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Introduction: To ensure the quality of clinical trial safety data, universal data standards are required. In 2019 the International Neonatal Consortium (INC) published a neonatal adverse event severity scale (NAESS) to standardize the reporting of adverse event (AE) severity. In this study the reliability of AE severity grading with INC NAESS was prospectively assessed in a real-world setting. Methods: Severity of AEs was assessed by two independent observers at each of four centers across the world. In each center two series of 30 neonatal adverse events were assessed by both observers: in a first phase with a generic (Common Terminology Criteria for Adverse Events, CTCAE) severity scale not specific to neonates, and in a second phase with INC NAESS (after a structured training). Intraclass correlation coefficients (ICC) were calculated to express inter-rater agreement in both phases, and bootstrap sampling was used to compare them. Results: 120 AEs were included in each of both phases. The ICC with the use of INC NAESS in phase 2 was 0.69. This represents a significant but modest improvement in comparison to the initial ICC of 0.66 in phase 1 (confidence interval of ratio of ICC in phase 2 to phase 1 = 1.005-1.146; excludes 1). The ICC was higher for those AEs for which a diagnosis specific AE severity table was available in INC NAESS (ICC 0.80). Discussion: Good inter-rater reliability of the INC NAESS was demonstrated in four neonatal intensive care units (NICUs) across the globe. The ICC is comparable to what is reported for scales with similar purposes in different populations. There is a modest, but significant, improvement in inter-rater agreement in comparison to the naïve phase without INC NAESS. The better performance when reviewers use AE-specific NAESS tables highlights the need to expand the number of AEs that are covered by specific criteria in the current version of INC NAESS.
RESUMO
OBJECTIVES: Rituximab (RTX) is a new treatment option in children with difficult-to-treat steroid-dependent nephrotic syndrome (SDNS). We evaluated the experience of our tertiary center and reviewed the current literature. METHODS: This is a retrospective single-center study evaluating the efficacy and safety of RTX in children with difficult-to-treat SDNS. Age at diagnosis, type and duration of immunosuppression, age at administration, dose of RTX, possible adverse events, number of relapses, duration of remission, and B-cell count after administration of RTX were analyzed. RESULTS: Nine children with a median age at diagnosis of nephrotic syndrome of 4.75 (range 1.33-11.33) years and a median age at administration of RTX of 16.08 (range 3.33-19.25) years were included. Before administration of RTX they had a median number of relapses per year of 1.70 (range 0.82-4.80). At last follow-up (median 2.75 years, range 0.58-3.92), a reduction in the number of relapses per year to 0.26 (range 0-2.18) was noted, despite cessation or lowering the dose of immunosuppressive therapy. Four patients achieved complete remission after the first administration of RTX, four more patients after subsequent doses of RTX. No severe adverse events were noted. CONCLUSION: RTX was an effective and safe therapeutic option in our cohort of children with difficult-to-treat SDNS, resulting in a significant reduction of yearly relapses in the absence of severe adverse events and facilitating the reduction of other immunosuppressive medication.
