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Decision tree analysis to predict the risk of intracranial haemorrhage after mild traumatic brain injury in patients taking DOACs.
Turcato, G, Zaboli, A, Pfeifer, N, Maccagnani, A, Tenci, A, Giudiceandrea, A, Zannoni, M, Ricci, G, Bonora, A, Brigo, F
The American journal of emergency medicine. 2021;:388-393
Abstract
BACKGROUND Although 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). AIM: To 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. METHODS Patients 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. RESULTS Among 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. CONCLUSIONS The 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.
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Predictors of post-traumatic complication of mild brain injury in anticoagulated patients: DOACs are safer than VKAs.
Cipriano, A, Park, N, Pecori, A, Bionda, A, Bardini, M, Frassi, F, Lami, V, Leoli, F, Manca, ML, Del Prato, S, et al
Internal and emergency medicine. 2021;(4):1061-1070
Abstract
Although mild traumatic brain injury (MTBI) in people on oral anticoagulant treatment (OAT) is a frequent challenge for Emergency Department (ED), strong guidelines recommendations are lacking. In the attempt to assess the safety profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs), we have recruited 473 patients with a MTBI on OAT (43.6% males; age 81.8 ± 8.7 years), admitted to the Pisa's University Hospital ED (Jan 2016-Oct 2018). All patients underwent a head CT scan with those with no sign of acute bleedings remaining under clinical observation for the ensuing 24 h. Fifty patients (10.6%, 95% CI: 8.1-13.7%) had immediate intracranial hemorrhage (ICH), with a prevalence of patient-important outcomes due to immediate ICH of 1.1% (95% CI 0.4-2.4%); 3 patients died (0.6%, 95% CI 0.2-1.8) and 2 required neurosurgical intervention. Immediate ICHs were more frequent in VKA-treated than in DOAC-treated patients (15.9 vs. 6.4%. RR 2.5. 95%CI 1.4-4.4. p < 0.05). Multivariate analysis identified that post-traumatic amnesia, evidence of trauma above clavicles, high blood glucose, high blood pressure (BP) at arrival, and low prothrombin activity were predictors of immediate ICH. The prevalence of delayed ICH was 1.0% (95%CI 0.4-2.5%) without differences between DOACs and VKAs. Despite ICH being a frequent complication of MTBI in patients on OAT, immediate and delayed patient-important outcomes are rare. DOACs have a better safety profile than VKAs. Simple clinical parameters such as blood pressure at arrival or blood glucose might provide useful predictors of immediate ICH.Trial registration number: 11924_CIPRIANO. Local ethics committee approval number 33096.
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A Randomized Controlled Trial of Precision Vestibular Rehabilitation in Adolescents following Concussion: Preliminary Findings.
Kontos, AP, Eagle, SR, Mucha, A, Kochick, V, Reichard, J, Moldolvan, C, Holland, CL, Blaney, NA, Collins, MW
The Journal of pediatrics. 2021;:193-199
Abstract
OBJECTIVE To compare the effectiveness of a 4-week precision vestibular rehabilitation intervention compared with a behavioral management control intervention for adolescents with vestibular symptoms/impairment within 21 days of a concussion. STUDY DESIGN This study used double-blind, randomized controlled trial design involving adolescent (12-18 years) patients with a diagnosed sport/recreation-related concussion with vestibular symptoms/impairment from a concussion-specialty clinic between October 2018 and February 2020. Eligible participants were randomized in a 1:1 to either a 4-week vestibular intervention group (VESTIB) or a behavioral management control group (CONTROL). CONTROLS (n = 25) were prescribed behavioral management strategies (eg, physical activity, sleep, hydration, nutrition, stress management) and instructed to perform stretching/physical activity (eg, walking, stationary cycle) 30 minutes/day. VESTIB (n = 25) were prescribed precision vestibular rehabilitation exercises and instructed to perform at-home exercises for 30 minutes/day. Primary outcomes were improvement in Vestibular/Ocular Motor Screening vestibular items (ie, horizontal/vertical vestibular-ocular reflex, visual motion sensitivity) at 4 weeks postenrollment. RESULTS We screened 310 and enrolled a total of 55 (18%) adolescent patients who were randomized to one of the interventions. Fifty of fifty-five (91%) participants completed all aspects of the study protocol. Participants in VESTIB improved significantly across the intervention period in horizontal (mean difference-1.628; 95% CI [-3.20, -0.06]; P = .04) and vertical (mean difference-2.24; 95% CI [-4.01, -0.48]; P = .01) vestibular-ocular reflex, but not visual motion sensitivity (mean difference-2.03; 95% CI [-4.26, 0.19]) of the Vestibular/Ocular Motor Screening score compared with CONTROLS. CONCLUSIONS Overall, the vestibular intervention group experienced greater clinical improvements in vestibular symptoms/impairment than controls across the 4-week intervention. TRIAL REGISTRATION ClinicalTrials.gov: NCT03555370.
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A randomized cohort study of the efficacy of PO magnesium in the treatment of acute concussions in adolescents.
Standiford, L, O'Daniel, M, Hysell, M, Trigger, C
The American journal of emergency medicine. 2021;:419-422
Abstract
INTRODUCTION/STUDY OBJECTIVE Concussions are becoming a growing concern in society today with one out of every five adolescents being affected. This accounts for 1.6 to 3.8 million emergency department visits annually. The current standard of care involves an initial period of mental rest with symptomatic care and symptom-based return to daily activities/sports. High dose IV magnesium has been proven to be neuroprotective in severe TBI. We hypothesized that oral magnesium replacement following a concussion will decrease the overall symptomatic period allowing a quicker return to functional baseline. METHODS We used a randomized cohort study involving patients aged 12-18 who presented within 48 h after a concussion. Our study design had a treatment arm including acetaminophen, ondansetron, and magnesium PO and a placebo arm of acetaminophen and ondansetron. We then utilized the Post- Concussion Severity Score (PCSS) to evaluate the extent of the patient's symptoms. This score was collected immediately prior to obtaining medications, 1 h, 48 h, and 120 h after starting the study. The study relied on outpatient follow up through phone conversations, and a Sports Medicine clinic locally. RESULTS Our data shows that there was a statistically significant decrease in the PCSS at 48 h (p = 0.016) in the magnesium group relative to the placebo treatment arm. This study does imply that magnesium supplementation has potential benefit in treatment of concussions acutely. CONCLUSION Oral magnesium replacement decreases symptoms acutely following a concussion and should be provided with symptomatic management following a concussion in the emergency setting.
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A Physiologically Based Approach to Prescribing Exercise Following a Sport-Related Concussion.
Worts, PR, Burkhart, SO, Kim, JS
Sports medicine (Auckland, N.Z.). 2019;(5):683-706
Abstract
Clinical management of concussion has evolved over the last 20 years, and complete cognitive and physical rest remains a common clinical recommendation. The duration of rest may vary widely, from 24-48 h to several weeks or until the patient's symptoms have resolved or returned to near baseline levels. Following a period of rest, a stepwise progression of exercise is used for gradual return to play or to work. Previous research in healthy people suggested that prolonged periods of physical inactivity consistently induced deleterious physiological and psychological effects. A growing body of evidence indicates that initiating exercise earlier in the recovery process following a concussion may reduce symptom burden and lower the incidence of post-concussion syndrome. Preliminary findings appear promising, but data on the appropriate exercise prescription for patients who recently sustained a concussion are limited. We reviewed the literature in healthy individuals and patients with concussion and post-concussion syndrome to develop a physiologically based exercise prescription for the days following a concussion. Using this, practitioners may shorten the rest period and initiate controlled exercise earlier during the recovery process following a concussion.
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Test Performance and Test-Retest Reliability of the Vestibular/Ocular Motor Screening and King-Devick Test in Adolescent Athletes During a Competitive Sport Season.
Worts, PR, Schatz, P, Burkhart, SO
The American journal of sports medicine. 2018;(8):2004-2010
Abstract
BACKGROUND The Vestibular/Ocular Motor Screening (VOMS) and King-Devick (K-D) test are tools designed to assess ocular or vestibular function after a sport-related concussion. PURPOSE To determine the test-retest reliability and rate of false-positive results of the VOMS and K-D test in a healthy athlete sample. STUDY DESIGN Cohort study (diagnosis); Level of evidence, 2. METHODS Forty-five healthy high school student-athletes (mean age, 16.11 ± 1.43 years) completed self-reported demographics and medical history and were administered the VOMS and K-D test during rest on day 1 (baseline). The VOMS and K-D test were administered again once during rest (prepractice) and once within 5 minutes of removal from sport practice on day 2 (removal). The Borg rating of perceived exertion scale was administered at removal. Intraclass correlation coefficients were used to determine test-retest reliability on the K-D test and the average near point of convergence (NPC) distance on the VOMS. Level of agreement was used to examine VOMS symptom provocation over the 3 administration times. Multivariate base rates were used to determine the rate of false-positive results when simultaneously considering multiple clinical cutoffs. RESULTS Test-retest reliability of total time on the K-D test (0.91 [95% CI, 0.86-0.95]) and NPC distance (0.91 [95% CI, 0.85-0.95]) was high across the 3 administration times. Level of agreement ranged from 48.9% to 88.9% across all 3 times for the VOMS items. Using established clinical cutoffs, false-positive results occurred in 2% of the sample using the VOMS at removal and 36% using the K-D test. CONCLUSION The VOMS displayed a false-positive rate of 2% in this high school student-athlete cohort. The K-D test's false-positive rate was 36% while maintaining a high level of test-retest reliability (0.91). Results from this study support future investigation of VOMS administration in an acutely injured high school athletic sample. Going forward, the VOMS may be more stable than other neurological and symptom report screening measures and less vulnerable to false-positive results than the K-D test.
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Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.
Cipriano, A, Pecori, A, Bionda, AE, Bardini, M, Frassi, F, Leoli, F, Lami, V, Ghiadoni, L, Santini, M
Internal and emergency medicine. 2018;(7):1077-1087
Abstract
Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.
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Concussion Biomarkers Assessed in Collegiate Student-Athletes (BASICS) I: Normative study.
Asken, BM, Bauer, RM, DeKosky, ST, Houck, ZM, Moreno, CC, Jaffee, MS, Weber, AG, Clugston, JR
Neurology. 2018;(23):e2109-e2122
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Abstract
OBJECTIVE To describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes. METHODS In this observational cohort study, β-amyloid peptide 42 (Aβ42), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Standardized normative distributions are reported for each biomarker. We evaluated main effects (analyses of variance) of sex and race, reporting demographic-specific normative metrics when appropriate. In a subset of 31 female participants, test-retest reliability (Pearson r) and reliable change indices (80%, 90%, and 95% confidence intervals) across a 6- to 12-month interval are reported for Aβ42, total tau, S100B, and UCH-L1. RESULTS Males exhibited higher UCH-L1 (p < 0.001, Cohen d = 0.75) and S100B (p < 0.001, d = 0.56) than females, while females had higher CNPase (p < 0.001, d = 0.43). Regarding race, black participants had higher baseline levels of UCH-L1 (p < 0.001, d = 0.61) and S100B (p < 0.001, d = 1.1) than white participants. Conversely, white participants had higher baseline levels of Aβ42 (p = 0.005, d = 0.28) and CNPase (p < 0.001, d = 0.46). Test-retest reliability was generally poor, ranging from -0.02 to 0.40, and Aβ42 significantly increased from time 1 to time 2. CONCLUSION Healthy collegiate athletes express concussion-related serum biomarkers in variable concentrations. Accounting for demographic factors such as sex and race is essential. Evidence suggested poor reliability for serum biomarkers; however, understanding how other factors influence biomarker expression, as well as knowledge of reliable change metrics, may improve clinical interpretation and future study designs.
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Utility of Serum Biomarkers in the Diagnosis and Stratification of Mild Traumatic Brain Injury.
Lewis, LM, Schloemann, DT, Papa, L, Fucetola, RP, Bazarian, J, Lindburg, M, Welch, RD
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2017;(6):710-720
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OBJECTIVE The objective was to compare test characteristics of a single serum concentration of glial fibrillary acidic protein (GFAP), S-100β, and ubiquitin carboxyl terminal hydrolase L1 (UCH-L1), obtained within 6 hours of head injury, to diagnose mild traumatic brain injury (mTBI) in head-injured subjects. METHODS Adults aged 18 to 80 years who presented to one of seven EDs with a blunt closed head injury underwent head CT within 4 hours of injury and had blood drawn for biomarker analysis within 6 hours of injury were eligible. Subjects were considered to have mTBI if they had an initial Glasgow Coma Scale (GCS) > 13 and met one or more of the following criteria: loss of consciousness (LOC), posttraumatic amnesia, or confusion. Subjects with mTBI and an abnormal head computed tomography (CT) scan were categorized as complicated mTBI; those with a normal head CT were categorized as uncomplicated mTBI; and subjects with a GCS = 15, no LOC, no posttraumatic amnesia, and no confusion were considered to not have a mTBI. Biomarker concentration measurements for GFAP and UCH-L1 were performed using an enzyme-linked immunosorbent assay. S-100β concentration was determined using an electrochemiluminescence immunoassay. Median biomarker concentration for each group was compared using the Kruskal-Wallis test. Logistic regression was used to determine area under the receiver operating curve (AUC) for each of the three biomarkers. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and negative and positive likelihood ratios (LRs) for the three biomarkers to differentiate between complicated mTBI, uncomplicated mTBI, and no mTBI were calculated. RESULTS A total of 247 subjects were enrolled and had adequate clinical and biomarker information for analysis. A total of 188 met criteria for mTBI, with 34 (18.1%) having an acute abnormality on CT (complicated mTBI). The mean (±SD) age of the study population was 45.8 (±17.3) years, and 59.9% were male. Median serum concentrations for all biomarkers were significantly different between groups, lowest in the no mTBI group, and progressively increasing in the uncomplicated and complicated mTBI groups (p < 0.0001). All three biomarkers were significant classifiers of mTBI versus no mTBI, with the following AUCs: GFAP, 0.70; S-100β, 0.69; and UCH-L1, 0.65 (p = 0.17). Sensitivity for mTBI was highest for S-100β (96.5%). NPVs ranged from 31% for UCH-L1 to 35% for GFAP. PPVs ranged from 75.5% for S-100β to 96.5% for GFAP. Negative LR ranged from 0.59 for GFAP to 0.71 for UCH-L1, with positive LR ranging from 1.0 for both UCH-L1 and S-100β to 8.7 for GFAP. CONCLUSION A single serum concentration of GFAP, UCH-L1, or S-100β within 6 hours of head injury may be useful in identifying and stratifying the severity of brain injury in emergency department patients with head trauma, but cannot reliably exclude a diagnosis of concussion. A positive GFAP was associated with the presence of concussion.
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A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion.
Lawrence, DW, Sharma, B
Brain injury. 2016;(8):960-8
Abstract
BACKGROUND Nutritional interventions are promising treatment adjuncts in the management of concussion. Vitamin D (VDH) supplementation has demonstrated neuroprotective properties in multiple models of acquired brain injury. OBJECTIVE Review the neuroprotective role of VDH supplementation following traumatic brain injury (TBI). METHODS A Medline search was conducted to review manuscripts investigating the influence of VDH status or supplementation on TBI outcomes. RESULTS The search identified 165 studies, of which five were included. Four manuscripts studied a rodent model of TBI, while one studied a clinical sample. Vitamin D monotherapy independently reduced inflammation and neuronal injury following TBI, with a more robust effect observed in combination with progesterone (PROG). One study demonstrated VDH deficiency exacerbates post-TBI inflammatory response. One study in a clinical sample found combination therapy superior to PROG alone or placebo in improving outcomes after severe TBI. One study observed a more robust response to low-dose VDH compared to high-dose VDH when given in combination with PROG. CONCLUSION A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI.