Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment.

BACKGROUND: Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. METHODS: Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events. RESULTS: Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. CONCLUSIONS: Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence.

Intimate partner violence and reproductive health among methamphetamine-using women in los angeles: a qualitative pilot study.

Abstract Among women, methamphetamine (meth) use has been associated with intimate partner violence (IPV); however, few studies have looked at the context of IPV. This qualitative pilot study explored the experiences of meth-using women in Los Angeles County regarding: (1) IPV in their most recent primary relationship; (2) use of contraception and reproductive health services; and (3) meth use during pregnancy. Participants (n=30) were recruited through community advertising and at three addiction treatment centers to participate in 15-20 minute, semi-structured interviews recorded with handwritten transcripts. The team analyzed transcripts for key themes. Participants reported IPV (n=19, 63%) as recipients (50%), perpetrators (40%), and/or both (27%), occurring mainly during active meth use or withdrawal. While most (n=25) continued meth use during at least one pregnancy, some (n=5, 17%) identified pregnancy as a motivation to quit or reduce use, suggesting an opportunity for intervention. Though most women knew about free and low-cost reproductive health services, few accessed them, with 33% citing aspects of meth use itself as a barrier. One-third (45/133) of reported pregnancies were terminated by abortion. Most women (67%) began using before age 18, suggesting need for screening and intervention among adolescents.

Up in smoke? A preliminary open-label trial of nicotine replacement therapy and cognitive behavioral motivational enhancement for smoking cessation among youth in Los Angeles.

In 2008-2009, we conducted a 6-week, open-label trial of transdermal nicotine replacement therapy and practical counseling for 34 adolescents seeking smoking cessation in Los Angeles. Dependent outcomes were study retention, use of the patch, and 7-day quit status at the end-of-study and at follow-up visits. Predictors of outcomes included cigarette dependence, withdrawal symptoms, demographic and psychiatric measures, and other substance use. Variables significant in bivariate analysis (p < .10) were retained in a multivariate model. Subjects had significant pre-to-post reductions in quit rates, dependence, and withdrawal symptoms. Subjects also reported a high number of comorbidities. Implications for clinicians are discussed.

Staff strategies for improving HIV detection using mobile HIV rapid testing.

This paper examines the performance of 13 mobile testing units (MTUs) and rapid HIV testing technology in Los Angeles County as reflected in the relationship between the cognitive strategies used by MTU staff regarding instructions to clients about picking up their test results and returning for test results, and following up with those clients who did not return, and the spatial distribution of MTUs and AIDS rates in 2003. Maps were created using geographic information systems (GIS) data on 93 MTU testing locations and 2003 AIDS cases data. MTU staff (N = 45) were interviewed and several themes were identified. MTU testing locations were clustered near high AIDS rate areas. Staff reports were obtained on 24 clients in the past 6 months who received HIV-negative test results and 24 clients during the same time period who received HIV-positive test results. Staff strategies that were used included keeping clients with them while rapid test results were being processed and adjusting to clients' schedules when arranging for picking up test results. Some staff used tangible incentives such as vouchers for area businesses to encourage preliminary HIV-positive clients to return for confirmatory test results. Staff also sought to convince clients who preliminarily tested HIV-positive to convert from anonymous to confidential testing in order to facilitate clients' linkage to treatment. The GIS findings and client risk data support the Centers for Disease Control and Prevention policy of implementing MTUs and rapid testing in large urban communities with high AIDS rates.

HIV partner notification: predictors of discussion and agreements from provider reports.

This study examines organizational, provider, client, and test-event level predictors of HIV partner notification (PN) discussion and agreements based on providers' most recent HIV-positive post-test counseling session. Staff (n = 621) were sampled from for-profit, nonprofit, and county government HIV testing organizations (N = 159) in Los Angeles County from 2003 to 2007. Among providers who conducted an HIV-positive post-test counseling session (n = 204), 65% discussed PN but only 10% had confirmed agreement to provider-involved PN (PIPN). In multi-level regression analyses PN discussion was predicted by provider HIV-test training and knowledge, and patients requesting a test while presenting HIV/AIDS symptoms. The strongest predictor of PIPN agreement was public health HIV testing settings followed by counseling by program managers or infectious disease specialists across settings. None of the injecting drug users or patients presenting with AIDS, but not requesting a test, agreed to PIPN. Organizational and provider-level interventions on PN will be needed to realize cost-effective benefits of expanded HIV testing and counseling.

Increasing the reach of HIV testing to young Latino MSM: results of a pilot study integrating outreach and services.

BACKGROUND: In the U.S., HIV infections are increasing among men who have sex with men (MSM), particularly young, racial/ethnic minority MSM. OBJECTIVE: To examine the feasibility of increasing HIV testing among young Latino MSM by integrating tailored outreach strategies with testing, counseling, and HIV medical services. DESIGN: Descriptive study comparing demographic characteristics, behaviors, and HIV test results of clients from the intervention period with clients who tested during other time periods. RESULTS: Clients in the intervention period were younger and more likely to be Latino than those in other time periods. In addition, clients who received outreach were more likely than those who did not receive outreach to report methamphetamine use, sex with an HIV-positive person, and sex with a sex worker. CONCLUSION: Venue-based and selective media outreach, in combination with linking rapid testing to HIV care, may help overcome some of the barriers to testing among high-risk young Latino MSM.

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence.

OBJECTIVE: To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA-cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. METHODS: Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice daily; N=37) for 12-weeks under double-blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions. RESULTS: There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA-cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0-2 MA-positive urines), but not heavier (3-6 MA-positive urines) MA use during baseline (OR=2.81, 95% CI=1.61-4.93, p<0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost five cigarettes per day (p=0.0002). CONCLUSION: Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light-MA users is warranted.

Client encounters in alternative HIV testing sites: counselors' perceptions and experiences.

In this study, the authors explored HIV test counselors' perceptions of and experiences working with "difficult" and "good" clients in alternative HIV testing sites. Trained interviewers made field observations and conducted sixteen 60-minute, semistructured interviews with counselors. Counselors reported 7 main characteristics of difficult clients: (1) uncooperative, (2) mean, (3) inebriated, (4) threatening, (5) "crazy," (6) sexually inappropriate, and (7) aesthetically unappealing/overly appealing. They also identified 3 main characteristics of good clients: (1) communicative, (2) responsive, and (3) vulnerable. In addition, HIV test counselors used 4 strategies to deal with difficult clients: (1) received help from other counselors, (2) refused to test or threatened to refuse to test, (3) verbally confronted clients, and (4) "followed the forms" (ie, asked the necessary questions on the standard risk assessment forms). Results highlight the combined importance of patient characteristics, HIV test counselor characteristics, and the testing environment in contributing to difficult and good encounters in alternative HIV testing sites and point to the need for better training and support services in this area.

Varenicline treatment for methamphetamine dependence: A randomized, double-blind phase II clinical trial.

BACKGROUND: Previous studies have suggested that varenicline, an α4ß2 nicotinic receptor partial agonist, and α7 nicotinic receptor full agonist, may be effective for the treatment of methamphetamine (MA) dependence due to dopaminergic effects, relief of glutamatergic and cognitive dysfunction, and activation of nicotinic cholinergic systems. This study aimed to determine if varenicline (1 mg BID) resulted in reduced methamphetamine use compared to placebo among treatment-seeking MA-dependent volunteers. METHODS: Treatment-seeking MA-dependent volunteers were randomized to varenicline 1 mg twice daily (n = 27) or placebo (n = 25) and cognitive behavioral therapy for 9 weeks. The primary outcomes were the proportion of participants achieving end-of-treatment-abstinence (EOTA, MA-negative urine specimens during weeks 8 and 9) and the treatment effectiveness score (TES, number of MA-negative urine specimens) for varenicline versus placebo. RESULTS: There was no significant difference in EOTA between varenicline (15%, 4/27) and placebo (20%, 5/25; p = 0.9). There was some suggestion that urinary confirmed medication compliance corresponded with EOTA in the varenicline condition, though it did not reach statistical significance, OR = 1.57 for a 100 ng/ml increase in urine varenicline, p = 0.10, 95% CI (0.99, 3.02). There was no significant difference in mean TES in the varenicline condition (8.6) compared to the placebo condition (8.1), and treatment condition was not a statistically significant predictor of TES, IRR = 1.01, p = 0.9, 95% CI (0.39, 2.70). CONCLUSIONS: The results of this study indicate that 1 mg varenicline BID was not an effective treatment for MA dependence among treatment-seeking MA-dependent volunteers.

Outcomes of blood and oral fluid rapid HIV testing: a literature review, 2000-2006.

Rapid HIV antibody testing is a new technology whose implementation promises to facilitate the early detection of persons with HIV/AIDS. The goal of this study was to review and summarize the literature from 2000-2006 regarding four outcomes of rapid (including both blood and oral fluid) HIV testing: rates of client acceptance; rates of clients' receiving their test results; rates of entry into medical care for those found to be HIV positive; and the efficacy of prevention counseling after testing. A total of 116 studies in peer-reviewed journals were screened. Twenty-six met the screening criteria (published in peer-reviewed journals and focused on at least one of the outcomes of interest) and were selected for review. Considerable variation was found in client acceptance rates with the highest rates among pregnant women in labor and delivery units and the lowest rates in needle exchange and bath-house settings. The evidence shows that most persons tested with a rapid test receive their test result. Three studies on entry into medical care among those who were newly identified HIV positive found rates of 47%, 82%, and 97% of clients adhering to their first medical appointment. No long-term medical follow-up studies were found. Only one study examined the efficacy of prevention counseling after rapid testing and found no statistically significant differences in the number of sexually transmitted diseases (STDs) conventional versus rapid HIV testers contracted following testing.

Failure to return for HIV test results: a pilot study of three community testing sites.

BACKGROUND: Individuals at elevated risk of contracting HIV frequently fail to return for their test result. Because rapid HIV antibody testing is still not widely implemented, failure to return for test results under conditions of standard testing remains a problem. METHODS: Direct field observation and semistructured interviews with clients (N = 16) and test counselors (N = 16) of 3 community HIV testing sites were conducted. RESULTS: Clients faced 5 barriers to receiving their result: (1) fear, (2) busyness, (3) apathy,(4) inebriation at the time of testing, and (5) testing "on a whim." Motivators that encouraged clients to receive their results were (1) positive counselor/client interactions, (2) client-friendly policies regarding picking up the test result, (3) clients' psychological "need to know," (4) incentives for picking up the result, and (5) established protocols for contacting clients who fail to return. CONCLUSION: Findings highlight the need for interventions to improve the return rate for HIV results.

Ibudilast may improve attention during early abstinence from methamphetamine.

BACKGROUND: Inattention is a deficit related to instilling abstinence from methamphetamine (MA) dependence. This study aimed to determine whether ibudilast (IB; 50mg bid) improves attentional abilities compared to placebo during early abstinence from MA dependence. METHODS: Attention was assessed in 11 MA-dependent non-treatment seeking participants in a phase IB safety-interaction trial. The Conners' Continuous Performance Test-II (CPT-II), a measure of sustained attention and response inhibition, was administered at baseline and on day 22, 48h post a MA challenge under placebo (P; n=6) or IB 50mg bid (n=5). Group differences were compared using Mann-Whitney U Tests. Groups were similar at baseline in premorbid intellectual functioning, attention deficit hyperactivity symptom scores, impulsivity ratings, and education level, but differed in age. Demographically corrected T-scores for CPT-II performances were utilized. RESULTS: Although no group differences in sustained attention existed at baseline, at follow-up, the IB group (Mdn=44.4) showed reduced variability in response times compared with the P group (Mdn=69.9), U=0.00, z=-2.74, p=.006, r=.83. The IB group (Mdn=45.8) also gave fewer perseverative responses than the P group (Mdn=67.0), U=2.00, z=-2.50, p=.01, r=.75. No other significant differences were observed. CONCLUSIONS: Findings suggest that IB may have a protective effect on sustained attention during early abstinence from MA dependence. This may guide thinking about mechanism of action should IB demonstrate efficacy as a treatment for MA dependence.

Communicating indeterminate HIV Western blot test results to clients: an observational study of three community testing sites.

This study examined HIV test counselors' beliefs and practices regarding communicating indeterminate HIV test results to clients. There are many reasons for an indeterminate HIV antibody/ Western blot assay including early HIV infection, infection with other contagious diseases, autoimmune diseases, and second or subsequent pregnancies in women. Field observations of three community HIV testing sites and semistructured interviews with 16 HIV test counselors were conducted from August 2002 through June 2003. Counselors defined an indeterminate test result in different ways. They also presented several different theories of causation, yet failed to mention two potential causes of an indeterminate result, association with large animals and infection with other (non-HIV-1) HIV strains. Counselors' understanding of the meaning of an indeterminate HIV test result varied a great deal. Some counselors believed that an indeterminate result truly was ambiguous while others believed it was indicative of being either HIV-positive or HIV-negative. Counselors' primary advice to clients who received an indeterminate result was to retest immediately without a waiting period. Counselors reported that communicating indeterminate test results to clients was a challenging task because clients who received such a result were confused, angry, and/or mistrustful. Results highlight the need for further research to provide reliable estimates of the extensiveness of indeterminate HIV test results and to further assess the nature of counselor and client responses to indeterminate test results.

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study.

BACKGROUND: Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans. METHODS: Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS). RESULTS: As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo. CONCLUSIONS: Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy.

Anonymous versus confidential HIV testing: client and provider decision making under uncertainty.

Six intensive observational studies of HIV testing sites were undertaken in order to improve understanding of confidential and anonymous testing. Three sites offered only confidential testing (a large health maintenance organization's Urgent Care clinic, the same organization's HIV clinic, and a private medical practitioner's office), one offered only anonymous testing (a free clinic), and two offered a choice of confidential or anonymous testing (a thrift shop alternate testing site and a mobile testing unit). Multiple data collection strategies were used including direct field observation, semistructured interviews with clients and providers, and document and policy analysis. Using an organizational/interactional uncertainty framework, this study found that the choice between anonymous and confidential testing is a central aspect of the HIV testing process, that some clients are unclear about the differences between anonymous and confidential testing, that alternate testing sites' providers play a significant role in encouraging confidential rather than anonymous testing in order to further their organization's resource needs and public health goals, and that testing counselors' may consider that some clients prefer anonymous testing because of fear of stigma, discrimination, or loss of privacy.

Evaluating the accessibility of HIV testing organizations.

Consumer-based indicators were developed to evaluate the accessibility of private and public nonhospital HIV testing organizations. A comprehensive roster of 148 nonhospital HIV testing organizations in Los Angeles County was constructed from publicly available listings. A telephone survey protocol was used to contact sites and assess consumer relevant accessibility measures. Only 50% of the sites could be contacted and indicated that HIV testing was available. Hence, a consumer who tried to reach one site had only a 50-50 chance of success. HIV testing sites differed with regard to how frequently they offered testing; whether they offered anonymous and/or confidential testing; what types of counseling they provided; how quickly test results were available; and how friendly, helpful, attentive, and knowledgeable about testing procedures their attendants were. HIV testing sites must make their services accessible and be perceived by consumers as responsive if they are to be effective service providers.

Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use.

AIMS: Two previous randomized trials found an effect for bupropion in reducing methamphetamine use in the subgroup with lower frequency of methamphetamine use at baseline. This study aimed to replicate these results by comparing bupropion versus placebo in methamphetamine-dependent participants with less than daily methamphetamine use at baseline. METHODS: Methamphetamine-dependent volunteers reporting methamphetamine use on ≤29 of past 30 days were randomized to bupropion 150 mg twice daily (n = 41) or placebo (n = 43) and out-patient counseling for 12 weeks. The primary outcome was the proportion achieving end-of-treatment (EOT) methamphetamine abstinence (weeks 11 and 12) for bupropion versus placebo. A post-hoc analysis compared EOT abstinence by medication adherence assessed via plasma bupropion/hydroxybupropion level. RESULTS: There was no significant difference in EOT abstinence between bupropion (29%, 12 of 41) and placebo (14%, six of 43; P = 0.087). Among participants receiving bupropion, EOT abstinence was significantly higher in participants assessed as medication adherent by plasma bupropion/hydroxybupropion levels (54%, seven of 13) compared to non-adherent participants (18%, five of 28; P = 0.018). Medication adherence by plasma levels was low (32%). CONCLUSIONS: Bupropion may be efficacious for reducing methamphetamine in people with less than daily baseline methamphetamine use, but the evidence remains inconclusive.