Implementation of an audit and feedback module targeting low-value clinical practices in a provincial trauma quality assurance program: a cost-effectiveness study.

BACKGROUND: Audit and Feedback (A&F) interventions based on quality indicators have been shown to lead to significant improvements in compliance with evidence-based care including de-adoption of low-value practices (LVPs). Our primary aim was to evaluate the cost-effectiveness of adding a hypothetical A&F module targeting LVPs for trauma admissions to an existing quality assurance intervention targeting high-value care and risk-adjusted outcomes. A secondary aim was to assess how certain A&F characteristics might influence its cost-effectiveness. METHODS: We conducted a cost-effectiveness analysis using a probabilistic static decision analytic model in the Québec trauma care continuum. We considered the Québec Ministry of Health perspective. Our economic evaluation compared a hypothetical scenario in which the A&F module targeting LVPs is implemented in a Canadian provincial trauma quality assurance program to a status quo scenario in which the A&F module is not implemented. In scenarios analyses we assessed the impact of A&F characteristics on its cost-effectiveness. Results are presented in terms of incremental costs per LVP avoided. RESULTS: Results suggest that the implementation of A&F module (Cost = $1,480,850; Number of LVPs = 6,005) is associated with higher costs and higher effectiveness compared to status quo (Cost = $1,124,661; Number of LVPs = 8,228). The A&F module would cost $160 per LVP avoided compared to status quo. The A&F module becomes more cost-effective with the addition of facilitation visits; more frequent evaluation; and when only high-volume trauma centers are considered. CONCLUSION: A&F module targeting LVPs is associated with higher costs and higher effectiveness than status quo and has the potential to be cost-effective if the decision-makers' willingness-to-pay is at least $160 per LVP avoided. This likely represents an underestimate of true ICER due to underestimated costs or missed opportunity costs. Results suggest that virtual facilitation visits, frequent evaluation, and implementing the module in high-volume centers can improve cost-effectiveness.

The current state of knowledge on care for co-occurring chronic pain and opioid use disorder: A scoping review.

BACKGROUND AND AIMS: Opioid use disorder often co-occurs with chronic pain but assessment and treatment of these co-occurring disorders is complex. This review aims to identify current treatments and delivery models for co-occurring chronic pain and opioid use disorder (OUD) documented in the scientific literature. DESIGN: Scoping review. METHODS: The review was conducted in six databases in June 2022 (no time limit): CINAHL, PsycINFO, Web of Science, Cochrane, PubMed and Embase. The PRISMA-ScR checklist was used to guide reporting. RESULTS: Forty-seven publications addressing the issue of co-occurring chronic pain and OUD management were included. Randomized controlled trials provide evidence for the effectiveness of opioid agonist treatments (OAT) such as methadone or buprenorphine/naloxone, as well as for combining OAT with Mindfulness-Oriented Recovery Enhancement or cognitive behavioural therapy. A number of other pharmacological treatments (opioid and nonopioid), nonpharmacological treatments (e.g. physiotherapy) and service delivery models (e.g. simultaneous treatment of comorbidities, interdisciplinary and interprofessional collaboration) are also underlined. In most cases, authors recommend a combination of strategies to meet patient needs. CONCLUSIONS: The scoping review reveals gaps in evidence-based knowledge to effectively care for co-occurring chronic pain and OUD, but several experts recommend the uptake of known 'best' practices such as integrated treatment of the multiple biopsychosocial dimensions of the co-occurring disorders as well as collaborative interdisciplinary work. CLINICAL RELEVANCE: Improving services is dependent on alleviating barriers such as working in silos, the costs associated with nonpharmacological treatments, and the double stigma associated with pain in people with a substance use disorder.

Clinical practice guideline recommendations to improve the mental health of adult trauma patients: protocol for a systematic review.

INTRODUCTION: Mental disorders are common in adult patients with traumatic injuries. To limit the burden of poor psychological well-being in this population, recognised authorities have issued recommendations through clinical practice guidelines (CPGs). However, the uptake of evidence-based recommendations to improve the mental health of trauma patients has been low until recently. This may be explained by the complexity of optimising mental health practices and interpretating CGPs scope and quality. Our aim is to systematically review CPG mental health recommendations in the context of trauma care and appraise their quality. METHODS AND ANALYSIS: We will identify CPG through a search strategy applied to Medline, Embase, CINAHL, PsycINFO and Web of Science databases, as well as guidelines repositories and websites of trauma associations. We will target CPGs on adult and acute trauma populations including at least one recommendation on any prevention, screening, assessment, intervention, patient and family engagement, referral or follow-up procedure related to mental health endorsed by recognised organisations in high-income countries. No language limitations will be applied, and we will limit the search to the last 15 years. Pairs of reviewers will independently screen titles, abstracts, full texts, and carry out data extraction and quality assessment of CPGs using the Appraisal of Guidelines Research and Evaluation (AGREE) II. We will synthesise the evidence on recommendations for CPGs rated as moderate or high quality using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation quality of evidence, strength of recommendation, health and social determinants and whether recommendations were made using a population-based approach. ETHICS AND DISSEMINATION: Ethics approval is not required, as we will conduct secondary analysis of published data. The results will be disseminated in a peer-reviewed journal, at international and national scientific meetings. Accessible summary will be distributed to interested parties through professional, healthcare quality and persons with lived experience associations. PROSPERO REGISTRATION NUMBER: (ID454728).

Social determinants of health and disparities in pediatric trauma care: protocol for a systematic review and meta-analysis.

BACKGROUND: Social determinants of health (SDH), including "the conditions in which individuals are born, grow, work, live and age" affect child health and well-being. Several studies have synthesized evidence about the influence of SDH on childhood injury risks and outcomes. However, there is no systematic evidence about the impact of SDH on accessing care and quality of care once a child has suffered an injury. We aim to evaluate the extent to which access to care and quality of care after injury are affected by children and adolescents' SDH. METHODS: Using Cochrane methodology, we will conduct a systematic review including observational and experimental studies evaluating the association between social/material elements contributing to health disparities, using the PROGRESS-Plus framework: place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, and social capital and care received by children and adolescents (≤ 19 years of age) after injury. We will consult published literature using PubMed, EMBASE, CINAHL, PsycINFO, Web of Science, and Academic Search Premier and grey literature using Google Scholar from their inception to a maximum of 6 months prior to submission for publication. Two reviewers will independently perform study selection, data extraction, and risk of bias assessment for included studies. The risk of bias will be assessed using the ROBINS-E and ROB-2 tools respectively for observational and experimental study designs. We will analyze data to perform narrative syntheses, and if enough studies are identified, we will conduct a meta-analysis using random effects models. DISCUSSION: This systematic review will provide a synthesis of evidence on the association between SDH and pediatric trauma care (access to care and quality of care) that clinicians and policymakers can use to better tailor care systems and promote equitable access and quality of care for all children. We will share our findings through clinical rounds, conferences, and publication in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023408467.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient's experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers. RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number. CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias. STUDY REGISTRATION: OSF - https://osf.io/7kea3.

Effectiveness of dexmedetomidine during surgery under general anaesthesia on patient-centred outcomes: a systematic review and Bayesian meta-analysis protocol.

INTRODUCTION: Dexmedetomidine is a promising pharmaceutical strategy to minimise opioid use during surgery. Despite its growing use, it is uncertain whether dexmedetomidine can improve patient-centred outcomes such as quality of recovery and pain. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL approximately in October 2023. We will include randomised controlled trials evaluating the impact of systemic intraoperative dexmedetomidine on patient-centred outcomes. Patient-centred outcome definition will be based on the consensus definition established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC). Our primary outcome will be the quality of recovery after surgery. Our secondary outcomes will be patient well-being, function, health-related quality of life, life impact, multidimensional assessment of postoperative acute pain, chronic pain, persistent postoperative opioid use, opioid-related adverse events, hospital length of stay and adverse events. Two reviewers will independently screen and identify trials and extract data. We will evaluate the risk of bias of trials using the Cochrane Risk of Bias Tool (RoB 2.0). We will synthesise data using a random effects Bayesian model framework, estimating the probability of achieving a benefit and its clinical significance. We will assess statistical heterogeneity with the tau-squared and explore sources of heterogeneity with meta-regression. We have involved patient partners, clinicians, methodologists, and key partner organisations in the development of this protocol, and we plan to continue this collaboration throughout all phases of this systematic review. ETHICS AND DISSEMINATION: Our systematic review does not require research ethics approval. It will help inform current clinical practice guidelines and guide development of future randomised controlled trials. The results will be disseminated in open-access peer-reviewed journals, presented at conferences and shared among collaborators and networks. PROSPERO REGISTRATION NUMBER: CRD42023439896.

Predictors of adverse outcomes in elders hospitalised for isolated orthopaedic trauma: a multicentre cohort study.

BACKGROUND: Patients >64 years of age now represent more than 51% of injury hospitalisations in Canada. The tools used to identify older patients who could benefit the most from an interdisciplinary approach include complex parameters difficult to collect in the ED, which suggests that better tools with higher accuracy and using items that can be derived from routinely collected data are needed. We aimed to identify variables that are associated with adverse outcomes in older patients admitted to a trauma centre for an isolated orthopaedic injury. METHODS: We conducted a multicentre retrospective cohort study between 1 April 2013 and 31 March 2019 on older patients hospitalised with a primary diagnosis of isolated orthopaedic injury (n=19 928). Data were extracted from the provincial trauma registry (Registre des traumatismes du Québec). We used multilevel logistic regression to estimate the associations between potential predictors and adverse outcomes (extended length of stay, mortality, complications, unplanned readmission and adverse discharge destination). RESULTS: Increasing age, male sex, specific comorbidities, type of orthopaedic injuries, increasing number of comorbidities, severe orthopaedic injury, head injuries and admission in the year before the injury were all significant predictors of adverse outcomes. CONCLUSION: We identified eight predictors of adverse outcomes in patients >64 years of age admitted to a trauma centre for orthopaedic injury. These variables could eventually be used to develop a clinical decision rule to identify elders who may benefit the most from interdisciplinary care.

Level of implementation of pain management and early mobilization strategies to prevent delirium in geriatric trauma patients: A mixed-methods study.

BACKGROUND: Pain 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. AIMS: To 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: Areas 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.

Current trauma team activation processes at Canadian trauma centres: A national survey.

BACKGROUND: Trauma team activation (TTA) allows the provision of specialized and timely care to improve outcomes for severely injured patients. Limited information is available on the current state of TTA in Canadian trauma centres (TC). Study objectives were to describe TTA processes, data and reports, along with the challenges and successes from a national perspective. METHODS: A mixed-methods, cross-sectional survey was undertaken with Canadian trauma leadership, utilizing a total population sampling strategy. The questionnaire, containing 108-items, was administered online between February-April 2022, utilizing a modified Dillman technique. Descriptive statistics and thematic analyses were performed. RESULTS: Trauma leaders from 9 out of 10 provinces responded for a response rate of 68% (32/47). Two-thirds (67%) of respondents worked in adult TC; 63% in a level I center. A higher proportion of pediatric TC had a two-tiered TT response (60% pediatric; 35% adult). The most common criteria were neurologic compromise (100% one-level TTA) and hypotension (pediatric: 100% one-level, 100% tier 1; adult: 92% one-level, 86% tier 1). All one-level TTA included penetrating trauma criteria. One-third of respondents reported using TTA subgroup criteria for pediatric, pregnant, and/or geriatric patients. There was variability with disciplines responding to TTA, with largest, most comprehensive teams for tier 1. Two-thirds of TC review activation compliance (under/overtriage), while 55% focus on non-compliance and reasons for missed TTA. The most frequent challenges related to TTA practices were reliable data collection (60%) while successes included were the establishment of TTA guidelines to improve team compliance (33%) and RN initiated TTA. CONCLUSIONS: Some TTA practices were similar among Canadian TC, while others showed variability. Findings provide opportunities for improvement, including a two-tier system, geriatric-specific criteria, and RN initiated TTA, and could help establish national standards and best practices. Compliance with standards has the potential to improve Canadian TTA practices and patient outcomes.

Clinical Practice Guideline Recommendations in Pediatric Mild Traumatic Brain Injury: A Systematic Review.

STUDY OBJECTIVE: Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. RESULTS: We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. CONCLUSIONS: We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.

Pediatric vs Adult or Mixed Trauma Centers in Children Admitted to Hospitals Following Trauma: A Systematic Review and Meta-Analysis.

Importance: 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. Objective: 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. Data Sources: MEDLINE, Embase, and Web of Science through March 2023. Study Selection: Studies comparing PTCs with ATCs, CTCs, or nondesignated hospitals for pediatric trauma populations (aged ≤19 years). Data Extraction and Synthesis: 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. Main Outcome(s) and Measure(s): 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). Results: 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. Conclusions and Relevance: 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.

Adaptation and Validation of the Standardized Swallowing Assessment Tool for Patients With Moderate-Severe Traumatic Brain Injury and Cervical Spinal Cord Injury.

Oropharyngeal dysphagia is common in moderate-severe traumatic brain injury (TBI) and cervical spinal cord injury (SCI) patients and can have serious consequences. Delaying feeding in these patients can also be detrimental. Nonetheless, the psychometric properties of screening tools that can promptly identify dysphagia have never been tested in these neurotrauma populations. This study aimed to: (1) adapt, translate, and validate the content of the French-Canadian version of the the Standardized Swallowing Assessment (SSA) tool to meet the needs of moderate-severe TBI and cervical SCI patients, (2) examine its inter-rater reliability and criterion-concurrent validation, and (3) evaluate its clinical utility from the perspectives of critical care nurses. The SSA tool was adapted and translated using an integrated method for the cultural adaptation and translation of tools. Eleven experts participated in the adaptation of the SSA tool, which led to the clarification of one item, as well as a new step and instructions for the screening procedure. Content validation (i.e., item and scale relevance) was evaluated by multidisciplinary team members (n = 17). The mean content validity index (CVI) score was 0.97 for the entire scale, while the mean CVI scores for individual items ranged from 0.82 to 1.0. A total of 60 neurotrauma patients were enrolled for inter-rater reliability and criterion-concurrent validation. Interrater reliability was determined by comparing two scores: one score from nurses responsible for the care of enrolled patients and one score from the research nurse. The weighted kappa coefficients for inter-rater reliability were 0.86 for moderate-severe TBI patients (n = 30) and 0.73 for cervical SCI patients (n = 30). A speech language therapist (SLT) also assessed dysphagia and results were used as the standard clinical reference criterion to determine concurrent validity (sensibility and specificity) of the adapted SSA tool. The sensitivity and specificity were 92% and 50% for moderate-severe TBI, and 77% and 75% for cervical SCI, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 65% and 87% in TBI patients, and 75% and 76% in SCI patients. Test accuracy was 71% and 77% for these same groups. The clinical utility of the tool was evaluated according to the following domains: appropriateness, accessibility of the required material, applicability, perceived effectiveness, and acceptability. Acceptability was the only domain with a level of agreement <80% (74%) among trauma critical care nurses (n = 49). Findings support the content validation and inter-rater reliability of the adapted French-Canadian version of the SSA tool in moderate-severe TBI and cervical SCI patients. Sensitivity was acceptable in both groups, but the specificity was lower, especially in moderate-severe TBI patients. Further validation of the adapted French-Canadian version of the SSA tool is needed in neurotrauma patients to confirm these results and to ensure safe dysphagia screening while avoiding oral feeding deferrals.

Clinical Practice Guideline Recommendations in Pediatric Orthopaedic Injury: A Systematic Review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 OF EVIDENCE: Level II-therapeutic study.

Development and characterization of a plant-derived norovirus-like particle vaccine.

BACKGROUND: Norovirus (NoV) is the most common cause of diarrheal episodes globally. Issues with in vitro cultivation systems, genetic variation, and animal models have hindered vaccine development. Plant-derived virus-like particles (VLPs) may address some of these concerns because they are highly immunogenic, can be administered by different routes, and can be rapidly produced to accommodate emerging viral strains. METHODS: NoV VLPs (NoVLP) composed of the surface viral protein (VP) 1 of the GI and GII genogroups were produced in Nicotiana benthamiana using an Agrobacterium tumefaciens-based recombinant transient expression system. Leaves from infiltrated plants were harvested and NoVLPs were extracted and purified. The safety and immunogenicity of the GII.4 NoVLP, the genotype currently causing most human disease, were subsequently examined in rabbits and mice. RESULTS: Fifteen GI and GII NoVLPs were successfully expressed in N. benthamiana and were structurally similar to NoV virions, as determined by cryogenic transmission electron microscopy. The NoVLP was well-tolerated, with no local or systemic signs of toxicity in rabbits. Three intramuscular doses of the GII.4 NoVLP adjuvanted with aluminum hydroxide induced robust IgG titers, IgG-secreting cells, histo-blood group antigen blocking titers, and IFNγ-secreting T cells in mice. In addition to circulating antibodies, oral administration of the NoVLP in mice induced significant IgA levels in feces, indicative of a mucosal response. CONCLUSIONS: The plant-made NoVLP vaccine was safe and immunogenic in mice and rabbits. Multi-modal vaccination, combining oral and intramuscular administration could be considered for future clinical development to maximize systemic and mucosal immune responses.

Evaluating the effectiveness of a multifaceted intervention to reduce low-value care in adults hospitalized following trauma: a protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: While 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. METHODS: We 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. DISCUSSION: On 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 REGISTRATION: This protocol has been registered on ClinicalTrials.gov (February 24, 2023, # NCT05744154 ).

Clinical practice guideline recommendations for pediatric solid organ injury care: A Systematic Review.

BACKGROUND: Observed variations in the management of pediatric solid organ injuries (SOIs) may be due to difficulty in finding and integrating recommendations from multiple clinical practice guidelines (CPGs) with heterogeneous methodological approaches. We aimed to systematically review CPG recommendations for pediatric SOIs. METHODS: We conducted a systematic review of CPGs including at least one recommendation targeting pediatric SOI populations, using Medical Analysis and Retrieval System Online, Excerpta Medica dataBASE, Web of Science, and websites of clinical organizations. Pairs of reviewers independently assessed eligibility, extracted data, and evaluated the quality of CPGs using the Appraisal of Guidelines Research and Evaluation II tool. We synthesized recommendations from moderate to high-quality CPGs using a recommendations matrix based on Grades of Recommendation, Assessment, Development, and Evaluation criteria. RESULTS: We identified eight CPGs, including three rated moderate or high quality. Methodological weaknesses included lack of stakeholder involvement beyond surgeons, consideration of applicability (e.g., implementation tools), and clarity around the definition of pediatric populations. Five of the 15 recommendations from moderate to high-quality CPGs were based on moderate quality evidence or were rated as strong; these reflected nonoperative management and angioembolization for renal injuries and required length of stay for liver and spleen injuries. CONCLUSION: We identified 15 recommendations on pediatric SOI management from 3 moderate or high-quality CPGs, but only one third were based on at least moderate-quality evidence or were rated as strong. Our results prompt the following recommendations for future CPG development or updates: (1) include all types of clinicians involved in the care of pediatric SOIs and patient and family representatives in the process, (2) develop clear definitions of the target population, and (3) provide advice and tools to promote implementation. Results also underline the urgent need for more rigorous research to support strong evidence-based recommendations in this population. LEVEL OF EVIDENCE: Systematic Review/Meta-analysis; Level III.

Clinical Practice Guideline Recommendations For Pediatric Multisystem Trauma Care: A Systematic Review.

OBJECTIVE: To systematically review clinical practice guidelines (CPGs) for pediatric multisystem trauma, appraise their quality, synthesize the strength of recommendations and quality of evidence, and identify knowledge gaps. BACKGROUND: Traumatic injuries are the leading cause of death and disability in children, who require a specific approach to injury care. Difficulties integrating CPG recommendations may cause observed practice and outcome variation in pediatric trauma care. METHODS: We conducted a systematic review using Medline, Embase, Cochrane Library, Web of Science, ClinicalTrials, and grey literature, from January 2007 to November 2022. We included CPGs targeting pediatric multisystem trauma with recommendations on any acute care diagnostic or therapeutic interventions. Pairs of reviewers independently screened articles, extracted data, and evaluated the quality of CPGs using "Appraisal of Guidelines, Research, and Evaluation II." RESULTS: We reviewed 19 CPGs, and 11 were considered high quality. Lack of stakeholder engagement and implementation strategies were weaknesses in guideline development. We extracted 64 recommendations: 6 (9%) on trauma readiness and patient transfer, 24 (38%) on resuscitation, 22 (34%) on diagnostic imaging, 3 (5%) on pain management, 6 (9%) on ongoing inpatient care, and 3 (5%) on patient and family support. Forty-two (66%) recommendations were strong or moderate, but only 5 (8%) were based on high-quality evidence. We did not identify recommendations on trauma survey assessment, spinal motion restriction, inpatient rehabilitation, mental health management, or discharge planning. CONCLUSIONS: We identified 5 recommendations for pediatric multisystem trauma with high-quality evidence. Organizations could improve CPGs by engaging all relevant stakeholders and considering barriers to implementation. There is a need for robust pediatric trauma research, to support recommendations.

Pediatric Moderate and Severe Traumatic Brain Injury: A Systematic Review of Clinical Practice Guideline Recommendations.

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE®, Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.

Educational needs and preferences of adult patients with acute or chronic pain: a mixed methods systematic review protocol.

OBJECTIVES: This review will aim to synthesize the available quantitative and qualitative evidence on the educational needs and preferences of adult patients with acute or chronic pain. INTRODUCTION: Acute and chronic pain are prevalent problems and are associated with significant individual and societal consequences. Education is a critical component of pain management. However, the impact of educational interventions on pain outcomes remains limited. The lack of patient input--what patients want to know and how they want to be informed--is one of the main issues underlying intervention design. INCLUSION CRITERIA: We will include qualitative, quantitative, and mixed methods studies describing the educational needs and preferences of adult patients with acute or chronic pain. METHODS: This review will follow the JBI guidelines for mixed methods systematic reviews. We will search MEDLINE (PubMed), Embase (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and ProQuest Dissertations and Theses. The search strategy will commence from the year 1990 onward and there will be no language restrictions. The retrieved titles, abstracts, and full-text reports will be screened by pairs of independent reviewers. These pairs of reviewers will also independently extract data using the JBI tools for mixed methods systematic reviews. Methodological quality will be assessed using the mixed methods appraisal tool. A convergent integrated approach to synthesis and integration of the quantitative and qualitative data will be used. REVIEW REGISTRATION: PROSPERO CRD42022303834.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review protocol.

INTRODUCTION: For close to a century opioid administration has been a standard of care to complement anaesthesia during surgery. Considering the worldwide opioid epidemic, this practice is now being challenged and there is a growing use of systemic pharmacological opioid minimising strategies. Our aim is to conduct a scoping review that will examine clinical trials that have evaluated the impact of intraoperative opioid minimisation strategies on patient-centred outcomes and identify promising strategies. METHODS AND ANALYSIS: Our scoping review will follow the framework developed by Arksey and O'Malley. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL from their inception approximately in March 2023. We will include randomised controlled trials, assessing the impact of systemic intraoperative pharmacologic opioid minimisation strategies on patient-centred outcomes. We define an opioid minimisation strategy as any non-opioid drug with antinociceptive properties administered during the intraoperative period. Patient-centred outcomes will be defined and classified based on the consensus definitions established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC group) and informed by knowledge users and patient partners. We will use a coproduction approach involving interested parties. Our multidisciplinary team includes knowledge users, patient partners, methodologists and knowledge user organisations. Knowledge users will provide input on methods, outcomes, clinical significance of findings, implementation and feasibility. Patient partners will participate in assessing the relevance of our design, methods and outcomes and help to facilitate evidence translation. We will provide a thorough description of available clinical trials, compare their reported patient-centred outcome measures with established recommendations and identify promising strategies. ETHICS AND DISSEMINATION: Ethics approval is not required for the review. Our scoping review will inform future research including clinical trials and systematic reviews through identification of important intraoperative interventions. Results will be disseminated through a peer-reviewed publication, presentation at conferences and through our network of knowledge user collaborators. REGISTRATION: Open Science Foundation (currently embargoed).