Predictors of persistent concussion symptoms in adults with acute mild traumatic brain injury presenting to the emergency department.

OBJECTIVE: To identify risk factors associated with persistent concussion symptoms in adults presenting to the emergency department (ED) with acute mild traumatic brain injury (TBI). METHODS: This was a secondary analysis of a randomized controlled trial conducted in three Canadian EDs whereby the intervention had no impact on recovery or healthcare utilization outcomes. Adult (18-64 years) patients with a mild TBI sustained within the preceding 48 h were eligible for enrollment. The primary outcome was the presence of persistent concussion symptoms at 30 days, defined as the presence of ≥ 3 symptoms on the Rivermead Post-concussion Symptoms Questionnaire. RESULTS: Of the 241 patients who completed follow-up, median (IQR) age was 33 (25 to 50) years, and 147 (61.0%) were female. At 30 days, 49 (20.3%) had persistent concussion symptoms. Using multivariable logistic regression, headache at ED presentation (OR: 7.7; 95% CI 1.6 to 37.8), being under the influence of drugs or alcohol at the time of injury (OR: 5.9; 95% CI 1.8 to 19.4), the injury occurring via bike or motor vehicle collision (OR: 2.9; 95% CI 1.3 to 6.0), history of anxiety or depression (OR: 2.4; 95% CI 1.2 to 4.9), and numbness or tingling at ED presentation (OR: 2.4; 95% CI 1.1 to 5.2), were found to be independently associated with persistent concussion symptoms at 30 days. CONCLUSIONS: Five variables were found to be significant predictors of persistent concussion symptoms. Although mild TBI is mostly a self-limited condition, patients with these risk factors should be considered high risk for developing persistent concussion symptoms and flagged for early outpatient follow-up.

RéSUMé: OBJECTIFS: Identifier les facteurs de risque associés aux symptômes persistants consécutifs à une commotion cérébrale chez les adultes se présentant au service des urgences avec un traumatisme cranio-cérébral aiguë. MéTHODES: Il s'agissait d'une analyse secondaire d'un essai contrôlé randomisé mené dans trois services d'urgence Canadien, dans lequel l'intervention n'a eu aucun impact sur le rétablissement ou les conséquences d'utilisation des soins de santé. L'essai clinique a été effectuée sur les patients adultes (âgés de 18 à 64 ans) avec un traumatisme cranio-cérébral léger (TCCL) soutenu dans les 48 heures précédentes. Le critère principal de jugement était la présence des symptômes de traumatisme crânien 30 jours après la commotion, définie comme la présence d'au moins 3 symptômes dans le questionnaire Rivermead sur les symptômes post-commotionnels. RéSULTATS: Parmi les 241 patients qui ont terminé le suivi, l'âge médian (EI) était de 33 ans (25 à 50) et 147 (61,0 %) étaient des femmes. À 30 jours, 49 (20,3 %) présentaient des symptômes persistants. En utilisant une régression logistique multivariée, des maux de tête à la présentation aux services d'urgence (OR: 7,7; IC à 95 % : 1,6 à 37,8), être sous l'influence de drogues ou d'alcool au moment de la commotion (OR : 5,9; IC à 95 % : 1,8 à 19,4), la blessure survenue à la suite d'une collision à vélo ou à moteur (OR : 2,9; IC à 95 %: 1,3 à 6,0), des antécédents d'anxiété ou de dépression (OR : 2,4; IC à 95 % : 1,2 à 4,9) et un engourdissement ou des picotements lors de la présentation aux services d'urgence (OR : 2,4; IC à 95 % : 1,1 à 5,2), se sont avérés être indépendamment associés aux symptômes persistants consécutifs à une commotion cérébrale à 30 jours CONCLUSIONS: Cinq variables se sont révélées être des indicateurs significatifs des symptômes persistants consécutifs à une commotion cérébrale. Bien que le TCCL soit principalement une condition auto-limitée, les patients présentant ces facteurs de risque doivent être considérés comme à haut risque de développer des symptômes persistants et signalés pour un suivi ambulatoire précoce.

Physician choices in pulmonary embolism testing.

BACKGROUND: Evidence-based guidelines advise excluding pulmonary embolism (PE) diagnosis using d-dimer in patients with a lower probability of PE. Emergency physicians frequently order computed tomography (CT) pulmonary angiography without d-dimer testing or when d-dimer is negative, which exposes patients to more risk than benefit. Our objective was to develop a conceptual framework explaining emergency physicians' test choices for PE. METHODS: We conducted a qualitative study using in-depth interviews of emergency physicians in Canada. A nonmedical researcher conducted in-person interviews. Participants described how they would test simulated patients with symptoms of possible PE, answered a knowledge test and were interviewed on barriers to using evidence-based PE tests. RESULTS: We interviewed 63 emergency physicians from 9 hospitals in 5 cities, across 3 provinces. We identified 8 domains: anxiety with PE, barriers to using the evidence (time, knowledge and patient), divergent views on evidence-based PE testing, inherent Wells score problems, the drive to obtain CT rather than to diagnose PE, gestalt estimation artificially inflating PE probability, subjective reasoning and cognitive biases supporting deviation from evidence-based tests and use of evidence-based testing to rule out PE in patients who are very unlikely to have PE. Choices for PE testing were influenced by the disease, environment, test qualities, physician and probability of PE. INTERPRETATION: Analysis of structured interviews with emergency physicians provided a conceptual framework to explain how these physicians use tests for suspected PE. The data suggest 8 domains to address when implementing an evidence-based protocol to investigate PE.

A randomized trial comparing prescribed light exercise to standard management for emergency department patients with acute mild traumatic brain injury.

BACKGROUND: There is a paucity of effective management strategies to prevent prolonged symptoms following mild traumatic brain injury (mTBI), and emerging evidence suggesting possible benefits of exercise. The objective of this trial was to determine whether adult patients presenting to the emergency department (ED) with a diagnosis of acute mTBI prescribed light exercise were less likely to develop persistent postconcussion symptoms (PCS). METHODS: This was a randomized controlled trial conducted in three Canadian EDs. Consecutive, adult (18-64 years) ED patients with an mTBI sustained within the preceding 48 hours were eligible for enrollment. The intervention group received discharge instructions prescribing 30 minutes of daily light exercise, and the control group was given standard mTBI instructions advising gradual return to exercise following symptom resolution. The primary outcome was the proportion of patients with PCS at 30 days, defined as the presence of three or more symptoms on the Rivermead Post-concussion Symptoms Questionnaire (RPQ). RESULTS: A total of 367 patients were enrolled (control group, n = 184; intervention, n = 183). Median age was 32 years and 201 (57.6%) were female. There was no difference in the proportion of patients with PCS at 30 days (control, 13.4% vs intervention, 14.6%; ∆1.2%, 95% confidence interval [CI] = -6.2 to 8.5). There were no differences in median change of RPQ scores, median number of return health care provider visits, median number of missed school or work days, or unplanned return ED visits within 30 days. Participants in the control group reported fewer minutes of light exercise at 7 days (30 vs 35; ∆5, 95% CI = 2 to 15). CONCLUSION: In this trial of prescribed early light exercise for acute mTBI, there were no differences in recovery or health care utilization outcomes. Results suggest that early light exercise may be encouraged as tolerated at ED discharge following mTBI, but this guidance is not sufficient to prevent PCS.

Neutrophils and neutrophil extracellular traps enhance venous thrombosis in mice bearing human pancreatic tumors.

Pancreatic cancer is associated with a high incidence of venous thromboembolism. Neutrophils have been shown to contribute to thrombosis in part by releasing neutrophil extracellular traps (NET). A recent study showed that increased plasma levels of the NET biomarker, citrullinated histone H3 (H3Cit), are associated with venous thromboembolism in patients with pancreatic and lung cancer but not in those with other types of cancer, including breast cancer. In this study, we examined the contribution of neutrophils and NET to venous thrombosis in nude mice bearing human pancreatic tumors. We found that tumor-bearing mice had increased circulating neutrophil counts and levels of granulocyte-colony stimulating factor, neutrophil elastase, H3Cit and cell-free DNA compared with controls. In addition, thrombi from tumor-bearing mice contained increased levels of the neutrophil marker Ly6G, as well as higher levels of H3Cit and cell-free DNA. Thrombi from tumor-bearing mice also had denser fibrin with thinner fibers consistent with increased thrombin generation. Importantly, either neutrophil depletion or administration of DNase I reduced the thrombus size in tumor-bearing but not in control mice. Our results, together with clinical data, suggest that neutrophils and NET contribute to venous thrombosis in patients with pancreatic cancer.

Increasing the sensitivity of the human microvesicle tissue factor activity assay.

INTRODUCTION: The TF-FVIIa complex is the primary activator of coagulation. Elevated levels of microvesicle (MV) bearing tissue factor (TF)-dependent procoagulant activity are detectable in patients with an increased risk of thrombosis. Several methods have been described to measure MV TF activity but they are hampered by limited sensitivity and specificity. The aim of this work was to increase the sensitivity of the MV TF activity assay (called Chapel Hill assay). MATERIAL AND METHODS: Improvements of the MV TF activity assay included i/ speed and time of centrifugation, ii/ use of a more potent inhibitory anti-TF antibody iii/ use of FVII and a fluorogenic substrate to increase specificity. RESULTS: The specificity of the MV TF activity assay was demonstrated by the absence of activity on MV derived from a knock-out-TF cell line using an anti-human TF monoclonal antibody called SBTF-1, which shows a higher TF inhibitory effect than the anti-human TF monoclonal antibody called HTF-1. Experiments using blood from healthy individuals, stimulated or not by LPS, or plasma spiked with 3 different levels of MV, demonstrated that the new assay was more sensitive and this allowed detection of MV TF activity in platelet free plasma (PFP) samples from healthy individuals. However, the assay was limited by an inter-assay variability, mainly due to the centrifugation step. CONCLUSIONS: We have improved the sensitivity of the MV TF activity assay without losing specificity. This new assay could be used to evaluate levels of TF-positive MV as a potential biomarker of thrombotic risk in patients.