BACKGROUND. In retinitis pigmentosa (RP), rod photoreceptors degenerate from 1 of many mutations, after which cones are compromised by oxidative stress. N-acetylcysteine (NAC) reduces oxidative damage and increases cone function/survival in RP models. We tested the safety, tolerability, and visual function effects of oral NAC in RP patients. METHODS. Subjects (n = 10 per cohort) received 600 mg (cohort 1), 1200 mg (cohort 2), or 1800 mg (cohort 3) NAC bid for 12 weeks and then tid for 12 weeks. Best-corrected visual acuity (BCVA), macular sensitivity, ellipsoid zone (EZ) width, and aqueous NAC were measured. Linear mixed-effects models were used to estimate the rates of changes during the treatment period. RESULTS. There were 9 drug-related gastrointestinal adverse events that resolved spontaneously or with dose reduction (maximum tolerated dose 1800 mg bid). During the 24-week treatment period, mean BCVA significantly improved at 0.4 (95% CI: 0.2–0.6, P < 0.001), 0.5 (95% CI: 0.3–0.7, P < 0.001), and 0.2 (95% CI: 0.02–0.4, P = 0.03) letters/month in cohorts 1, 2, and 3, respectively. There was no significant improvement in mean sensitivity over time in cohorts 1 and 2, but there was in cohort 3 (0.15 dB/month, 95% CI: 0.04–0.26). There was no significant change in mean EZ width in any cohort. CONCLUSION. Oral NAC is safe and well tolerated in patients with moderately advanced RP and may improve suboptimally functioning macular cones. A randomized, placebo-controlled trial is needed to determine if oral NAC can provide long-term stabilization and/or improvement in visual function in patients with RP. TRIAL REGISTRATION. NCT03063021. FUNDING. Mr. and Mrs. Robert Wallace, Mr. and Mrs. Jonathan Wallace, Rami and Eitan Armon, Marc Sumerlin, Cassandra Hanley, and Nacuity Pharmaceuticals, Inc.

To reduce the heavy reliance of public hospitals on drug sales and use of advanced technologies and to contain the escalating medical expenditures, Beijing implemented two rounds of comprehensive public hospital reform in 2017 and 2019, respectively. The first round focused on separating drug sales from hospital revenue (reform1), and the second round extended to include zero markup on medical consumables and price adjustments for medical services (reform2). To estimate how these two rounds of reform have affected public hospitals' revenue structures, we used observational data of medical revenues from 2016 to 2019 covering 354 healthcare facilities. A Panel-interrupted time-series (PITS) model was used to analyze the effects. The results suggest that the reforms have changed the structure of public hospitals' revenues. The proportion of drug sales in hospital revenues fell from 43.96% in 2016 (pre-reform) to 34.08% in 2019 (post-reform); the proportions of medical consumables decreased by 0.73% after reform 2; and the proportion of medical consultation service fees increased from 15.16% in 2016 to 24.51% in 2019. PITS analysis showed that the proportion of drug sales dropped by 5.46% in the month of reform 1, and it dropped by 0.20% per month on average after reform 2(p < 0.001). The proportion of medical consumables decreased by 0.04% per month on average after reform 2 (p < 0.001). The proportion of medical consultation service increased by 7.13% in the month of reform 1, and it increased by 0.14% per month on average after reform 2(p < 0.001). Similar trends were seen in hospital revenue structures from both inpatient services and from outpatient and accident and emergency services. Thus, Beijing's reforms successfully contained rising medical expenditures and optimized hospitals' revenue structures. These reforms can provide a reference for further public hospital reforms in China and other countries with similar systems.

Randomized trials have shown that medical male circumcision (MMC) reduces male HIV acquisition by 50% to 60%,^1-3 and that early initiation of antiretroviral therapy (ART) reduces HIV transmission by more than 90% in HIV-discordant couples.⁴ Mathematical modeling suggests that these interventions could mitigate the HIV epidemic in sub-Saharan Africa,^5-7 but there is limited empirical evidence for the population-level effects of these interventions on HIV incidence in real-world programs.

Background: The risk of HIV associated with hormonal contraceptives is controversial. We assessed hormonal contraceptive use and HIV incidence in HIV-discordant couples in Rakai, Uganda. Methods: HIV-discordant couples were retrospectively identified from a cohort between 1999 and 2009. Hormonal contraception included oral contraception, depomedroxyprogesterone acetate (DMPA), and implants (Norplant). Poisson regression estimated adjusted incidence rate ratios (adjIRRs) associated with hormonal contraceptive methods. A case–control subanalysis estimated odds ratios (ORs) of HIV associated with hormonal contraceptive, adjusted for viral load and age. Results: We identified 190 male HIV-positive/female HIV-negative (M+F−) and 159 male HIV- negative/female HIV-positive (M−F+) couples not using antiretroviral therapy or condoms. Female HIV incidence was 5.8/100 person-years (py) among nonhormonal contraceptive users, 12.0/100 py among oral contraceptive users [adjIRR 2.65, 95% confidence interval (CI) 0.82–8.60], 4.5 among Norplant users (adjIRR: 0.89, 95% CI 0.11–7.10), and 7.5/100 py among DMPA users (adjIRR 1.42, 95% CI 0.60–3.36). Male HIV incidence was 7.4/100 py during nonhormonal contraceptive use, 16.5/100 py during female oral contraceptive use (adjIRR 2.52, 95% CI 0.49–12.95), and 4.9/100 py with DMPA use (adjIRR 0.57, 95% CI 0.19–1.70). The number of female seroconverters was three among oral contraceptive users, one among Norplant users, and seven among DMPA users. Male seroconverters were two during female oral contraceptive use, none with Norplant use, and three with DMPA use. In a nested case–control analysis after adjustment for HIV viral load, the adjOR associated with oral contraceptive use was 1.59 (95% CI 0.32–97.85) for M+F− and 2.11 (95% CI 0.18–25.26) for M−F+ couples. For DMPA use, the adjOR was 1.44 (95% CI 0.46–4.51) for M+F− and 1.40 (95% CI 0.30–6.49) for M−F+ couples. Conclusion: We did not observe significant risk of HIV acquisition or transmission with oral contraceptives or DMPA use in HIV discordant couples, but several point estimates were above 1.0 and statistical power was limited.