica of Devic (NMO) is a syndrome which combines transverse myelitis and optic neuritis. For many years it was assumed that transverse myelitis and optic neuritis should be simultaneous, that optic neuritis should be bilateral, and that transverse myelitis must be complete. NMO was considered to be very rare. Through the 20th century there was a debate on whether NMO is a distinct nosologic entity or a form of MS. In 2005 it is now possible to distinguish NMO from MS on the basis of the clinical, imaging, serology and immunopathology profile. This distinction is necessary for the implementation of adequate treatments, as the relapsing form of the illness carries significant morbidity and mortality.

Devic's disease [neuromyelitis optica (NMO)] is an idiopathic inflammatory demyelinating disease of the CNS, characterized by attacks of optic neuritis and myelitis. The mechanisms that result in selective localization of inflammatory demyelinating lesions to the optic nerves and spinal cord are unknown. Serological and clinical evidence of B cell autoimmunity has been observed in a high proportion of patients with NMO. The purpose of this study was to investigate the importance of humoral mechanisms, including complement activation, in producing the necrotizing demyelination seen in the spinal cord and optic nerves. Eighty-two lesions were examined from nine autopsy cases of clinically confirmed Devic's disease. Demyelinating activity in the lesions was immunocytochemically classified as early active (21 lesions), late active (18 lesions), inactive (35 lesions) or remyelinating (eight lesions) by examining the antigenic profile of myelin degradation products within macrophages. The pathology of the lesions was analysed using a broad spectrum of immunological and neurobiological markers, and lesions were defined on the basis of myelin protein loss, the geography and extension of plaques, the patterns of oligodendrocyte destruction and the immunopathological evidence of complement activation. The pathology was identical in all nine patients. Extensive demyelination was present across multiple spinal cord levels, associated with cavitation, necrosis and acute axonal pathology (spheroids), in both grey and white matter. There was a pronounced loss of oligodendrocytes within the lesions. The inflammatory infiltrates in active lesions were characterized by extensive macrophage infiltration associated with large numbers of perivascular granulocytes and eosinophils and rare CD3(+) and CD8(+) T cells. There was a pronounced perivascular deposition of immunoglobulins (mainly IgM) and complement C9neo antigen in active lesions associated with prominent vascular fibrosis and hyalinization in both active and inactive lesions. The extent of complement activation, eosinophilic infiltration and vascular fibrosis observed in the Devic NMO cases is more prominent compared with that in prototypic multiple sclerosis, and supports a role for humoral immunity in the pathogenesis of NMO. Based on this study, future therapeutic strategies designed to limit the deleterious effects of complement activation, eosinophil degranulation and neutrophil/macrophage/microglial activation are worthy of further investigation.

Matrix metalloproteinases (MMPs) are increased in the CSF of patients with multiple sclerosis. Devic's neuromyelitis optica (DNO) is a demyelinating syndrome that involves the optic nerve and cervical cord but differs pathologically from multiple sclerosis. Therefore, we hypothesized that the type of inflammatory reaction that causes MMPs to be elevated in multiple sclerosis would be absent in patients with DNO. CSF was collected from 23 patients with relapsing-remitting or secondary progressive multiple sclerosis, all of whom were experiencing acute symptoms, from seven patients with DNO, and from seven normal volunteers. Diagnoses were made according to current criteria on the basis of clinical manifestations, imaging results and CSF studies. IgG synthesis was increased in the CSF of multiple sclerosis patients but not in that of DNO patients. Zymography, reverse zymography and ELISA (enzyme-linked immunosorbent assay) were used to measure gelatinase A (MMP-2), gelatinase B (MMP-9) and tissue inhibitors of metalloproteinases (TIMPs). Zymograms showed that multiple sclerosis patients had elevated MMP-9 compared with DNO patients and controls (P: < 0.05). TIMP-1 and TIMP-2 levels were similar in all three groups. We conclude that multiple sclerosis patients have higher MMP-9 levels in the CSF than patients with DNO, which supports the different pathological mechanisms of these diseases.

Seven newly diagnosed patients with Devic's neuromyelitis optica were treated with long-term prednisone and azathioprine, and were followed every 2 months for at least 18 months. Their Expanded Disability Status Scale score improved significantly (mean at baseline, 9; mean at 18 months, 3; p < 0.005), and no relapses occurred for more than 18 months. Multicenter controlled studies are needed to prove the efficacy of this therapeutic regimen.

Guillain-Barré syndrome can very rarely present with acute quadripares and cranial nerve involvement resembling a locked-in state. We describe a very unusual case of fulminant neuropathy in a child who was previously exposed to vincristine. The clinical picture resembled brain death; however, electrodiagnostic studies led to the diagnosis of a peripheral neuropathy. Serial electrodiagnostic studies and pathologic findings confirmed demyelination.

Over a period of 15 months we have seen 6 patients with long-standing history of subcutaneous heroin injections who experienced acute blurred vision, dysphagia, dysarthria, and generalized weakness. Decreased or absent deep tendon reflexes, pupillary abnormalities, incremental responses to fast repetitive nerve stimulation, and positive serology for Clostridia botulinum toxin A were found, but not in all cases. Muscle biopsies showed variable signs of neurogenic atrophy. In vitro electrophysiology studies revealed decreased end-plate potentials quantal content, confirming the presynaptic nature of the disorder. Mechanical ventilation was required in 5 patients. Half of the patients were treated with polyvalent antitoxiin. Prognosis was favorable, though recovery was slow. In conclusion, acute bulbar weakness with visual symptoms in patients with subcutaneous heroin abuse strongly suggets the possibility of wound botulism. High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity.