Faculty Bibliography

OBJECTIVE:To assess the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) stratified by age, number of previously attempted antiseizure medications (ASMs), and SCN1A pathogenic variant status. METHODS:In this post hoc analysis, data from three randomized controlled trials (RCTs) in patients with DS (2-18 years) were pooled and stratified by age (<4; ≥4 years), number of previous ASMs (1-3; 4-6; ≥7), and SCN1A pathogenic variant status (SCN1A+; SCN1A-). Stratified groups were assessed and compared with the pooled placebo group (change in monthly convulsive seizure frequency [MCSF], longest convulsive seizure-free interval, and Clinical Global Impression-Improvement [CGI-I] scale scores rated by parents/caregivers and investigators), and safety (treatment-emergent adverse events [TEAEs]: frequency, days to onset, and proportion resolved). RESULTS:Among 348 patients included in the RCTs, 216 were randomized to fenfluramine (0.7 mg/kg/day, n = 88; 0.4 mg/kg/day [with stiripentol], n = 43; 0.2 mg/kg/day, n = 85) and 132 to placebo. Compared with placebo, fenfluramine treatment (all doses combined) resulted in greater MCSF reductions, greater increases in longest convulsive seizure-free intervals, and a higher proportion of parents/caregivers and investigators reporting clinically meaningful improvement ("Much Improved", "Very Much Improved") on CGI-I scores across all stratified groups. CGI-I scores were consistent across fenfluramine doses in most stratified groups, but patients with the fewest number of previous ASMs had the greatest frequency of clinically meaningful improvement on investigator-rated CGI-I scores. Safety outcomes were similar across all strata. Most TEAEs resolved by end-of-study. SIGNIFICANCE/CONCLUSIONS:Fenfluramine treatment was associated with improved seizure outcomes and global functioning compared with placebo regardless of age, number of previous ASMs, and SCN1A status in patients with DS. Fenfluramine was well-tolerated; no new safety signals were identified. Further studies with larger sample sizes (including adults) and a priori inferential analyses of stratified groups are warranted. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:Patients with Dravet syndrome struggle with seizures and everyday life. In three studies, patients aged 2-18 years received fenfluramine or placebo (sugar pill). Fenfluramine lowered seizures without many side effects. Researchers combined results from these studies to see how fenfluramine worked in different patient groups based on age, number of previous medications, and a gene called SCN1A. They looked at seizure reduction and whether doctors felt patients had improved. In all groups, fenfluramine worked better than placebo, with similar side effects. Researchers believe fenfluramine helped these patients, but some groups were small, so these results need to be confirmed.

PURPOSE OF REVIEW/OBJECTIVE:The coronavirus disease 2019 pandemic, shifting health policy and increasing vaccine hesitancy have all increased the likelihood healthcare practitioners will encounter vaccine-preventable diseases in children. Both front-line and consulting clinicians need to be able to identify these previously rare diseases and their neurologic complications, particularly in un- or under-vaccinated children. RECENT FINDINGS/RESULTS:As diseases previously considered rare or eliminated reemerge, more is known about direct and indirect consequences of peripheral and central nervous system infection in children-both in general and specific to individual vaccine-preventable diseases. Primary and secondary neurologic complications can be acute, subacute, chronic, or arise years later. Advances in imaging and molecular identification along with better understanding of underlying disease pathophysiology can all aid earlier identification, treatment, prognostication, and recovery. SUMMARY/CONCLUSIONS:While the benefits of childhood vaccination programs clearly outweigh the risks for the majority of children, in light of current realities the goal of this guide is to better prepare front-line and consulting clinicians to identify and manage vaccine-preventable diseases and their neurologic complications in un- or under-vaccinated children as they increasingly encounter them now and in the future.

BACKGROUND:People with multiple sclerosis (pwMS) treated with anti-CD20 monoclonal antibodies have an elevated infection risk, yet long-term comparative data with oral fumarates are limited. OBJECTIVE:To compare infection incidence, healthcare resource utilization, and relapse outcomes among pwMS receiving fumarate or anti-CD20 therapy for ⩾2 years. METHODS:This retrospective propensity-matched (1:2) analysis used US Komodo Health claims (1 January 2016-31 May 2022) for pwMS aged 18-64 years with ⩾2 years of continuous follow-up. Outcomes were assessed using Poisson generalized linear models. RESULTS: = 0.021). CONCLUSIONS:Fumarate therapy was associated with a lower infection risk versus anti-CD20s. The infection rate in the fumarates group remained relatively stable over time, but it progressively increased in the anti-CD20 group, with the most prominent differences observed at year 4 and beyond.

PURPOSE OF REVIEW/OBJECTIVE:Aberrant activation of the RAS-RAF-MEK-ERK signaling pathway contributes to numerous malignancies, congenital syndromes, and cardiovascular disorders, establishing MEK inhibitors (MEKi) as crucial therapeutic agents. MEKi demonstrate substantial clinical benefit as monotherapy (e.g., NF1-associated tumors) or combination therapy (e.g., melanoma, glioma, congenital RASopathies). Cardiovascular adverse events, primarily asymptomatic reductions in left ventricular ejection fraction (LVEF), have prompted intensive echocardiographic monitoring. RECENT FINDINGS/RESULTS:Emerging evidence indicates that isolated mild LVEF decreases rarely progress to symptomatic heart failure, raising concerns about unnecessary treatment interruptions driven by overly rigorous imaging protocols. Integrating cardiac biomarkers into monitoring strategies could offer a more pragmatic approach, guiding echocardiographic evaluations based on biomarker elevation or symptoms. Expert recommendations advocate personalized, risk-adapted surveillance frameworks. High-risk patients include those with baseline cardiovascular conditions, abnormal biomarker profiles, or significant clinical symptoms. Normal-risk patients can be safely monitored clinically, reserving imaging for biomarker changes or symptom onset. Prospective studies should seek to validate these recommendations.

This consensus statement represents an update to Mental Health in Elite Athletes: International Olympic Committee Consensus Statement (2019) To advance a more standardised, evidence-based approach to mental health in elite athletes, an International Olympic Committee (IOC) Consensus Group critically evaluated the current science via a systematic literature review, sought consensus using Delphi methodology and provided recommendations relevant to this topic. Key themes include that mental health symptoms and disorders are (1) common among elite athletes; (2) may have sport-related aetiologies and manifestations; and (3) can impact performance. Routine screening for and monitoring of mental health symptoms and disorders in elite athletes using validated instruments is recommended. Management strategies should promote mental well-being in addition to preventing and treating mental health symptoms and disorders. These strategies should address all contributors to mental health symptoms, including factors within the environments in which athletes train and compete. Treatment may include psychotherapy, medication and other culturally or contextually appropriate modalities. With appropriate support and treatment, many athletes experiencing mental health symptoms and disorders can continue to train and compete safely, but sometimes modification of sport participation may be necessary. Elite athletes who are transitioning out of sport, elite Para athletes and elite young (adolescent) athletes are relatively understudied and may have distinct mental health concerns, in addition to those impacting elite athletes in general.

BACKGROUND/UNASSIGNED:The transition from hospital discharge to home is a critical period prone to gaps in care. Telemedicine has potential to smooth this transition; however, few educational interventions assess the unique skills required for high-quality telemedicine care at this critical juncture. OBJECTIVE/UNASSIGNED:standardized patient (SP) encounters in internal medicine residents' actual clinics to assess telemedicine skills in the post-discharge period. METHODS/UNASSIGNED:We developed 2 cases portraying recently discharged patients, designed behaviorally anchored assessment checklists, created mock electronic health record entries, and scheduled telemedicine visits in residents' clinics throughout the 2023-2024 academic year. SPs assessed skills as "not done," "partly done," or "well done" across 5 skill domains: Information Gathering, Relationship Development, Education and Counseling, Telemedicine-Specific Skills, and Care Transition Skills. We analyzed differences in the percentage of "well done" items, fit an ordinal mixed-effects model to assess for performance by case and postgraduate year (PGY) level, and surveyed residents. RESULTS/UNASSIGNED:All 42 (100%) PGY-1s and PGY-2s in our program participated in 79 total encounters. Residents performed well in core communication domains but struggled with Telemedicine-Specific Skills, Care Transition Skills, and Education and Counseling skills. PGY-2 performance was stronger than PGY-1 performance in these domains. Among residents who completed both cases, performance in case 2, which took place 6 months after case 1, was stronger; this effect was driven by PGY-1 performance. Twenty-nine of 31 residents (94%) reported this intervention improved their telemedicine skills. CONCLUSIONS/UNASSIGNED:We report a high-fidelity strategy that captures telemedicine skill development in the context of patient care.

OBJECTIVES/OBJECTIVE:To review the current evidence regarding thyroid artery embolization (TAE) for the management of benign and select malignant thyroid diseases and to present expert consensus recommendations from the North American Society for Interventional Thyroidology (NASIT) on patient selection, indications, technical considerations, safety, clinical outcomes, and the role of TAE in contemporary thyroid disease management. METHODS:A multidisciplinary consensus was developed through literature review and expert input addressing indications, technique, outcomes, and controversies, including comparisons with surgery, thermal ablation and radioactive iodine therapy. RESULTS:TAE is effective for large-volume disease (>30 mL) and substernal extension, achieving 32-73% volume reduction at 6 months with improvement in symptoms and cosmesis. In hyperthyroidism (Graves' disease and toxic multinodular goiter), euthyroid rates exceed 70% with durability up to 50 months. Preoperative use reduces operative time and blood loss. Complications are typically mild and self-limited; serious events are rare. Advances include pressure-enabled embolization and collateral flow management. CONCLUSIONS:TAE is a safe, effective, and durable option for selected patients with large symptomatic benign nodules and goiters, with additional roles in hyperthyroidism and as a surgical adjunct. Further studies are needed to standardize technique and define its role relative to other therapies.

BackgroundSubjective cognitive decline (SCD) is increasingly recognized in some cases as an early clinical stage in the Alzheimer's disease continuum, yet the factors that predict which individuals will progress to objective impairment remain poorly understood.ObjectiveWe evaluated risk factor differences and cognitive domain markers associated with progression in participants with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer's Disease Research Center.MethodsWe included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline.ResultsOverall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) versus 17.3 (2.1)), Hispanic ethnicity (50.0% versus 11.0%), and hypercholesterolemia (adjusted odds ratio: 6.67) were risk factors for progression in SCD, p ≤ 0.05, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all).ConclusionsThese findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.