Faculty Bibliography

OBJECTIVE: To assess the cost-effectiveness of Intervention for HIV-Seropositive injection drug users--Research and Evaluation (INSPIRE), designed to reduce risky sexual and needle-sharing behaviors in research sites in four US cities (2001-2003). METHODS: We collected data on program and participant costs. We used a mathematical model to estimate the number of sex partners of injection drug users expected to become infected with human immunodeficiency virus (HIV) (with and without intervention), cost of treatment for sex partners who became infected, and the effect of infection on partners' quality-adjusted life expectancy. We determined the minimum effect that INSPIRE must have on condom use among participants for the intervention to be cost-saving (intervention cost less than savings from averted HIV infections) or cost-effective (net cost per quality-adjusted life year saved less than $50,000). RESULTS: The intervention cost was $870 per participant. It would be cost-saving if it led to 53 percent reduction in the proportion of participants who had any unprotected sex in 1 year and cost-effective with 17 percent reduction. If behavior change lasted 3 months, the cost-effectiveness threshold was 66 percent; if 3 years, the threshold was 6 percent. CONCLUSIONS: Although cost-saving thresholds may not be achievable by the intervention, we anticipate that cost-effectiveness thresholds will be attained

Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities

Although most cases of hepatitis C virus (HCV) infection are associated with injection drug use, there are few data regarding the impact of putative barriers such as psychiatric disease and intercurrent drug use on HCV treatment outcomes. To define the impact of characteristics often cited as reasons for withholding HCV treatment, we studied HCV treatment in a real world sample of 76 recovering heroin users maintained on methadone. Overall, 21 (28%) had a sustained virological response and 18 (24%) discontinued treatment early. Although there was a modest decrement in response rates in patients reporting a preexisting psychiatric history (p = .01), neither intercurrent drug use nor short duration of pretreatment drug abstinence led to significant reductions in virological outcomes (p = .09 and p = .18, respectively.) We conclude that injection drug users can be safely and effectively treated for HCV despite multiple barriers to treatment when they are treated in a setting that can address their special needs

We prospectively assessed the effect of oral methadone on the corrected QT interval (QTc) among 160 patients free of structural heart disease and measured serum methadone concentrations and simultaneous QTc intervals in a subset of 44 participants. Mean +/- SD QTc increased by 12.4 +/- 23 ms (p <0.001) at 6 months, by 10.7 +/- 30 ms (p <0.001) at 12 months, and the QTc change from baseline to 12 months correlated with the trough (r = 0.37, p = 0.008) and peak (r = 0.32, p = 0.03) serum methadone concentrations

Despite the high prevalence of hepatitis C virus (HCV) infection among drug users enrolled in methadone maintenance treatment programs, few drug users are being treated with combination therapy. The most significant barrier to treatment is lack of access to comprehensive HCV-related care. We describe a pilot program to integrate care for HCV infection with substance abuse treatment in a setting of maintenance treatment with methadone. This on-site, multidisciplinary model of care includes comprehensive screening and treatment for HCV infection, assessment of eligibility, counseling with regard to substance abuse, psychiatric services, HCV support groups, directly observed therapy, and enhanced linkages to a tertiary care system for diagnostic procedures. Our approach has led to high levels of adherence, with liver biopsy and substantial rates of initiation of antiviral therapy. Two cases illustrate the successful application of this model to patients with HCV infection complicated by active substance abuse and psychiatric comorbidity

STUDY OBJECTIVE: To evaluate the effects of methadone on QT-interval dispersion. DESIGN: Single-center, prospective, cohort study. SETTING: Methadone maintenance treatment facility. PATIENTS: One hundred eighteen patients who were newly admitted to the facility. Intervention. Twelve-lead electrocardiograms (ECGs) were performed in patients at both baseline and 6 months after the start of methadone therapy. MEASUREMENTS AND MAIN RESULTS: The ECGs were manually interpreted, and investigators were blinded to time interval and methadone dose. At least eight discernible ECG leads were required for study inclusion. Mean differences between baseline and follow-up rate-corrected QT (QTc) interval and QT dispersion were compared. Multivariate associations between clinical characteristics and magnitude of change in QT dispersion were assessed using linear regression. Mean +/- SD baseline QT dispersion was 32.9 +/- 12 msec, which increased to 42.4 +/- 15 msec (+9.5 +/- 18.6 msec, p<0.0001) after 6 months of therapy. The QTc increased by a similar magnitude (+14.1 msec, p<0.0001). No QT dispersion value exceeded 100 msec. The only variable associated with a greater increase in QT dispersion was antidepressant therapy (20 vs 8.5 msec, p=0.04). CONCLUSION: Methadone modestly increased both QTc interval and QT dispersion. Increased QT dispersion reflects heterogeneous cardiac repolarization and occurs with nonantiarrhythmic agents, such as synthetic opioids. However, the magnitude of this effect appears to be substantially less with methadone than with antiarrhythmic drugs

Recent studies indicate that severe chronic pain is common among patients in methadone maintenance treatment (MMT), but no qualitative studies have examined such patients' experiences of pain and pain treatment. This study used qualitative methods to explore the experiences of MMT patients with chronic pain. Twelve patients screening positive for chronic severe pain on the Brief Pain Inventory were interviewed for the study. Results suggest that chronic severe pain has major consequences in the lives of methadone maintenance patients and may be linked to illegal drug use, social isolation, and role failure. A variety of barriers limited access to effective treatment. A common complaint with care was providers' lack of concern or inability to 'listen.' Patients who were satisfied with treatment focuses on the psychosocial dimensions of care. These preliminary results suggest that treatment approaches should emphasize emotional support, negotiation of explanatory models, and an emphasis on the psychosocial sequelae of pain. However, more research is needed to guide the development of effective treatment strategies

The objective of this study was to determine outcomes of referring drug users (DUs) with chronic hepatitis C for clinical evaluation and care. Two hundred twenty-eight persons with detectable hepatitis C virus RNA were given expedited referrals for evaluation and possible treatment of hepatitis C from a prospective study cohort of current and former opiate-addicted DUs. Four outcomes were analyzed: accepted referral, arrived for clinical evaluation, had liver biopsy, and received treatment. One hundred twenty-seven participants (56%) accepted referral, of whom 54 (43%) arrived for evaluation. Of these participants, 12 (22%) had liver biopsy, and 4 (7%) were treated. Multivariate logistic regression revealed that HIV-infected DUs were significantly less likely to accept referral (adjusted odds ratio [O(Radj)], 0.51; 95% confidence interval [CI], 0.30-0.88), and older participants were more likely to keep an appointment (O(Radj), 1.06/y; 95% CI, 1.00-1.12). Of HIV-seropositive participants, those with a history of injection were more likely to accept referral (O(Radj), 3.60; 95% CI, 1.08-11.96), and those with higher HIV load (O(Radj), 0.50/log10; 95% CI, 0.26-0.94) and Hispanic ethnicity (O(Radj), 0.26; 95% CI, 0.07-0.89) were less likely to keep an appointment. Despite expedited referrals for hepatitis C care, only a few participants received an evaluation, and even far fewer were treated. Because increasingly effective treatment is available, better methods are urgently needed to improve evaluation and treatment of HCV-infected DUs, including those coinfected with HIV