Primate-specific ORF0 contributes to retrotransposon-mediated diversity.

LINE-1 retrotransposons are fast-evolving mobile genetic entities that play roles in gene regulation, pathological conditions, and evolution. Here, we show that the primate LINE-1 5'UTR contains a primate-specific open reading frame (ORF) in the antisense orientation that we named ORF0. The gene product of this ORF localizes to promyelocytic leukemia-adjacent nuclear bodies. ORF0 is present in more than 3,000 loci across human and chimpanzee genomes and has a promoter and a conserved strong Kozak sequence that supports translation. By virtue of containing two splice donor sites, ORF0 can also form fusion proteins with proximal exons. ORF0 transcripts are readily detected in induced pluripotent stem (iPS) cells from both primate species. Capped and polyadenylated ORF0 mRNAs are present in the cytoplasm, and endogenous ORF0 peptides are identified upon proteomic analysis. Finally, ORF0 enhances LINE-1 mobility. Taken together, these results suggest a role for ORF0 in retrotransposon-mediated diversity.

Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis.

Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age-dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age-related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age-related anxiety-like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation.

Identification and Management of Pelvic Fractures in Prehospital and Emergency Department Settings.

INTRODUCTION: This study aims to describe the characteristics of patients with a pelvic fracture treated at a level 1 trauma center, the proportion of prehospital undertriage and the use of pelvic circumferential compression device (PCCD). METHODS: This is a retrospective cohort study. Prehospital and inhospital medical records of adults (≥16 y old) with a pelvic fracture who were treated at Hopital de l'Enfant-Jesus-CHU de Québec (Quebec City, Canada), a university-affiliated level 1 trauma center, between September 01, 2017 and September 01, 2021 were reviewed. Isolated hip or pubic ramus fracture were excluded. Data are presented using proportions and means with standard deviations. RESULTS: A total of 228 patients were included (males: 62.3%; mean age: 54.6 [standard deviation 21.1]). Motor vehicle collision (47.4%) was the main mechanism of injury followed by high-level fall (21.5%). Approximately a third (34.2%) needed at least one blood transfusion. Compared to those admitted directly, transferred patients were more likely to be male (73.0% versus 51.3%, P < 0.001) and to have a surgical procedure performed at the trauma center (71.3% versus 46.9%, P < 0.001). The proportion of prehospital undertriage was 22.6%. Overall, 17.1% had an open-book fracture and would have potentially benefited from a prehospital PCCD. Forty-six transferred patients had a PCCD applied at the referral hospital of which 26.1% needed adjustment. CONCLUSIONS: Pelvic fractures are challenging to identify in the prehospital environment and are associated with a high undertriage of 22.6%. Reducing undertriage and optimizing the use of PCCD are key opportunities to improve care of patients with a pelvic fracture.

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.

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.

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.

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.

Identification of bona fide B2 SINE retrotransposon transcription through single-nucleus RNA-seq of the mouse hippocampus.

Currently, researchers rely on generalized methods to quantify transposable element (TE) RNA expression, such as RT-qPCR and RNA-seq, that do not distinguish between TEs expressed from their own promoter (bona fide) and TEs that are transcribed from a neighboring gene promoter such as within an intron or exon. This distinction is important owing to the differing functional roles of TEs depending on whether they are independently transcribed. Here we report a simple strategy to examine bona fide TE expression, termed BonaFide-TEseq. This approach can be used with any template-switch based library such as Smart-seq2 or the single-cell 5' gene expression kit from 10x, extending its utility to single-cell RNA-sequencing. This approach does not require TE-specific enrichment, enabling the simultaneous examination of TEs and protein-coding genes. We show that TEs identified through BonaFide-TEseq are expressed from their own promoter, rather than captured as internal products of genes. We reveal the utility of BonaFide-TEseq in the analysis of single-cell data and show that short-interspersed nuclear elements (SINEs) show cell type-specific expression profiles in the mouse hippocampus. We further show that, in response to a brief exposure of home-cage mice to a novel stimulus, SINEs are activated in dentate granule neurons in a time course that is similar to that of protein-coding immediate early genes. This work provides a simple alternative approach to assess bona fide TE transcription at single-cell resolution and provides a proof-of-concept using this method to identify SINE activation in a context that is relevant for normal learning and memory.

Impact of Early Tracheostomy Versus Late or No Tracheostomy in Nonneurologically Injured Adult Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: The optimal timing of tracheostomy in nonneurologically injured mechanically ventilated critically ill adult patients is uncertain. We conducted a systematic review of randomized controlled trials to evaluate the effect of early versus late tracheostomy or prolonged intubation in this population. DATA SOURCES: We searched MEDLINE, Embase, CENTRAL, CINAHL, and Web of science databases for randomized controlled trials comparing early tracheostomy (<10 d of intubation) with late tracheostomy or prolonged intubation in adults. DATA SELECTION: We selected trials comparing early tracheostomy (defined as being performed less than 10 d after intubation) with late tracheostomy (performed on or after the 10th day of intubation) or prolonged intubation and no tracheostomy in nonneurologically injured patients. The primary outcome was overall mortality. Secondary outcomes included ventilator-associated pneumonia, duration of mechanical ventilation, ICU, and hospital length of stay. DATA EXTRACTION: Two reviewers screened citations, extracted data, assessed the risk of bias, and classification of Grading of Recommendations, Assessment, Development, and Evaluation independently. DATA SYNTHESIS: Our search strategy yielded 8,275 citations, from which nine trials (n = 2,457) were included. We did not observe an effect on the overall mortality of early tracheostomy compared with late tracheostomy or prolonged intubation (risk ratio, 0.91, 95% CI, 0.82-1.01; I2 = 18%). Our results were consistent in all subgroup analyses. No differences were observed in ICU and hospital length of stay, duration of mechanical ventilation, incidence of ventilator-acquired pneumonia, and complications. Our trial sequential analysis showed that our primary analysis on mortality was likely underpowered. CONCLUSION: In our systematic review, we observed that early tracheostomy, as compared with late tracheostomy or prolonged intubation, was not associated with a reduction in overall mortality. However, we cannot exclude a clinically relevant reduction in mortality considering the level of certainty of the evidence. A well-designed trial is needed to answer this important clinical question.

Interdisciplinary strategies to prevent long-term and detrimental opioid use following trauma: a stakeholder consensus study.

OBJECTIVE: Prolonged opioid use is common following traumatic injuries. Although preventive strategies have been recommended, the evidence supporting their use is low. The objectives of this study were to select interdisciplinary strategies to prevent long-term, detrimental opioid use in trauma patients for further evaluation and to identify implementation considerations. DESIGN: A consensus study using the nominal group technique. SETTING: Four trauma systems in Canada. SUBJECTS: Participants included expert clinicians and decision makers, and people with lived experience. METHODS: Participants had to discuss the relevance and implementation of 15 strategies and then rank them using a 7-point Likert scale. Implementation considerations were identified through a synthesis of discussions. RESULTS: A total of 41 expert stakeholders formed the nominal groups. Overall, eight strategies were favored: 1) using multimodal approach for pain management, 2) professional follow-up in physical health, 3) assessment of risk factors for opioid misuse, 4) physical stimulation, 5) downward adjustment of opioids based on patient recovery, 6) educational intervention for patients, 7) training offered to professionals on how to prescribe opioids, and 8) optimizing communication between professionals working in different settings. Discussions with expert stakeholders revealed the rationale for the selected strategies and identified issues to consider when implementing them. CONCLUSION: This stakeholder consensus study identified, for further scientific study, a set of interdisciplinary strategies to promote appropriate opioid use following traumatic injuries. These strategies could ultimately decrease the burden associated with long-term opioid use.

Birthweight, gestational age, and early school trajectory.

BACKGROUND: Birthweight and gestational age are important factors of not only newborn health by also child development and can contribute to delayed cognitive abilities. However, no study has analyzed the association of birthweight and gestational age with school trajectory measured simultaneously by school entry, grade repetition, and school dropout. This study aims, first, to analyze the association of birthweight or gestational age with school entry, and second, to explore the relationship between birthweight or gestational age and grade repetition and school dropout among children in Ouagadougou, Burkina Faso. METHODS: This study used longitudinal data from the Ouagadougou Health and Demographic Surveillance System. Our samples consisted of children born between 2008 and 2014 who were at least three years old at the beginning of the 2017-18 school year. Samples included 13,676, 3152, and 3498 children for the analysis of the school entry, grade repetition, and dropout, respectively. A discrete-time survival model was used to examine the relationship between birthweight or gestational age and school entry, grade repetition, and dropout. The association between birthweight or gestational age and age at school entry were assessed using a Poisson regression. RESULTS: The incidence rate of school entry was 18.1 per 100 people-years. The incidence of first repetition and dropout were 12.6 and 5.9, respectively. The probability of school entry decreased by 31% (HR:0.69, 95%CI: 0.56-0.85) and 8% (HR:0.92, 95%CI: 0.85-0.99) for children weighing less than 2000 g and those weighing between 2000 and 2499 g, respectively, compared to those born with a normal weight (weight ≥ 2500 g). The age at school entry of children with a birthweight less than 2000 g and between 2000 and 2499 g was 7% (IRR: 1.07, 95%CI: 1.06-1.08) and 3% (IRR: 1.03, 95%CI: 1.00-1.06) higher than children born at a normal birthweight, respectively. Gestational age was not associated with school entry or age at school entry. Similarly, birthweight and gestational age were not associated with grade repetition or dropout. CONCLUSION: This study shows that low birthweight is negatively associated with school entry and age at school entry in Ouagadougou. Efforts to avoid low birthweights should be part of maternal and prenatal health care because the associated difficulties may be difficult to overcome later in the child's life. Further longitudinal studies are needed to better understand the relationship between development at birth and school trajectory.

Tracheostomy versus prolonged intubation in moderate to severe traumatic brain injury: a multicentre retrospective cohort study.

PURPOSE: Tracheostomy is a surgical procedure that is commonly performed in patients admitted to the intensive care unit (ICU). It is frequently required in patients with moderate to severe traumatic brain injury (TBI), a subset of patients with prolonged altered state of consciousness that may require a long period of mechanical respiratory assistance. While many clinicians favour the use of early tracheostomy in TBI patients, the evidence in favour of this practice remains scarce. The aims of our study were to evaluate the potential clinical benefits of tracheostomy versus prolonged endotracheal intubation, as well as whether the timing of the procedure may influence outcome in patients with moderate to severe TBI. METHODS: We conducted a retrospective multicentre cohort study based on data from the provincial integrated trauma system of Quebec (Québec Trauma Registry). The study population was selected from adult trauma patients hospitalized between 2013 and 2019. We included patients 16 yr and older with moderate to severe TBI (Glasgow Coma Scale score < 13) who required mechanical ventilation for 96 hr or longer. Our primary outcome was 30-day mortality. Secondary outcomes included hospital and ICU mortality, six-month mortality, duration of mechanical ventilation, ventilator-associated pneumonia, ICU and hospital length of stay as well as orientation of patients upon discharge from the hospital. We used propensity score covariate adjustment. To overcome the effect of immortal time bias, an extended Cox shared frailty model was used to compare mortality between groups. RESULTS: From 2013 to 2019, 26,923 patients with TBI were registered in the Québec Trauma Registry. A total of 983 patients who required prolonged endotracheal intubation for 96 hr or more were included in the study, 374 of whom underwent a tracheostomy and 609 of whom remained intubated. We observed a reduction in 30-day mortality (adjusted hazard ratio, 0.33; 95% confidence interval, 0.21 to 0.53) associated with tracheostomy compared with prolonged endotracheal intubation. This effect was also seen in the ICU as well as at six months. Tracheostomy, when compared with prolonged endotracheal intubation, was associated with an increase in the duration of mechanical respiratory assistance without any increase in the length of stay. No effect on mortality was observed when comparing early vs late tracheostomy procedures. An early procedure was associated with a reduction in the duration of mechanical respiratory support as well as hospital and ICU length of stay. CONCLUSION: In this multicentre cohort study, tracheostomy was associated with decreased mortality when compared with prolonged endotracheal intubation in patients with moderate to severe TBI. This effect does not appear to be modified by the timing of the procedure. Nevertheless, the generalization and application of these results remains limited by potential residual time-dependent indication bias.

RéSUMé: INTRODUCTION: La trachéotomie est une intervention chirurgicale communément pratiquée chez les personnes admises à l'unité de soins intensifs (USI). Elle est fréquemment requise chez les patient·es victimes d'un traumatisme craniocérébral (TCC) modéré à grave, un sous-groupe présentant une altération prolongée de l'état de conscience qui peut nécessiter une longue période d'assistance respiratoire mécanique. Bien que bon nombre de cliniciens et cliniciennes soient favorables à l'utilisation d'une trachéotomie précoce chez cette patientèle, les données probantes en faveur de cette pratique restent insuffisantes. Les objectifs de notre étude étaient d'évaluer l'effet de la trachéotomie par rapport à l'intubation endotrachéale prolongée, ainsi que si le moment où la procédure est effectuée pouvait influencer cet effet, chez les personnes ayant subi un TCC modéré à grave. MéTHODES: Nous avons effectué une étude de cohorte rétrospective multicentrique basée sur le système provincial intégré de traumatologie du Québec (Registre des traumatismes du Québec). La population de l'étude a été sélectionnée parmi les patient·es adultes victimes de traumatismes hospitalisé·es entre 2013 et 2019. Nous avons inclus les patient·es âgé·es de 16 ans et plus présentant un TCC modéré à grave (score sur l'échelle de coma de Glasgow [GCS] < 13) ayant nécessité une assistance respiratoire mécanique pendant 96 h ou plus. Notre critère d'évaluation principal était la mortalité à 30 jours. Les critères d'évaluation secondaires comprenaient la mortalité hospitalière et à l'USI, la mortalité à 6 mois, la durée d'assistance respiratoire mécanique, les pneumonies acquises en lien avec l'assistance respiratoire mécanique, les durées de séjour à l'USI et à l'hôpital ainsi que l'orientation des patient·es à leur sortie de l'hôpital. Nous avons utilisé un score de propension pour l'ajustement des covariables. Pour corriger l'effet du biais du temps immortel, un modèle de régression de la fragilité partagée de Cox étendu a été utilisé pour estimer la mortalité entre les groupes. RéSULTATS: De 2013 à 2019, 26 923 personnes victimes de TCC ont été inscrites dans le Registre des traumatismes du Québec. Un total de 983 patient·es ayant nécessité une intubation endotrachéale prolongée de 96 h ou plus ont été inclus·es dans l'étude, dont 374 ont subi une trachéotomie et 609 sont resté·es intubé·es. Nous avons observé une réduction de la mortalité à 30 jours (aHR : 0,33 [0,21 − 0,53]) associée à la trachéotomie en comparaison à l'intubation endotrachéale prolongée. Cet effet a également été observé à l'USI ainsi qu'à 6 mois. La trachéotomie, comparée à l'intubation endotrachéale prolongée, était associée à une augmentation de la durée d'assistance respiratoire mécanique sans augmentation de la durée de séjour. Aucun effet sur la mortalité n'a été observé en comparant les procédures de trachéotomie précoces et tardive. Une procédure précoce a été associée à une réduction de la durée d'assistance respiratoire mécanique ainsi que la durée de séjour à l'USI et à l'hôpital. CONCLUSION: Dans cette étude de cohorte multicentrique, nous avons observé que la trachéotomie est associée à une diminution de la mortalité en comparaison à l'intubation endotrachéale prolongée chez la patientèle ayant subi un TCC modéré ou grave. Cet effet ne semble pas modifié par le moment de la procédure durant l'hospitalisation. La généralisation et l'application de ces résultats restent toutefois limitées par un biais d'indication résiduel potentiel.

Injury outcomes across Canadian trauma systems: a historical cohort study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

RéSUMé: OBJECTIF: La plupart des systèmes de traumatologie nord-américains disposent de centres de traumatologie (CT) désignés, y compris de niveau I (centres métropolitains ultraspécialisés à volume élevé), de niveau II (centres urbains spécialisés à volume moyen) et/ou de niveau III (centres semi-ruraux ou ruraux). La configuration des systèmes de traumatologie varie d'une province à l'autre et nous ne savons pas comment ces différences influent sur la répartition de la patientèle et sur les issues. Notre objectif était de comparer le mélange de cas des patient·es, le volume de cas et les issues ajustées en fonction du risque des adultes ayant subi un traumatisme majeur admis·es dans des CT désignés de niveaux I, II et III dans l'ensemble des systèmes de traumatologie canadiens. MéTHODE: Dans une étude de cohorte historique nationale, nous avons extrait des données des registres provinciaux canadiens de traumatologie sur les patient·es ayant subi un traumatisme majeur traité·es entre 2013 et 2018 dans tous les CT désignés de niveau I, II ou III en Colombie-Britannique, en Alberta, au Québec et en Nouvelle-Écosse, les CT de niveau I et II au Nouveau-Brunswick, et dans quatre CT en Ontario. Nous avons utilisé des modèles linéaires généralisés à plusieurs niveaux pour comparer la mortalité, les admissions en unité de soins intensifs (USI) et les modèles de risque compétitif pour la durée du séjour à l'hôpital et à l'USI. L'Ontario n'a pas pu être inclus dans les comparaisons des devenirs parce qu'il n'y avait pas de données démographiques pour cette province. RéSULTATS: L'échantillon de l'étude comptait 50 959 patient·es. La répartition des patient·es dans les CT de niveaux I et II était similaire d'une province à l'autre, mais nous avons observé des différences significatives dans le mélange des cas et les volumes pour les CT de niveau III. Il y avait une faible variation de la mortalité ajustée en fonction du risque et des durées de séjour entre les provinces et les CT, mais la variation interprovinciale et intercentre des admissions à l'USI ajustées en fonction du risque était élevée. CONCLUSION: Nos résultats suggèrent que les différences dans le rôle fonctionnel des CT selon leur niveau de désignation d'une province à l'autre entraînent des variations importantes dans la répartition des patient·es, le nombre de cas, l'utilisation des ressources et les issues cliniques. Ces résultats mettent en évidence les possibilités d'amélioration des soins de traumatologie au Canada et soulignent la nécessité de disposer de données normalisées sur les blessures dans la population pour appuyer les efforts nationaux d'amélioration de la qualité.

Strategies to prevent long-term opioid use following trauma: a Canadian practice survey.

PURPOSE: To evaluate how Canadian clinicians involved in trauma patient care and prescribing opioids perceive the use and effectiveness of strategies to prevent long-term opioid therapy following trauma. Barriers and facilitators to the implementation of these strategies were also assessed. METHODS: We conducted a web-based cross-sectional survey. Potential participants were identified by trauma program managers and directors of the targeted departments in three Canadian provinces. We designed our questionnaire using standard health survey research methods. The questionnaire was administered between April 2021 and November 2021. RESULTS: Our response rate was 47% (350/744), and 52% (181/350) of participants completed the entire survey. Most respondents (71%, 129/181) worked in teaching hospitals. Multimodal analgesia (93%, 240/257), nonsteroidal anti-inflammatory agents (77%, 198/257), and physical stimulation (75%, 193/257) were the strategies perceived to be the most frequently used. Several preventive strategies were perceived to be very effective by over 80% of respondents. Of these, some that were reported as not being frequently used were perceived to be among the most effective ones, including guidelines or protocols, assessing risk factors for opioid misuse, physical health follow-up by a professional, training for clinicians, patient education, and prescription monitoring systems. Staff shortages, time constraints, and organizational practices were identified as the main barriers to the implementation of the highest ranked preventive strategies. CONCLUSIONS: Several strategies to prevent long-term opioid therapy following trauma are perceived as being effective by those prescribing opioids in this population. Some of these strategies appear to be commonly used in everyday practice and others less so. Future research should focus on which preventive strategies should be given higher priority for implementation before assessing their effectiveness.

RéSUMé: OBJECTIF: Évaluer comment les cliniciens canadiens impliqués dans les soins aux patients traumatisés et prescrivant des opioïdes perçoivent l'utilisation et l'efficacité des stratégies visant à prévenir le traitement prolongé par opioïde après un traumatisme. Les obstacles et facilitateurs de la mise en œuvre de ces stratégies ont aussi été analysés. MéTHODES: Nous avons réalisé une enquête transversale via le Web. Les participants potentiels ont été identifiés par les gestionnaires et directeurs de programmes de traumatologie des départements ciblés dans trois provinces canadiennes. Nous avons conçu notre questionnaire en utilisant la méthodologie de recherche usuelle des enquêtes de santé. Le questionnaire a été administré entre avril 2021 et novembre 2021. RéSULTATS: Notre taux de réponse a été de 47 % (350/744) et 52 % (181/350) des participants ont complété l'enquête dans sa totalité. La majorité des personnes interrogées (71 %, 129/181) travaillait dans des hôpitaux universitaires. L'analgésie multimodale (93 %, 240/257), les anti-inflammatoires non stéroïdiens (77 %, 198/257) et la stimulation physique (75 %, 193/257) étaient les stratégies perçues comme étant le plus fréquemment utilisées. Plusieurs stratégies préventives étaient perçues comme étant très efficaces par plus de 80 % des répondants. Parmi celles-ci, certaines étaient signalées comme n'étant pas utilisées très souvent, mais perçues comme étant les plus efficaces, notamment les lignes directrices et protocoles évaluant les facteurs de risque d'utilisation abusive des opioïdes, le suivi de la santé physique par un professionnel, la formation des cliniciens, l'éducation des patients et les systèmes de suivi des prescriptions. La pénurie de personnels, les contraintes de temps et les pratiques de l'établissement ont été identifiées comme étant les principaux obstacles à la mise en place des stratégies préventives classées parmi les premières. CONCLUSIONS: Plusieurs stratégies de prévention du traitement par opioïdes à long terme après un traumatisme sont perçues comme efficaces par ceux qui les prescrivent à cette population de patients. Certaines de ces stratégies apparaissent comme couramment utilisées dans la pratique quotidienne et d'autres moins souvent. La recherche future devrait se concentrer sur la détermination des stratégies préventives auxquelles il faudrait accorder la plus grande priorité de mise en œuvre avant d'évaluer leur efficacité.

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.

Automated APACHE II and SOFA score calculation using real-world electronic medical record data in a single center.

The integration of illness severity and organ dysfunction scores into clinical practice, including the APACHE II and SOFA scores, has been challenging due to constraints associated to manual score calculation. With electronic medical records (EMR), score calculation automation using data extraction scripts has emerged as a solution. We aimed to demonstrate that APACHE II and SOFA scores calculated with an automated EMR-based data extraction script predict important clinical endpoints. In this retrospective cohort study, every adult patient admitted to one of our three ICUs, between July 1, 2019, and December 31, 2020, were enrolled. For every patient, an automated ICU admission APACHE II score was calculated using EMR data and minimal clinician input. Fully automated daily SOFA scores were calculated for every patient. 4 794 ICU admissions met our selection criteria. Of these ICU admissions, 522 deaths were recorded (10.9% in-hospital mortality rate). The automated APACHE II was discriminant for in-hospital mortality (AU-ROC = 0.83 (95% CI 0.81-0.85)). We observed an association between the APACHE II score and ICU LOS, with a statistically significant mean increase of 1.1 days of ICU LOS (1.1 [1-1.2]; p = < .0001) for each 10 units increase in APACHE score. SOFA score curves did not discrimate significantly between survivors and non-survivors. A partially automated APACHE II score, calculated with real-world EMR data using an extraction script, is associated with in-hospital mortality risk. The automated APACHE II score could potentially constitute an acceptable surrogate of ICU acuity to be used in resource allocation and triaging, especially in time of high demand for ICU beds.

A Canadian consensus-based list of urgent and specialized in-hospital trauma care interventions to assess the accuracy of prehospital trauma triage protocols: a modified Delphi study.

BACKGROUND: Injury severity scales have traditionally been used to assess the performance of prehospital trauma triage protocols, but they correlate weakly with the urgent needs of specialized trauma care interventions. This study aimed to develop a list of in-hospital urgent and specialized trauma care interventions that require direct transport to the highest-level trauma centre within the catchment area. METHODS: Based on a list of potential participants we obtained using data on training, experience, geographic location, affiliations and role within key trauma organizations, we recruited multidisciplinary trauma experts (including prehospital, emergency, surgery and intensive care clinicians, epidemiologists and clinician/decision-makers) from across Canada to complete a 3-round modified Delphi survey. We conducted a literature review of the criteria used to define urgent and specialized trauma care, and included all diagnostic and therapeutic interventions presented in previously published studies in the list of interventions to present to the panellists. The final list was determined by our advisory committee, 5 clinicians with experience in trauma care. Participants were asked to rate their level of agreement for potentially including the 38 items as urgent and specialized trauma care interventions on a 9-point Likert scale. Interventions were retained if more than 67% of participants moderately or strongly agreed (7-9 on the Likert scale). Interventions that did not reach consensus were presented again in the subsequent round. RESULTS: Twenty-three panellists were recruited. The response rate was 91%, 96% and 83% for the 3 rounds. After the Delphi process, 30 of the 38 interventions, including endotracheal intubation, blood product administration and angioembolization, and abdominal, thoracic, neurosurgical, spinal and/or orthopedic operations (excluding hip or limb surgery, and toe or finger amputation), were selected. Hospital admission to the intensive care unit and/or for observation of brain, spinal, thoracic or abdominal injuries were also retained. CONCLUSION: We developed a Canadian consensus-based list of urgent and specialized in-hospital trauma care interventions requiring direct transportation to a major trauma centre. This list should help standardize assessments of current protocols and derive new triage tools.

Comparison of trauma care structures, processes and outcomes between the English National Health Service and Quebec, Canada.

BACKGROUND: Comparisons across trauma systems are key to identifying opportunities to improve trauma care. We aimed to compare trauma service structures, processes and outcomes between the English National Health Service (NHS) and the province of Quebec, Canada. METHODS: We conducted a multicentre cohort study including admissions of patients aged older than 15 years with major trauma to major trauma centres (MTCs) from 2014/15 to 2016/17. We compared structures descriptively, and time to MTC and time in the emergency department (ED) using Wilcoxon tests. We compared mortality, and hospital and intensive care unit (ICU) length of stay (LOS) using multilevel logistic regression with propensity score adjustment, stratified by body region of the worst injury. RESULTS: The sample comprised 36 337 patients from the NHS and 6484 patients from Quebec. Structural differences in the NHS included advanced prehospital medical teams (v. "scoop and run" in Quebec), helicopter transport (v. fixed-wing aircraft) and trauma team leaders. The median time to an MTC was shorter in Quebec than in the NHS for direct transports (1 h v. 1.5 h, p < 0.001) but longer for transfers (2.5 h v. 6 h, p < 0.001). Time in the ED was longer in Quebec than in the NHS (6.5 h v. 4.0 h, p < 0.001). The adjusted odds of death were higher in Quebec for head injury (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.09-1.51) but lower for thoracoabdominal injuries (OR 0.69, 95% CI 0.52-0.90). The adjusted median hospital LOS was longer for spine, torso and extremity injuries in the NHS than in Quebec, and the median ICU LOS was longer for spine injuries. CONCLUSION: We observed significant differences in the structure of trauma care, delays in access and risk-adjusted outcomes between Quebec and the NHS. Future research should assess associations between structures, processes and outcomes to identify opportunities for quality improvement.

Interhospital Variations in Resource Use Intensity for In-hospital Injury Deaths: A Retrospective Multicenter Cohort Study.

OBJECTIVE: Evaluate interhospital variation in resource use for in-hospital injury deaths. BACKGROUND: Significant variation in resource use for end-of-life care has been observed in the US for chronic diseases. However, there is an important knowledge gap on end-of-life resource use for trauma patients. METHODS: We conducted a multicenter, retrospective cohort study of injury deaths following hospitalization in any of the 57 trauma centers in a Canadian trauma system (2013-2016). Resource use intensity was measured using activity-based costing (2016 $CAN) according to time of death (72 h, 3-14 d, ≥14 d). We used multilevel log-linear regression to model resource use and estimated interhospital variation using intraclass correlation coefficients (ICC). RESULTS: Our study population comprised 2044 injury deaths. Variation in resource use between hospitals was observed for all 3 time frames (ICC = 6.5%, 6.6%, and 5.9% for < 72 h, 3-14 d, and ≥14 d, respectively). Interhospital variation was stronger for allied health services (ICC = 18 to 26%), medical imaging (ICC = 4 to 10%), and the ICU (ICC = 5 to 6%) than other activity centers. We observed stronger interhospital variation for patients < 65 years of age (ICC = 11 to 34%) than those ≥65 (ICC = 5 to 6%) and for traumatic brain injury (ICC = 5 to 13%) than other injuries (ICC = 1 to 8%). CONCLUSIONS: We observed variation in resource use intensity for injury deaths across trauma centers. Strongest variation was observed for younger patients and those with traumatic brain injury. Results may reflect variation in level of care decisions and the incidence of withdrawal of life-sustaining therapies.