Outcomes of a novel ED observation pathway for mild traumatic brain injury and associated intracranial hemorrhage

BackgroundRecent studies have shown that the majority of non-anticoagulated patients with small subdural or subarachnoid intracranial hemorrhage (ICH) in the setting of mild traumatic brain injury do not experience clinical deterioration or require neurosurgical intervention. We implemented a novel ED observation pathway to reduce unnecessary admissions among patients with ICH in the setting of mild TBI (complicated mild TBI, cmTBI).MethodsProspective, single-center study of ED patients presenting to a Level-1 Trauma Center, 4/2016–12/2018. Inclusion criteria: head injury with GCS ≥ 14, minor positive CT findings (i.e. subdural hematoma <1 cm). Exclusion criteria: GCS < 14, multi-system trauma procedural intervention or admission, epidural hematoma, skull fracture, seizure, anticoagulant/antiplatelet use beyond aspirin, physician discretion. Outcomes: pathway completion rate, ED length-of-stay (LOS), neurosurgical intervention, hospital LOS, 7-day return visits.Results138 patients met all pathway criteria and were included in analysis. 113/138 (81.9%) patients were discharged home after observation with mean ED LOS of 17.3 h (median 15.4 h, SD +/− 10.5) including 91/111 (81.9%) patients transferred from outside hospitals (median 18.1 h, SD +/− 11.0). Increased age and aspirin use were correlated with pathway non-completion requiring admission, but not due to hematoma expansion. Among admitted patients, none required neurosurgical intervention. Seven (5.1%) 7-day return visits occurred, 3 (2%) related to initial cmTBI; 1 (0.9%) was admitted for neurologic monitoring.ConclusionsED observation for patients with cmTBI resulted in an 82% pathway completion rate, including outside hospital transfers. These results suggest that patients with cmTBI may be safely discharged from the ED after a brief period of observation. Our pathway protocol and implementation involved neurosurgical consultation and the ability to perform repeat neurologic exams in the ED. Future studies should examine the feasibility of non-transfer protocols for appropriately selected patients and access to neurosurgical expertise in the community setting.     

Analysis of Clinical and Laboratory Risk Factors of Post-Traumatic Intracranial Hemorrhage in Patients on Direct Oral Anticoagulants with Mild Traumatic Brain Injury: An Observational Multicenter Cohort

BackgroundAssessing the risk of intracranial hemorrhage (ICH) in patients with a mild traumatic brain injury (MTBI) who are taking direct oral anticoagulants (DOACs) is challenging. Currently, extensive use of computed tomography (CT) is routine in the emergency department (ED).ObjectiveThis study aims to investigate whether the clinical and laboratory characteristics presented at the ED evaluation can also estimate the risk of post-traumatic ICH in DOAC-treated patients with MTBI.MethodsA retrospective observational study was conducted in three EDs in Italy from January 1, 2016 to March 15, 2020. All patients treated with DOACs who were evaluated for an MTBI in the ED were enrolled. The primary outcome of the study was the presence of post-traumatic ICH in the head CT performed in the ED.ResultsOf 930 patients on DOACs with MTBI who were enrolled, 6.8% (63 of 930) had a post-traumatic ICH and 1.5% (14 of 930) were treated with surgery or died as a result of the ICH. None of the laboratory factors were associated with an increased risk of ICH. On multivariate analysis, previous neurosurgical intervention, major trauma dynamic, post-traumatic loss of consciousness, post-traumatic amnesia, Glasgow Coma Scale score of 14, and evidence of trauma above the clavicles were associated with a higher risk of post-traumatic ICH. The net clinical benefit provided by risk factor assessment appears superior to the strategy of performing CT on all DOAC-treated patients.ConclusionsAssessment of the clinical characteristics presented at ED admission can help identify DOAC-treated patients with MTBI who are at risk of ICH.     

Clinical Benefit of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves

PurposeThe use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and bioprosthetic heart valve is still controversial. The aim of this study was to compare the tolerability and effectiveness of treatment with DOACs versus vitamin K antagonists (VKAs) in patients with AF and a bioprosthetic heart valve in clinical practice.MethodsData for this study were sourced from the multicenter, prospectively maintained AF Research Database (NCT03760874), which includes all patients with AF undergoing follow-up at participating centers through outpatient visits every 3–6 months. The rates of occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism), major bleed, and intracranial hemorrhage (ICH) were assessed. These data were used for quantifying the net clinical benefit (NCB) of DOACs versus VKAs, in accordance with the following formula: (Thromboembolic events incidence rate with VKAs – Thromboembolic events incidence rate with DOACs) – Weighting factor × (ICH rate with DOACs – ICH incidence rate with VKAs). The database was retrospectively queried for patients with AF who were prescribed a DOAC or VKA and had a history of bioprosthetic heart valve replacement.FindingsA total of 434 patients with AF (DOACs, n = 211; VKAs, n = 223) were identified. Propensity score matching identified 130 patients prescribed DOACs (apixaban, 55.4%; rivaroxaban, 30.0%; dabigatran, 13.1%; edoxaban, 1.4%) and the same number of VKA recipients (warfarin, 89.2%; acenocoumarol, 10.8%). The mean (SD) duration of follow-up was 26.8 (2.3) months. The incidence rates of thromboembolic events were 1.3 per 100 person-years in the DOAC group versus 2.0 per 100 person-years in the VKA group (P = 0.14). The incidence rates of major bleed events were 2.6 per 100 person-years in the DOAC group versus 4.9 per 100 person-years in the VKA group (P = 0.47). The incidence rates of ICH were 0.38 per 100 person-years in the DOAC group versus 1.16 in the VKA group (hazard ratio = 0.33; 95% CI, 0.05–2.34; P = 0.3). A positive NCB of DOACs over VKAs of +1.87 was found.ImplicationsAccording to these data from clinical practice, DOACs seem to be associated with a greater NCB versus VKAs in patients with AF with a bioprosthetic heart valve, primarily due to lower rates of both major bleeds and thromboembolic events.     

Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis

ObjectiveThe antifibrinolytic agent tranexamic acid (TXA) has demonstrated clinical benefit in trauma patients with severe bleeding, but its effectiveness in patients with traumatic brain injury (TBI) is unclear. We conducted a systematic review to evaluate the following research question: In ED patients with or at risk of intracranial hemorrhage (ICH) secondary to TBI, does TXA compared to placebo improve patients' outcomes?MethodsMEDLINE, EMBASE, CINAHL, and other databases were searched for randomized controlled trial (RCT) or quasi-RCT studies that compared the effect of TXA to placebo on outcomes of TBI patients. The main outcomes of interest included mortality, neurologic function, hematoma expansion, and adverse effects. We used “Grading quality of evidence and strength of recommendations” to assess the quality of trials. Two authors independently abstracted data using a data collection form. Results from studies were pooled when appropriate.ResultsOf 1030 references identified through the search, 2 high-quality RCTs met inclusion criteria. The effect of TXA on mortality had a pooled relative risk of 0.64 (95% confidence interval [CI], 0.41-1.02); on unfavorable functional status, a relative risk of 0.77 (95% CI, 0.59-1.02); and on ICH progression, a relative risk of 0.76 (95% CI, 0.58-0.98). No serious adverse effects (such as thromboembolic events) associated with TXA group were reported in the included trials.ConclusionPooled results from the 2 RCTs demonstrated statistically significant reduction in ICH progression with TXA and a nonstatistically significant improvement of clinical outcomes in ED patients with TBI. Further evidence is required to support its routine use in patients with TBI.     

Is repeat head CT necessary in patients with mild traumatic intracranial hemorrhage

BackgroundPatients with traumatic intracranial hemorrhage (TIH) frequently receive repeat head CT scans (RHCT) to assess for progression of TIH. The utility of this practice has been brought into question, with some studies suggesting that in the absence of progressive neurologic symptoms, the RHCT does not lead to clinical interventions.MethodsThis was a retrospective review of consecutive patients with CT-documented TIH and GCS ≥ 13 presenting to an academic emergency department from 2009 to 2013. Demographic, historical, and physical exam variables, number of CT scans during admission were collected with primary outcomes of: neurological decline, worsening findings on repeat CT scan, and the need for neurosurgical intervention.ResultsOf these 1126 patients with mild traumatic intracranial hemorrhage, 975 had RHCT. Of these, 54 (5.5% (4.2–7.2 95 CI) had neurological decline, 73 (7.5% 5.9–9.3 95 CI) had hemorrhage progression on repeat CT scan, and 58 (5.9% 4.5–7.6 95 CI) required neurosurgical intervention. Only 3 patients (0.3% 0.1–0.9% 95 CI) underwent neurosurgical intervention due to hemorrhage progression on repeat CT scan without neurological decline. In this scenario, the number of RHCT scans needed to be performed to identify this one patient is 305.ConclusionsRHCT after initial findings of TIH and GCS ≥ 13 leading to a change to operative management in the absence of neurologic progression is a rare event. A protocol that includes selective RHCT including larger subdural hematomas or patients with coagulopathy (vitamin K inhibitors and anti-platelet agents) may be a topic for further study.     

Risk factors associated with intracranial bleeding and neurosurgery in patients with mild traumatic brain injury who are receiving direct oral anticoagulants

BackgroundThe established clinical risk factors for post-traumatic intracranial bleeding have not been evaluated in patients receiving DOACs yet.AimEvaluating the association between clinic and patient characteristics and post-traumatic intracranial bleeding (ICH) in patients with mild traumatic brain injury (MTBI) and DOACs.MethodsThis is a retrospective observational study conducted on three Emergency Departments. Multivariate analysis provided association in terms of OR with the risk of ICH. The performance of the multivariate model, described in a nomogram, has been tested with discrimination and decision curve analysis.ResultsOf 473 DOACs patients with MTBI, 8.5% had post-traumatic ICH. On multivariable analysis, major dynamics (odds ratio [OR] 6.255), post-traumatic amnesia (OR 3.961), post-traumatic loss of consciousness (LOC, OR 7.353), Glasgow Coma Scale (GCS) score < 15 (OR 3.315), post-traumatic headache (OR 4.168) and visible trauma above the clavicles (OR 3.378) were associated with a higher likelihood of ICH. The multivariate model, used for the nomogram construction, showed a good performance (AUC bias corrected with 5000 bootstraps resample 0.78). The DCAs showed a net clinical benefit of the prognostic model.ConclusionsClinical risk factors can be used in DOACs patients to better define the risk of post-traumatic ICH.     

The efficacy of tranexamic acid for brain injury: A meta-analysis of randomized controlled trials

BackgroundTranexamic acid shows some treatment efficacy for traumatic brain injury. This systematic review and meta-analysis is conducted to investigate the efficacy of tranexamic acid for traumatic brain injury.MethodsThe databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases are systematically searched for collecting the randomized controlled trials (RCTs) regarding the efficacy of tranexamic acid for traumatic brain injury.ResultsThis meta-analysis has included six RCTs. Compared with placebo group in patients with traumatic brain injury, tranexamic acid results in remarkably reduced mortality (risk ratio (RR) = 0.91; 95% confidence interval (CI) = 0.85 to 0.97; P = 0.004) and growth of hemorrhagic mass (RR = 0.78; 95% CI = 0.61 to 0.99; P = 0.04), but has no important impact on neurosurgery (RR = 0.99; 95% CI = 0.85 to 1.15; P = 0.92), extracranial surgery (RR = 1.00; 95% CI = 0.97 to 1.04; P = 0.99), unfavorable outcome (Glasgow Outcome Scale, GOS) (RR = 0.72; 95% CI = 0.47–1.11; P = 0.14), pulmonary embolism (RR = 1.86; 95% CI = 0.42–8.29; P = 0.42), and deep venous thrombosis (RR = 0.97; 95% CI = 0.64–1.47; P = 0.88).ConclusionsTranexamic acid is associated with substantially reduced mortality and growth of hemorrhagic mass in patients with traumatic brain injury, but the need of neurosurgery and extracranial surgery, as well as the risk of unfavorable outcome (GOS) are similar between tranexamic acid and placebo.     

Use of Neuroimaging for Children With Seizure in General and Pediatric Emergency Departments

BackgroundSeizure is a common reason for children to visit the emergency department (ED). Pediatric and general EDs may obtain computed tomography (CT) scans of the head for seizure at different rates.ObjectiveTo compare rates of head CT for pediatric seizure between general and pediatric EDs.MethodsThis was a retrospective cohort study using the National Hospital Ambulatory Medical Care Survey for patients <21 years of age presenting to an ED with a chief complaint or diagnosis of seizure between 2006 to 2017. Of these patients, we compared head CT use between general and pediatric EDs among patients with fever, trauma, and co-diagnosis of epilepsy using univariable risk differences and in a multivariable logistic regression model.ResultsMore than 5 (5.4) million (78.8%) and 1.5 million (21.2%) pediatric patients with seizure presented to general and pediatric EDs, respectively. Of those, 22.4% (1.21 million) and 13.2% (192,357) underwent CT scans of the head, respectively, a risk difference of 9.2% (95% confidence interval [CI] 2.3–16.1). General EDs obtained CT scans of the head more often in patients with epilepsy (risk difference 17.9% [95% CI 4.0–31.9]), without fever (12.2% [95% CI 3.1–21.4]), and without trauma (10.6% [95% CI 4.4–16.8]). Presenting to a general ED, being afebrile, or having trauma were associated with head CT with adjusted odds ratios of 1.7 (95% CI 1.0–3.2), 4.9 (95% CI 2.6–9.2), and 2.0 (95% CI 1.2–3.4), respectively. Age, gender, and epilepsy were not associated with head CT among all patients with seizure.ConclusionsChildren with seizure are more likely to undergo CT scans of the head at general EDs compared with pediatric EDs.     

Four-factor prothrombin complex concentrate for the reversal of factor Xa inhibitors for traumatic intracranial hemorrhage

ObjectiveThe objective of this study was to determine the effectiveness and safety of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitors in patients with traumatic intracranial hemorrhage (ICH).MethodsThis was a retrospective cohort study of patients taking factor Xa inhibitors with traumatic ICH between March 1, 2015 and August 31, 2017 at two trauma centers. The primary outcome was in-hospital mortality in patients who received 4F-PCC (4F-PCC group) compared to those who did not (no reversal group). Secondary outcomes included functional recovery, hospital and intensive care unit (ICU) length of stay (LOS), and thromboembolic complications.ResultsThere were 62 patients included in the study. Injury Severity Score (ISS) was significantly higher in the 4F-PCC group (17.6 vs. 12.1, p = 0.019). The 4F-PCC group had a significantly higher mortality (22.9% vs. 3.7%, p = 0.034) and longer ICU LOS (2.5 vs. 1.4 days, p = 0.0024). The no reversal group had a significantly higher incidence of ischemic stroke/transient ischemic attack (TIA) (0% vs. 14.8%, p = 0.019). After controlling for ISS, there was no significant difference in mortality (p = 0.20), ICU LOS (p = 0.64), or ischemic stroke/TIA (p = 0.94). There was no difference in hospital LOS, discharge disposition, final Activity Measure for Post Acute Care daily activity score, VTE, or MI.ConclusionPatients with a higher ISS received 4F-PCC preferentially, which led to an apparent mortality benefit the no reversal group. After adjusting for baseline differences between groups, there was no difference in mortality, functional recovery, hospital and ICU LOS, or thromboembolic complications.     

Body Temperature after EMS Transport: Association with Traumatic Brain Injury Outcomes

Introduction: Low body temperatures following prehospital transport are associated with poor outcomes in patients with traumatic brain injury (TBI). However, a minimal amount is known about potential associations across a range of temperatures obtained immediately after prehospital transport. Furthermore, a minimal amount is known about the influence of body temperature on non-mortality outcomes. The purpose of this study was to assess the correlation between temperatures obtained immediately following prehospital transport and TBI outcomes across the entire range of temperatures. Methods: This retrospective observational study included all moderate/severe TBI cases (CDC Barell Matrix Type 1) in the pre-implementation cohort of the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH/NINDS: 1R01NS071049). Cases were compared across four cohorts of initial trauma center temperature (ITCT): <35.0°C [Very Low Temperature (VLT)]; 35.0–35.9°C [Low Temperature (LT)]; 36.0–37.9°C [Normal Temperature (NT)]; and ≥38.0°C [Elevated Temperature (ET)]. Multivariable analysis was performed adjusting for injury severity score, age, sex, race, ethnicity, blunt/penetrating trauma, and payment source. Adjusted odds ratios (aORs) with 95% confidence intervals (CI) for mortality were calculated. To evaluate non-mortality outcomes, deaths were excluded and the adjusted median increase in hospital length of stay (LOS), ICU LOS and total hospital charges were calculated for each ITCT group and compared to the NT group. Results: 22,925 cases were identified and cases with interfacility transfer (7361, 32%), no EMS transport (1213, 5%), missing ITCT (2083, 9%), or missing demographic data (391, 2%) were excluded. Within this study cohort the aORs for death (compared to the NT group) were 2.41 (CI: 1.83–3.17) for VLT, 1.62 (CI: 1.37–1.93) for LT, and 1.86 (CI: 1.52–3.00) for ET. Similarly, trauma center (TC) LOS, ICU LOS, and total TC charges increased in all temperature groups when compared to NT. Conclusion: In this large, statewide study of major TBI, both ETs and LTs immediately following prehospital transport were independently associated with higher mortality and with increased TC LOS, ICU LOS, and total TC charges. Further study is needed to identify the causes of abnormal body temperature during the prehospital interval and if in-field measures to prevent temperature variations might improve outcomes.     

Different Coagulation Indicators in Predicting Clinical Outcomes for Patients With Direct Oral Anticoagulants: A Systematic Review and Meta-analysis

PurposeThere are many anticoagulant test indexes available for direct oral anticoagulants (DOACs), but how to select the appropriate index and the index cutoff values are still controversial. This is the first study, to our knowledge, to assess the association of different coagulation indicators with clinical outcomes among DOACs using a meta-analysis of observational studies.MethodsA medical literature search was conducted using PubMed, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Library from inception to February 2020. Studies that reported relationships between coagulation indexes and clinical outcomes or the diagnostic value of coagulation assays were included in the analysis.FindingsA total of 17 articles (7 meta-analyses and 10 systematic reviews) from 8904 citations were included in the analysis. In the analysis of bleeding events with coagulation indexes for DOACs, for peak prothrombin time level (cutoff value of 19–25 s), the pooled results found a sensitivity of 0.61 (95% CI, 0.44–0.75) and a specificity of 0.71 (95% CI, 0.49–0.86). For rivaroxaban, the trough anti–factor Xa concentration (AXA-C) (cutoff value of 400–500 ng/mL) had a sensitivity of 0.53 (95% CI, 0.16–0.87) and a specificity of 0.87 (95% CI, 0.71–0.94), with a diagnostic odds ratio of 7 (95% CI, 2–32). For apixaban, trough AXA-C had a sensitivity of 0.85 (95% CI, 0.60–0.96) and a specificity of 0.83 (95% CI, 0.52–0.95). The AUC of the AXA-C peak was higher than that of the trough AXA-C for apixaban, with a higher sensitivity and specificity. Compared with trough concentration of anti–factor IIa for dabigatran, the peak concentration had a higher specificity (98%) at the cutoff value of 484 ng/mL. In the analysis of thromboembolic events with coagulation indexes for DOACs, peak and trough prothrombin time values were not typically correlated with subsequent symptomatic venous thromboembolism, without a sensitivity or specificity higher than 90%. Trough AXA-C had a sensitivity of 100% and but a low specificity (<50%) for rivaroxaban-apixaban. Trough AXA-C had a sensitivity of 100% and a specificity of 32% with a cutoff value of 108 ng/mL for dabigatran.ImplicationPeak prothrombin time (19–25 s) and AXA-C had a better predictive value on bleeding outcomes for rivaroxaban and apixaban, whereas peak concentration of anti–factor IIa activity can be an indicator for dabigatran. Coagulation indexes might not be a good indicator of thromboembolic events of DOACs. Because the limited studies focused on association of coagulation indicators and clinical outcomes, more studies are needed to verify this in the future.     

Association of skull fracture with in-hospital mortality in severe traumatic brain injury patients

IntroductionTo identify the association between skull fracture (SF) and in-hospital mortality in patients with severe traumatic brain injury (TBI).Materials and methodsThis multicenter cohort study included a retrospective analysis of data from the Japan Trauma Data Bank (JTDB). JTDB is a nationwide, prospective, observational trauma registry with data from 235 hospitals. Adult patients with severe TBI (Glasgow Coma Scale <9, head Abbreviated Injury Scale (AIS) ≥ 3, and any other AIS < 3) who were registered in the JTDB between January 2004 and December 2017 were included in the study. Patients who (a) were < 16 years old, (b) developed cardiac arrest before or at hospital arrival, and (c) had burns and penetrating injuries were excluded from the study. In-hospital mortality was the primary outcome assessed. Multivariable logistic regression analyses were performed to calculate the adjusted odds ratios (ORs) of SF and their 95% confidence intervals (CIs) for in-hospital mortality.ResultsA total of 9607 patients were enrolled [median age: 67 (interquartile range: 50–78) years] in the study. Among those patients, 3574 (37.2%) and 6033 (62.8%) were included in the SF and non-SF groups, respectively. The overall in-hospital mortality rate was 44.1% (4238/9607). A multivariate analysis of the association between SF and in-hospital mortality yielded a crude OR of 1.63 (95% CI: 1.47–1.80). A subgroup analysis of the association of skull vault fractures, skull base fractures, and both fractures together with in-hospital mortality yielded adjusted ORs of 1.60 (95% CI: 1.42–1.98), 1.40 (95% CI: 1.16–1.70), and 2.14 (95% CI: 1.74–2.64), respectively, relative to the non-SF group.ConclusionsThis observational study showed that SF is associated with in-hospital mortality among patients with severe TBI. Furthermore, patients with both skull base and skull vault fractures were associated with higher in-hospital mortality than those with only one of these injuries.     

Predictors of intensive care unit length of stay and intracranial pressure in severe traumatic brain injury

ObjectiveThe aim of this study was to explore the relationship of intracranial pressure (ICP) with intensive care unit (ICU) length of stay in a large cohort of severe traumatic brain injury patients and identify factors associating with prolonged ICU course.MethodsThis was a single-center database review of de-identified research data that had been prospectively collected; setting: neurosurgical ICU, Ben Taub General Hospital, Houston, TX.ResultsIn a cohort of 438 severe traumatic brain injury (TBI) patients, 149 (34%) had a motor Glasgow Coma Scale score of 1 to 3 on admission and 284 (65%) had 4 to 5. Intracranial pressure during the ICU course was 19.8 ± 11.2 mm Hg. Favorable outcome was obtained in 148 (34%), and unfavorable, in 211 (48%) patients with a mortality of 28%. ICU length of stay (LOS) was 19.4 ± 13.9 days. Joint modeling of ICP and ICU LOS was undertaken, adjusted for the International Mission for Prognosis and Analysis of Clinical Trials in TBI admission prognostic indicators. A higher ICP was not significantly associated with longer ICU LOS (P = .4). However, presence of a mass lesion on admission head computed tomography was strongly correlated with a prolonged ICU LOS (P = .0007). Diffuse injuries with basal cistern compression or midline shift were marginally associated with a longer ICU LOS (P = .053).ConclusionsICP, as monitored and managed according to BTF guidelines, is not associated with ICU length of stay. Patients with severe TBI and a mass lesion on admission head computed tomography were found to have prolonged ICU LOS independently of other indicators of injury severity and intracranial pressure course.     

The Long-Term Prognosis in People With Recent Onset Low Back Pain From Emergency Departments: An Inception Cohort Study

Most studies investigating the course of recent-onset low back pain (LBP) included patients from primary care. We aimed to describe the prognosis in people with recent-onset LBP presenting to emergency departments (EDs) and to identify prognostic factors for nonrecovery. This inception cohort study with a 1-year follow-up recruited 600 consecutive acute LBP patients presenting to 4 EDs. The outcomes measured the days to recover from pain, recover from disability, return to previous work hours and duties, and complete recovery. Within 12 months, 73% of participants (95% confidence interval [CI] = 69–77) recovered from pain, 86% (95% CI = 82–90) recovered from disability, 79% (95% CI = 71–87) returned to previous work hours and duties, and 70% (95% CI = 66–74) completely recovered. The median recovery times were 67 days (95% CI = 54–80) to recover from pain, 37 days (95% CI = 31–43) to recover from disability, 37 days (95% CI = 25–49) to return to previous work hours and duties, and 70 days (95% CI = 57–83) to recover completely. Higher pain levels, a higher perceived risk of persistent LBP, more days of reduced activity due to LBP, more pain sites, and higher duration of LBP were associated with complete nonrecovery within 6 months.PerspectiveThis information relates to prognosis and to likely recovery times for patients with recent-onset LBP in EDs. The findings also confirm previous factors associated with poor outcomes in patients with recent-onset LBP.     

Stroke Risk and Outcomes in Patients With Traumatic Brain Injury: 2 Nationwide Studies

ObjectiveTo investigate whether patients with traumatic brain injury (TBI) have an increased risk of stroke or poststroke mortality.Participants and MethodsUsing Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 30,165 patients with new TBI and 120,660 persons without TBI between January 1, 2000, and December 31, 2004. The risk of stroke was compared between 2 cohorts through December 31, 2008. To investigate the association between in-hospital mortality after stroke and history of TBI, we conducted a case-control study of 7751 patients with newly diagnosed stroke between January 1, 2005, and December 31, 2008.ResultsThe TBI cohort had an increased stroke risk (hazard ratio [HR], 1.98; 95% CI, 1.86-2.11). Among patients with stroke, those with a history of TBI had a higher risk of poststroke mortality compared with those without TBI (odds ratio, 1.57; 95% CI, 1.13-2.19). In the TBI cohort, factors associated with stroke were history of TBI hospitalization (HR, 3.14; 95% CI, 2.77-3.56), emergency care for TBI (HR, 3.37; 95% CI, 2.88-3.95), brain hemorrhage (HR, 2.69; 95% CI, 2.43-2.99), skull fracture (HR, 3.00; 95% CI, 2.42-3.71), low income (HR, 2.65; 95% CI, 2.16-3.25), and high medical expenditure for TBI care (HR, 2.26; 95% CI, 2.09-2.43). The severity of TBI was also correlated with poststroke mortality.ConclusionsTraumatic brain injury was associated with risk of stroke and poststroke mortality. The relationship between TBI and poststroke mortality does not seem to transcend all age groups. This research shows the importance of prevention, early recognition, and treatment of stroke in this vulnerable population.     

Can the “important brain injury criteria” predict neurosurgical intervention in mild traumatic brain injury? A validation study

BackgroundThere is variability in the management of patients presenting to the emergency department (ED) with mild traumatic brain injury (MTBI) and abnormal findings on their initial head computed tomography (CT). The main objective of this study was to validate the value of the Important Brain Injury (IBI) criteria, introduced by the Canadian CT-Head Rule, in predicting the need for surgical intervention. The secondary objective was to identify independent predictors for neurosurgical intervention.MethodsThis is a post hoc analysis of a prospective cohort of adult patients presenting to the ED of one tertiary care, academic center, between 2008 and 2012, with MTBI and an abnormal initial head CT. Neurosurgical intervention was at the discretion of the treating physician. The sensitivity and specificity of the IBI criteria were calculated with 95% confidence intervals (CI95%). A multivariate logistic regression model was used to identify independent predictors for neurosurgical intervention with the direct entry method.ResultsA total of 678 patients (male = 65.9%, mean age = 62.5 years) were included, of whom 114 (16.8%) required neurosurgical intervention. All patients requiring neurosurgical intervention met IBI criteria on their initial head CT (sensitivity of 100% [CI95% 96.8–100]). However, 368 (65.2%) patients with findings of IBI did not require neurosurgical intervention (specificity of 34.8% [CI95% 30.8–38.8]). Age over 65 was independently associated with neurosurgical intervention in the IBI population.ConclusionThe IBI criteria for MTBI identified all patients who required neurosurgical intervention; however its specificity is low.     

A systematic review and Bayesian network meta‐analysis of risk of intracranial hemorrhage with direct oral anticoagulants

Essentials

• Risk of intracranial hemorrhage (ICH) may differ between direct oral anticoagulants (DOACs).
• We compared the risk of ICH between DOACs using network meta‐analysis.
• Dabigatran 110 mg and 150 mg were safer than rivaroxaban on Bayesian analysis.
• Dabigatran 110 mg ranked as the safest DOAC while rivaroxaban ranked last.

Summary

Background

The comparative risk of intracranial hemorrhage (ICH) among direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban and edoxaban) remains unclear.

Objective

To determine the difference in risk of ICH between DOACs

Methods

Seventeen randomized controlled trials (RCTs) were selected using PubMed/MEDLINE, EMBASE and CENTRAL (Inception, 31 December 2017). Estimates were reported as odds ratio (OR) with 95% credible interval (CR.I) in Bayesian network meta‐analysis (NMA), and OR with 95% confidence interval (CI) in traditional meta‐analyses. Relative ranking probability of each group was generated based on surface under the cumulative ranking curve (SUCRA).

Results

In NMA of 116 618 patients from 17 RCTs (apixaban = 19 495 patients, rivaroxaban = 14 157 patients, dabigatran = 16 074 patients, edoxaban = 11 652 patients, and comparator = 55 315 patients), all DOACs were safer than warfarin for risk of ICH. Dabigatran 110 mg ranked as the safest drug (SUCRA, 0.85) and reduced the risk of ICH by 56% compared to rivaroxaban (OR, 0.44; 95% Cr.I, 0.22–0.82). Pairwise meta‐analysis validated these findings, showing that DOACs were safer than warfarin (OR, 0.46; 95% CI, 0.35–0.59). Subgroup analysis showed that the benefit was present when DOACs were used in non‐valvular atrial fibrillation (NVAF) (OR, 0.51; 95% CI, 0.38–0.68) or venous thromboembolism (VTE) (OR, 0.32; 95% CI, 0.18–0.58).

Conclusion

Dabigatran 110 mg may be the safest choice among any anticoagulant regarding risk of ICH. Both dabigatran 110 mg and 150 mg were safer than rivaroxaban.

     

Decision tree analysis to predict the risk of intracranial haemorrhage after mild traumatic brain injury in patients taking DOACs

BackgroundAlthough the preliminary evidence seems to confirm a lower incidence of post-traumatic bleeding in patients treated with direct oral anticoagulants (DOACs) compared to those on vitamin K antagonists (VKAs), the recommended management of mild traumatic brain injury (MTBI) in patients on DOACs is the same as those on the older VKAs, risking excessive use of CT in the emergency department (ED).AimTo determine which easily identifiable clinical risk factors at the first medical evaluation in the ED may indicate an increased risk of post-traumatic intracranial haemorrhage (ICH) in patients on DOACs with MTBI.MethodsPatients on DOACs who were evaluated in the ED for an MTBI from 2016 to 2020 at four centres in Northern Italy were considered. A decision tree analysis using the chi-square automatic interaction detection (CHAID) method was conducted to assess the risk of post-traumatic ICH after an MTBI. Known pre- and post-traumatic clinical risk factors that are easily identifiable at the first medical evaluation in the ED were used as input predictor variables.ResultsAmong the 1146 patients on DOACs in this study, post-traumatic ICH was present in 6.5% (75/1146). Decision tree analysis using the CHAID method found post-traumatic TLOC, post-traumatic amnesia, major trauma dynamic, previous neurosurgery and evidence of trauma above the clavicles to be the strongest predictors associated with the presence of post-traumatic ICH in patients on DOACs. The absence of a concussion seems to indicate subgroups at very low risk of requiring neurosurgery.ConclusionsThe machine-based CHAID model identified distinct prognostic groups of patients with distinct outcomes based on clinical factors. Decision trees can be useful as guides for patient selection and risk stratification.     

Rationale,methodology, and implementation of a nationwide multicenter randomized controlled trial of long-term mild hypothermia for severe traumatic brain injury (the LTH-1 trial)

BackgroundTraumatic brain injury (TBI) is a major public health problem recently, however, no intervention showing convincing efficacy. Therapeutic hypothermia with a relatively long duration (more than 48 h), as a promising treatment measure, might improve the patient outcome following severe TBI.Methods/designThe LTH-1 trial is a prospective, nationwide multicenter, randomized, controlled clinical trial to examine the efficacy and safety of long-term mild hypothermia in adult patients after severe traumatic brain injury. A total of 300 consecutive patients will be recruited from 15 large neurosurgical centers in China. The eligible patient will be randomized to receive either long-term mild hypothermia (34–35 °C) for 5 days, or normothermia (36–37 °C). Additionally, a standardized management protocol will be used in all patients. The primary end point is the neurological outcome 6 months post-injury on the Glasgow Outcome Scale. The secondary outcomes include GOS score at one month post-injury, mortality during six months after injury, length of ICU and hospital stay, intracranial pressure control and Glasgow Coma Scale score during the hospital stay and frequency of complications during the six-month follow-up period.DiscussionLong-term hypothermia is recommended by most recent studies and its efficacy urgently needs to be established in randomized controlled settings. The LTH-1 trial, together with other ongoing studies, will present more evidence for optimal use of hypothermia in severe TBI patients.     

Mortality on DOACs Versus on Vitamin K Antagonists in Atrial Fibrillation: Analysis of the Hungarian Health Insurance Fund Database

PurposeLimited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period.MethodsThe Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0–3, 4–6, and 7–12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled.FindingsA 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30–59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40–0.77, P = 0.001) in the lower (0-1) CHA₂DS₂-VASc score segment and in those with fewer (0–1) bleeding risk factors (HR = 0.50, CI 0.34–0.73, P = 0.001). The RRR in mortality with DOACs was 33% within the first 3 months, and 6% in the second year.ImplicationsThromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA₂DS₂-VASc score, and those with fewer bleeding risk factors.