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Background: A considerable inter‐individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood. Objectives: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration‐to‐dose ratio (CDR) and discussed the clinical implications of the findings. Methods: We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses. Findings: A positive association was found between CDR and the homozygous CYP2B6*6 genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations. Conclusions: This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes. [ABSTRACT FROM AUTHOR]

Background and aims: The INTRO‐HCV randomized controlled trial conducted in Norway over 2017–2019 found that integrated treatment, compared with standard‐of‐care hospital treatment, for hepatitis C virus (HCV) with direct‐acting antivirals (DAAs) improved treatment outcomes among people who inject drugs (PWID). We evaluated cost‐effectiveness of the INTRO‐HCV intervention. Design: A Markov health state transition model of HCV disease progression and treatment with cost‐effectiveness analysis from the health‐provider perspective. Primary cost, utility, and health outcome data were derived from the trial. Costs and health benefits (quality‐adjusted life‐years, QALYs) were tracked over 50 years. Probabilistic and univariate sensitivity analyses investigated DAA price reductions and variations in HCV treatment and disease care cost assumptions, using costs from different countries (Norway, United Kingdom, United States, France, Australia). Setting and participants: PWID attending community‐based drug treatment centers for people with opioid dependence in Norway. Measurements Incremental cost‐effectiveness ratio (ICER) in terms of cost per QALY gained, compared against a conventional (€70 000/QALY) willingness‐to‐pay threshold for Norway and lower (€20 000/QALY) threshold common among high‐income countries. Findings Integrated treatment resulted in an ICER of €13 300/QALY gained, with 99% and 71% probability of being cost‐effective against conventional and lower willingness‐to‐pay thresholds, respectively. A 30% lower DAA price reduced the ICER to €6 900/QALY gained, with 91% probability of being cost‐effective at the lower willingness‐to‐pay threshold. A 60% and 90% lower DAA price had 36% and >99% probability of being cost‐saving, respectively. Sensitivity analyses suggest integrated treatment was cost‐effective at the lower willingness‐to‐pay threshold (>60% probability) across different assumptions on HCV treatment and disease care costs with 30% DAA price reduction, and became cost‐saving with 60%–90% price reductions. Conclusions: Integrated hepatitis C virus treatment for people who inject drugs in community settings is likely cost‐effective compared with standard‐of‐care referral pathways in Norway and may be cost‐saving in settings with particular characteristics. [ABSTRACT FROM AUTHOR]

Background The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. Methods and findings INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. Conclusions Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. Trial registration ClinicalTrials.gov.no NCT03155906, Author(s): Lars T. Fadnes 1,2,*, Christer Frode Aas 1,2, Jørn Henrik Vold 1,2, Rafael Alexander Leiva 3, Christian Ohldieck 1, Fatemeh Chalabianloo 1,2, Svetlana Skurtveit 4,5, Ole Jørgen Lygren 1,6, [...]

Assess the association between oral and general health related quality of life using oral impacts on daily performances (OIDP) and the quality of life tool EQ-5D-5L from EuroQoL among patients with substance use disorder (SUD) who receive opioid agonist therapy. 609 patients with SUD completed the EQ-5D-5L. A dental sub-study of 167 patients completed OIDP and an oral examination when attending outpatient clinics in Western Norway for their opioid agonist therapy. The merged analytical sample consisted of 165 patients. The association between OIDP and EQ-5D-5L was assessed by Spearman's rho and a linear multiple variable regression analysis. A line graph and a Pen's parade displayed the distributions of OIDP sum scores and EQ-5D-5L index values. Overall mean summary- and index EQ-5D-5L scores were 9.97 (sd 3.25) and 0.69 (sd 0.22). Mean score for OIDP was 9.75 (sd 9.59). Spearman's rho was 0.34 (p <.01) between OIDP and EQ-5D-5L summary scores. Linear regression revealed an association adjusted for sex and age of 0.12 (95% CI 0.07–0.17) and a coefficient of determination of 0.1460. This study reveals a strong association between OIDP and EQ-5D-5L reflecting the importance of oral health to general health for patients with SUD. Health care professionals should pay attention to oral health. Effective interventions might improve patients' oral and health related quality of life. [ABSTRACT FROM AUTHOR]

There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016–2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: −2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (−0.50; −4.59, 3.59; 0.810). Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations. [ABSTRACT FROM AUTHOR]