Abstract INTRODUCTION Glioblastoma (GBM) standard treatment consists of maximum and safe surgical resection, followed by radiation therapy in combination with temozolomide. Some patients show radiological and/or clinical deterioration soon after radiotherapy treatment. Early MRI changes, in the first 3 months following radiation is considered pseudo-progression. After this initial period, changes are considered as tumor recurrence. However, cases of early radiological deterioration have been related to radionecrosis. When tumor progression is suspected on imaging, it may causes treatment withdrawal or change. Therefore, for a certain percentage of patients, effective treatment could be abandoned in the presence of radionecrosis. METHODS The aim of the study is to assess the prevalence of radionecrosis at the Hôpital de l'Enfant-Jésus. This is a retrospective, observational case-control study evaluating recurrent GBM patients who underwent a second resection surgery. RESULTS The charts of 110 GBM patients with second resection were retrospectively reviewed (men: 62%, mean age: 58.3 years). Among these patients, we observed 87 cases of GBM recurrence as compared to 23 cases of radionecrosis (21%). No statistically significant difference was observed between the two groups regarding demographics, survival, Karnofsky performance status, type of surgery and treatments received. However, in the radionecrosis group, decreases in time between the 2 surgeries (55.3 vs. 24.3 weeks, p = 0.006) and in the number of cycles of chemotherapy received (5.7 vs. 3.7 weeks, p = 0.004) were observed as compared to GBM group. CONCLUSIONS This study characterizes demographically the patients with second surgery for suspicion of GBM in order to better adapt the treatments. Clinical and radiological data could not differentiate radionecrosis from true tumor recurrence or progression. A prospective study will be carried out as a second step, in order to determine radiological or molecular factors that could predict the presence of radionecrosis.

BackgroundThis update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial—North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units.Methods/designProtocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials (https://doi.org/10.4172/2167-0870.1000284) and Trials (https://doi: 10.1186/s13063-019–3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis.Trial registrationClinical Trials.gov NCT02399267.

BackgroundPain management and early mobilization strategies are recommended in clinical practice guidelines for the prevention of delirium in older adults. However, available data on the implementation of these strategies in trauma are limited. AimsTo describe the use of pain management and early mobilization strategies in older adults at a level I trauma center, as well as the facilitators and barriers to their implementation. MethodsA convergent mixed methods study was used. Quantitative data were collected from sixty medical records. Qualitative data was collected through a focus group with healthcare providers to explore their perspectives regarding the use of the target practices and on barriers and facilitators to their implementation. Descriptive statistics were calculated, and a thematic analysis using an inductive and deductive interpretative descriptive approach was undertaken. ResultsA question on the presence/absence of pain was the most frequently documented pain assessment method. Pain assessment was poorly documented. Frequencies of non-opioid and opioid administrations were similar, but non-pharmacological strategies were not widely used. The first mobilization was performed quickly and was most commonly to a chair. The focus group discussion confirmed many of the data collected in the medical records. Barriers to implementing the targeted strategies were primarily related to organizational context and facilitation processes. ConclusionsAreas for improvement were identified including pain assessment, the use of non-pharmacological pain management strategies and ambulation as a mobilization strategy. Our findings will serve as a starting point for optimizing and adapting practices for geriatric trauma patients and evaluating their impact.

Adult trauma centers (ATCs) have been shown to decrease injury mortality and morbidity in major trauma, but a synthesis of evidence for pediatric trauma centers (PTCs) is lacking. To assess the effectiveness of PTCs compared with ATCs, combined trauma centers (CTCs), or nondesignated hospitals in reducing mortality and morbidity among children admitted to hospitals following trauma. MEDLINE, Embase, and Web of Science through March 2023. Studies comparing PTCs with ATCs, CTCs, or nondesignated hospitals for pediatric trauma populations (aged ≤19 years). This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. Pairs of reviewers independently extracted data and evaluated risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions tool. A meta-analysis was conducted if more than 2 studies evaluated the same intervention-comparator-outcome and controlled minimally for age and injury severity. Subgroup analyses were planned for age, injury type and severity, trauma center designation level and verification body, country, and year of conduct. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess certainty of evidence. Primary outcomes were mortality, complications, functional status, discharge destination, and quality of life. Secondary outcomes were resource use and processes of care, including computed tomography (CT) and operative management of blunt solid organ injury (SOI). A total of 56 studies with 286 051 participants were included overall, and 34 were included in the meta-analysis. When compared with ATCs, PTCs were associated with a 41% lower risk of mortality (OR, 0.59; 95% CI, 0.46-0.76), a 52% lower risk of CT use (OR, 0.48; 95% CI, 0.26-0.89) and a 64% lower risk of operative management for blunt SOI (OR, 0.36; 95% CI, 0.23-0.57). The OR for complications was 0.80 (95% CI, 0.41-1.56). There was no association for mortality for older children (OR, 0.71; 95% CI, 0.47-1.06), and the association was closer to the null when PTCs were compared with CTCs (OR, 0.73; 95% CI, 0.53-0.99). Results remained similar for other subgroup analyses. GRADE certainty of evidence was very low for all outcomes. In this systematic review and meta-analysis, results suggested that PTCs were associated with lower odds of mortality, CT use, and operative management for SOI than ATCs for children admitted to hospitals following trauma, but certainty of evidence was very low. Future studies should strive to address selection and confounding biases.

Lack of adherence to recommendations on pediatric orthopaedic injury care may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aimed to identify CPGs for pediatric orthopaedic injury care, appraise their quality, and synthesize the quality of evidence and the strength of associated recommendations. We searched Medline, Embase, Cochrane CENTRAL, Web of Science and websites of clinical organizations. CPGs including at least one recommendation targeting pediatric orthopaedic injury populations on any diagnostic or therapeutic intervention developed in the last 15 years were eligible. Pairs of reviewers independently extracted data and evaluated CPG quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. We synthesized recommendations from high-quality CPGs using a recommendations matrix based on the GRADE Evidence-to-Decision framework. We included 13 eligible CPGs, of which 7 were rated high quality. Lack of stakeholder involvement and applicability (i.e., implementation strategies) were identified as weaknesses. We extracted 53 recommendations of which 19 were based on moderate or high-quality evidence. We provide a synthesis of recommendations from high-quality CPGs that can be used by clinicians to guide treatment decisions. Future CPGs should aim to use a partnership approach with all key stakeholders and provide strategies to facilitate implementation. This study also highlights the need for more rigorous research on pediatric orthopaedic trauma. Level II-therapeutic study.

Alzheimer's disease (AD) is experienced by > 600,000 Canadians. Disease-modifying therapies (DMTs) for earlier stages of disease are in development. Existing health system capacity constraints and the need for biomarker-driven diagnostics to confirm DMT eligibility are concerning. This study aimed to characterize the capacity gap related to early AD (eAD) treatment with DMTs in Canada. A capacity model was developed to simulate the flow of a patient from screening to treatment for eAD to quantify the gap between available and required healthcare resources and qualify the bottlenecks restricting the patient journey at a provincial and national level. The model inputs (epidemiological, human resource, and clinical) were evidence-based, healthcare professional-, and patient advocate-informed. The model estimated that nationally < 2% of patients would have access to the required healthcare resources for treatment with a DMT. Eligibility assessment represented the step with the largest capacity gap across all provinces, with a wait list of about 382,000 Canadians one year following DMT introduction. The top three resource gaps included AD specialist time and positron emission tomography and magnetic resonance imaging exam slots. Sensitivity analysis showed that full reliance on cerebrospinal fluid for eligibility testing increased capacity for assessment by about 47,000 patients. This model highlights that the Canadian health system is critically under-resourced to diagnose, assess, and treat patients with eAD with DMT. It underscores an urgent need for national policy and provincial resource allocation to close the gap.

COA8-related leukoencephalopathy is a recently described rare cavitating leukoencephalopathy caused by biallelic variants in the COA8 gene. Clinically, it presents heterogeneously and usually follows a bi-phasic clinical course with a period of acute onset and regression, followed by stabilization, and in some cases, even subtle improvement. We present a 4-year-old boy with a homozygous 2.5 kilobase pair deletion in the COA8 gene following a severe neurological deterioration resulting in death weeks after onset. Brain MRI revealed a distinctive pattern of cavitating leukodystrophy predominantly involving the posterior cerebral white matter which improved upon a follow-up MRI a month later. Brain pathology displayed overall white matter destruction with gliosis and infiltration by macrophages. There was preservation of astrocytes around blood vessels and axons around the zones of demyelination. This study is the first neuropathological examination of COA8-related leukoencephalopathy and provides further characterization of the clinical and MRI phenotype.

BackgroundWhile simple Audit & Feedback (A&F) has shown modest effectiveness in reducing low-value care, there is a knowledge gap on the effectiveness of multifaceted interventions to support de-implementation efforts. Given the need to make rapid decisions in a context of multiple diagnostic and therapeutic options, trauma is a high-risk setting for low-value care. Furthermore, trauma systems are a favorable setting for de-implementation interventions as they have quality improvement teams with medical leadership, routinely collected clinical data, and performance-linked to accreditation. We aim to evaluate the effectiveness of a multifaceted intervention for reducing low-value clinical practices in acute adult trauma care.MethodsWe will conduct a pragmatic cluster randomized controlled trial (cRCT) embedded in a Canadian provincial quality assurance program. Level I–III trauma centers (n = 30) will be randomized (1:1) to receive simple A&F (control) or a multifaceted intervention (intervention). The intervention, developed using extensive background work and UK Medical Research Council guidelines, includes an A&F report, educational meetings, and facilitation visits. The primary outcome will be the use of low-value initial diagnostic imaging, assessed at the patient level using routinely collected trauma registry data. Secondary outcomes will be low-value specialist consultation, low-value repeat imaging after a patient transfer, unintended consequences, determinants for successful implementation, and incremental cost-effectiveness ratios.DiscussionOn completion of the cRCT, if the intervention is effective and cost-effective, the multifaceted intervention will be integrated into trauma systems across Canada. Medium and long-term benefits may include a reduction in adverse events for patients and an increase in resource availability. The proposed intervention targets a problem identified by stakeholders, is based on extensive background work, was developed using a partnership approach, is low-cost, and is linked to accreditation. There will be no attrition, identification, or recruitment bias as the intervention is mandatory in line with trauma center designation requirements, and all outcomes will be assessed with routinely collected data. However, investigators cannot be blinded to group allocation and there is a possibility of contamination bias that will be minimized by conducting intervention refinement only with participants in the intervention arm.Trial registrationThis protocol has been registered on ClinicalTrials.gov (February 24, 2023, #NCT05744154).

Most North American trauma systems have designated trauma centres (TCs) including level I (ultraspecialized high-volume metropolitan centres), level II (specialized medium-volume urban centres), and/or level III (semirural or rural centres). Trauma system configuration varies across provinces and it is unclear how these differences influence patient distributions and outcomes. We aimed to compare patient case mix, case volumes, and risk-adjusted outcomes of adults with major trauma admitted to designated level I, II, and III TCs across Canadian trauma systems. In a national historical cohort study, we extracted data from Canadian provincial trauma registries on major trauma patients treated between 2013 and 2018 in all designated level I, II, or III TCs in British Columbia, Alberta, Quebec, and Nova Scotia; level I and II TCs in New Brunswick; and four TCs in Ontario. We used multilevel generalized linear models to compare mortality and intensive care unit (ICU) admission and competitive risk models for hospital and ICU length of stay (LOS). Ontario could not be included in outcome comparisons because there were no population-based data from this province. The study sample comprised 50,959 patients. Patient distributions in level I and II TCs were similar across provinces but we observed significant differences in case mix and volumes for level III TCs. There was low variation in risk-adjusted mortality and LOS across provinces and TCs but interprovincial and intercentre variation in risk-adjusted ICU admission was high. Our results suggest that differences in the functional role of TCs according to their designation level across provinces leads to significant variations in the distribution of patients, case volumes, resource use, and clinical outcomes. These results highlight opportunities to improve Canadian trauma care and underline the need for standardized population-based injury data to support national quality improvement efforts.