Developing a process to measure actual harm from medication errors in paediatric inpatients: From design to implementation.

AIMS: The potential harm associated with medication errors is widely reported, but data on actual harm are limited. When actual harm has been measured, assessment processes are often poorly described, limiting their ability to be reproduced by other studies. Our aim was to design and implement a new process to assess actual harm resulting from medication errors in paediatric inpatient care. METHODS: Prescribing errors were identified through retrospective medical record reviews (n = 26 369 orders) and medication administration errors through direct observation (n = 5137 administrations) in a tertiary paediatric hospital. All errors were assigned potential harm severity ratings on a 5-point scale. Multidisciplinary panels reviewed case studies for patients assigned the highest three potential severity ratings and determined the following: actual harm occurrence and severity level, plausibility of a link between the error(s) and identified harm(s) and a confidence rating if no harm had occurred. RESULTS: Multidisciplinary harm panels (n = 28) reviewed 566 case studies (173 prescribing related and 393 administration related) and found evidence of actual harm in 89 (prescribing = 22, administration = 67). Eight cases of serious harm cases were found (prescribing = 1, administration = 7) and no cases of severe harm. The panels were very confident in 65% of cases (n = 302) where no harm was found. Potential and actual harm ratings varied. CONCLUSIONS: This harm assessment process provides a systematic method for determining actual harm from medication errors. The multidisciplinary nature of the panels was critical in evaluating specific clinical, therapeutic and contextual considerations including care delivery pathways, therapeutic dose ranges and drug-drug and drug-disease interactions.

Gene therapy-based strategies for spinal muscular atrophy-an Asia-Pacific perspective.

Onasemnogene abeparvovec has been life-changing for children with spinal muscular atrophy (SMA), signifying the potential and progress occurring in gene- and cell-based therapies for rare genetic diseases. Hence, it is important that clinicians gain knowledge and understanding in gene therapy-based treatment strategies for SMA. In this review, we describe the development and translation of onasemnogene abeparvovec from clinical trials to healthcare practice and share knowledge on the facilitators and barriers to implementation. Rapid and accurate SMA diagnosis, awareness, and education to safely deliver gene therapy to eligible patients and access to expertise in multidisciplinary management for neuromuscular disorders are crucial for health system readiness. Early engagement and intersectoral collaboration are required to surmount complex logistical processes and develop policy, governance, and accountability. The collection and utilisation of real-world evidence are also an important part of clinical stewardship, informing ongoing improvements to care delivery and access. Additionally, a research-enabled clinical ecosystem can expand scientific knowledge and discovery to optimise future therapies and magnify health impacts. Important ethical, equity, economic, and sustainability issues are evident, for which we must connect globally.

Short- and long-term effects of an electronic medication management system on paediatric prescribing errors.

Electronic medication management (eMM) systems are designed to improve safety, but there is little evidence of their effectiveness in paediatrics. This study assesses the short-term (first 70 days of eMM use) and long-term (one-year) effectiveness of an eMM system to reduce prescribing errors, and their potential and actual harm. We use a stepped-wedge cluster randomised controlled trial (SWCRCT) at a paediatric referral hospital, with eight clusters randomised for eMM implementation. We assess long-term effects from an additional random sample of medication orders one-year post-eMM. In the SWCRCT, errors that are potential adverse drug events (ADEs) are assessed for actual harm. The study comprises 35,260 medication orders for 4821 patients. Results show no significant change in overall prescribing error rates in the first 70 days of eMM use (incident rate ratio [IRR] 1.05 [95%CI 0.92-1.21], but a 62% increase (IRR 1.62 [95%CI 1.28-2.04]) in potential ADEs suggesting immediate risks to safety. One-year post-eMM, errors decline by 36% (IRR 0.64 [95%CI 0.56-0.72]) and high-risk medication errors decrease by 33% (IRR 0.67 [95%CI 0.51-0.88]) compared to pre-eMM. In all periods, dose error rates are more than double that of other error types. Few errors are associated with actual harm, but 71% [95%CI 50-86%] of patients with harm experienced a dose error. In the short-term, eMM implementation shows no improvement in error rates, and an increase in some errors. A year after eMM error rates significantly decline suggesting long-term benefits. eMM optimisation should focus on reducing dose errors due to their high frequency and capacity to cause harm.

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy.

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.

Associations between double-checking and medication administration errors: a direct observational study of paediatric inpatients.

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 double-checking 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 double-checking, 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.

A national study of the processes and outcomes of paediatric formulary applications in Australia.

OBJECTIVE: To evaluate the processes by which pharmaceuticals are added to the formularies of Australian paediatric hospitals. DESIGN: Descriptive study of the processes and outcomes of all submissions to Australian paediatric hospital drug and therapeutics committees from 1 July 2010 to 31 December 2011. SETTING: All eight tertiary paediatric hospitals in Australia. PARTICIPANTS: Interviews with committee secretaries or delegates and document analysis. MAIN OUTCOME MEASURES: Total number of formulary applications, stratified by therapeutic class, approval rates for each hospital and quality of supporting information. RESULTS: One hundred and twenty applications were considered during the study period, with most applications approved (range, 67%-100%). Neurological agents were the most common therapeutic class considered. A conflict of interest was declared for 10 applications (8%). Forty-five (38%) were independently reviewed by a statewide medicines advisory committee or hospital pharmacist. Several committees approved identical applications during the period of review and with different outcomes. For applications submitted for new drugs or new indications (95 applications), supporting data included randomised controlled trials (37/95), case series (36/95), product information (34/95) and narrative reviews (29/95). Few applications (14/95) included a systematic review or meta-analysis. No application included an evaluation of the risk of bias of supporting studies. CONCLUSIONS: There is limited high-quality evidence informing paediatric hospital-based drug approvals. Approval processes vary considerably among institutions with substantial duplication of effort and variable outcomes. Resources and training appear insufficient given the technical complexity of submissions. A national, standardised approach to hospital-based drug evaluation could reduce overlap and improve decision making.

Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials.

BACKGROUND: Antiviral prophylaxis is commonly used in recipients of solid-organ transplants with the aim of preventing the clinical syndrome associated with cytomegalovirus infection. We undertook a systematic review to investigate whether this approach affects risks of cytomegalovirus disease and death. METHODS: Randomised controlled trials of prophylaxis with antiviral medications for cytomegalovirus disease in solid-organ-transplant recipients were identified. Data were combined in meta-analyses by a random-effects model. FINDINGS: Compared with placebo or no treatment, prophylaxis with aciclovir, ganciclovir, or valaciclovir significantly reduced the risks of cytomegalovirus disease (19 trials, 1981 patients; relative risk 0.42 [95% CI 0.34-0.52]), cytomegalovirus infection (17 trials, 1786 patients; 0.61 [0.48-0.77]), and all-cause mortality (17 trials, 1838 patients; 0.63 [0.43-0.92]), mainly owing to lower mortality from cytomegalovirus disease (seven trials, 1300 patients; 0.26 [0.08-0.78]). Prophylaxis also lowered the risks of disease caused by herpes simplex or zoster virus, bacterial infections, and protozoal infections, but not fungal infection, acute rejection, or graft loss. Meta-regression showed no significant difference in the risk of cytomegalovirus disease or all-cause mortality by organ transplanted or cytomegalovirus serostatus; no conclusions were possible for cytomegalovirus-negative recipients of negative organs. In trials of direct comparisons, ganciclovir was more effective than aciclovir in preventing cytomegalovirus disease. Valganciclovir and intravenous ganciclovir were as effective as oral ganciclovir. INTERPRETATION: Prophylaxis with antiviral medications reduces the risk of cytomegalovirus disease and associated mortality in recipients of solid-organ transplants. This approach should be used routinely in cytomegalovirus-positive recipients and in cytomegalovirus-negative recipients of organs positive for the virus.