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Background Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies. Methods This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index). Results For the 74 children (median age 10.3 years; range 3–18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1–100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment. Conclusions With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.

Introduction Hospitals have become an important venue for identifying medical patients with occult suicidality. This article describes the implementation of a quality improvement project at the National Institutes of Health Clinical Center (NIHCC) to systematically screen medical/surgical inpatients for suicide risk. Methods Using the Plan-Do-Study-Act method, questions from the Ask Suicide-Screening Questions (ASQ) tool were deployed with medical inpatients aged 10 years and older between April 2018 and April 2019. Goals included the development of a training program, policy and procedure review, electronic medical record integration and data collection, and ongoing management and troubleshooting. Results A total of 4,284 patients were screened for suicide risk with a nurse screening compliance rate of 94.3%. Prevalence data on patients aged 10 years and older revealed an overall screen positive rate of 2.3% (97/4,284), with 3.1% of youth aged 10 to 24 years and 2.2% of adults screening positive. Of the 97 patients who screened positive, 96 were non-acute positive screens. Of the full sample, only 1 patient (0.02%) was deemed acute positive, requiring a 1:1 observer and full safety precautions. Conclusion Universal suicide risk screening was successfully implemented in the NIHCC without incurring a need for additional resources. The intermediate step of a brief suicide safety assessment is a critical part of the workflow, providing guidance for determining appropriate follow-up in a safe and efficient manner that spares limited mental health and hospital resources. Given the increasing suicide rates in the general population, medical venues offer important opportunities for early detection, assessment, and referral.