Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Predictors of Noninvasive Ventilation Failure in the Post-Extubation Period: A Systematic Review and Meta-Analysis.

OBJECTIVES: To identify factors associated with failure of noninvasive ventilation (NIV) in the post-extubation period. DATA SOURCES: We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to February 28, 2022. STUDY SELECTION: We included English language studies that provided predictors of post-extubation NIV failure necessitating reintubation. DATA EXTRACTION: Two authors conducted data abstraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios (ORs) mean difference (MD), respectively. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty. DATA SYNTHESIS: We included 25 studies ( n = 2,327). Illness-related factors associated with increased odds of post-extubation NIV failure were higher critical illness severity (OR, 3.56; 95% CI, 1.96-6.45; high certainty) and a diagnosis of pneumonia (OR, 6.16; 95% CI, 2.59-14.66; moderate certainty). Clinical and biochemical factors associated with moderate certainty of increased risk of NIV failure post-extubation include higher respiratory rate (MD, 1.54; 95% CI, 0.61-2.47), higher heart rate (MD, 4.46; 95% CI, 1.67-7.25), lower Pa o2 :F io2 (MD, -30.78; 95% CI, -50.02 to -11.54) 1-hour after NIV initiation, and higher rapid shallow breathing index (MD, 15.21; 95% CI, 12.04-18.38) prior to NIV start. Elevated body mass index was the only patient-related factor that may be associated with a protective effect (OR, 0.21; 95% CI, 0.09-0.52; moderate certainty) on post-extubation NIV failure. CONCLUSIONS: We identified several prognostic factors before and 1 hour after NIV initiation associated with increased risk of NIV failure in the post-extubation period. Well-designed prospective studies are required to confirm the prognostic importance of these factors to help further guide clinical decision-making.

In adults hospitalized with COVID-19, adding baricitinib vs. dexamethasone to remdesivir did not differ for MV-free survival.

SOURCE CITATION: Wolfe CR, Tomashek KM, Patterson TF, et al. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial. Lancet Respir Med. 2022;10:888-99. 35617986.

Association of age with death and withdrawal of life-sustaining therapy after severe traumatic brain injury.

BACKGROUND: Compared to younger age, older age (≥ 65 yr) is associated with worse outcomes after severe traumatic brain injury (TBI). We sought to describe the association of older age with in-hospital death and aggressiveness of intervention. METHODS: We conducted a retrospective cohort study of adult (age ≥ 16 yr) patients with severe TBI admitted to a single academic tertiary care neurotrauma centre between January 2014 and December 2015. We collected data through chart review as well as from our institutional administrative database. We provided descriptive statistics and used multivariable logistic regression to evaluate the independent association of age with the primary outcome, in-hospital death. The secondary outcome was early withdrawal of life-sustaining therapy. RESULTS: There were 126 adult patients (median age 67 yr [Q1-Q3, 33-80 yr]) with severe TBI during the study period who met our eligibility criteria. The most common mechanism was high-velocity blunt injury (55 patients [43.6%]). The median Marshall score was 4 (Q1-Q3, 2-6), and the median Injury Severity Score was 26 (Q1-Q3, 25-35). After controlling for confounders including clinical frailty, pre-existing comorbidity, injury severity, Marshall score and neurologic examination at admission, we observed that older patients were more likely than younger patients to die in hospital (odds ratio 5.10, 95% confidence interval 1.65-15.78). Older patients were also more likely to experience early withdrawal of life-sustaining therapy and less likely to receive invasive interventions. CONCLUSION: After controlling for confounding factors relevant to older patients, we observed that age was an important and independent predictor of in-hospital death and early withdrawal of life-sustaining therapy. The mechanism by which age influences clinical decision-making independent of global and neurologic injury severity, clinical frailty and comorbidities remains unclear.

Efficacy and Safety of Low Molecular Weight Heparin Versus Unfractionated Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-analysis.

PURPOSE: Trauma patients are at high risk of VTE. We summarize the efficacy and safety of LMWH versus UFH for the prevention of VTE in trauma patients. METHODS: We searched 6 databases from inception through March 12, 2021. We included randomized controlled trials (RCTs) or observational studies comparing LMWH versus UFH for thromboprophylaxis in adult trauma patients. We pooled effect estimates across RCTs and observational studies separately, using random-effects model and inverse variance weighting. We assessed risk of bias using the Cochrane tool for RCTs and the Risk of Bias in Non-Randomized Studies (ROBINS)-I tool for observational studies and assessed certainty of findings using Grading of Recommendations, Assessment, Development and Evaluations methodology. RESULTS: We included 4 RCTs (879 patients) and 8 observational studies (306,747 patients). Based on pooled RCT data, compared to UFH, LMWH reduces deep vein thrombosis (RR 0.67, 95% CI 0.50 to 0.88, moderate certainty) and VTE (RR 0.68, 95% CI 0.51 to 0.90, moderate certainty). As compared to UFH, LMWH may reduce pulmonary embolism [adjusted odds ratio from pooled observational studies 0.56 (95% CI 0.50 to 0.62)] and mortality (adjusted odds ratio from pooled observational studies 0.54, 95% CI 0.45 to 0.65), though based on low certainty evidence. There was an uncertain effect on adverse events (RR from pooled RCTs 0.80, 95% CI 0.48 to 1.33, very low certainty) and heparin induced thrombocytopenia [RR from pooled RCTs 0.26 (95% CI 0.03 to 2.38, very low certainty)]. CONCLUSIONS: Among adult trauma patients, LMWH is superior to UFH for deep vein thrombosis and VTE prevention and may additionally reduce pulmonary embolism and mortality. The impact on adverse events and heparin induced thrombocytopenia is uncertain.

Prognostic factors for development of acute respiratory distress syndrome following traumatic injury: a systematic review and meta-analysis.

BACKGROUND: Our purpose was to summarise the prognostic associations between various clinical risk factors and development of acute respiratory distress syndrome (ARDS) following traumatic injury. METHODS: We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with development of post-traumatic ARDS, as defined by either the American-European Consensus Conference or Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS (Quality in Prognosis Studies) tool and certainty of findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. RESULTS: We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with development of post-traumatic ARDS (adjusted OR 1.19, 95% CI 1.15-1.24 for each additional litre of crystalloid administered within the first 6 h after injury; high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic White race, blunt mechanism of injury, presence of head injury, pulmonary contusion or rib fracture and increasing chest injury severity. CONCLUSIONS: We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform development of risk stratification tools.

Prognostic Factors Associated With Development of Venous Thromboembolism in Critically Ill Patients-A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify prognostic factors for the development of venous thromboembolism in the ICU. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021. STUDY SELECTION: We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among critically ill patients. DATA EXTRACTION: Two authors performed data extraction and risk-of-bias assessment. We pooled adjusted odds ratios and adjusted hazard ratios for prognostic factors using random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. DATA SYNTHESIS: We included 39 observational cohort studies involving 729,477 patients. Patient factors with high or moderate certainty of association with increased odds of venous thromboembolism include older age (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29 per 10 yr), obesity (adjusted odds ratio, 1.25; 95% CI, 1.18-1.32), active malignancy (adjusted odds ratio, 1.70; 95% CI, 1.18-2.44), history of venous thromboembolism (adjusted odds ratio, 4.77; 95% CI, 3.42-6.65), and history of recent surgery (adjusted odds ratio, 1.77; 95% CI, 1.26-2.47). ICU-specific factors with high or moderate certainty of association with increased risk of venous thromboembolism include sepsis (adjusted odds ratio, 1.41; 95% CI, 1.12-1.78), lack of pharmacologic venous thromboembolism prophylaxis (adjusted odds ratio, 1.80; 95% CI, 1.14-2.84), central venous catheter (adjusted odds ratio, 2.93; 95% CI, 1.98-4.34), invasive mechanical ventilation (adjusted odds ratio, 1.74; 95% CI, 1.36-2.24), and use of vasoactive medication (adjusted odds ratio, 1.86; 95% CI, 1.23-2.81). CONCLUSIONS: This meta-analysis provides quantitative summaries of the association between patient-specific and ICU-related prognostic factors and the risk of venous thromboembolism in the ICU. These findings provide the foundation for the development of a venous thromboembolism risk stratification tool for critically ill patients.

Inotropes, vasopressors, and mechanical circulatory support for treatment of cardiogenic shock complicating myocardial infarction: a systematic review and network meta-analysis.

PURPOSE: To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction. SOURCE: We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality. PRINCIPAL FINDINGS: We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis. CONCLUSION: The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding. STUDY REGISTRATION: Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020.

RéSUMé: OBJECTIF: Comparer l'efficacité relative des thérapies de soutien (inotropes, vasopresseurs et assistance circulatoire mécanique [ACM]) chez les patients adultes atteints d'un choc cardiogénique compliquant un infarctus aigu du myocarde. SOURCES: Nous avons réalisé une revue systématique et une méta-analyse en réseau et effectué des recherches dans six bases de données depuis leur création jusqu'à décembre 2021 pour en tirer les études randomisées contrôlées (ERC). Nous avons évalué les inotropes, les vasopresseurs et les ACM dans des réseaux distincts. Deux réviseurs ont effectué la recherche, l'évaluation du texte intégral et l'extraction. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des résultats. Le critère d'évaluation d'intérêt était la mortalité toutes causes confondues à 30 jours. CONSTATATIONS PRINCIPALES: Nous avons inclus 17 ERC. Parmi les inotropes (sept ERC, 1145 patients), le lévosimendan a probablement réduit la mortalité par rapport au placebo (rapport de cotes [RC], 0,53; intervalle de confiance [IC] à 95 %, 0,33 à 0,87; certitude modérée), mais principalement en cas de choc de sévérité moindre. La milrinone (RC, 0,52; IC 95 %, 0,19 à 1,39; certitude faible) et la dobutamine (RC, 0,67, IC 95 %, 0,30 à 1,49; certitude faible) pourraient n'avoir aucun effet sur la mortalité par rapport au placebo. En ce qui concerne l'ACM (huit ERC, 856 patients), il pourrait n'y avoir aucun effet sur la mortalité avec un ballon intra-aortique (IABP) (RC, 0,94; IC 95 %, 0,69 à 1,28; certitude faible) ou un ACM percutané (ACMp) (RC, 0,96; IC 95 %, 0,47 à 1,98; certitude faible), par rapport à une stratégie sans ACM. L'utilisation d'un ballon intra-aortique était associée à moins de saignements majeurs par rapport à une ACMp. Nous n'avons trouvé que deux ERC évaluant les vasopresseurs, ce qui n'a pas fourni suffisamment de données pour la méta-analyse. CONCLUSION: Les résultats de cette revue systématique et de la méta-analyse en réseau indiquent que le lévosimendan réduit la mortalité par rapport au placebo chez les patients présentant un choc cardiogénique de faible gravité. Le ballon intra-aortique et l'ACMp n'ont eu aucun effet sur la mortalité par rapport à une stratégie sans ACM, mais l'ACMp était associée à des taux plus élevés de saignements majeurs. ENREGISTREMENT DE L'éTUDE: Center for Open Science ( https://osf.io/ky2gr ); enregistrée le 10 novembre 2020.

Outcomes and Resource Utilization Among Patients Admitted to the Intensive Care Unit Following Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a common condition, accounting for a significant number of intensive care unit (ICU) admissions. However, little is known about outcomes and costs among ICU patients admitted with acute exacerbations of COPD (AECOPD). We studied predictors of inhospital mortality and costs of ICU admissions for AECOPD. METHODS: Data were obtained from a prospectively maintained registry from 2 ICUs from 2011 to 2016, including adult patients (age ≥ 18) with an ICU discharge diagnosis of AECOPD. The primary outcome was hospital mortality. Secondary outcomes included ICU length of stay, resource utilization, total hospital costs, and cost per survivor. RESULTS: We included 390 patients, of which 27.2% died in hospital. Independent predictors of inhospital mortality included age (odds ratio [OR]: 1.95, CI: 1.58-2.67) and the presence of clinical frailty (OR: 4.12, CI: 2.26-6.95). The mean total hospital costs were Can$35 059, with a cost per survivor of Can$48 191. Factors associated with increased cost included transfer from an inpatient setting, severity of illness, and previous ICU admission. CONCLUSIONS: Approximately a quarter of patients admitted to ICU with AECOPD died during hospitalization, and these patients accrued significant costs. This study identifies important factors associated with poor outcome in this at-risk population, which has value in risk stratification and patient or family discussions addressing goals of care.

Techniques for blood loss estimation in major non-cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Estimated blood loss (EBL) is an important tool in clinical decision-making and surgical outcomes research. It guides perioperative transfusion practice and serves as a key predictor of short-term perioperative risks and long-term oncologic outcomes. Despite its widespread clinical and research use, there is no gold standard for blood loss estimation. We sought to systematically review and compare techniques for intraoperative blood loss estimation in major non-cardiac surgery with the objective of informing clinical estimation and research standards. SOURCE: A structured search strategy was applied to Ovid Medline, Embase, and Cochrane Library databases from inception to March 2020, to identify studies comparing methods of intraoperative blood loss in adult patients undergoing major non-cardiac surgery. We summarized agreement between groups of pairwise comparisons as visual estimation vs formula estimation, visual estimation vs other, and formula estimation vs other. For each of these comparisons, we described tendencies for higher or lower EBL values, consistency of findings, pooled mean differences, standard deviations, and confidence intervals. PRINCIPLE FINDINGS: We included 26 studies involving 3,297 patients in this review. We found that visual estimation is the most frequently studied technique. In addition, visual techniques tended to provide lower EBL values than formula-based estimation or other techniques, though this effect was not statistically significant in pooled analyses likely due to sample size limitations. When accounting for the contextual mean blood loss, similar case-to-case variation exists for all estimation techniques. CONCLUSIONS: We found that significant case-by-case variation exists for all methods of blood loss evaluation and that there is significant disagreement between techniques. Given the importance placed on EBL, particularly for perioperative prognostication models, clinicians should consider the universal adoption of a practical and reproducible method for blood loss evaluation. TRIAL REGISTRATION: PROSPERO (CRD42015029439); registered: 18 November 2015.PROSPERO (CRD42015029439); registered: 18 November 2015.

RéSUMé: OBJECTIF: Les pertes sanguines estimées constituent un outil important dans la prise de décision clinique et la recherche sur les pronostics chirurgicaux. Elles guident la pratique transfusionnelle périopératoire et servent de prédicteur clé des risques périopératoires à court terme ainsi que des devenirs oncologiques à long terme. Malgré l'utilisation répandue de cette modalité en clinique et en recherche, il n'existe pas de référence absolue pour l'estimation des pertes sanguines. Nous avons tenté de passer systématiquement en revue et de comparer les techniques d'estimation des pertes sanguines peropératoires dans les chirurgies non cardiaques majeures, avec pour objectif d'informer l'évaluation clinique et les normes de recherche. SOURCE: Une stratégie de recherche structurée a été appliquée aux bases de données Ovid Medline, Embase et Cochrane Library de leur création à mars 2020 afin d'identifier les études comparant les méthodes d'estimation des pertes sanguines peropératoires chez des patients adultes subissant une chirurgie non cardiaque majeure. Nous avons résumé la concordance entre des groupes de comparaisons par paires en tant qu'estimation visuelle vs estimation par formule, estimation visuelle vs autre, et estimation par formule vs autre. Pour chacune de ces comparaisons, nous avons décrit les tendances vers des valeurs d'estimations des pertes sanguines plus élevées ou plus basses, la cohérence des résultats, les différences moyennes combinées, les écarts type et les intervalles de confiance. CONSTATATIONS PRINCIPALES: Dans ce compte rendu, 26 études portant sur 3297 patients ont été examinées. L'estimation visuelle est la technique la plus fréquemment étudiée. En outre, les techniques visuelles avaient tendance à donner des valeurs d'estimation des pertes sanguines plus basses que les estimations fondées sur des formules ou d'autres techniques, bien que cet effet n'ait pas eu de signification statistique dans les analyses combinées, probablement en raison des limites liées aux tailles d'échantillon. En tenant compte des pertes sanguines moyennes contextuelles, une variation similaire au cas par cas est apparue avec toutes les techniques d'estimation. CONCLUSION: Nous avons observé qu'une variation significative au cas par cas était présente avec toutes les méthodes d'évaluation des pertes sanguines et qu'il y a un désaccord significatif entre les techniques. Étant donné l'importance octroyée à l'estimation des pertes sanguines, particulièrement dans les modèles de pronostication périopératoire, les cliniciens devraient envisager l'adoption universelle d'une méthode pratique et reproductible d'évaluation des pertes sanguines. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42015029439); enregistrée le : 18 novembre 2015.

Hospital resource use and costs among abdominal aortic aneurysm repair patients admitted to the intensive care unit.

BACKGROUND: Abdominal aortic aneurysm (AAA) repair is associated with significant morbidity and mortality. As a result, many of these patients are monitored postoperatively in the intensive care unit (ICU). However, little is known about resource utilization and costs associated with ICU admission in this population. We sought to evaluate predictors of total costs among patients admitted to the ICU after repair of nonruptured or ruptured AAA. METHODS: We retrospectively analyzed prospectively collected data (2011-2016) of ICU patients admitted after AAA repair. The primary outcome was total hospital costs. We used elastic net regression to identify pre-ICU admission predictors of hospitalization costs separately for nonruptured and ruptured AAA patients. RESULTS: We included 552 patients in the analysis. Of these, 440 (79.7%) were admitted after repair of nonruptured AAA, and 112 (20.3%) were admitted after repair of ruptured AAA. The mean age of patients with nonruptured AAA was 74 (standard deviation, 9) years, and the mean age of patients with ruptured AAA was 70 (standard deviation, 8) years. Median total hospital cost (in Canadian dollars) was $21,555 (interquartile range, $17,798-$27,294) for patients with nonruptured AAA and $33,709 (interquartile range, $23,173-$53,913) for patients with ruptured AAA. Among both nonruptured and ruptured AAA patients, increasing age, illness severity, use of endovascular repair, history of chronic obstructive pulmonary disease, and excessive blood loss (≥4000 mL) were associated with increased costs, whereas having an anesthesiologist with vascular subspecialty training was associated with lower costs. CONCLUSIONS: Patient-, procedure-, and clinician-specific variables are associated with costs in patients admitted to the ICU after repair of AAA. These factors may be considered future targets in initiatives to improve cost-effectiveness in this population.

The Association of Frailty With Adverse Outcomes After Multisystem Trauma: A Systematic Review and Meta-analysis.

BACKGROUND: Frailty strongly predicts adverse outcomes in a variety of clinical settings; however, frailty-related trauma outcomes have not been systematically reviewed and quantitatively synthesized. Our objective was to systematically review and meta-analyze the association between frailty and outcomes (mortality-primary; complications, health resource use, and patient experience-secondary) after multisystem trauma. METHODS: After registration (CRD42018104116), we applied a peer-reviewed search strategy to MEDLINE, EMBASE, and Comprehensive Index to Nursing and Allied Health Literature (CINAHL) from inception to May 22, 2019, to identify studies that described: (1) multisystem trauma; (2) participants ≥18 years of age; (3) explicit frailty instrument application; and (4) relevant outcomes. Excluded studies included those that: (1) lacked a comparator group; (2) reported isolated injuries; and (3) reported mixed trauma and nontrauma populations. Criteria were applied independently, in duplicate to title/abstract and full-text articles. Risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tool. Effect measures (adjusted for prespecified confounders) were pooled using random-effects models; otherwise, narrative synthesis was used. RESULTS: Sixteen studies were included that represented 5198 participants; 9.9% of people with frailty died compared to 4.2% of people without frailty. Frailty was associated with increased mortality (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.37-1.71), complications (adjusted OR, 2.32; 95% CI, 1.72-3.15), and adverse discharge (adjusted OR, 1.78; 95% CI, 1.29-2.45). Patient function, experience, and resource use outcomes were rarely reported. CONCLUSIONS: The presence of frailty is significantly associated with mortality, complications, and adverse discharge disposition after multisystem trauma. This provides important prognostic information to inform discussions with patients and families and highlights the need for trauma system optimization to meet the complex needs of older patients.

Postoperative Adverse Events are Associated with Oncologic Recurrence Following Curative-intent Resection for Lung Cancer.

BACKGROUND: Up to 50% of patients suffer short-term postoperative adverse events (AEs) and metastatic recurrence in the long-term following curative-intent lung cancer resection. The association between AEs, particularly infectious in nature, and disease recurrence is controversial. We sought to evaluate the association of postoperative AEs on risk of developing recurrence and recurrence-free survival (RFS) following curative-intent lung resection surgery. METHODS: All lung cancer resections at a single institution (January 2008-July 2015) were included, with prospective collection of AEs using the Thoracic Morbidity & Mortality System. Cox proportional hazards models were used to estimate the effect of AEs on recurrence, with results presented as hazard ratio (HR) with 95% confidence interval (CI). An a priori, clinically driven approach to predictor variable selection was used. Kaplan-Meier curves were used examine the relationship between AE and RFS. p < 0.05 was considered statistically significant. RESULTS: 892 patients underwent curative-intent resection. 342 (38.3%) patients experienced an AE; 69 (7.7%) patients developed infectious AEs. 17.6% (n = 157) of patients had disease recurrence after mean follow-up of 26.5 months. Severe (Grade IV) AEs were associated with increased risk of recurrence (3.40; 95% CI 1.56-7.41) and a trend to decreased RFS. Major infectious AEs were associated with increased risk of recurrence (HR 1.71; CI 1.05-2.8) and earlier time to recurrence (no infectious AE 66 months, minor infectious 41 months, major infectious 54 months; p = 0.02). CONCLUSION: For patients undergoing curative-intent lung cancer resection, postoperative AEs associated with critical illness or major infection were associated with increased risk of oncologic recurrence.

Correction to: Postoperative Adverse Events are Associated with Oncologic Recurrence Following Curative­intent Resection for Lung Cancer.

The original version of this article unfortunately contained a mistake in author names. The given and family names of all the authors was transposed. The author names are corrected with this correction. The original article has been corrected.

Early identification of the need for major intervention in patients with traumatic hemorrhage: development and internal validation of a simple bleeding score.

BACKGROUND: Failure to rapidly identify bleeding in trauma patients leads to substantial morbidity and mortality. We aimed to develop and validate a simple bedside score for identifying bleeding patients requiring escalation of care beyond initial resuscitation. METHODS: We included patients with major blunt or penetrating trauma, defined as those with an Injury Severity Score greater than 12 or requiring trauma team activation, at The Ottawa Hospital from September 2014 to September 2017. We used logistic regression for derivation. The primary outcome was a composite of the need for massive transfusion, embolization or surgery for hemostasis. We prespecified clinical, laboratory and imaging predictors using findings from our prior systematic review and survey of Canadian traumatologists. We used an AIC-based stepdown procedure based on the Akaike information criterion and regression coefficients to create a 5-variable score for bedside application. We used bootstrap internal validation to assess optimism-corrected performance. RESULTS: We included 890 patients, of whom 133 required a major intervention. The main model comprised systolic blood pressure, clinical examination findings suggestive of hemorrhage, lactate level, focused assessment with sonography in trauma (FAST) and computed tomographic imaging. The C statistic was 0.95, optimism-corrected to 0.94. A simplified Canadian Bleeding (CAN-BLEED) score was devised. A score cut-off of 2 points yielded sensitivity of 97.7% (95% confidence interval [CI] 93.6 to 99.5) and specificity 73.2% (95% CI 69.9 to 76.3). An alternative version that included mechanism of injury rather than CT had lower discriminative ability (C statistic = 0.89). CONCLUSION: A simple yet promising bleeding score is proposed to identify highrisk patients in need of major intervention for traumatic bleeding and determine the appropriateness of early transfer to specialized trauma centres. Further research is needed to evaluate the performance of the score in other settings, define interrater reliability and evaluate the potential for reduction of time to intervention.

CONTEXTE: Les délais dans la détection des saignements actifs chez les patients en traumatologie entraînent une morbidité et une mortalité élevées. L'objectif était d'élaborer et de valider une échelle simple, à utiliser en contexte clinique pour repérer les patients qui présentent un saignement actif et qui nécessitent une intensification des soins après la réanimation initiale. MÉTHODES: Les critères d'inclusion étaient les suivants : admission à l'Hôpital d'Ottawa entre septembre 2014 et septembre 2017 pour un traumatisme contondant ou pénétrant, et score de gravité de la blessure supérieur à 12 ou mobilisation de l'équipe de traumatologie. Nous avons fait la dérivation par régression logistique. Le principal critère d'évaluation était la nécessité d'une transfusion massive, d'une embolisation ou d'une opération pour rétablir l'hémostase. Nous avons établi les facteurs prédictifs décelables en clinique, en laboratoire et à l'imagerie en fonction des résultats que nous avons obtenus dans le cadre d'une revue systématique et d'un sondage mené auprès de traumatologues canadiens. Nous avons utilisé une procédure avec ajustement selon le critère d'information d'Akaike (AIC) et des coefficients de régression afin de créer une échelle à 5 variables applicable en contexte clinique. Pour ce qui est de la validation interne, nous avons ajusté les valeurs dites « optimistes ¼ à l'aide de la méthode d'autoamorçage (bootstrap). RÉSULTATS: Nous avons inclus 890 patients, dont 133 nécessitaient une intervention majeure. Le modèle de base intégrait la pression artérielle systolique, les constatations cliniques indiquant une hémorragie, le taux de lactate, les résultats de l'échographie ciblée en traumatologie (FAST) et les résultats de la tomodensitométrie (TMD). La statistique C s'élevait à 0,95 (0,94 après ajustement). Nous avons conçu une échelle canadienne simplifiée d'évaluation des saignements actifs (CANBLEED). Un seuil de 2 points a généré une sensibilité de 97,7 % (intervalle de confiance [IC] à 95 % de 93,6 à 99,5) et une spécificité de 73,2 % (IC à 95 % de 69,9 à 76,3). Une deuxième version, qui tient compte du mécanisme de blessure plutôt que des résultats de la TMD, avait un pouvoir de discrimination inférieur (statistique C = 0,89). CONCLUSION: Nous proposons une échelle d'évaluation des saignements actifs simple, mais prometteuse. Celle-ci vise à repérer les patients à haut risque qui nécessitent une intervention majeure pour un saignement d'origine traumatique ainsi qu'à déterminer la pertinence d'un transfert précoce dans un centre de traumatologie. Des études complémentaires seront nécessaires afin d'évaluer l'échelle dans d'autres milieux, d'établir sa fiabilité interévaluateurs et d'évaluer le potentiel de réduction des délais d'intervention.

Predictors of mortality and cost among surgical patients requiring rapid response team activation.

Background: Prior studies of rapid response team (RRT) implementation for surgical patients have demonstrated mixed results with respect to reductions in poor outcomes. The aim of this study was to identify predictors of in-hospital mortality and hospital costs among surgical inpatients requiring RRT activation. Methods: We analyzed data prospectively collected from May 2012 to May 2016 at The Ottawa Hospital. We included patients who were at least 18 years of age, who were admitted to hospital, who received either preoperative or postoperative care, and and who required RRT activation. We created a multivariable logistic regression model to describe mortality predictors and a multivariable generalized linear model to describe cost predictors. Results: We included 1507 patients. The in-hospital mortality rate was 15.9%. The patient-related factors most strongly associated with mortality included an Elixhauser Comorbidity Index score of 20 or higher (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.96-6.60) and care designations excluding admission to the intensive care unit and cardiopulmonary resuscitation (OR 3.52, 95% CI 2.25-5.52). The strongest surgical predictors included neurosurgical admission (OR 2.09, 95% CI 1.17-3.75), emergent surgery (OR 2.04, 95% CI 1.37-3.03) and occurrence of 2 or more operations (OR 1.73, 95% CI 1.21-2.46). Among RRT factors, occurrence of 2 or more RRT assessments (OR 2.01, 95% CI 1.44-2.80) conferred the highest mortality. Increased cost was strongly associated with admitting service, multiple surgeries, multiple RRT assessments and medical comorbidity. Conclusion: RRT activation among surgical inpatients identifies a population at high risk of death. We identified several predictors of mortality and cost, which represent opportunities for future quality improvement and patient safety initiatives.

Contexte: Les études sur la mobilisation d'équipes d'intervention rapide (EIR) auprès de patients en chirurgie ont donné des résultats mitigés quant à la réduction des issues négatives. La présente étude visait à déterminer les facteurs prédictifs de coûts pour les hôpitaux et de mortalité chez les patients en chirurgie nécessitant la mobilisation d'une EIR. Méthodes: Nous avons analysé des données recueillies de manière prospective de mai 2012 à mai 2016 à l'Hôpital d'Ottawa. Nous avons inclus les patients hospitalisés de 18 ans et plus qui ont reçu des soins préopératoires ou postopératoires et qui ont nécessité l'intervention d'une EIR. Nous avons ensuite créé un modèle de régression logistique multivariée pour décrire les facteurs prédictifs de mortalité et un modèle linéaire généralisé multivarié pour décrire les facteurs prédictifs de coûts. Résultats: Nous avons retenus 1507 patients. Le taux global de mortalité à l'hôpital était de 15,9 %. Les principaux facteurs de mortalité liés au patient étaient un indice de comorbidité d'Elixhauser supérieur ou égal à 20 (rapport de cotes [RC] 3,60, intervalle de confiance [IC] à 95 % 1,96­6,60) et des objectifs de soins excluant l'admission à l'unité des soins intensifs et la réanimation cardiorespiratoire (RC 3,52, IC à 95 % 2,25­5,52). Les principaux facteurs prédictifs liés aux interventions sont l'admission en neurochirurgie (RC 2,09, IC à 95 % 1,17­3,75), l'intervention chirurgicale d'urgence (RC 2,04, IC à 95 % 1,37­3,03) et le fait d'avoir subi au moins 2 opérations (RC 1,73, IC à 95 % 1,21­2,46). Parmi les facteurs liés aux EIR, la tenue d'au moins 2 évaluations par l'EIR s'accompagnait du mortalité le plus élevé (RC 2,01, IC à 95 % 1,44­2,80). L'augmentation des coûts était étroitement associée au service d'admission, aux interventions chirurgicales multiples, aux évaluations multiples par l'EIR et à la comorbidité médicale. Conclusion: La mobilisation d'EIR auprès de patients en chirurgie permet de mettre en évidence une population à risque élevé de décès. Nous avons découvert plusieurs facteurs prédictifs de mortalité et de coûts, dont on pourra se servir pour améliorer la qualité des soins et la sécurité des patients.

Necrotizing Soft Tissue Infection: Diagnostic Accuracy of Physical Examination, Imaging, and LRINEC Score: A Systematic Review and Meta-Analysis.

OBJECTIVE: We sought to summarize accuracy of physical examination, imaging, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score in diagnosis of necrotizing soft tissue infection (NSTI) in adults with a soft tissue infection clinically concerning for NSTI. SUMMARY OF BACKGROUND DATA: NSTI is a life-threatening diagnosis. Delay to diagnosis and surgical management is associated with increased mortality. METHODS: We searched 6 databases from inception through November 2017. We included English-language studies reporting diagnostic accuracy of testing or LRINEC Score. Outcome was NSTI confirmed by surgery or histopathology. Two reviewers screened all citations and extracted data independently. Summary measures were obtained from the Hierarchical Summary Receiver Operating Characteristic model. RESULTS: From 2,290 citations, we included 23 studies (n = 5982). Of physical examination signs, pooled sensitivity and specificity for fever was 46.0% and 77.0% respectively, for hemorrhagic bullae 25.2% and 95.8%, and for hypotension 21.0% and 97.7%. Computed tomography (CT) had sensitivity of 88.5% and specificity of 93.3%, while plain radiography had sensitivity of 48.9% and specificity of 94.0%. Finally, LRINEC ≥ 6 had sensitivity of 68.2% and specificity of 84.8%, while LRINEC ≥ 8 had sensitivity of 40.8% and specificity of 94.9%. CONCLUSIONS: Absence of any 1 physical examination feature (eg, fever or hypotension) is not sufficient to rule-out NSTI. CT is superior to plain radiography. LRINEC had poor sensitivity, and should not be used to rule-out NSTI. Given the poor sensitivity of these tests, a high clinical suspicion warrants early surgical consultation for definitive diagnosis and management.

Frailty and Associated Outcomes and Resource Utilization Among Older ICU Patients With Suspected Infection.

OBJECTIVES: Suspected infection and sepsis are common conditions seen among older ICU patients. Frailty has prognostic importance among critically ill patients, but its impact on outcomes and resource utilization in older patients with suspected infection is unknown. We sought to evaluate the association between patient frailty (defined as a Clinical Frailty Scale ≥ 5) and outcomes of critically ill patients with suspected infection. We also evaluated the association between frailty and the quick Sequential Organ Failure Assessment score. DESIGN: Analysis of a prospectively collected registry. SETTING: Two hospitals within a single tertiary care level hospital system between 2011 and 2016. PATIENTS: We analyzed 1,510 patients 65 years old or older (at the time of ICU admission) and with suspected infection at the time of ICU admission. Of these, 507 (33.6%) were categorized as "frail" (Clinical Frailty Scale ≥ 5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. A total of 558 patients (37.0%) died in-hospital. Frailty was associated with increased risk of in-hospital death (adjusted odds ratio, 1.81 [95% CIs, 1.34-2.49]). Frailty was also associated with higher likelihood of discharge to long-term care (adjusted odds ratio, 2.06 [95% CI, 1.50-2.64]) and higher likelihood of readmission within 30 days (adjusted odds ratio, 1.83 [95% CI, 1.38-2.34]). Frail patients had increased ICU resource utilization and total costs. The combination of frailty and quick Sequential Organ Failure Assessment greater than or equal to 2 further increased the risk of death (adjusted odds ratio, 7.54 [95% CI, 5.82-9.90]). CONCLUSIONS: The presence of frailty among older ICU patients with suspected infection is associated with increased mortality, discharge to long-term care, hospital readmission, resource utilization, and costs. This work highlights the importance of clinical frailty in risk stratification of older ICU patients with suspected infection.

Outcomes of hospitalized hematologic oncology patients receiving rapid response system activation for acute deterioration.

BACKGROUND: Patients with hematologic malignancies who are admitted to hospital are at increased risk of deterioration and death. Rapid response systems (RRSs) respond to hospitalized patients who clinically deteriorate. We sought to describe the characteristics and outcomes of hematologic oncology inpatients requiring rapid response system (RRS) activation, and to determine the prognostic accuracy of the SIRS and qSOFA criteria for in-hospital mortality of hematologic oncology patients with suspected infection. METHODS: We used registry data from two hospitals within The Ottawa Hospital network, between 2012 and 2016. Consecutive hematologic oncology inpatients who experienced activation of the RRS were included in the study. Data was gathered at the time of RRS activation and assessment. The primary outcome was in-hospital mortality. Logistical regression was used to evaluate for predictors of in-hospital mortality. RESULTS: We included 401 patients during the study period. In-hospital mortality for all included patients was 41.9% (168 patients), and 145 patients (45%) were admitted to ICU following RRS activation. Among patients with suspected infection at the time of RRS activation, Systemic Inflammatory Response Syndrome (SIRS) criteria had a sensitivity of 86.9% (95% CI 80.9-91.6) and a specificity of 38.2% (95% CI 31.9-44.8) for predicting in-hospital mortality, while Quick Sequential Organ Failure Assessment (qSOFA) criteria had a sensitivity of 61.9% (95% CI 54.1-69.3) and a specificity of 91.4% (95% CI 87.1-94.7). Factors associated with increased in-hospital mortality included transfer to ICU after RRS activation (adjusted odds ratio [OR] 3.56, 95% CI 2.12-5.97) and a higher number of RRS activations (OR 2.45, 95% CI 1.63-3.69). Factors associated with improved survival included active malignancy treatment at the time of RRS activation (OR 0.54, 95% CI 0.34-0.86) and longer hospital length of stay (OR 0.78, 95% CI 0.70-0.87). CONCLUSIONS: Hematologic oncology inpatients requiring RRS activation have high rates of subsequent ICU admission and mortality. ICU admission and higher number of RRS activations are associated with increased risk of death, while active cancer treatment and longer hospital stay are associated with lower risk of mortality. Clinicians should consider these factors in risk-stratifying these patients during RRS assessment.

Prognostic accuracy of the Hamilton Early Warning Score (HEWS) and the National Early Warning Score 2 (NEWS2) among hospitalized patients assessed by a rapid response team.

BACKGROUND: Rapid response teams (RRTs) respond to hospitalized patients experiencing clinical deterioration and help determine subsequent management and disposition. We sought to evaluate and compare the prognostic accuracy of the Hamilton Early Warning Score (HEWS) and the National Early Warning Score 2 (NEWS2) for prediction of in-hospital mortality following RRT activation. We secondarily evaluated a subgroup of patients with suspected infection. METHODS: We retrospectively analyzed prospectively collected data (2012-2016) of consecutive RRT patients from two hospitals. The primary outcome was in-hospital mortality. We calculated the number needed to examine (NNE), which indicates the number of patients that need to be evaluated in order to detect one future death. RESULTS: Five thousand four hundred ninety-one patients were included, of whom 1837 (33.5%) died in-hospital. Mean age was 67.4 years, and 51.6% were male. A HEWS above the low-risk threshold (≥ 5) had a sensitivity of 75.9% (95% confidence interval (CI) 73.9-77.9) and specificity of 67.6% (95% CI 66.1-69.1) for mortality, with a NNE of 1.84. A NEWS2 above the low-risk threshold (≥ 5) had a sensitivity of 84.5% (95% CI 82.8-86.2), and specificity of 49.0% (95% CI: 47.4-50.7), with a NNE of 2.20. The area under the receiver operating characteristic curve (AUROC) was 0.76 (95% CI 0.75-0.77) for HEWS and 0.72 (95% CI: 0.71-0.74) for NEWS2. Among suspected infection patients (n = 1708), AUROC for HEWS was 0.79 (95% CI 0.76-0.81) and for NEWS2, 0.75 (95% CI 0.73-0.78). CONCLUSIONS: The HEWS has comparable clinical accuracy to NEWS2 for prediction of in-hospital mortality among RRT patients.