Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs.

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.

Bone mineral density and vitamin D status in ambulatory and non-ambulatory children with cerebral palsy.

UNLABELLED: This study assessed distal femur and lumbar spine bone mineral density (BMD) Z-scores in children with cerebral palsy. BMD z-score was lower in non-ambulatory than in ambulatory children. Somewhat surprisingly, among ambulatory children, those with better walking abilities had higher BMD z-score than those with more impaired walking ability. INTRODUCTION: Children with cerebral palsy (CP) have increased risk for low bone mineral density (BMD). The aim was to explore the difference in BMD at the distal femur and lumbar spine between ambulatory and non-ambulatory children with CP and the relationship between vitamin D status and BMD. METHODS: Fifty-one children (age range 8-18 years; 20 girls) with CP participated. Their BMD Z-scores were measured in the lumbar spine and the distal femur using dual X-ray absorptiometry, and 25-hydroxy-vitamin D (25-OHD) concentrations were measured in serum. Children with GMFCS level I-III were defined as 'walkers' while children with level IV-V were defined as 'non-walkers. RESULTS: Non-walkers had lower mean BMD Z-scores (range -1.7 to -5.4) than walkers at all sites (range -0.8 to -1.5). Among walkers, BMD Z-scores at the distal femur were lower in those with GMFCS level II than with level I (p values < 0.004). A similar difference was found between the affected and unaffected limb in children with hemiplegia. Mean 25-OHD concentration was 45 nmol/L (SD = 18); lower in walkers (mean = 41 nmol/L; SD = 18) than in non-walkers (mean = 53 nmol/L; SD = 19; p = 0.041). There were no correlations between 25-OHD and BMD z-scores. CONCLUSIONS: The main predictor of low BMD Z-scores in the distal femur was the inability to walk, but the results suggest that the degree of the neuromotor impairment may also be a significant predictor. Vitamin D status did not correlate with BMD z-scores.