OBJECTIVE:To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF). METHODS:MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose. Primary efficacy endpoints included newborn and infant severe RSV-associated medically attended lower respiratory tract illness within 180 days after birth. The RSV-A and RSV-B serum neutralizing antibody titers were determined in a subset of pregnant participants and their newborns. RESULTS:In this final analysis, 7,420 pregnant participants were randomized, and 7,307 children were born (RSVpreF n=3,660, placebo n=3,647). Vaccine efficacy , defined as protection against newborn and infant severe RSV-associated medically attended lower respiratory tract illness, was 82.4% (95% CI, 57.5-93.9) and 70.0% (95% CI, 50.6-82.5) within 90 and 180 days of birth, respectively. The RSVpreF induced robust immune responses in pregnant participants and resulted in highly efficient transfer of maternal antibodies to their newborns across subgroups (by gestational age at delivery and at vaccination, number of days from vaccination to delivery, country, maternal age). Final RSVpreF safety results in pregnant and newborn and infant participants were consistent with the primary analysis with no new safety concerns identified. CONCLUSION:This final analysis of MATISSE trial data confirms the primary analysis conclusions: Maternal vaccination with RSVpreF has a favorable safety profile in both pregnant and newborn and infant participants and demonstrates efficacy against RSV-associated lower respiratory tract illness in infants through age 6 months. The RSVpreF induces robust immune responses in pregnant individuals, with corresponding high RSV-neutralizing titers in their newborns. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov , NCT04424316.
Background:Atypical teratoid rhabdoid tumor (ATRT) is a rare pediatric central nervous system tumor with little data on the efficacy of upfront treatment strategies. This study reports prognostic factors and survival of children with newly diagnosed ATRT at high-volume centers treated as per the Children's Oncology Group trial ACNS0333. Methods:Data were collected retrospectively from 13 institutions. Included subjects were children with newly diagnosed ATRT, treated as per ACNS0333, a single-arm phase III trial of intensive chemotherapy and radiation therapy (RT). Data were analyzed to assess the prognostication of clinical variables and estimates of event-free survival (EFS) and overall survival (OS). Results:Eighty subjects were included, with a median age at diagnosis of 18 months, 70% had localized disease, and 53% underwent complete tumor resection at the time of diagnosis. Fifty patients (63%) completed all therapy phases, while 12 patients (15%) experienced progression during treatment. Fifty-three patients (66%) received post-induction consolidation with high-dose chemotherapy and stem cell rescue (HDC/SCR), and 55 (69%) received RT. The 4-year EFS and OS for the entire cohort were 49% and 53%, respectively. Patients completing all therapy phases had superior outcomes (4-year EFS: 63%; OS: 67%). Absence of disease post-induction correlated with improved outcomes (4-year EFS: 64%; OS: 70%), and patients with primary spinal cord tumors had poor outcomes despite intensive therapy. Conclusions:Children with ATRT treated as per ACNS0333 with multi-modal therapy, including HDC/SCR and RT, have improved survival compared to those treated without RT and is higher than previously reported on study.
This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019, developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of the anti-severe acute respiratory syndrome coronavirus 2 neutralizing antibody pemivibart as pre-exposure prophylaxis. The recommendation is based on evidence derived from a systematic review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Information on pemivibart is included in the U.S. Food and Drug Administration Emergency Use Authorization for this agent.
Abstract Introduction Unintentional ocular exposure to epinephrine nasal spray (10 mg/mL epinephrine) is a potential safety concern. Although epinephrine is used in multiple ocular formulations, unintentional ocular administration of epinephrine nasal spray was assessed to determine tolerability and support the overall safety profile. Methods A non-GLP ocular tolerability study was conducted using six naïve New Zealand White rabbits (3 males, 3 females). Vehicle control or epinephrine nasal spray (1 mg) was applied to the right or left eye, respectively, once on Day 1. Animals were monitored over seven days for mortality, clinical signs, body weight changes, ophthalmic findings, ocular irritation (using the Modified Hackett-McDonald Scoring System), and gross necropsy findings. Results Epinephrine nasal spray was well tolerated with no mortality, clinical abnormalities, or changes in body weight. Ophthalmic examinations via indirect ophthalmoscopy and slit-lamp biomicroscopy revealed no signs of irritation or ocular toxicity. No gross pathological changes were noted at necropsy. Conclusion A single topical administration of epinephrine nasal spray (10 mg/mL) in rabbit eyes was not associated with any adverse effects, indicating a low risk of ocular toxicity. These results support the safety of epinephrine nasal spray in the event of unintentional ocular exposure and taken together with epinephrine’s use in other ocular formulations, suggest that no further nonclinical ocular studies are necessary.
OBJECTIVES:To compare the effects of initiating physical therapy (PT) immediately versus resting before starting PT on pain and dysfunction over 12 months in adolescent athletes (10-19 years) with active lumbar spondylolysis. METHODS:This prospective multicentre trial randomised participants to immediate PT or rest before PT. The immediate PT group began PT within 7 days and progressed based on pain and function. The rest before PT group started PT once symptoms resolved and progressed based on time. The primary outcome was pain and disability (Micheli Functional Scale) between groups over time, measured at baseline, 1 (primary end point), 3 and 12 months. Time to return to sport and the recurrence rate of low back pain (LBP) were also assessed. Outcomes were analysed using an intention-to-treat approach. RESULTS:Sixty-four participants (median age 14.2 years; 40% female) were randomised to immediate PT (n=30) and rest before PT (n=34). At 1 month, the immediate PT group showed significant improvements in pain and disability (mean difference on Micheli Functional Scale of 21.3, 95% CI 28.7 to 13.9; p<0.001). They also returned to sport 38 days sooner (p<0.001), with fewer recurrences of LBP over 12 months (3% vs 29%; p=0.01). There were no adverse events. CONCLUSIONS:Clinicians may consider prescribing PT immediately after diagnosing active lumbar spondylolysis instead of rest. Immediate PT showed greater initial improvements in pain and dysfunction, a quicker return to sport and a lower recurrence of LBP compared with rest before PT among adolescent athletes with spondylolysis. TRIAL REGISTRATION NUMBER:NCT05505981.
