Riikka Mari Berg-Pedersen's research while affiliated with Oslo University Hospital and other places

Methadone (R,S‐methadone) can prolong the QT interval. R‐methadone inhibits cardiac potassium channel function less than S‐methadone. We tested if switching from methadone to R‐methadone would reduce corrected QT (QTc) intervals in methadone maintenance treatment (MMT) patients. Nine patients, with automatically read QTc intervals ≥450 ms, were required to detect a 20 ms (clinically relevant) reduction in QTc intervals with 15 ms standard deviation (SD) and 90% power. Nine stabilized MMT patients, using median (range) 70 (40–120) mg methadone, were included. Data (ECG recordings, serum samples, and withdrawal symptoms) were collected both before drug intake (C min ) and at 3 h after drug intake (C max ), and were collected on the day before the switch from methadone to equipotent R‐methadone dose and at 14 and 28 days after the switch. A cardiologist calculated QTc intervals retrospectively. Serum electrolytes and methadone concentrations were measured. Mean QTc intervals at C min were 472 ms and 422 ms on methadone (automatically and manually read) and 414 ms on R‐methadone (manually read). Mean (SD) change in QTc intervals was −8 (10) ms ( p = 0.047) at C min but non‐significant at C max . R‐methadone showed a concentration‐dependent relationship with QTc intervals. Switching to R‐methadone reduced QTc intervals, but far less than the 20 ms considered clinically relevant.

Background We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID). Methods We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment. Results A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% CI 58.2-77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI 26.1-45.4]) during control conditions (risk difference 33.1% [95% CI 20.0-46.2]; risk ratio 1.9 [95% CI 1.4-2.6]). The intervention was superior in terms of treatment completion (aOR 4.8 [95% CI 1.8-12.8]; p = 0.002) and time to treatment initiation (aHR 4.0 [95% CI 2.5-6.3]; p < 0.001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI 50.8-70.9]) during intervention and in 66 of 102 (64.7% [95% CI 54.6-73.9]) during control conditions. Conclusions An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation. Clinical Trial Registration NCT04220645

Background: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. Methods: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. Discussion: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care. Trial registration: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.