Prescribing naloxone to actively injecting heroin users: a program to reduce heroin overdose deaths.

Heroin overdose deaths have increased alarmingly in Chicago over the past decade. Naloxone, an opioid antagonist with no abuse potential, has been used to reverse opiate overdose in emergency medical settings for decades. We describe here a program to educate opiate users in the prevention of opiate overdose and its reversal with intramuscular naloxone. Participant education and naloxone prescription are accomplished within a large comprehensive harm reduction program network. Since institution of the program in January 2001, more than 3,500 10 ml (0.4 mg/ml) vials of naloxone have been prescribed and 319 reports of peer reversals received. The Medical Examiner of Cook County reported a steady increase in heroin overdose deaths since 1991, with a four-fold increase between 1996 and 2000. This trend reversed in 2001, with a 20% decrease in 2001 and 10% decreases in 2002 and 2003.

Preclinical and clinical performance of the Efoora test, a rapid test for detection of human immunodeficiency virus-specific antibodies.

Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized HIV-1 EIA.

Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses.

We examined in vivo the influence of cytochrome P4503A4 (CYP3A4) activity, measured by the 30 min plasma 1'OH-midazolam/midazolam ratio after oral administration of 7.5 mg midazolam, on the methadone steady-state trough plasma concentrations in a group of 32 patients in methadone maintenance treatment. Patients were grouped as receiving 'low' (up to 99 mg/day, n = 10), 'high' (100-199 mg/day, n = 11) and 'very high' (> or = 200 mg/day, n = 11) doses of methadone, and the CYP3A4 metabolic activity was compared between the three groups. (S)-methadone and (R,S)-methadone, but not (R)-methadone, concentrations to dose ratios significantly correlated with the midazolam ratios (r(2) = -0.17, P = 0.018; r(2) = -0.14, P = 0.032; r(2) = -0.10, P = 0.083, respectively), with a 76% higher CYP3A4 activity in the very high-dose group as compared with the low-dose group. Significant differences in the CYP3A4 activity were calculated between the three groups (P = 0.0036), and group-to-group comparisons, using the Bonferroni correction, showed a significant difference between the low-dose and the very high-dose group (P = 0.0039), between the high-dose and the very high-dose group (P = 0.0064), but not between the low-dose and the high-dose group (P = 0.070). The higher CYP3A4 activity measured in patients receiving very high methadone doses could contribute to the need for higher doses in some patients, due to an increased metabolic clearance. This, however, must be confirmed by a prospective study.

Optimizing long-term response to methadone maintenance treatment: a 152-week follow-up using higher-dose methadone.

We report the clinical course over 152 weeks of 245 patients in methadone maintenance treatment: 144 high dose (HD) patients (> or = 100 mg/d, mean 211 mg/d), and 101 control (C) patients (< 100 mg/d, mean 65 mg/d). After 152 weeks the mean methadone doses were 284.9 mg/d (range 13-1100 mg/d) and 94.0 mg/d (range 10-500 mg/d), respectively. Overall retention in treatment was 59% over the 152 weeks, with the HD group having significantly better retention (61.1% vs. 46.3%) and lower rates of positive urine toxicologies (16.0% vs. 36.6%). Mortality was statistically the same for the HD group (2/144, 1.4%) and the C group (2/101, 1.9%) over the 152-week period. We conclude that doses of methadone exceeding 100 mg/d are safe and effective in long-term maintenance treatment. We attribute the favorable outcomes we report to a model of treatment that emphasizes medication management in the treatment of opioid addiction.