Ongoing Drug Use Research Articles

Capsule endoscopy for obscure gastrointestinal bleeding in patients with comorbid rheumatic diseases.

Background and Aim. We evaluated the association between patients with rheumatic diseases (RD) suffering from obscure gastrointestinal bleeding (OGIB) and positive capsule endoscopy (CE) findings. Methods. All CE procedures performed on patients with RD and OGIB were assessed from a large database at St. Paul's Hospital (Vancouver, BC, Canada) between December 2001 and April 2011. A positive finding on CE was defined as any pathology, including ulcers/erosions, vascular lesions, and mass lesions, perceived to be the source of bleeding. Results. Of the 1133 CEs performed, 41 (4%) complete CEs were for OGIB in patients with RD. Of these, 54% presented with overt bleeding. Mean age was 66 years. Positive findings were seen in 61% of patients. Ulcerations/erosions (36%) and vascular lesions (36%) were the most common findings. Significant differences between the RD versus non-RD populations included: inpatient status, nonsteroidal anti-inflammatory drug (NSAIDs) use, oral steroid use, and mean Charlson index score (all P ≤ 0.008). Similar nonsignificant trends were seen between positive and negative CEs among the RD population. Conclusions. The correlation between RD and positive CE findings is likely influenced by ongoing anti-inflammatory drug use, poorer health status, and a predisposition for angiodysplastic lesions.

Cannabis and stimulant disorders and readmission 2 years after first-episode psychosis

Few studies have examined the impact of stimulant use on outcome in early psychosis. Ceasing substance use may lead to positive outcomes in psychosis. To examine whether baseline cannabis or stimulant disorders and ongoing drug use predict readmission within 2 years of a first psychosis admission. Predictors of readmission were examined with Cox regression in 7269 people aged 15-29 years with a first psychosis admission. Baseline cannabis and stimulant disorders did not predict readmission. A stimulant disorder diagnosis prior to index psychosis admission predicted readmission, but a prior cannabis disorder diagnosis did not. Ongoing problem drug use predicted readmission. The lowest rate of readmission occurred in people whose baseline drug problems were discontinued. Prior admissions with stimulant disorder may be a negative prognostic sign in first-episode psychosis. Drug use diagnoses at baseline may be a good prognostic sign if they are identified and controlled.

Derivation of a risk scale and quantification of risk factors for serious adverse events in adult emergency department syncope patients

Determining the appropriate disposition of emergency department (ED) syncope patients is challenging. Previously developed decision tools have poor diagnostic test characteristics and methodological flaws in their derivation that preclude their use. We sought to develop a scale to risk-stratify adult ED syncope patients at risk for serious adverse events (SAEs) within 30 days. We conducted a medical record review to include syncope patients age ≥ 16 years and excluded patients with ongoing altered mental status, alcohol or illicit drug use, seizure, head injury leading to loss of consciousness, or severe trauma requiring admission. We collected 105 predictor variables (demographics, event characteristics, comorbidities, medications, vital signs, clinical examination findings, emergency medical services and ED electrocardiogram/monitor characteristics, investigations, and disposition variables) and information on the occurrence of predefined SAEs. Univariate and multiple logistic regression analyses were performed. Among 505 enrolled patient visits, 49 (9.7%) suffered an SAE. Predictors of SAE and their resulting point scores were as follows: age ≥ 75 years (1), shortness of breath (2), lowest ED systolic blood pressure < 80 mm Hg (2), Ottawa Electrocardiographic Criteria present (2), and blood urea nitrogen > 15 mmol/L (3). The final score calculated by addition of the individual scores for each variable (range 0-10) was found to accurately stratify patients into low risk (score < 1, 0% SAE risk), moderate risk (score 1, 3.7% SAE risk), or high risk (score > 1, ≥ 10% SAE risk). We derived a risk scale that accurately predicts SAEs within 30 days in ED syncope patients. If validated, this will be a potentially useful clinical decision tool for emergency physicians, may allow judicious use of health care resources, and may improve patient care and safety.

Mycobacterium neoaurum Causing Prosthetic Valve Endocarditis

Mycobacterium neoaurum rarely causes bacteremia, and infection usually occurs in immunocompromised hosts. Prosthetic Valve Endocarditis (PVE) due to Non Tuberculous Mycobacteria (NTM) is rare; Mycobacterium neoaurum has never been implicated in this disease. We report a case of Mycobacterium neoaurum prosthetic valve endocarditis with favorable response to therapy. *Corresponding author: AnupamKumar, University of Connecticut Health Center, 263 Farmington Ave Farmington, 06030 CT, USA, E-mail: drkumar83@gmail.com Received January 28, 2013; Accepted August 23, 2013; Published August 25, 2013 Citation: Anupam Kumar (2013) Mycobacterium neoaurum Causing Prosthetic Valve Endocarditis. J Pulmon Resp Med S14: 006. doi:10.4172/2161-105X.S14006 Copyright: © 2013 Anupam Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Case Report A 30 year old Caucasian male presented to the emergency department with shortness of breath and palpitations of 2 weeks duration associated with fever and chills. His past medical history was significant for multiple episodes of MRSA endocarditis in the setting of intravenous drug use, for which he had undergone bovine mitral valve replacement a year prior. He admitted to continued intravenous drug use despite recurrent endocarditis and valve replacement. His vital signs on admission were temperature of 101.4°F, pulse rate of 106 per minute, blood pressure of 98/58 mm Hg and respiratory rate of 20 per minute. A Grade 3/6 holosystolic murmur was heard best at the mitral area and radiated to the axilla. The lower extremities were warm to touch. Distal pulses were intact and symmetric. A detailed neurological exam was unremarkable. Admission laboratory tests showed a WBC count of 16.8K/mm3 with neutrophil predominance (84%). Serum electrolytes, blood urea nitrogen, creatinine, creatine kinase (CK) and liver function tests were within the normal range. Chest x-ray showed no abnormality, and electrocardiogram showed normal sinus rhythm with mild left atrial enlargement. Blood cultures were drawn and the patient was started on empiric antibiotic therapy with vancomycin, ceftriaxone and rifampin for provisional diagnosis of prosthetic valve endocarditis. A transthoracic echocardiogram revealed extensive vegetations on the prosthetic mitral valve with mild obstruction to mitral inflow and a normal ejection fraction (Figure 1). The gram stain of the blood smear was initially reported as rods with both gram positive and gramnegative characteristics (Figure 2). However, the acid-fast stain turned positive and three blood culture bottles (aerobic) eventually grew Mycobacterium species (Figure 3). The organism was further identified as Mycobacterium neoaurum using the 16s ribosomal DNA sequencing method. The patient was treated with an anti-mycobacterial regimen based on susceptibility data: IV tobramycin, oral azithromycin and oral moxifloxacin. On day ten of his hospital stay he developed severe abdominal pain. CT scan of the abdomen revealed a splenic infarct (Figure 4) as well as left renal infarct (Figure 5). MRI of brain revealed one centimeter brain abscess (Figure 6). Surgical intervention was discouraged given his ongoing drug use. The patient’s condition Figure 1: Echocardiogram showing vegetations on the prosthetic mitral valve with mild obstruction to mitral inflow. Figure 2: Gram stain showing organism with gram positive and gram negative characteristics. Figure 3: Ziehl Neelsen staining demonstrating acid fast organisms suggestive of mycobacteria species. Citation: Anupam Kumar (2013) Mycobacterium neoaurum Causing Prosthetic Valve Endocarditis. J Pulmon Resp Med S14: 006. doi:10.4172/2161105X.S14-006

Multilevel Predictors of Concurrent Opioid Use during Methadone Maintenance Treatment among Drug Users with HIV/AIDS

BackgroundOngoing drug use during methadone maintenance treatment (MMT) negatively affects outcomes of HIV/AIDS care and treatment for drug users. This study assessed changes in opioid use, and longitudinal predictors of continued opioid use during MMT among HIV-positive drug users in Vietnam, with the aim of identifying changes that might enhance program efficacy.MethodsWe analyze data of 370 HIV-positive drug users (mean age 29.5; 95.7% male) taking MMT at multi-sites. Opioid use was assessed at baseline, 3, 6, and 9 months using interviews and heroin confirmatory urine tests. A social ecological model was applied to explore multilevel predictors of continued opioid use, including individual, interpersonal, community and service influences. Generalized estimating equations (GEE) statistical models were constructed to adjust for intra-individual correlations.ResultsOver 9 month follow-up, self-reported opioid use and positive heroin urine test substantially decreased to 14.6% and 14.4%. MMT helped improve referrals and access to health care and social services. However, utilization of social integration services was small. GEE models determined that participants who were older (Adjusted Odd Ratio - AOR = 0.97 for 1 year increase), had economic dependents (AOR = 0.33), or were referred to TB treatment (AOR = 0.53) were less likely to continue opioid use. Significant positive predictors of ongoing opioid use included frequency of opioid use prior to MMT, peer pressure, living with sexual partners, taking antiretroviral treatment, other health concerns and TB treatment.ConclusionThese findings show that MMT in the Vietnamese context can dramatically reduce opioid use, which is known to be associated with reduced antiretroviral (ART) adherence. Disease stage and drug interactions between antiretrovirals or TB drugs and MMT could explain some of the observed predictors of ongoing drug use; these findings could inform changes in MMT program design and implementation.

Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes

To examine the relationship of anxiety and depression symptoms with treatment outcomes (treatment discontinuation, rates of ongoing use of illicit drugs and likelihood of preterm delivery) in opioid-dependent pregnant women and describe their use of psychotropic medications. Secondary data analysis from a randomized clinical trial of treatment for opioid dependence during pregnancy. A total of 175 opioid-dependent pregnant women, of whom 131 completed treatment. Symptoms of anxiety and depression were captured with the 15-item Mini International Neuropsychiatric Interview (MINI) screen. Use of illicit drugs was measured by urine drug screening. Preterm delivery was defined as delivery prior to 37 weeks' gestation. Self-reported use of concomitant psychotropic medication at any point during the study was recorded. Women reporting only anxiety symptoms at study entry were more likely to discontinue treatment [adjusted odds ratio (OR) = 4.56, 95% confidence interval (CI) : 1.91-13.26, P = 0.012], while those reporting only depression symptoms were less likely to discontinue treatment (adjusted OR = 0.14, 95% CI : 0.20-0.88, P = 0.036) compared to women who reported neither depression nor anxiety symptoms. No statistically significant between-group differences were observed for ongoing illicit drug use or preterm delivery. A majority (61.4%) of women reported use of concomitant psychotropic medication at some point during study participation. Opioid agonist-treated pregnant patients with co-occurring symptoms of anxiety require additional clinical resources to prevent premature discontinuation.

Barriers to HIV treatment among people who use injection drugs

Recent research has confirmed the efficacy of employing highly active antiretroviral therapy (HAART) to prevent the transmission of HIV. However, barriers to the use of HAART among people who use injection drugs (PWIDs) remain an international concern. We review recent findings regarding factors determining effective HIV treatment among PWIDs and describe their possible impact on efforts to curb HIV incidence using HAART. Internationally, HIV-seropositive PWIDs continue to experience suboptimal HIV treatment outcomes compared with other risk groups. Recent findings have better elucidated the role of ongoing illicit drug use in limiting access and adherence to HAART. However, recent research has also increasingly demonstrated the important role that social, environmental and structural factors, resulting from the criminalization of PWIDs, have in placing barriers to optimal HAART use among this population. Treatment as prevention strategies for PWIDs will only be maximally effective if structural barriers to effective addiction and HIV treatment, which stem from the ongoing criminalization of this population, are addressed.

A retrospective chart review of the clinical and psychosocial profile of psychotic adolescents with co-morbid substance use disorders presenting to acute adolescent psychiatric services at Tygerberg Hospital

&lt;p&gt;&lt;strong&gt;Background.&lt;/strong&gt; A large number of adolescents meet criteria for ‘dual diagnosis’ (a psychiatric disorder plus co-morbid substance use disorder (SUD), which prolongs treatment response and complicates intervention strategies. The current service model in Cape Town divides the care of such patients into psychiatric treatment and a separate substance use intervention. Child and adolescent mental health services face the challenge of high rates of readmission of adolescents into psychiatric facilities before utilisation of community-based substance abuse services.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective.&lt;/strong&gt; There is a scarcity of available treatment guidelines for dual-diagnosis adolescents, and a lack of systematically documented epidemiological and clinical data in South African adolescent populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method.&lt;/strong&gt; A retrospective chart review of adolescent psychiatric admissions to the Tygerberg Adolescent Psychiatric Unit during 2010 was conducted. Relevant epidemiological, clinical and demographic data for those presenting with a dual diagnosis (specifically psychotic disorders and SUD) was recorded.&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results.&lt;/strong&gt; Results suggest a high prevalence of SUD among adolescents presenting with a first-episode psychosis. Statistically significant correlations with lower levels of education were found in those with ongoing substance abuse (specifically cannabis and methamphetamine), and a significant relationship between choice of debut drug and ongoing drug use was also demonstrated. Risk factors for SUD (psychosocial adversities, childhood trauma, family and community exposure to substances, early debut drug ages), risky sexual behaviours, and clinical psychiatric profiles of adolescents with dual diagnosis are described.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions.&lt;/strong&gt; This cohort had an enhanced risk as a result of genetic vulnerability and environmental availability of substances, and the findings emphasise the differences in presentation, choice of drugs of abuse and psychosocial difficulties of adolescents with a dual diagnosis presenting to a psychiatric facility. We aim to influence role-players to provide more integrated services, and highlight the need for future prospective studies in this adolescent group to assist in improving outcomes.&lt;/p&gt;

Provider and clinic‐level correlates of deferring antiretroviral therapy for people who inject drugs: a survey of North American HIV providers

BackgroundInjection drug users (IDUs) face numerous obstacles to receiving optimal HIV care, and have been shown to underutilize antiretroviral therapy (ART). We sought to estimate the degree to which providers of HIV care defer initiation of ART because of injection drug use and to identify clinic and provider-level factors associated with resistance to prescribing ART to IDUs.MethodsWe administered an Internet-based survey to 662 regular prescribers of ART in the United States and Canada. Questionnaire items assessed characteristics of providers' personal demographics and training, site of clinical practice and attitudes about drug use. Respondents then rated whether they would likely prescribe or defer ART for hypothetical patients in a series of scenarios involving varying levels of drug use and HIV disease stage.ResultsSurvey responses were received from 43% of providers invited by email and direct mail, and 8.5% of providers invited by direct mail only. Overall, 24.2% of providers reported that they would defer ART for an HIV-infected patient with a CD4+ cell count of 200 cells/mm3 if the patient actively injected drugs, and 52.4% would defer ART if the patient injected daily. Physicians were more likely than non-physician providers to defer ART if a patient injected drugs (adjusted odds ratio 2.6, 95% CI 1.4-4.9). Other predictors of deferring ART for active IDUs were having fewer years of experience in HIV care, regularly caring for fewer than 20 HIV-infected patients, and working at a clinic serving a population with low prevalence of injection drug use. Likelihood of deferring ART was directly proportional to both CD4+ cell count and increased frequency of injecting.ConclusionsMany providers of HIV care defer initiation of antiretroviral therapy for patients who inject drugs, even in the setting of advanced immunologic suppression. Providers with more experience of treating HIV, those in high injection drug use prevalence areas and non-physician providers may be more willing to prescribe ART despite on-going injection drug use. Because of limitations, including low response rate and use of a convenience sample, these findings may not be generalizable to all HIV care providers in North America.

Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics

BackgroundMost methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users.Methods/DesignWe plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV-infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm.DiscussionThis paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence.Trial RegistrationClinicalTrials.gov: NCT01442311

Serum cortisol and dehydroepiandrosterone‐sulfate levels in schizophrenic patients and their first‐degree relatives

Alterations in cortisol and dehydroepiandrosterone sulfate (DHEA-S) levels are thought to play a role in the pathophysiology of neuropsychiatric disorders, including schizophrenia. The aim of this study was to investigate the role of serum cortisol and DHEA-S in the pathophysiology of schizophrenia. Sixty schizophrenic patients, 70 healthy first-degree relatives, and 60 healthy volunteers were included. Sociodemographic characteristics, data regarding disease duration and severity, as well as ongoing and previous drug use were recorded. Serum cortisol and DHEA-S levels were measured. Serum cortisol and DHEA-S levels were significantly higher in the schizophrenia group compared with the first-degree relatives and controls (P < 0.05). Serum cortisol levels in the first-degree relatives were significantly higher than in the healthy controls (P < 0.05). There was no significant difference between the first-degree relatives and healthy-controls in terms of DHEA-S levels and between the three groups in terms of serum cortisol/DHEA-S ratios. Elevated serum cortisol levels in schizophrenic patients might be associated with the role of cortisol in the pathophysiology of schizophrenia. Also, the elevation of serum cortisol levels in first-degree relatives compared to controls suggests that similar pathophysiological processes might have a role in individuals without any disease symptoms, but with a genetic predisposition for schizophrenia. Elevated serum DHEA-S levels might be the result of a compensatory response to elevated cortisol levels. Serum cortisol and DHEA-S levels may be used as a biological marker for the diagnosis of schizophrenia; however, further studies with larger sample sizes are warranted to support this finding.

Substance use after participation in laboratory studies involving smoked cocaine self-administration

Objective Laboratory studies in which drugs of abuse are self- or experimenter-administered to non-treatment-seeking research volunteers provide valuable data about new pharmacotherapies for substance use disorders, as well as behavioral and performance data for understanding the neurobiology of drug abuse. This paper analyzed follow-up data from six smoked cocaine self-administration laboratory studies, in order to determine whether changes in substance use occurred 1 and 3 months after study participation compared to pre-study baseline. Methods Ninety-eight healthy, non-treatment-seeking cocaine users were admitted to inpatient and combined inpatient/outpatient studies lasting from 12 to 105 days. The studies allowed participants to self-administer repeated doses of smoked cocaine (0, 6, 12, 25, and/or 50 mg per dose) on multiple occasions. Participants returned for follow-up at 1 and 3 months, at which time self-reported consumption of cocaine, alcohol, marijuana, and nicotine was assessed. Results Compared to baseline ($374.04/week, S.D. $350.09), cocaine use significantly decreased at 1 month ($165.13/week, S.D. $165.56) and 3 months ($118.59/week, S.D. $110.48) after study participation ( p < 0.001; results based on the 39 participants who completed all 3 time points). This decrease was not accompanied by a change in other drug use, e.g., a compensatory increase in alcohol, marijuana or nicotine use. Conclusion Study participation was not associated with increased post-study cocaine, alcohol, marijuana, or nicotine use. Thus, human laboratory models of cocaine self-administration, conducted in non-treatment-seeking research volunteers, are relatively safe, and study participation does not exacerbate ongoing drug use.

The subjective effects of alcohol–tobacco co-use: An ecological momentary assessment investigation.

Alcohol and tobacco use covary at multiple levels of analysis, and co-use of the 2 substances may have profound health consequences. To characterize the motivationally relevant processes contributing to co-use, the current study used ecological momentary assessment (EMA) to examine the subjective consequences of naturally occurring simultaneous use of alcohol and tobacco. Current smokers who reported frequently drinking alcohol (N=259) used electronic diaries to monitor their daily experiences for 21 days. Participants responded to prompted assessments and also initiated recordings when they smoked a cigarette or completed the first drink in a drinking episode. Momentary reports of smoking and alcohol consumption were associated with one another, and these effects remained after adjustment for occasion- and person-level covariates. When participants consumed alcohol, they reported increased pleasure and decreased punishment from the last cigarette. Smoking was associated with small increases in pleasure from the last drink. Ratings of buzzed and dizzy were synergistically affected by co-use of alcohol and tobacco. Co-use was also followed by higher levels of craving for both alcohol and tobacco. Results point to the importance of reward and incentive processes in ongoing drug use and suggest that alcohol intensifies real-time reports of the motivational consequences of smoking more strongly than smoking affects corresponding appraisals of alcohol effects.

Characteristics of childhood cancer survivors who attend long-term follow-up (LTFU) clinic.

9566 Background: Although the Children’s Oncology Group developed LTFU guidelines for childhood cancer survivors, the majority of adult survivors do not receive risk-based care through a LTFU program. This study aimed to identify characteristics of pediatric cancer survivors who return to a LTFU Clinic for care compared with patients who do not. Methods: Chart review of patients eligible to be seen in the LTFU Clinic who completed treatment between 1/1990 and 11/2010. Patient characteristics (demographics, school functioning, high-risk behaviors such as using drugs, alcohol, cigarettes) and treatment characteristics (diagnosis, treatment) were abstracted from medical records. Review of 137 charts so far revealed that eligible patients ranged in age from 6 to 37 years (M = 22.5, SD = 6.8), were 52.6% male, 88.3% Caucasian, and completed treatment about 13 years earlier. Point biserial correlations and Chi-square analyses were used to determine associations between patient and treatment characteristics and LTFU attendance. Results: 46.7% of patients had attended LTFU Clinic within 2 years of their last recommended follow-up. Current age was significantly inversely associated with current attendance, rpb = -.47, p < .001. Similarly, patients aged >18 were less likely to be current compared with patients <18, χ2(1) = 30.45, p < .001. There were no significant differences based on treatment received (surgery, radiation, chemotherapy), risk status for late effects, or documented late effects. Patients were less likely to be current if they had a documented psychiatric disorder (e.g., depression, anxiety), χ2(1) = 5.79, p = .016 or had reported past or ongoing drug use, χ2(1) = 4.68, p = .031. For patients >18 at last visit, there was a non-significant trend suggesting those who were married were more likely to be current, χ2(1) = 2.83, p = .09. Conclusions: Adult survivors of childhood cancer are less likely than younger counterparts to participate in recommended LTFU at a pediatric institution. Significant factors associated with current attendance included age and psychosocial issues, such as documented psychiatric problems and drug use. Patients like these may require additional monitoring to promote engagement in LTFU care.

Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 362

Drug and alcohol use have been associated with a worse prognosis in short-term and cross-sectional analyses of HIV-infected populations, but longitudinal effects on adherence to antiretroviral therapy (ART) and clinical outcomes in advanced AIDS are less well characterized. We assessed self-reported drug and alcohol use in AIDS patients, and examined their association with non-adherence and death or disease progression in a multicenter observational study. We defined non-adherence as reporting missed ART doses in the 48 hours before study visits. The association between drug use and ART non-adherence was evaluated using repeated measures generalized estimating equation (GEE) models. The association between drug and alcohol use and time to new AIDS diagnosis or death was evaluated via Cox regression models, controlling for covariates including ART adherence. Of 643 participants enrolled between 1997 and 1999 and followed through 2007, at entry 39% reported ever using cocaine, 24% amphetamines, and 10% heroin. Ongoing drug use during study follow-up was reported by 9% using cocaine, 4% amphetamines, and 1% heroin. Hard drug (cocaine, amphetamines, or heroin) users had 2.1 times higher odds (p=0.001) of ART non-adherence in GEE models and 2.5 times higher risk (p=0.04) of AIDS progression or death in Cox models. Use of hard drugs was attenuated as a risk factor for AIDS progression or death after controlling for non-adherence during follow-up (HR = 2.11, p=0.08), but was still suggestive of a possible adherence-independent mechanism of harm. This study highlights the need to continuously screen and treat patients for drug use as a part of ongoing HIV care.

Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort.

Differences in antiretroviral distribution into the central nervous system (CNS) may impact neurocognitive status. We assessed the relationship between estimates of antiretroviral therapy penetration into the CNS, using a published ranking system, and neurocognitive status in HIV-positive participants with plasma HIV-1 RNA (vRNA) suppression. Participants with at least 6 weeks ongoing antiretroviral drug use and vRNA less than 50 copies/ml (N = 2636; 83% male, median baseline CD4 T cells: 244 cells/μl) had at least one neuroscreen assessment [Trail Making Test, Part A and B; Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol] at 10 413 neurovisits. Neuroscreen test scores were demographically adjusted and converted to Z-scores (NPZ3: lower scores imply more impairment). Central nervous system penetration effectiveness (CPE) ranks of 0.0 (low), 0.5 (medium), or 1.0 (high) were assigned to antiretrovirals and summed per regimen, per neurovisit. Multivariate linear regression models using generalized estimating equations assessed NPZ3 scores with respect to antiretroviral regimen. Covariates were retained if P ≤ 0.1. A final model demonstrated that better NPZ3 scores were associated with higher CPE among participants taking more than three antiretroviral drugs (+0.07 per one unit increase in CPE score; P = 0.004) but not among participants with three or less antiretroviral drugs in the regimen (+0.01; P = 0.5). Results were adjusted for demographics, injection drug use, hepatitis C virus serostatus, CD4 cell count (current and nadir), baseline vRNA, antiretroviral experience, and years since first antiretroviral drug use. Use of antiretroviral drugs with better estimated CNS penetration may be associated with better neurocognitive functioning; some people may require more than three antiretroviral drugs to treat HIV in the CNS. Clinically this means antiretroviral regimens could be designed to optimize estimated CNS penetration without sacrificing virologic and immunologic benefits.

The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers

Impulsivity and craving have been independently hypothesized to contribute to sustained drug use and relapse in addiction. The primary focus of this project was to determine the relationship between impulsivity and craving in 85 cocaine-dependent and 73 methamphetamine-dependent, non-treatment-seeking volunteers. Drug use was assessed with a 14-item, self-report drug and alcohol use questionnaire. Self report instruments utilized included the Barratt Impulsivity Scale (BIS) and the Visual Analog Scale (VAS), which probed “just before your last use of cocaine (for cocaine-dependent participants) or methamphetamine (for methamphetamine-dependent participants), how much craving did you experience?” The groups were similar with respect to recent use of cocaine or methamphetamine, alcohol, nicotine, and marijuana. Analysis of variance (ANOVA) did not reveal significant differences between cocaine and methamphetamine groups for total impulsivity or total craving. Simple linear regression revealed correlations between total impulsivity and total craving in cocaine (r2=0.05, p≤0.03) and methamphetamine users (r2=0.09, p≤0.008). Participants were separated into high impulsivity (HIBIS) or low impulsivity (LOBIS) subgroups using a median split. ANOVA revealed significantly higher craving in the HIBIS group versus the LOBIS group in methamphetamine users (p≤0.02), but not in cocaine users. For both cocaine and methamphetamine groups, level of impulsivity and craving were found to be related to some drug use variables including years of alcohol use, severity of withdrawal, and craving level following drug use. Taken together, this study shows a marginal relationship between impulsivity and craving, which may further the understanding of motivational factors contributing to ongoing drug use and addiction in psychostimulant users.

Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 362

Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 362

Effectiveness and tolerability of combination treatment of chronic hepatitis C in illicit drug users: Meta-analysis of prospective studies

Background: Hepatitis C virus (HCV) infection is a global health problem. In Western countries, illicit drug users (IDUs) constitute the largest proportion of HCV patients. International guidelines no longer regard ongoing illicit drug use as a contraindication to antiviral therapy for chronic hepatitis C (CHC). Nonetheless, in clinical practice, few IDUs have access to HCV treatment, likely because many physicians believe these patients will have poor adherence or a lack of treatment efficacy. Objective: The aim of this study was to assess effectiveness and tolerability of combination treatment with ribavirin plus recombinant or pegylated interferon-α in the treatment of CHC in IDUs. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched for relevant studies published in English between 2000 and December 2008. The following terms were searched: chronic hepatitis C, interferons, antiviral agents, methadone, and substance-related disorders. Full-text articles and abstracts were searched using predefined criteria. A manual search of abstracts from 8 international meetings of hepatologists was also conducted. Only prospective studies with a sample size >15 and a homogeneous treatment schedule were included. Articles were extracted independently by 2 of the authors using an electronic standardized form including study quality indicators. Results: Sixteen prospective studies were included, and data from a cohort of 953 IDUs were analyzed. The estimated overall sustained virologic response (SVR) and dropout (DO) rates in IDUs were 52% (95% CI, 44%–60%) and 26% (18%–35%, 95% CI), respectively. The rate of psychiatric severe adverse events (SAEs) that led to treatment discontinuation was 2% (95% CI, 1%–3%). These prevalences were not significantly different from those reported in registration trials of treatment of CHC that excluded IDUs from the study population (SVR, 50% [95% CI, 39%–61%]; DO, 26% [95% CI, 12%–41%]; and psychiatric SAEs, 2% [95% CI, 0%–6%]). By subgroup analysis, active ongoing drug use negatively affected the rate of treatment success (39% [95% CI, 30%–49%] vs 55% [95% CI, 45%–64%]; P = 0.02). Conclusion: Based on data from 16 prospective clinical studies of CHC treatment in IDUs published in the past 10 years, findings on effectiveness and tolerability are comparable to those in the general population.

Injection drug use cessation and use of North America's first medically supervised safer injecting facility

Background Vancouver, Canada has a pilot supervised injecting facility (SIF), where individuals can inject pre-obtained drugs under the supervision of medical staff. There has been concern that the program may facilitate ongoing drug use and delay entry into addiction treatment. Methods We used Cox regression to examine factors associated with the time to the cessation of injecting, for a minimum of 6 months, among a random sample of individuals recruited from within the Vancouver SIF. In further analyses, we evaluated the time to enrolment in addiction treatment. Results Between December 2003 and June 2006, 1090 participants were recruited. In Cox regression, factors independently associated with drug use cessation included use of methadone maintenance therapy (Adjusted Hazard Ratio [AHR] = 1.57 [95% Confidence Interval [CI]: 1.02–2.40]) and other addiction treatment (AHR = 1.85 [95% CI: 1.06–3.24]). In subsequent analyses, factors independently associated with the initiation of addiction treatment included: regular SIF use at baseline (AHR = 1.33 [95% CI: 1.04–1.72]); having contact with the addiction counselor within the SIF (AHR = 1.54 [95% CI: 1.13–2.08]); and Aboriginal ancestry (AHR = 0.66 [95% CI: 0.47–0.92]). Conclusions While the role of addiction treatment in promoting injection cessation has been well described, these data indicate a potential role of SIF in promoting increased uptake of addiction treatment and subsequent injection cessation. The finding that Aboriginal persons were less likely to enroll in addiction treatment is consistent with prior reports and demonstrates the need for novel and culturally appropriate drug treatment approaches for this population.