Despite the remarkable benefits of nusinersen and other disease-modifying therapies in spinal muscular atrophy (SMA), patients may still experience clinical manifestations of the disease. Here we assessed the potential for high-dose nusinersen to rapidly slow neurodegeneration and lead to improved outcomes for patients. The global, three-part, phase 2/3 DEVOTE trial evaluated the efficacy and safety of high-dose nusinersen (50-mg loading dose; 28-mg maintenance dose) in individuals with SMA. In Part B, treatment-naive individuals (n = 75) were randomized 2:1 to 50/28 mg or 12/12 mg nusinersen. In a supportive open-label cohort (Part C), nusinersen-experienced individuals (12/12 mg for more than 1 year) were enrolled. The primary endpoint (Part B infantile-onset participants) was a 6-month change in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score comparing 50/28 mg with matched ENDEAR participants (n = 20) who received sham. DEVOTE met its primary endpoint: at day 183, the CHOP-INTEND total score significantly improved (+15.1 points) in those who received 50/28 mg nusinersen and worsened (−11.1 points) in matched ENDEAR participants who received sham (difference, 26.19 (95% confidence interval = 20.7 to 31.74); statistical testing was performed using the joint-rank test where the difference in ranks was 26.06 (95% confidence interval = 17.9 to 34.2; P < 0.0001). The safety profile of 50/28 mg nusinersen was similar to the 12/12 mg regimen. The data support that high-dose nusinersen provides benefit in patients with SMA, with a generally well-tolerated safety profile. ClinicalTrials.gov registration: https://clinicaltrials.gov/study/NCT04089566. EudraCT no: 2019-002663-10.

Objetivo: Describir las trayectorias sensoriales, salud, participación y necesidades de apoyo de adultos con sordoceguera funcional grave y su relevancia para atención primaria. Diseño: Estudio transversal de microdatos públicos anonimizados de EDAD Hogares 2020 y Centros 2023. Emplazamiento: España; viviendas familiares y establecimientos residenciales, analizados separadamente. Participantes: Adultos con afectación visual y auditiva concurrente: 634 en Hogares y 1.113 en Centros; 92 y 191 cumplieron el criterio de sordoceguera. Se incluyeron respuestas directas e indirectas (proxy). Mediciones principales: Características demográficas, edades de inicio, salud, ocio, accesibilidad, cuidados y decisiones cotidianas. Se estimaron porcentajes ponderados e intervalos aproximados de incertidumbre del 95% (UI95%) mediante bootstrap. Las comparaciones ajustadas fueron exploratorias. Resultados: Las medianas de edad fueron 85 y 90 años. La salud regular, mala o muy mala alcanzó el 88,3% (UI95%: 80,4–94,8) en Hogares y el 71,1% (63,7–78,2) en Centros. En Hogares, el 24,3% tenía cuidados no cubiertos (UI95%: 14,0–35,4). En Centros, el 29,5% no realizaba ocio (22,9–37,0) y la participación en decisiones osciló entre el 3,6% y el 37,2%. Las dificultades tecnológicas alcanzaron el 73,6% en Hogares y el 85,9% en Centros. Las respuestas proporcionadas por informantes indirectos representaron el 57,7% en Hogares y el 53,1% en Centros. Conclusiones: Predominan edades avanzadas, con trayectorias heterogéneas y necesidades que trascienden los cuidados básicos. Atención primaria puede contribuir mediante valoración sensorial integral, comunicación accesible y coordinación de apoyos sanitarios y sociales adaptados a las preferencias personales.

Background: Deafblindness is a distinct disability with major implications for communication, mobility, access to information, and participation. Population estimates vary substantially. Methods: We conducted a secondary cross-sectional analysis of nationally representative Spanish microdata from EDAD-Households 2020 and EDAD-Centres 2023, including persons aged ≥ 6 years. Functional deafblindness was defined as severe limitation in one sensory domain with at least moderate limitation in the other, accounting for residual functioning with assistive products. Weighted prevalence estimates and approximate 95% uncertainty intervals (UI) were obtained using a cluster bootstrap. Results: The integrated population represented 44.9 million persons. The primary definition identified an estimated 45,951 persons with functional deafblindness, corresponding to 102.3 per 100,000 population (95% UI, 82.5–125.1). Prevalence increased markedly with age, reaching 438.0 per 100,000 among persons aged ≥ 65 years. A broader sensitivity definition yielded 202.3 per 100,000 (95% UI, 175.8–231.2). Conclusions: Functional deafblindness affects tens of thousands of people in Spain and is concentrated at older ages and in residential settings. Population-based estimates are needed to complement administrative data and inform equitable planning of specialized, accessible health, social-care, and communication services.