Diagnostic performance of biomarker S100B and guideline adherence in routine care of mild head trauma

Abstract Background The Scandinavian Neurotrauma Committee (SNC) has recommended the use of serum S100B as a biomarker for mild low-risk Traumatic brain injuries (TBI). This study aimed to assess the adherence to the SNC guidelines in clinical practice and the diagnostic performance of S100B in patients with TBI. The aims of this study were to examine adherence to the SNC guideline and the diagnostic accuracy of serum protein S100B. Methods Data of consecutive patients of 18 years and above who presented to the emergency department (ED) at Helsingborg Hospital with isolated head injuries, were retrieved from hospital records. Patients with multitrauma, follow-up visits, and visits managed by a nurse without physician involvement were excluded. Results A total of 1671 patients were included of which 93 (5.6%) had intracranial hemorrhage. CT scans were performed in 62% of patients. S100B was measured in 26% of patients and 30% of all measurements targeted the low-risk mild head injuries indicated by the guideline. S100B's recommended cut-off value (≥ 0.10 µg/L) had a 100% sensitivity, 47% specificity, 10.1% positive predictive value, and 100% negative predictive value—if applied to the target SNC category (SNC 4). If applied to all patients tested, the sensitivity was 93% for traumatic intracranial hemorrhage (TICH). Current ED practices were adherent to the SNC guideline in 55% of patients. Non-adherent practices occurred in 64% of patients with low-risk mild head injuries (SNC4) including overtesting or undertesting of S100B and CT scans. Conclusion Adherence to guidelines was low and associated with a higher admission rate than non-adherence practice but no significant increase in missed TICH or death associated with non-adherence to guideline was found. In routine care, we found that the sensitivity and NPV of serum protein S100B was excellent and safely ruled out TICH when measured in the patient category recommended by the guideline. However, measuring serum protein S100B in patients not recommended by the guideline rendered unacceptably low sensitivity with possible missed TICHs as a consequence. To further delineate the magnitude and impact of non-adherence, more studies are needed

Features of urine S100B and its ability to rule out intracranial hemorrhage in patients with head trauma : a prospective trial

Purpose: Traumatic brain injury causes morbidity and mortality worldwide. S100B is the most documented emergency brain biomarker and its urine-assay might be advantageous because of easier sampling. The primary aim was to evaluate urine S100B’s ability to rule out intracranial hemorrhage. Secondary aims included S100B temporal pattern for 48 h post-trauma and chemical properties of urine that affect urine S100B. Methods: Patients with head trauma were sampled for serum and urine S100B. Patients who were admitted for intracranial hemorrhage were sampled for 48 h to assess S100B-level, renal function, urine-pH, etc. Results: The negative predictive value of serum S100B was 97.0% [95% confidence interval (CI) 89.5–99.2%] and that of urine S100B was 89.1% (95% CI 85.5–91.9%). The specificity of serum S100B was 34.4% (95% CI 27.7–41.6%) and that of urine was 67.1% (95% CI 59.4–74.1%). Urine-pH correlated strongly with urine S100B during the first 6-h post-trauma. Trend-analysis of receiver operator characteristics of S100B in serum, urine the arithmetic difference between serum and urine S100B showed the largest area under the curve for arithmetic difference, which had a negative predictive value of 93.1% (95% CI 89.1–95.8%) and a specificity of 71.8% (95% CI 64.4–78.4%). Conclusion: This study cannot support ruling out intracranial hemorrhage with urine S100B. Urine-pH might affect urine S100B and merits further studies. Serum and urine S100B have poor concordance and interchangeability. The arithmetic difference had a slightly better area under the curve and can be worth exploring in certain subgroups

Application of NICE or SNC guidelines may reduce the need for computerized tomographies in patients with mild traumatic brain injury : A retrospective chart review and theoretical application of five guidelines

Background: Traumatic brain injuries continue to be a significant cause of mortality and morbidity worldwide. Most traumatic brain injuries are classified as mild, with a low but not negligible risk of intracranial hemorrhage. To help physicians decide which patients might benefit from a computerized tomography (CT) of the head to rule out intracranial hemorrhage, several clinical decision rules have been developed and proven effective in reducing the amount of negative CTs, but they have not been compared against one another in the same cohort as to which one demonstrates the best performance. Methods: This study involved a retrospective review of the medical records of patients seeking care between January 1 and December 31, 2017 at Helsingborg Hospital, Sweden after head trauma. The Canadian CT Head Rule (CCHR), the New Orleans Criteria (NOC), the National Emergency X-Radiography Utilization Study II (NEXUS II), the National Institute of Health and Care Excellence (NICE) guideline and the Scandinavian Neurotrauma Committee (SNC) guideline were analyzed. A theoretical model for each guideline was constructed and applied to the cohort to yield a theoretical CT-rate for each guideline. Performance parameters were calculated and compared. Results: One thousand three hundred fifty-three patients were included; 825 (61%) CTs were performed, and 70 (5.2%) cases of intracranial hemorrhage were found. The CCHR and the NOC were applicable to a minority of the patients, while the NEXUS II, the NICE, and the SNC guidelines were applicable to the entire cohort. A theoretical application of the NICE and the SNC guidelines would have reduced the number of CT scans by 17 and 9% (P = < 0.0001), respectively, without missing patients with intracranial hemorrhages requiring neurosurgical intervention. Conclusion: A broad application of either NICE or the SNC guidelines could potentially reduce the number of CT scans in patients suffering from mTBI in a Scandinavian setting, while the other guidelines seemed to increase the CT frequency. The sensitivity for intracranial hemorrhage was lower than in previous studies for all guidelines, but no fatality or need for neurosurgical intervention was missed by any guideline when they were applicable

Prospective comparison of capillary and venous brain biomarker S100B : Capillary samples have large inter-sample variation and poor correlation with venous samples

Background: Guidelines for the emergency management of mild traumatic brain injury have been used for over a decade and are considered safe. However, they recommend computerized tomography for at least half of these patients. The Scandinavian Neurotrauma Committee guideline uses serum S100B protein level to rule out intracranial hemorrhage. Analysis of capillary serum S100B protein level has not yet been employed for this purpose. The primary aim of this study was to investigate the correlation and agreement of capillary and venous serum S100B protein level over a spectrum of concentrations typical for mild traumatic brain injury. Methods: Eighteen patients with traumatic intracranial hemorrhage and 39 volunteers without trauma to the head within the past 7 days were recruited. Blood was sampled from patients with intracranial hemorrhage daily up to four consecutive days and healthy volunteers were sampled once during the study. One venous and two capillary samples were drawn at each sampling event. Samples were analyzed using the Cobas e411 S100 electrochemiluminescence assay. Results: Median serum S100B protein level of capillary sampling 1 was 0.12 (IQR 0.075-0.21) μg/l and median serum S100B protein level of capillary sampling 2 was 0.13 (IQR 0.08-0.22) μg/l. Median serum S100B protein level of all venous samples was 0.05 (IQR 0.03-0.07) μg/l. Correlation plots of capillary and venous samples showed poor correlation and Bland-Altman plots showed a large dispersion of samples and wide limits of agreement. Conclusion: The results of this study indicate that correlation and agreement between capillary and venous samples are low, and because of this, we cannot recommend studies on capillary serum S100B protein level to rule out intracranial hemorrhage in mild traumatic brain injury. Given the limitations of the current sampling and analysis methods of capillary protein S100B protein level, we conclude that evaluating its predictive ability to rule out intracranial hemorrhage should be withheld until more reliable methods can be incorporated into the study design

Management of Traumatic Brain Injury in the Emergency Department : Guideline Adherence and Patient Safety

Background: Traumatic brain injury is a common reason not only for emergency visits worldwide but also for significant morbidity and mortality. Several clinical guidelines exist but adherence is generally low. Aim: To study attitudes toward computed tomography of the head among emergency department Change to physicians throughout the article who manage patients with trauma to the head and doctors' adherence to guidelines. Methods: Quantitative questionnaire study with questionnaires collected over 3 months before introduction of new guidelines. After introduction, intermission of 8 months passed when information and education were given. Thereafter, questionnaires were collected for another 3 months. Results: A total of 694 patients were registered at the emergency department. A total of 161 questionnaires were analyzed; 50.9% did not use guidelines, 39% before intermission, and 60.5% after. When Canadian CT Head Rule was applied, 30.4% of patients with no loss of consciousness were referred to computed tomography, violating guideline recommendation. Conclusion: Guidelines are designed to improve performance but are not always applied correctly or as frequently as intended. Information and education did not increase guideline adherence. To improve guideline adherence, more innovative measures than formal guidelines must be undertaken. To find out what these measures are, we suggest qualitative studies to elucidate interventions that will have bigger impact on performance

Microwave scan and brain biomarkers to rule out intracranial hemorrhage : study protocol of a planned prospective study (MBI01)

Purpose: The aim of this planned study is to evaluate the ability of a cranial microwave scanner in conjunction with nine brain biomarkers (Aβ40, Aβ42, GFAP, H-FABP, S100B, NF-L, NSE, UCH-L1 and IL-10) to detect and rule out traumatic intracranial hemorrhage in an emergency department setting. Traumatic brain injury is a world-wide topic of interest for researchers and clinicians. It affects 2% of the population per annum and presents challenges for physicians as patients’ initial signs and symptoms do not always correlate with the extent of brain injury. The gold standard for diagnosis of intracranial hemorrhage is head computerized tomography (CT) with the drawbacks of high cost and radiation exposure. A fast, secure way of diagnosing without these drawbacks has potential to make care more effective and reduce cost. Methods: Study will be prospective and enroll adult, consenting patients with head trauma who seek emergency department care. Only patients where the treating physician prescribes a head-CT will be included. The microwave scan and blood sampling will be performed in close temporal proximity to the CT scan. Results will be analyzed with sensitivity, specificity and receiver operator characteristics analysis to provide the best combination of a number of biomarkers and the microwave scan. Conclusion: This study will explore the diagnostic accuracy of a head microwave scanner in combination with biomarkers in ruling out intracranial hemorrhage in traumatic brain injury patients presenting to the emergency department. Potentially, this combined diagnostic approach could achieve both high sensitivity and high specificity, thereby reducing the need of CT-head scans when managing these patients. Clinicaltrials.gov identifier: NCT04666766. Registered December 11, 2020

Comparison of the predictive value of two international guidelines for safe discharge of patients with mild traumatic brain injuries and associated intracranial pathology

Purpose: To determine and compare the sensitivity, specificity, and proportion of patients eligible for discharge by the Brain Injury Guidelines and the Mild TBI Risk Score in patients with mild traumatic brain injury and concomitant intracranial injury. Methods: Retrospective review of the medical records of adult patients with traumatic intracranial injuries and an initial Glasgow Coma Scale score of 14–15, who sought care at Helsingborg Hospital between 2014/01/01 and 2019/12/31. Both guidelines were theoretically applied. The sensitivity, specificity, and percentage of the cohort that theoretically could have been discharged by either guideline were calculated. The outcome was defined as death, in-hospital intervention, admission to the intensive care unit, requiring emergency intubation due to intracranial injury, decreased consciousness, or seizure within 30 days of presentation. Results: Of the 538 patients included, 8 (1.5%) and 10 (1.9%) were eligible for discharge according to the Brain Injury Guidelines and the Mild TBI Risk Score, respectively. Both guidelines had a sensitivity of 100%. The Brain Injury Guidelines had a specificity of 2.3% and the Mild TBI Risk Score had a specificity of 2.9%. Conclusion: There was no difference between the two guidelines in sensitivity, specificity, or proportion of the cohort eligible for discharge. Specificity and proportion of cohort eligible for discharge were lower than each guideline’s original study. At present, neither guideline can be recommended for implementation in the current or similar settings

Ways to improve guideline adherence in the emergency department: an interview study on the management of traumatic brain injuries

PurposeThe aim was to explore factors affecting guideline adherence among doctors in the emergency department and to explore the general perception about local guidelines for traumatic brain injuries.MethodsThirty semi-structured interviews were conducted with doctors with experience working in the emergency department regarding different aspects of guideline use, with emphasis on the management of traumatic brain injuries. Twenty-eight interviews were included for analysis. The interviews were recorded, transcribed, and analysed iteratively. Emergent codes were identified and organised into themes and subthemes.ResultsEight themes were identified. Barriers were centred on low availability of local guidelines and guideline document design. Facilitating factors included a concise document, appropriate visual aids, high accessibility, and encouragement by management and senior peers. The local guidelines on traumatic brain injuries were regarded as distinct, but it was occasionally difficult to determine when they were applicable. Mandatory admission of patients on anticoagulants was sometimes perceived as excessive. Biomarker S100b was believed to sometimes lead to delayed care.ConclusionThe participants believed that guideline adherence would increase by facilitating guideline availability, by providing concise, easy-to-understand, and well-illustrated guidelines available in printed form, as well as establishing a culture that promotes guideline use. The local guidelines for traumatic brain injuries were appreciated, but could be improved

Management of mild traumatic brain injury–trauma energy level and medical history as possible predictors for intracranial hemorrhage

Purpose: Head trauma is common in the emergency department. Identifying the few patients with serious injuries is time consuming and leads to many computerized tomographies (CTs). Reducing the number of CTs would reduce cost and radiation. The aim of this study was to evaluate the characteristics of adults with head trauma over a 1-year period to identify clinical features predicting intracranial hemorrhage. Methods: Medical record data have been collected retrospectively in adult patients with traumatic brain injury. A total of 1638 patients over a period of 384 days were reviewed, and 33 parameters were extracted. Patients with high-energy multitrauma managed with ATLS™ were excluded. The analysis was done with emphasis on patient history, clinical findings, and epidemiological traits. Logistic regression and descriptive statistics were applied. Results: Median age was 58 years (18–101, IQR 35–77). High age, minor head injury, new neurological deficits, and low trauma energy level correlated with intracranial hemorrhage. Patients younger than 59 years, without anticoagulation or antiplatelet therapy who suffered low-energy trauma, had no intracranial hemorrhages. The hemorrhage frequency in the entire cohort was 4.3% (70/1638). In subgroup taking anticoagulants, the frequency of intracranial hemorrhage was 8.6% (10/116), and in the platelet-inhibitor subgroup, it was 11.8% (20/169). Conclusion: This study demonstrates that patients younger than 59 years with low-energy head trauma, who were not on anticoagulants or platelet inhibitors could possibly be discharged based on patient history. Maybe, there is no need for as extensive medical examination as currently recommended. These findings merit further studies

Antiplatelet therapy contributes to a higher risk of traumatic intracranial hemorrhage compared to anticoagulation therapy in ground-level falls : a single-center retrospective study

Background: Traumatic brain injury (TBI) is a common injury and constitutes up to 3% of emergency department (ED) visits. Current studies show that TBI is most commonly inflicted in older patients after ground-level falls. These patients often take medications affecting coagulation such as anticoagulants or antiplatelet drugs. Guidelines for ED TBI-management assume that anticoagulation therapy (ACT) confers a higher risk of traumatic intracranial hemorrhage (TICH) than antiplatelet therapy (APT). However, recent studies have challenged this. This study aimed to evaluate if oral anticoagulation and platelet inhibitors affected rate of TICH in head-trauma patients with ground-level falls. Methods: This was a retrospective review of medical records during January 1, 2017 to December 31, 2017 and January 1 2020 to December 31, 2020 of all patients seeking ED care because of head-trauma. Patients ≥ 18 years with ground-level falls were included. Results: The study included 1938 head-trauma patients with ground-level falls. Median age of patients with TICH was 81 years. The RR for TICH in APT-patients compared to patients without medication affecting coagulation was 1.72 (p = 0.01) (95% Confidence Interval (CI) 1.13–2.60) and 1.08 (p = 0.73), (95% CI 0.70–1.67) in ACT-patients. APT was independently associated with TICH in regression analysis (OR 1.59 (95% CI 1.02–2.49), p = 0.041). Conclusion: This study adds to the growing evidence that APT-patients with ground-level falls might have as high or higher risk of TICH than ACT-patients. This is not addressed in the current guidelines which may need to be updated. We therefore recommend broad prospective studies