Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials.

BACKGROUND: Interferon-based hepatitis C virus (HCV) therapy is safe and effective among people receiving opioid substitution therapy (OST), but treatment uptake remains low. Our aim was to evaluate the impact of OST and drug use during therapy on completion, adherence, sustained virologic response (SVR12), and safety of ledipasvir/sofosbuvir ± ribavirin. METHODS: The phase 3 ION studies evaluated a fixed-dose combination of ledipasvir/sofosbuvir ± ribavirin administered for 8, 12, or 24 weeks in patients with chronic HCV genotype 1. People with clinically significant drug use (prior 12 months) or noncannabinoids detected at screening by urine drug tests (not explained by prescriptions) were ineligible. Stored samples were available from ION-1 for retrospective testing for illicit drugs by enzyme-linked immunosorbent assay. RESULTS: Among 1952 patients enrolled in the ION studies, 4% (n = 70) were receiving OST. Among those receiving (n = 70) and not receiving OST (n = 1882), there was no difference in treatment completion (97% vs 98%; P = .40), ≥80% adherence (93% vs 92%; P = 1.00), SVR12 (94% vs 97%; P = .28), and serious adverse events (4% vs 3%; P = .43), respectively. Among participants in the ION-1 trial, 23% (n = 196) used illicit drugs during therapy (15% cannabinoids alone; 8% other illicit drugs ± cannabinoids). There was no difference in treatment completion, ≥80% adherence, SVR12, or serious AEs in those with no drug use during treatment compared with those who used cannabinoids and/or other illicit drugs. No cases of HCV reinfection were observed in the 24 weeks following treatment. CONCLUSIONS: OST and drug use during HCV therapy did not impact treatment completion, adherence, SVR12, or safety. CLINICAL TRIALS REGISTRATION: ION-1 (NCT01701401); ION-2 (NCT01768286); and ION-3 (NCT01851330).

Care and environment in midwife-led and obstetric-led units: a comparison of mothers' and birth partners' perceptions.

BACKGROUND: Health-care design recognises the importance of people-environment interactions, and maternity units have responded by encouraging 'homely' environments. Birthing women and birth partners have been separately surveyed about their experiences of the maternity environment and midwifery care, but not to date as dyads. METHOD(S): Postal return survey of mothers and birth partners from nine maternity units (six midwife-led; three obstetric-led) in England, at eight days postnatally in 2004-5. Questions concerned participants' general and specific impressions of the unit environment and of the care given. A repeated measures analysis of variance was used to explore interactions between mothers and partners and different types of unit. The Wilcoxon signed rank test was used for skewed satisfaction scores. Loglinear models were used to analyse mothers' and partners' cited comments, factoring in types of unit. FINDINGS: 515 Dyads responded (response rate 50%). Mothers and partners were generally positive, but *mothers were more so. They rated the birth surroundings (Z = -8.083; p < 0.001) and the midwifery care (Z = -7.177; p < 0.001) more highly than their partners; these findings were significant in both types of unit. Loglinear analysis found that mothers especially were more likely to find midwife-led units 'homely' (Z = 2.496; p = 0.013), 'calming' (Z = 9.61; p < 0.001): and 'clean' (Z = 4.08, p < 0.001). Obstetric-led units were more likely to be thought 'stuffy' (Z = -3.51, p < 0.001). Partners were more likely to agree that there was a lack of privacy (Z = 3.401; p = 0.001), and that there was a lack of facilities for them, particularly within obstetric-led units. CONCLUSIONS: Although generally positive, birth partners were significantly less positive than the birthing mothers about a range of environmental and care variables. The primary focus is and should be the birthing woman, but the partner nevertheless has an interactive role to play, and improving his experience may assist this function.

Self-rated "no-" and "low-" risk pregnancy: a comparison of outcomes for women in obstetric-led and midwife-led units in England.

BACKGROUND: Debate in the United Kingdom about place of birth often concerns obstetric-led units and midwife-led units and relates to notions of risk and safety. Outcomes for these two types of unit are often not comparable because of the restricted selection criteria for midwife-led units. The purpose of this study was to compare outcomes for women intending to give birth in these different types of unit and whose self-rated pregnancy risk level was "none" or "low." METHODS: Self-completion questionnaires were distributed to mothers 8 days after the birth in 9 units (6 midwife led 3 obstetric led) over a 6-month period. RESULTS: Completed questionnaires were received from 432 women (midwife led = 294, obstetric led = 138). Mothers in midwife-led units spent shorter times in labor in the unit (p < 0.01), received less analgesia (p < 0.01) and had fewer interventions (p < 0.01), and were more likely to have a normal delivery (p < 0.01) than women in obstetric-led units. Similar differences were found for both primiparous and multiparous women. In terms of the number of midwives attending each woman, analysis of covariance suggested different models of care depending on type of unit (p < 0.05) and parity (p < 0.01). CONCLUSIONS: Since these mothers' self-rated risk level was none or low, some comparability of outcomes is permissible. It appears that models of care are significantly different in obstetric-led units compared with midwife-led units, leading to greater likelihood of intrapartum intervention, need for analgesia, and assisted or operative delivery. A randomized controlled trial examining such units would permit a conclusive examination of these outcomes.