{
  "abstract": "Introduction Glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have been shown to rule out CT-detectable intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours after injury. These biomarkers have been validated across different laboratory-based and point-of-care testing platforms. The combined biomarker test has been incorporated into several mTBI management algorithms in Europe. However, data regarding its real-world application, including patients with neurological comorbidities and its impact on reducing CT utilisation or emergency department (ED) length of stay, are lacking. This study will evaluate the performance of an automated laboratory-based assay for serum GFAP and UCH-L1 when integrated into a standardised clinical pathway for the diagnostic management of patients with mTBI. In addition, the study will assess its potential value in reducing CT scan prescription and ED time.Methods and analysis This single-centre observational study, with prospective data collection before and after the implementation of a combined test measuring GFAP and UCH-L1 in the clinical laboratory, will be conducted at Hospital Universitario 12 de Octubre, Madrid, Spain. Patients with clinically defined mTBI will be managed according to a newly implemented clinical pathway including biomarker testing. mTBI will be defined using predefined clinical criteria including a plausible traumatic mechanism, Glasgow Coma Scale score 13–15 assessed 30 min or more after injury, and compatible signs and/or symptoms of brain injury. Eligible patients must undergo blood sampling within 12 hours of injury and before imaging prescription. The effectiveness of this management approach will be compared with a previously established cohort of patients, prospectively enrolled under identical inclusion and exclusion criteria. A cohort of 1000 patients with mTBI, in whom biomarker testing was used in their management, will be included in the post implementation group. The pre-implementation cohort will be drawn from a comparable time period. The primary outcome measures are: the diagnostic performance of GFAP and UCH-L1, measured using an automated assay, for discriminating between patients with positive and negative findings on brain CT scans; the safety of the new clinical pathway in terms of complications such as unexpected surgery or deterioration, as well as the reduction in CT use after the implementation. Secondary objectives will be reduction in ED times and direct costs, as well as physicians’ compliance with the algorithms.Ethics and dissemination The study was reviewed by the Institutional Research Committee of Hospital 12 de Octubre, Madrid, Spain (Ref TP25/0144) and deemed exempt from formal ethical approval and informed consent requirements. This study’s results will be presented at national and international meetings, including meetings of patient associations, and published in peer-reviewed journals.Trial registration number NCT07311486.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Alfonso Lagares"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Monica Maldonado"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Andreea Baciu"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Leandro Tosi"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Carlos Loynaz"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Sofia Martinez"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain",
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain",
        "Department of Surgery, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Ana María Castaño León"
    },
    {
      "affiliations": [
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain"
      ],
      "name": "Julia Hernández-Sánchez"
    },
    {
      "affiliations": [
        "Digital Health Group, Instituto de investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Comunidad de Madrid, Spain"
      ],
      "name": "Noelia García Barrio"
    },
    {
      "affiliations": [
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain"
      ],
      "name": "Javier de la Cruz"
    },
    {
      "affiliations": [
        "Instituto de Investigación Sanitaria imas12, Hospital Universitario 12 de Octubre, Madrid, Spain"
      ],
      "name": "Sofia Sánchez"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Ana Lopez Jiménez"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Cecilia Cueto-Felgueroso"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Laura Carrasco"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Eva Marquez"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Alba María Fernández del Pozo"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Cecilia Amil"
    },
    {
      "affiliations": [
        "Servicio de Análisis Clínicos-Bioquímica Clínica, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain"
      ],
      "name": "Alejandro Arias"
    },
    {
      "affiliations": [
        "R&D Immunoassays, Chemin de l'Orme, bioMérieux, Marcy l'Etoile, France"
      ],
      "name": "Odile Mejan"
    }
  ],
  "title": "Study protocol for investigating real-world implementation of a combined glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) blood test in the management of adult mild traumatic brain injury in a single-centre European emergency department: the IMPACTS-BRAINI study",
  "uid": "3657a2d2-a3e0-5238-a9a6-94e1997adf99"
}