This report summarises the Clinical Endpoints Special Session held during the 62nd annual symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV), convened at Tivoli Vredenburg, Utrecht, The Netherlands. The session brought together clinicians, regulators, industry representatives, and a patient voice to consider the state of clinical endpoints in trials for inherited retinal disorders (IRDs). Discussions covered the adequacy of current endpoints, challenges of disease heterogeneity, regulatory expectations, operational feasibility, and the perspectives of patients. The session highlighted the need to anchor emerging endpoints to clinically meaningful outcomes and to minimise assessment burdens.
Neuroblastoma constitutes the most common extracranial solid tumor encountered in children under 5 years of age. The clinical course is highly variable, ranging from spontaneous tumor regression in very young infants to a highly aggressive disease in older children. 5-year survival of > 90% in low and intermediate-risk disease compares to < 60% in those with high-risk neuroblastoma despite recent genetic and clinical advances. Treatment strategies vary significantly in intensity depending on the aggressiveness of disease with surgery playing a pivotal role in the management. A solid understanding of different risk groups, individualized management, and outcomes is important for pediatric surgeons to achieve best outcomes, and provide highest quality advice at the multidisciplinary tumor board meeting. This article offers a narrative update on the diagnosis and management of neuroblastoma in childhood and highlights some of the key controversies in the surgical management of the disease.
The European LeukemiaNet has periodically issued guidelines for the diagnosis and management of acute myeloid leukemia (AML) in adults. These consensus recommendations, most recently updated in 2022, incorporate recent advances in genomic testing, disease detection methods, target identification, and response assessment. Whilst similarities exist between AML in children and adults, pediatric AML is frequently characterized by unique cytogenetic and molecular features, which require distinct genetic and immunophenotypic diagnostics, therapeutic approaches, response assessment criteria, and supportive care strategies. To address these specific needs, an international panel of pediatric hematologist-oncologists, biologists, geneticists, and laboratory medicine scientists convened to develop recommendations for the diagnosis and management of AML in children, adolescents, and young adults (hereafter termed pediatric AML) that are discussed in this special report.
Background:Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced in Catalonia (Spain, 2023-2024 season onwards) and Italy (2024-2025 season). The United Kingdom (UK) instead introduced maternal RSV vaccination (RSVpreF) in the 2024-2025 season. Our aim was to analyse emergency department (ED) attendances and admissions to hospital following RSVpreF and nirsevimab introduction, with hospitals in Iceland and Romania, where no intervention was introduced, used as comparators. Methods:Multi-national retrospective analysis of ED attendances and admissions for all diagnoses, respiratory diagnoses excluding bronchiolitis, and bronchiolitis from all hospitals in Catalonia (Spain), four UK hospitals (Bristol, Edinburgh, Glasgow, and Leicester), and one hospital in Italy (Rome), Romania (Bucharest), and Iceland (Reykjavík) from April 2018 to March 2025. Bronchiolitis diagnoses in the 2024-2025 season were compared to previous pre-intervention seasons (2018-2023, excluding the 2020-2021 COVID-19 year) by applying a generalised linear model in Poisson regression to obtain risk ratios (RR) and 95% confidence intervals (95% CI). Findings:In the 2024-2025 season, in Catalonia, there was a reduction in the RR for bronchiolitis ED attendances and admissions in infants of age <6 months (RR 0.45; 95% CI 0.43-0.47 and RR 0.40; 95% CI 0.37-0.43, respectively). This was not seen in Rome, where the RR for ED attendances with bronchiolitis in infants of age <6 months was 1.09 (95% CI 0.92-1.30) and the RR for admissions was 1.12 (95% CI 0.83-1.52). In the UK, for infants of age <6 months with bronchiolitis, there was a significant but modest reduction in 1 out of 4 hospitals for ED attendances (Leicester; RR 0.91, 95% CI 0.85-0.97) and in 2 out of 4 hospitals for admissions (Leicester; RR 0.80, 95% CI 0.69-0.94 and Edinburgh; RR 0.85, 95% CI 0.76-0.95). Interpretation:In Catalonia, there was a sustained reduction in bronchiolitis ED attendances and admissions for infants in the 2024-2025 season. However, no substantial reduction in bronchiolitis ED attendances or admissions was observed in Rome or the UK. These differences are likely to relate to the reduced uptake of RSV prevention products in these settings compared to Catalonia. Funding:None.
Background Since 2015, the National Institute for Health and Care Excellence (NICE) guidelines have recommended antenatal magnesium sulfate (MgSO 4 ) for mothers in preterm labour (<30 weeks’ gestation) to reduce the risk of cerebral palsy (CP) in the preterm baby. However, the implementation of this guideline in clinical practice was slow, and MgSO 4 use varied between maternity units. In 2018, the PRrevention of Cerebral palsy in PreTerm labour (PReCePT) programme, an evidence-based quality improvement (QI) intervention to improve use of MgSO 4 , was rolled out across England. Earlier evaluation found this programme to be effective and cost-effective over the first 12 months. We extended the original evaluation to determine the programme’s longer-term impact over 4 years, its impact in later preterm births, the impact of the COVID-19 pandemic, and to compare MgSO 4 use in England (where PReCePT was implemented) to Scotland and Wales (where it was not). Methods Quasi-experimental longitudinal study using data from the National Neonatal Research Database on babies born <30 weeks’ gestation and admitted to a National Health Service neonatal unit. Primary outcome was the percentage of eligible mothers receiving MgSO 4 , aggregated to the national level. Impact of PReCePT on MgSO 4 use was estimated using multivariable linear regression. The net monetary benefit (NMB) of the programme was estimated. Results MgSO 4 administration rose from 65.8% in 2017 to 85.5% in 2022 in England. PReCePT was associated with a 5.8 percentage points improvement in uptake (95% CI 2.69 to 8.86, p<0.001). Improvement was greater when including older preterm births (<34 weeks’ gestation, 8.67 percentage points, 95% CI 6.38 to 10.96, p<0.001). Most gains occurred in the first 2 years following implementation. PReCePT had a NMB of £597 000 with 89% probability of being cost-effective. Following implementation, English uptake appeared to accelerate compared with Scotland and Wales. There was some decline in use coinciding with the onset of the pandemic. Conclusions The PReCePT QI programme cost-effectively improved use of antenatal MgSO 4 , with anticipated benefits to the babies who have been protected from CP.
