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      Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury

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          Abstract

          Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70–0.88) for GFAP, 0.80 (0.71–0.89) for UCH-L1, and 0.75 (0.65–0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B ( p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.

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          Indications for computed tomography in patients with minor head injury.

          Computed tomography (CT) is widely used as a screening test in patients with minor head injury, although the results are often normal. We performed a study to develop and validate a set of clinical criteria that could be used to identify patients with minor head injury who do not need to undergo CT. In the first phase of the study, we recorded clinical findings in 520 consecutive patients with minor head injury who had a normal score on the Glasgow Coma Scale and normal findings on a brief neurologic examination; the patients then underwent CT. Using recursive partitioning, we derived a set of criteria to identify all patients who had abnormalities on CT scanning. In the second phase, the sensitivity and specificity of the criteria for predicting a positive scan were evaluated in a group of 909 patients. Of the 520 patients in the first phase, 36 (6.9 percent) had positive scans. All patients with positive CT scans had one or more of seven findings: headache, vomiting, an age over 60 years, drug or alcohol intoxication, deficits in short-term memory, physical evidence of trauma above the clavicles, and seizure. Among the 909 patients in the second phase, 57 (6.3 percent) had positive scans. In this group of patients, the sensitivity of the seven findings combined was 100 percent (95 percent confidence interval, 95 to 100 percent). All patients with positive CT scans had at least one of the findings. For the evaluation of patients with minor head injury, the use of CT can be safely limited to those who have certain clinical findings.
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            Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: communicating the performance of diagnostic tests.

            * Diagnostic accuracy studies address how well a test identifies the target condition of interest. * Sensitivity, specificity, predictive values and likelihood ratios (LRs) are all different ways of expressing test performance. * Receiver operating characteristic (ROC) curves compare sensitivity versus specificity across a range of values for the ability to predict a dichotomous outcome. Area under the ROC curve is another measure of test performance. * All of these parameters are not intrinsic to the test and are determined by the clinical context in which the test is employed. * High sensitivity corresponds to high negative predictive value and is the ideal property of a "rule-out" test. * High specificity corresponds to high positive predictive value and is the ideal property of a "rule-in" test. * LRs leverage pre-test into post-test probabilities of a condition of interest and there is some evidence that they are more intelligible to users.
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              Comparison of the Canadian CT Head Rule and the New Orleans Criteria in patients with minor head injury.

              Current use of cranial computed tomography (CT) for minor head injury is increasing rapidly, highly variable, and inefficient. The Canadian CT Head Rule (CCHR) and New Orleans Criteria (NOC) are previously developed clinical decision rules to guide CT use for patients with minor head injury and with Glasgow Coma Scale (GCS) scores of 13 to 15 for the CCHR and a score of 15 for the NOC. However, uncertainty about the clinical performance of these rules exists. To compare the clinical performance of these 2 decision rules for detecting the need for neurosurgical intervention and clinically important brain injury. In a prospective cohort study (June 2000-December 2002) that included 9 emergency departments in large Canadian community and university hospitals, the CCHR was evaluated in a convenience sample of 2707 adults who presented to the emergency department with blunt head trauma resulting in witnessed loss of consciousness, disorientation, or definite amnesia and a GCS score of 13 to 15. The CCHR and NOC were compared in a subgroup of 1822 adults with minor head injury and GCS score of 15. Neurosurgical intervention and clinically important brain injury evaluated by CT and a structured follow-up telephone interview. Among 1822 patients with GCS score of 15, 8 (0.4%) required neurosurgical intervention and 97 (5.3%) had clinically important brain injury. The NOC and the CCHR both had 100% sensitivity but the CCHR was more specific (76.3% vs 12.1%, P<.001) for predicting need for neurosurgical intervention. For clinically important brain injury, the CCHR and the NOC had similar sensitivity (100% vs 100%; 95% confidence interval [CI], 96%-100%) but the CCHR was more specific (50.6% vs 12.7%, P<.001), and would result in lower CT rates (52.1% vs 88.0%, P<.001). The kappa values for physician interpretation of the rules, CCHR vs NOC, were 0.85 vs 0.47. Physicians misinterpreted the rules as not requiring imaging for 4.0% of patients according to CCHR and 5.5% according to NOC (P = .04). Among all 2707 patients with a GCS score of 13 to 15, the CCHR had sensitivities of 100% (95% CI, 91%-100%) for 41 patients requiring neurosurgical intervention and 100% (95% CI, 98%-100%) for 231 patients with clinically important brain injury. For patients with minor head injury and GCS score of 15, the CCHR and the NOC have equivalent high sensitivities for need for neurosurgical intervention and clinically important brain injury, but the CCHR has higher specificity for important clinical outcomes than does the NOC, and its use may result in reduced imaging rates.
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                Author and article information

                Journal
                J Neurotrauma
                J. Neurotrauma
                neu
                Journal of Neurotrauma
                Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                0897-7151
                1557-9042
                15 January 2016
                15 January 2016
                : 33
                : 2
                : 203-214
                Affiliations
                [ 1 ]Department of Emergency Medicine, Wayne State University , Detroit, Michigan.
                [ 2 ]Department of Emergency Medicine, Washington University , St. Louis, Missouri.
                [ 3 ]Department of Anesthesiology and Intensive Care, Clinical Sciences in Malmo , Malmo, Sweden.
                [ 4 ]Department of Radiology, University of California San Diego Health System , San Diego, California.
                [ 5 ]Berry Consultants , Austin, Texas.
                [ 6 ]Department of Emergency Medicine, University of Florida , Gainesville, Florida.
                [ 7 ]Neurostudies.net , Decatur, Georgia.
                [ 8 ]Department of Neurosurgery, Pecs University , Pecs, Hungary.
                [ 9 ]Department of Neurosurgery, University of Szeged , Szeged, Hungary.
                [ 10 ]U.S. Army Medical Research and Materiel Command , Fort Detrick, Maryland.
                [ 11 ]Applied Neurobiology, Silver Spring, Maryland.
                [ 12 ]Center for Military Psychiatry and Neuroscience Walter Reed Army Institute of Research , Silver Spring, Maryland.
                [ 13 ]Center of Innovative Research, Banyan Biomarkers, Inc. , Alachua, Florida.
                [ 14 ]Department of Radiology, University of Pennsylvania , Philadelphia, Pennsylvania.
                [ 15 ]Department of Radiology, Shields Health Care Group , Brockton, Massachusetts.
                [ 16 ]Department of Emergency Medicine, University of Rochester School of Medicine , Rochester, New York.
                Author notes
                Address correspondence to: Robert D. Welch, MD, MS, Department of Emergency Medicine, Wayne State University Detroit, MI 48230, E-mail: rwelch@ 123456med.wayne.edu
                Article
                10.1089/neu.2015.4149
                10.1089/neu.2015.4149
                4722555
                26467555
                c65a973e-0b5d-4685-b6eb-41fd875977b8
                © Robert D. Welch, et al. 2015; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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                Figures: 4, Tables: 5, References: 34, Pages: 12
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