Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

Hepatitis C virus core antigen: A simplified treatment monitoring tool, including for post-treatment relapse.

BACKGROUND: Simple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. OBJECTIVES: This study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. STUDY DESIGN: Plasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy. The sensitivity and specificity of the HCVcAg assay was compared to the HCV RNA assay (gold standard). RESULTS: A total of 335 samples from 92 enrolled participants were assessed (mean 4 time-points per participant). At baseline, end of treatment response (ETR) and sustained virological response (SVR) visits, the sensitivity of the HCVcAg assay with quantifiable HCV RNA threshold was 94% (95% CI: 88%, 98%), 56% (21%, 86%) and 100%, respectively. The specificity was between 98 to 100% for all time-points assessed. HCVcAg accurately detected all six participants with viral recurrence, demonstrating 100% sensitivity and specificity. One participant with detectable (non-quantifiable) HCV RNA and non-reactive HCVcAg at SVR12 subsequently cleared HCV RNA at SVR24. CONCLUSIONS: HCVcAg demonstrated high sensitivity and specificity for detection of pre-treatment and post-treatment viraemia. This study indicates that confirmation of active HCV infection, including recurrent viraemia, by HCVcAg is possible. Reduced on-treatment sensitivity of HCVcAg may be a clinical advantage given the moves toward simplification of monitoring schedules.

Feasibility and outcome of substitution treatment of heroin-dependent patients in specialized substitution centers and primary care facilities in Germany: a naturalistic study in 2694 patients.

BACKGROUND: In many countries, buprenorphine and methadone are licensed for the maintenance treatment (MT) of opioid dependence. Despite many short-term studies, little is known about the long-term (12-month) effects of these treatments in different settings, i.e. primary care-based (PMC) and specialized substitution centers (SSCs). OBJECTIVES: To describe over a period of 12 months: (1) mortality, retention and abstinence rates; (2) changes in concomitant drug use, somatic and mental health; and (3) to explore differences between different types of provider settings. METHODS: 12-Month prospective-longitudinal naturalistic study with four waves of assessment in a prevalence sample of N=2694 maintenance patients, recruited from a nationally representative sample of N=223 substitution physicians. RESULTS: The 12-month retention rate was 75%; the mortality rate 1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to drug-free addiction treatment. Concomitant drug use decreased and somatic health status improved. No significant improvements were observed for mental health and quality of life. When controlling for initial severity, small PMC settings revealed better retention, abstinence and concomitant drug use rates. CONCLUSION: The study underlines the overall 12-month effectiveness of various forms of agonist MT. Findings reveal relatively high retention rates, low mortality rates, and improvements in most 12-month outcome domains, except for mental health and quality of life. PMC settings appear to be a good additional option to improve access to MTs.

Co-consumption of benzodiazepines in heroin users, methadone-substituted and codeine-substituted patients.

Concomitant consumption of benzodiazepines (BZDs) and opioids is a major problem in patients with opioid dependence. It may have substantial impact on morbidity, mortality and clinical course. The current retrospective study aims to determine whether there are differences in the additional use of BZDs among addicts regularly taking methadone or codeine medications in treatment and untreated addicts injecting heroin. The records of 1,685 patients admitted for detoxification were analyzed using bivariate analysis and multiple logistic regression analysis. Demographic and drug related variables were considered, both as possible confounders and predictors of concomitant BZD use. Daily intake of BZDs was reported in 44.4% of the patients. Patients treated with methadone or codeine medications report daily intake of BZDs significantly more often than the heroin-dependent patients (p < 0.01). Using multiple regression analyses, the results were confirmed as independent from the assessed possible confounders. Further we found that daily use of alcohol or barbiturates, early onset of opioid use (p < 0.01), unemployment, having a substance dependent family member with, and a history of imprisonment (for all p < 0.05) were associated with concomitant daily consumption of BZDs in opioid dependent subjects. These finding underline the need to further explore the causes, interactions and consequences of concomitant BZD and opiate use.

Treatment of chronic hepatitis C in patients with drug dependence: time to change the rules?

AIMS: Approximately 170 million people world-wide are chronically infected with the hepatitis C virus (HCV). While the seroprevalence in the general population ranges between 0.2 and 2%, 50-90% of injection drug users are chronically HCV-infected. However, most patients who are drug abusers are still excluded from treatment of chronic HCV infection with interferon (IFN)-alpha. Due to the recent treatment advances resulting in sustained response rates between 50 and 80%, it becomes increasingly important to reflect the still existing contraindications and restrictions for IFN-alpha treatment, especially for patients with intravenous drug use (IDU) with or without psychiatric comorbidity. METHODS: We reviewed clinical trials that focus on the treatment of chronic hepatitis C in patients with drug addiction published between 1987 and 2003. FINDINGS: Only seven clinical trials investigating HCV treatment among drug users were found: four open prospective uncontrolled trials and three controlled trials. Thus far, no trials using pegylated IFN-alpha have been conducted. Data about sustained response and adherence in HCV-infected methadone substituted patients were either comparable to control groups or to representative clinically controlled trials using the same treatment regimen (IFN-alpha monotherapy or combined with ribavirin). Patients with former or present drug abuse seem more likely to discontinue treatment early. HCV-infected IDUs tended to be older with higher inflammatory activity and stage of fibrosis when interferon treatment was started. Psychiatric comorbidity did not negatively influence adherence or treatment outcome. CONCLUSIONS: There is no clinical evidence suggesting that HCV treatment with IFN-alpha should be limited to IDUs or methadone substituted patients. However, more prospective controlled trials on HCV treatment for patients with IDU are needed to establish and apply new rules and guidelines.

Alcohol consumption in heroin users, methadone-substituted and codeine-substituted patients--frequency and correlates of use.

This retrospective study aims to determine whether there is a difference in the additional consumption of alcohol between addicts treated with methadone or dihydrocodeine (DHC) and untreated addicts injecting heroin. 1685 patients admitted for opioid withdrawal between 1991 and 1997 were reviewed. Cross-reference tables and multiple logistic regression analyses were carried out. 28% of patients take more than 40 g of alcohol daily (on average 176 g). We found that patients who are treated with methadone or DHC drink alcohol significantly more often daily than the heroin-dependent patients (p < 0.01). Using multiple regression analyses, the results were confirmed. Additionally, we found that co-abuse of alcohol was predicted by male gender, longer duration of drug use, additional daily consumption of tetrahydrocannabinol and daily consumption of benzodiazepines. Alcohol consumption by opioid-addicted patients treated with methadone or DHC presents a serious medical problem. Co-abuse of alcohol will receive more attention.