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Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real‐world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment‐related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real‐world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks. [ABSTRACT FROM AUTHOR]

Background Double-checking the administration of medications has been standard practice in paediatric hospitals around the world for decades. While the practice is widespread, evidence of its effectiveness in reducing errors or harm is scarce. Objectives To measure the association between double-checking, and the occurrence and potential severity of medication administration errors (MAEs); check duration; and factors associated with doublechecking adherence. Methods Direct observational study of 298 nurses, administering 5140 medication doses to 1523 patients, across nine wards, in a paediatric hospital. Independent observers recorded details of administrations and double-checking (independent; primed--one nurse shares information which may influence the checking nurse; incomplete; or none) in real time during weekdays and weekends between 07:00 and 22:00. Observational medication data were compared with patients' medical records by a reviewer (blinded to checking-status), to identify MAEs. MAEs were rated for potential severity. Observations included administrations where double-checking was mandated, or optional. Multivariable regression examined the association between doublechecking, MAEs and potential severity; and factors associated with policy adherence. Results For 3563 administrations double-checking was mandated. Of these, 36 (1.0%) received independent double-checks, 3296 (92.5%) primed and 231 (6.5%) no/incomplete double-checks. For 1577 administrations double-checking was not mandatory, but in 26.3% (n=416) nurses chose to double-check. Where double-checking was mandated there was no significant association between double-checking and MAEs (OR 0.89 (0.65-1.21); p=0.44), or potential MAE severity (OR 0.86 (0.65-1.15); p=0.31). Where double-checking was not mandated, but performed, MAEs were less likely to occur (OR 0.71 (0.54-0.95); p=0.02) and had lower potential severity (OR 0.75 (0.57-0.99); p=0.04). Each double-check took an average of 6.4 min (107 hours/1000 administrations). Conclusions Compliance with mandated double-checking was very high, but rarely independent. Primed double-checking was highly prevalent but compared with single-checking conferred no benefit in terms of reduced errors or severity. Our findings raise questions about if, when and how double-checking policies deliver safety benefits and warrant the considerable resource investments required in modern clinical settings. [ABSTRACT FROM AUTHOR]

Background: Many studies have explored the effect of electronic medication management systems (EMMS) on doctors' and nurses' work, but few have focused specifically on pharmacists' work. Aim: This study examined how implementation of a commercial EMMS affected the work of pharmacists in an Australian paediatric hospital. In particular, the study investigated whether any pharmacy tasks changed or were eliminated, or whether new tasks emerged following EMMS introduction. Methods: Two rounds of semistructured interviews with pharmacists, one 4 months and the other 1 year after EMMS implementation, were conducted. In total, 17 pharmacists were interviewed, comprising inpatient, outpatient and oncology pharmacists, as well as pharmacy managers. Results: EMMS implementation eliminated a small number of tasks, changed some tasks and created many new work tasks for pharmacists. These new tasks included helping doctors and nurses to use the EMMS, duplicated data entry and the review of additional information. Pharmacists held the view that their workload had increased and that additional pharmacists were necessary to cope with the new work requirements associated with the EMMS. Some problems were perceived to be the result of implementation of a US‐designed EMMS that did not fully support Australian pharmacy workflows. Conclusion: Implementation of an EMMS in a paediatric hospital affected pharmacists' work in a variety of ways, predominately by introducing new tasks. Anticipating how workflows will change with EMMS implementation is challenging. Undertaking regular reviews of workflow and planning for an increased burden on pharmacy staff is likely to improve the transition from paper to electronic medication management. [ABSTRACT FROM AUTHOR]

Aim: Intravenous immunoglobulin (IVIG) is an expensive therapy used in immunodeficiency and autoimmune disorders. Increasing demands and consequent shortages result in a need for usage to conform to guidelines.Method: We retrospectively evaluated IVIG use for neuroimmunological indications and adherence to existing guidelines in a major Australian paediatric hospital between 2000 and 2014.Results: One-hundred and ninety-six children (96 male, 100 female; mean age at disease onset 6y 5mo [range 3mo-15y 10mo], mean age at first IVIG dose 7y 2mo [range 3mo-16y 5mo]) received IVIG for neuroimmunological indications during the study period (28.1% had Guillain-Barré syndrome), representing 15.5% of all hospital indications. In total, 1669 IVIG courses were administered (total 57 221g, median 78g/patient, range 12-5748g). The highest median numbers of courses were in chronic inflammatory demyelinating polyneuropathies, opsoclonus-myoclonus ataxia syndrome, suspected immune-mediated epilepsies, and Rasmussen's encephalitis. Adverse reactions occurred in 25.5% of patients, but these were mostly minor. Outcome at follow-up was best in anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, Guillain-Barré syndrome, and myasthenia gravis, and worst in Rasmussen's encephalitis and epilepsies. The total cost of IVIG was US$2 595 907 (median $3538/patient, range $544-260 766). Of patients receiving IVIG, 45.4% to 57.1% were given the therapy for 'weak' indications or indications 'not listed' in international guidelines. Some entities commonly treated with IVIG in current practice, such as anti-NMDAR encephalitis and transverse myelitis, are not listed in most guidelines.Interpretation: Our study demonstrates that IVIG is generally well tolerated but expensive, and discloses discrepancies between guidelines and clinical practice in paediatric neurology, suggesting both the need for greater adherence to current recommendations, and for recommendations to be updated to accommodate emerging indications. [ABSTRACT FROM AUTHOR]