Posterior uveal melanoma in adolescents and children: current perspectives

Recognizing that <1% of all uveal melanomas occur in young persons, and that very few clinicians encounter more than a few such cases over an extended career, we felt that a retrospective review of literature and sharing of our clinical experience would be appropriate to remind readers about this age subgroup of patients with posterior uveal melanoma. This interest stems from the increase in reported cases of uveal melanoma in younger individuals and recent advances in the field

Efficacy and Safety of Modafinil for Improving Daytime Wakefulness in Patients Treated Previously With Psychostimulants

Objectives: To assess the efficacy and safety of modafinil for improving wakefulness in narcolepsy patients treated previously with psychostimulants. Background: Modafinil has become a standard therapy for improving daytime wakefulness in narcolepsy patients and may be a useful therapeutic alternative to psychostimulants used to improve waking function in other medical conditions. Modafinil is chemically dissimilar to and has a pharmacological profile that differs from the psychostimulants. Modafinil has a low abuse potential and is well tolerated. Methods: Patients (N = 151) with narcolepsy who had been unsatisfactorily treated with dextroamphetamine (N = 48), methylphenidate (N = 66), or pemoline (N = 37) were enrolled in this 6-week, open-label, multicenter study. Following a 2-week washout period, patients received modafinil once daily (Week 1, 200 mg; Weeks 2-6, 200 or 400 mg). Efficacy was evaluated at Weeks 1, 2, and 6 using the Epworth Sleepiness Scale and the Clinical Global Impression of Change. Adverse events were monitored throughout the study. Results: Treatment with modafinil improved daytime wakefulness versus baseline regardless of which psychostimulant was taken previously. Mean ESS scores were improved after 1 week of treatment with modafinil. Improvements were maintained throughout the 6 weeks of treatment (all P \u3c 0.001 versus baseline after washout). At Week 6, 79% of all patients were considered to be clinically improved relative to post-washout baseline. The most frequent adverse events were headache, nausea, and insomnia; the majority of adverse events were mild or moderate in nature. Approximately 70% of patients were receiving 400 mg of modafinil once daily at the end of the study. Conclusion: During this 6-week, open-label study, modafinil was an effective and well-tolerated treatment for improving daytime wakefulness in narcolepsy patients previously treated with psychostimulants. (C) 2002 Elsevier Science B.V. All rights reserved

Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p &lt; 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q &lt; 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes