In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety. (Funded by Receptos; TOUCHSTONE ClinicalTrials.gov number, NCT01647516.).
Background Colorectal cancer screening programmes worldwide have been disrupted during the COVID-19 pandemic. We aimed to estimate the impact of hypothetical disruptions to organised faecal immunochemical test-based colorectal cancer screening programmes on short-term and long-term colorectal cancer incidence and mortality in three countries using microsimulation modelling. Methods In this modelling study, we used four country-specific colorectal cancer microsimulation models-Policy1-Bowel (Australia), OncoSim (Canada), and ASCCA and MISCAN-Colon (the Netherlands)-to estimate the potential impact of COVID-19-related disruptions to screening on colorectal cancer incidence and mortality in Australia, Canada, and the Netherlands annually for the period 2020-24 and cumulatively for the period 2020-50. Modelled scenarios varied by duration of disruption (3, 6, and 12 months), decreases in screening participation after the period of disruption (0%, 25%, or 50% reduction), and catch-up screening strategies (within 6 months after the disruption period or all screening delayed by 6 months). Findings Without catch-up screening, our analysis predicted that colorectal cancer deaths among individuals aged 50 years and older, a 3-month disruption would result in 414-902 additional new colorectal cancer diagnoses (relative increase 0•1-0•2%) and 324-440 additional deaths (relative increase 0•2-0•3%) in the Netherlands, 1672 additional diagnoses (relative increase 0•3%) and 979 additional deaths (relative increase 0•5%) in Australia, and 1671 additional diagnoses (relative increase 0•2%) and 799 additional deaths (relative increase 0•3%) in Canada between 2020 and 2050, compared with undisrupted screening. A 6-month disruption would result in 803-1803 additional diagnoses (relative increase 0•2-0•4%) and 678-881 additional deaths (relative increase 0•4-0•6%) in the Netherlands, 3552 additional diagnoses (relative increase 0•6%) and 1961 additional deaths (relative increase 1•0%) in Australia, and 2844 additional diagnoses (relative increase 0•3%) and 1319 additional deaths (relative increase 0•4%) in Canada between 2020 and 2050, compared with undisrupted screening. A 12-month disruption would result in 1619-3615 additional diagnoses (relative increase 0•4-0•9%) and 1360-1762 additional deaths (relative increase 0•8-1•2%) in the Netherlands, 7140 additional diagnoses (relative increase 1•2%) and 3968 additional deaths (relative increase 2•0%) in Australia, and 5212 additional diagnoses (relative increase 0•6%) and 2366 additional deaths (relative increase 0•8%) in Canada between 2020 and 2050, compared with undisrupted screening. Providing immediate catch-up screening could minimise the impact of the disruption, restricting the relative increase in colorectal cancer incidence and deaths between 2020 and 2050 to less than 0•1% in all countries. A post-disruption decrease in participation could increase colorectal cancer incidence by 0•2-0•9% and deaths by 0•6-1•6% between 2020 and 2050, compared with undisrupted screening. Interp...
The sphingosine‐1‐phosphate 1 receptor (S1P1R) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P1R and S1P5R receptors in clinical development for the treatment of chronic immune‐mediated, inflammatory diseases. This first‐in‐human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose‐escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose‐limiting toxicities. The most common ozanimod‐related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady‐state volume of distribution (73–101 L/kg), moderate oral clearance (204–227 L/h), and an elimination half‐life of approximately 17 to 21 hours. Ozanimod produced a robust dose‐dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose‐dependent negative chronotropic effect was observed following the first dose, with the dose‐escalation regimen attenuating the first‐dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once‐daily regimens under clinical investigation.
INTRODUCTION This pilot study was designed to compare the effectiveness of intermittent occlusion therapy (IO-Therapy) using liquid crystal glasses versus continuous occlusion therapy using traditional adhesive patches for treating amblyopia. DESIGN A randomized controlled trial. Children 3–8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn optimal refractive correction (if needed) for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO-Therapy Group with liquid crystal glasses (Amblyz™), set at 30-second opaque/transparent intervals (occluded 50% of wear time) or a 2-hour continuous Patching Group (occluded 100% of wear time). For each patient, visual acuity was measured with the ATS-HOTV method before and after 12 weeks of treatment. RESULTS At the conclusion of the first 12 week-treatment interval, data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15±0.12 (95% CI=0.09 to 0.15) logMAR in the IO-Therapy Group (N=19) and 0.15±0.11 (95% CI=0.1 to 0.15) logMAR in the Patching Group (N=15). Improvements in both groups were significant. The difference between groups was not statistically significant (P=0.73). No adverse effects were reported. CONCLUSION In this pilot study, IO-Therapy with Amblyz liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3–8 years of age with moderate amblyopia. A larger randomized clinical trial is needed to confirm results in future.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.