Stuart Gordon Nicholls

Background: Children with inherited metabolic diseases (IMDs) often have high care needs that require extensive involvement of family caregivers. This study aimed to describe caregiver experiences, including management of children’s needs at home, and the impacts of that management on family time, finances, and caregiver and child health-related quality of life (HRQoL). Methods: In this sub-study within a larger cohort study, participants were family caregivers of children ≤ 12 years old diagnosed with an IMD, from across Canada. We collected cross-sectional data using an online questionnaire consisting of validated measures and team-developed questions, and analyzed data descriptively. Results: Seventy-one caregivers participated and reported using a range of supports and interventions to care for their children with IMDs, with dietary supports being most common (77.1%). Twenty-seven participants (45%) reported spending ≥ 4 extra hours per week assisting their child with care supports at home and 28 reported ≥ 6 missed days of work by caregivers in the past year for IMD care. All participants reported fulfillment from caregiving tasks, although 82% reported mental struggles related to caregiving. Based on caregiver reports, children with IMDs had lower HRQoL relative to population normative data. We observed lower median scores for several HRQoL subscales among children with IMDs classified as progressive with multi-system involvement relative to other IMDs. Conclusion: We identified important impacts of IMD care for family caregivers. Relief from high levels of caregiving responsibility and time should be a priority for the development of healthcare policies and interventions, to improve health and well-being for both children and their caregivers.

Patient and public involvement (PPI) in the design and conduct of clinical trials has been increasingly encouraged by funders as an essential ingredient in

Background/Objectives: Patient and public involvement (PPI) in the design, conduct, and dissemination of pragmatic trials may make trial results more relevant and meaningful. The nature of PPI in paediatric pragmatic trials has been poorly characterized in the literature. This study examined the prevalence and nature of PPI in paediatric pragmatic trials and lessons learned from researchers’ experiences. Methods: For this mixed methods study, we conducted an online survey and semi-structured interviews with corresponding authors of published paediatric pragmatic trials, identified using an online search filter in MEDLINE. Descriptive statistics and qualitative thematic analysis were used to analyse the data. Results: PPI was reported by 71/127 (56%) survey respondents. Reported impacts of PPI in the survey included the following: more feasible interventions (71%), higher-quality research (57%), improved recruitment and retention (57%), and increased applicability of research findings (57%). Both survey and interview participants identified that insufficient resources, time, and training for relationship development were challenges to PPI in paediatric trials. Three themes were identified from the semi-structured interview data (recruitment and engagement, sustaining PPI relationships, and PPI value added). Conclusions: PPI aligns with the purpose and intended impact of pragmatic trials, and paediatric researchers perceive that PPI leads to increased research relevance, quality, and dissemination. There is, however, a need for institutional and funding bodies to invest in PPI partnership, including offering support for researchers and providing opportunities for children, youth, and parents as PPI partners.

Objective: To conduct a randomised, open label comparison of the effectiveness and safety of intravenous vernakalant and intravenous procainamide for the management of acute atrial fibrillation in the emergency department. Design: Randomised clinical trial (RAFF4 trial). Setting: 12 tertiary care emergency departments in Canada. Participants: Patients with acute atrial fibrillation for whom acute rhythm control was a safe option. Interventions: Patients were randomised (1:1) to an intravenous infusion of vernakalant or procainamide; when rapid conversion did not occur, patients were offered electrical cardioversion. Main outcomes and measures: The primary outcome was conversion to sinus rhythm within 30 minutes of drug infusion completion. Secondary outcomes included time to conversion to sinus rhythm and whether the patient required electrical cardioversion. Results: Of the 350 enrolled eligible patients, baseline characteristics were similar in the procainamide (n=172) and vernakalant (n=178) groups. For the primary outcome of conversion success, vernakalant was more effective (62.4% v 48.3%; adjusted absolute difference 15.0%, 95% confidence interval 4.6% to 25.0%, P=0.005; adjusted odds ratio 1.87, 95% confidence interval 1.2 to 2.9, P=0.006). With vernakalant, time to conversion was faster (21.8 v 44.7 minutes; mean difference −22.9, 95% confidence interval −29.9 to −16.0, Pv 44.2%; odds ratio 0.62, 95% confidence interval 0.39 to 0.96, P=0.033). Adverse events were similar in both groups, were generally mild and brief, and most patients were discharged home. Subgroup analysis strongly favoured vernakalant for conversion in patients younger than 70 years (73.3% v 47.2%; adjusted odds ratio 3.1, 95% confidence interval 1.7 to 5.5, P=0.001, interaction P=0.005). Conclusions: In this head-to-head comparison, vernakalant was superior to procainamide for patients with higher conversion rates and faster times to conversion. Therefore, vernakalant is a safe and highly effective intravenous alternative for the rapid cardioversion and discharge home of patients with acute atrial fibrillation. Trial registration: ClinicalTrials.gov NCT04485195

Background: Granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, are associated with bone pain, potentially impacting treatment adherence. This study hypothesized that a 5-day regimen of filgrastim would result in less bone pain than single-dose pegfilgrastim in patients receiving chemotherapy for early breast cancer. Methods: In this multicenter, open-label, randomized controlled trial, patients requiring prophylactic G-CSF during chemotherapy were randomly assigned 1:1 to receive either 5-day filgrastim or pegfilgrastim. The primary outcome was patient-reported bone pain, assessed as area under the curve of daily pain scores (0 = no pain to 10 = worst pain) over the first 5 days following G-CSF in cycle 1. Secondary outcomes included bone pain in cycles 2-4, febrile neutropenia, hospitalizations, chemotherapy delays, dose reductions, early discontinuations, chemotherapy-related deaths, health-related quality of life, and health-care resource utilization. Results: From June 2021 to March 2023, a total of 233 patients were randomly assigned, with 219 analyzed (110 filgrastim and 109 pegfilgrastim) after excluding those who withdrew before receiving treatment. Adjusting for stratification factors and prespecified baseline covariates using repeated measures linear regression, the mean area under the curve (0-40) for cycle 1 bone pain was 10.2 (11.2) for 5-day filgrastim and 10.2 (9.81) for pegfilgrastim, with an adjusted mean difference of 0.70 (95% confidence interval = 1.62 to 3.02; P = .556). Although no clinically significant differences were observed in most secondary outcomes, the 5-day filgrastim group exhibited a numerically higher incidence of febrile neutropenia (6.4% vs 0.9%, P = .065) and hospitalization (10.0% vs 3.7%, P = .106). Conclusion: There was no significant difference in bone pain between 5-day filgrastim and pegfilgrastim.