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Item Comorbid Conditions Among Adults 50 Years and Older With Traumatic Brain Injury: Examining Associations With Demographics, Healthcare Utilization, Institutionalization, and 1-Year Outcomes(Wolters Kluwer, 2019) Kumar, Raj G.; Olsen, Jennifer; Juengst, Shannon B.; Dams-OʼConnor, Kristen; OʼNeil-Pirozzi, Therese M.; Hammond, Flora M.; Wagner, Amy K.; Physical Medicine and Rehabilitation, School of MedicineObjectives: To assess the relationship of acute complications, preexisting chronic diseases, and substance abuse with clinical and functional outcomes among adults 50 years and older with moderate-to-severe traumatic brain injury (TBI). Design: Prospective cohort study. Participants: Adults 50 years and older with moderate-to-severe TBI (n = 2134). Measures: Clusters of comorbid health conditions empirically derived from non-injury International Classification of Diseases, Ninth Revision codes, demographic/injury variables, and outcome (acute and rehabilitation length of stay [LOS], Functional Independence Measure efficiency, posttraumatic amnesia [PTA] duration, institutionalization, rehospitalization, and Glasgow Outcome Scale-Extended (GOS-E) at 1 year). Results: Individuals with greater acute hospital complication burden were more often middle-aged men, injured in motor vehicle accidents, and had longer LOS and PTA. These same individuals experienced higher rates of 1-year rehospitalization and greater odds of unfavorable GOS-E scores at 1 year. Those with greater chronic disease burden were more likely to be rehospitalized at 1 year. Individuals with more substance abuse burden were most often younger (eg, middle adulthood), black race, less educated, injured via motor vehicle accidents, and had an increased risk for institutionalization. Conclusion: Preexisting health conditions and acute complications contribute to TBI outcomes. This work provides a foundation to explore effects of comorbidity prevention and management on TBI recovery in older adults.Item Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study(American Medical Association, 2021) McCrea, Michael A.; Giacino, Joseph T.; Barber, Jason; Temkin, Nancy R.; Nelson, Lindsay D.; Levin, Harvey S.; Dikmen, Sureyya; Stein, Murray; Bodien, Yelena G.; Boase, Kim; Taylor, Sabrina R.; Vassar, Mary; Mukherjee, Pratik; Robertson, Claudia; Diaz-Arrastia, Ramon; Okonkwo, David O.; Markowitz, Amy J.; Manley, Geoffrey T.; TRACK-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Bullock, M. Ross; Chesnut, Randall; Corrigan, John D.; Crawford, Karen; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Goldman, Dana; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Jain, Sonia; Keene, C. Dirk; Korley, Frederick K.; Kramer, Joel; Kreitzer, Natalie; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Ngwenya, Laura B.; Noel, Florence; Nolan, Amber; Palacios, Eva; Perl, Daniel; Puccio, Ava; Rabinowitz, Miri; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Sherer, Mark; Toga, Arthur; Valadka, Alex; Wang, Kevin; Yue, John K.; Yuh, Esther; Zafonte, Ross; Psychiatry, School of MedicineImportance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, setting, and participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures: Moderate or severe TBI. Main outcomes and measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.Item Health and Cognition among Adults with and without Traumatic Brain Injury: A Matched Case-Control Study(Taylor & Francis, 2022) Kumar, Raj G.; Ketchum, Jessica M.; Hammond, Flora M.; Novack, Thomas A.; O’Neil-Pirozzi, Therese M.; Silva, Marc A.; Dams-O’Connor, Kristen; Physical Medicine and Rehabilitation, School of MedicineObjectives: To evaluate associations between traumatic brain injury (TBI) and presence of health conditions, and to compare associations of health and cognition between TBI cases and controls. Methods: This matched case-control study used data from the TBI Model Systems National Database (TBI cases) and Midlife in the United States II and Refresher studies (controls). 248 TBI cases were age-, sex-, race-, and education-matched without replacement to three controls. Cases and controls were compared on prevalence of 18 self-reported conditions, self-rated health, composite scores from the Brief Test of Adult Cognition by Telephone. Results: The following conditions were significantly more prevalent among TBI cases versus controls: anxiety/depression (OR = 3.12, 95% CI: 2.20, 4.43, p < .001), chronic sleeping problems (OR = 2.76, 95% CI: 1.86, 4.10, p < .001), headache/migraine (OR = 2.61, 95% CI: 1.50, 4.54, p = .0007), and stroke (OR = 6.42, 95% CI: 2.93, 14.10, p < .001). The relationship between self-rated health and cognition significantly varied by TBI (pinteraction = 0.002). Conclusion: Individuals with TBI have greater odds of selected neurobehavioral conditions compared to their demographically similar uninjured peers. Among persons with TBI there was a stronger association between poorer self-rated health and cognition than controls. TBI is increasingly conceptualized as a chronic disease; current findings suggest post-TBI health management requires cognitive supports.Item Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial(Springer, 2022) Hergenroeder, Georgene W.; Yokobori, Shoji; Choi, Huimahn Alex; Schmitt, Karl; Detry, Michelle A.; Schmitt, Lisa H.; McGlothlin, Anna; Puccio, Ava M.; Jagid, Jonathan; Kuroda, Yasuhiro; Nakamura, Yukihiko; Suehiro, Eiichi; Ahmad, Faiz; Viele, Kert; Wilde, Elisabeth A.; McCauley, Stephen R.; Kitagawa, Ryan S.; Temkin, Nancy R.; Timmons, Shelly D.; Diringer, Michael N.; Dash, Pramod K.; Bullock, Ross; Okonkwo, David O.; Berry, Donald A.; Kim, Dong H.; Neurological Surgery, School of MedicineBackground: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome. Methods: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. Results: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. Conclusions: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.Item National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome(Wolters Kluwer, 2021) Katz, Douglas I.; Bernick, Charles; Dodick, David W.; Mez, Jesse; Mariani, Megan L.; Adler, Charles H.; Alosco, Michael L.; Balcer, Laura J.; Banks, Sarah J.; Barr, William B.; Brody, David L.; Cantu, Robert C.; Dams-O’Connor, Kristen; Geda, Yonas E.; Jordan, Barry D.; McAllister, Thomas W.; Peskind, Elaine R.; Petersen, Ronald C.; Wethe, Jennifer V.; Zafonte, Ross D.; Foley, Éimear M.; Babcock, Debra J.; Koroshetz, Walter J.; Tripodis, Yorghos; McKee, Ann C.; Shenton, Martha E.; Cummings, Jeffrey L.; Reiman, Eric M.; Stern, Robert A.; Psychiatry, School of MedicineObjective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.Item Patterns of Functional Change Five to Ten Years after Moderate-Severe Traumatic Brain Injury(Mary Ann Liebert, Inc., 2021) Hammond, Flora M.; Malec, James F.; Corrigan, John D.; Whiteneck, Gale G.; Hart, Tessa; Dams-O’Connor, Kristen; Novack, Thomas A.; Bogner, Jennifer; Dahdah, Marie N.; Eagye, C.B.; Sevigny, Mitch; Ketchum, Jessica M.; Physical Medicine and Rehabilitation, School of MedicineThis study aims to characterize the patterns of functional change experienced between 5 and 10 years after moderate-severe traumatic brain injury (TBI). The study included TBI Model Systems national database participants (N = 372) at six sites who experienced TBI, received inpatient rehabilitation, and were followed at 5 and 10 years post-TBI. Outcome measures included self- or proxy-reported Functional Independence Measure (FIMTM) structured interview at 5 and 10 years post-TBI and domain change indices (DCIs) at 10 years to assess subjective change over the previous 5 years. When all seven FIM and subjective DCI subscales were considered together, 69% reported improvement in at least one subscale and 41% reported decline in at least one subscale; 51% reported more domains improved than declined, and 20% reported more domains declined than improved. Age at injury, post-traumatic amnesia duration, FIM, and depression and anxiety at year 5 were associated with FIM change and DCI measures. Although most persons with moderate-severe TBI do not experience widespread change from year 5 to 10 on individual FIM subscales or perceived domain-specific subscales, the vast majority do report change in one or more domains, with more improvement than decline and more change in subjective DCI than in FIM. Clinicians and researchers should be alert to the possibility of both positive and deleterious changes many years after TBI.Item Primary Language and Participation Outcomes in Hispanics With Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study(Wolters Kluwer, 2021) Sander, Angelle M.; Ketchum, Jessica M.; Lequerica, Anthony H.; Pappadis, Monique R.; Bushnik, Tamara; Hammond, Flora M.; Sevigny, Mitch; Physical Medicine and Rehabilitation, School of MedicineObjective: To examine the relationship between primary language and participation outcomes in English- and Spanish-speaking persons with complicated mild to severe traumatic brain injury (TBI) at 1 year post-injury. Setting: Community following discharge from inpatient rehabilitation. Participants: A total of 998 Hispanic participants with outcomes available at year 1 follow-up; 492 (49%) indicated English as their primary language and 506 (51%) indicated Spanish as their primary language. Design: Prospective, multicenter, cross-sectional, observational cohort study. Main measures: Community participation at 1 year post-injury was assessed by 3 domains of the Participation Assessment with Recombined Tools-Objective (PART-O): Out and About, Productivity, and Social Relations. Results: Unadjusted group comparisons showed better participation outcomes for English versus Spanish speakers for all PART-O domains and for the Balanced Total score. After controlling for relevant covariates, English-speaking participants had significantly better PART-O Balanced Total scores and better scores on the Social Relations domain, although effect sizes were small. Conclusions: Hispanic persons with TBI whose primary language is Spanish may require greater assistance integrating socially back into their communities after TBI. However, potential cultural differences in value placed on various social activities must be considered. Potential cultural bias inherent in existing measures of participation should be investigated in future studies.Item Societal Participation of People With Traumatic Brain Injury Before and During the COVID-19 Pandemic: A NIDILRR Traumatic Brain Injury Model Systems Study(Elsevier, 2023) Venkatesan, Umesh M.; Adams, Leah M.; Rabinowitz, Amanda R.; Agtarap, Stephanie; Bombardier, Charles H.; Bushnik, Tamara; Chiaravalloti, Nancy D.; Juengst, Shannon B.; Katta-Charles, Sheryl; Perrin, Paul B.; Pinto, Shanti M.; Weintraub, Alan H.; Whiteneck, Gale G.; Hammond, Flora M.; Physical Medicine and Rehabilitation, School of MedicineObjective: To examine the effect of the COVID-19 pandemic on societal participation in people with moderate-to-severe traumatic brain injury (TBI). Design: Cross-sectional retrospective cohort. Setting: National TBI Model Systems centers, United States. Participants: TBI Model Systems enrollees (N=7003), ages 16 and older and 1-30 years postinjury, interviewed either prepandemic (PP) or during the pandemic (DP). The sample was primarily male (72.4%) and White (69.5%), with motor vehicle collisions as the most common cause of injury (55.1%). Interventions: Not applicable. Main outcome measure: The 3 subscales of the Participation Assessment with Recombined Tools-Objective: Out and About (community involvement), Productivity, and Social Relations. Results: Out and About, but not Productivity or Social Relations, scores were appreciably lower among DP participants compared to PP participants (medium effect). Demographic and clinical characteristics showed similar patterns of association with participation domains across PP and DP. When their unique contributions were examined in regression models, age, self-identified race, education level, employment status, marital status, income level, disability severity, and life satisfaction were variably predictive of participation domains, though most effects were small or medium in size. Depression and anxiety symptom severities each showed small zero-order correlations with participation domains across PP and DP but had negligible effects in regression analyses. Conclusions: Consistent with the effect of COVID-19 on participation levels in the general population, people with TBI reported less community involvement during the pandemic, potentially compounding existing postinjury challenges to societal integration. The pandemic does not appear to have altered patterns of association between demographic/clinical characteristics and participation. Assessing and addressing barriers to community involvement should be a priority for TBI treatment providers. Longitudinal studies of TBI that consider pandemic-related effects on participation and other societally linked outcomes will help to elucidate the potential longer-term effect the pandemic has on behavioral health in this population.Item Traumatic brain injury: progress and challenges in prevention, clinical care, and research(Elsevier, 2022) Maas, Andrew I. R.; Menon, David K.; Manley, Geoffrey T.; Abrams, Mathew; Åkerlund, Cecilia; Andelic, Nada; Aries, Marcel; Bashford, Tom; Bell, Michael J.; Bodien, Yelena G.; Brett, Benjamin L.; Büki, András; Chesnut, Randall M.; Citerio, Giuseppe; Clark, David; Clasby, Betony; Cooper, D. Jamie; Czeiter, Endre; Czosnyka, Marek; Dams-O'Connor, Kristen; De Keyser, Véronique; Diaz-Arrastia, Ramon; Ercole, Ari; van Essen, Thomas A.; Falvey, Éanna; Ferguson, Adam R.; Figaji, Anthony; Fitzgerald, Melinda; Foreman, Brandon; Gantner, Dashiell; Gao, Guoyi; Giacino, Joseph; Gravesteijn, Benjamin; Guiza, Fabian; Gupta, Deepak; Gurnell, Mark; Haagsma, Juanita A.; Hammond, Flora M.; Hawryluk, Gregory; Hutchinson, Peter; van der Jagt, Mathieu; Jain, Sonia; Jain, Swati; Jiang, Ji-Yao; Kent, Hope; Kolias, Angelos; Kompanje, Erwin J. O.; Lecky, Fiona; Lingsma, Hester F.; Maegele, Marc; Majdan, Marek; Markowitz, Amy; McCrea, Michael; Meyfroidt, Geert; Mikolić, Ana; Mondello, Stefania; Mukherjee, Pratik; Nelson, David; Nelson, Lindsay D.; Newcombe, Virginia; Okonkwo, David; Orešič, Matej; Peul, Wilco; Pisică, Dana; Polinder, Suzanne; Ponsford, Jennie; Puybasset, Louis; Raj, Rahul; Robba, Chiara; Røe, Cecilie; Rosand, Jonathan; Schueler, Peter; Sharp, David J.; Smielewski, Peter; Stein, Murray B.; von Steinbüchel, Nicole; Stewart, William; Steyerberg, Ewout W.; Stocchetti, Nino; Temkin, Nancy; Tenovuo, Olli; Theadom, Alice; Thomas, Ilias; Torres Espin, Abel; Turgeon, Alexis F.; Unterberg, Andreas; Van Praag, Dominique; van Veen, Ernest; Verheyden, Jan; Vande Vyvere, Thijs; Wang, Kevin K. W.; Wiegers, Eveline J. A.; Williams, W. Huw; Wilson, Lindsay; Wisniewski, Stephen R.; Younsi, Alexander; Yue, John K.; Yuh, Esther L.; Zeiler, Frederick A.; Zeldovich, Marina; Zemek, Roger; InTBIR Participants and Investigators; Physical Medicine and Rehabilitation, School of MedicineTraumatic brain injury (TBI) has the highest incidence of all common neurological disorders, and poses a substantial public health burden. TBI is increasingly documented not only as an acute condition but also as a chronic disease with long-term consequences, including an increased risk of late-onset neurodegeneration. The first Lancet Neurology Commission on TBI, published in 2017, called for a concerted effort to tackle the global health problem posed by TBI. Since then, funding agencies have supported research both in high-income countries (HICs) and in low-income and middle-income countries (LMICs). In November 2020, the World Health Assembly, the decision-making body of WHO, passed resolution WHA73.10 for global actions on epilepsy and other neurological disorders, and WHO launched the Decade for Action on Road Safety plan in 2021. New knowledge has been generated by large observational studies, including those conducted under the umbrella of the International Traumatic Brain Injury Research (InTBIR) initiative, established as a collaboration of funding agencies in 2011. InTBIR has also provided a huge stimulus to collaborative research in TBI and has facilitated participation of global partners. The return on investment has been high, but many needs of patients with TBI remain unaddressed. This update to the 2017 Commission presents advances and discusses persisting and new challenges in prevention, clinical care, and research. In LMICs, the occurrence of TBI is driven by road traffic incidents, often involving vulnerable road users such as motorcyclists and pedestrians. In HICs, most TBI is caused by falls, particularly in older people (aged ≥65 years), who often have comorbidities. Risk factors such as frailty and alcohol misuse provide opportunities for targeted prevention actions. Little evidence exists to inform treatment of older patients, who have been commonly excluded from past clinical trials—consequently, appropriate evidence is urgently required. Although increasing age is associated with worse outcomes from TBI, age should not dictate limitations in therapy. However, patients injured by low-energy falls (who are mostly older people) are about 50% less likely to receive critical care or emergency interventions, compared with those injured by high-energy mechanisms, such as road traffic incidents. Mild TBI, defined as a Glasgow Coma sum score of 13–15, comprises most of the TBI cases (over 90%) presenting to hospital. Around 50% of adult patients with mild TBI presenting to hospital do not recover to pre-TBI levels of health by 6 months after their injury. Fewer than 10% of patients discharged after presenting to an emergency department for TBI in Europe currently receive follow-up. Structured follow-up after mild TBI should be considered good practice, and urgent research is needed to identify which patients with mild TBI are at risk for incomplete recovery. The selection of patients for CT is an important triage decision in mild TBI since it allows early identification of lesions that can trigger hospital admission or life-saving surgery. Current decision making for deciding on CT is inefficient, with 90–95% of scanned patients showing no intracranial injury but being subjected to radiation risks. InTBIR studies have shown that measurement of blood-based biomarkers adds value to previously proposed clinical decision rules, holding the potential to improve efficiency while reducing radiation exposure. Increased concentrations of biomarkers in the blood of patients with a normal presentation CT scan suggest structural brain damage, which is seen on MR scanning in up to 30% of patients with mild TBI. Advanced MRI, including diffusion tensor imaging and volumetric analyses, can identify additional injuries not detectable by visual inspection of standard clinical MR images. Thus, the absence of CT abnormalities does not exclude structural damage—an observation relevant to litigation procedures, to management of mild TBI, and when CT scans are insufficient to explain the severity of the clinical condition. Although blood-based protein biomarkers have been shown to have important roles in the evaluation of TBI, most available assays are for research use only. To date, there is only one vendor of such assays with regulatory clearance in Europe and the USA with an indication to rule out the need for CT imaging for patients with suspected TBI. Regulatory clearance is provided for a combination of biomarkers, although evidence is accumulating that a single biomarker can perform as well as a combination. Additional biomarkers and more clinical-use platforms are on the horizon, but cross-platform harmonisation of results is needed. Health-care efficiency would benefit from diversity in providers. In the intensive care setting, automated analysis of blood pressure and intracranial pressure with calculation of derived parameters can help individualise management of TBI. Interest in the identification of subgroups of patients who might benefit more from some specific therapeutic approaches than others represents a welcome shift towards precision medicine. Comparative-effectiveness research to identify best practice has delivered on expectations for providing evidence in support of best practices, both in adult and paediatric patients with TBI. Progress has also been made in improving outcome assessment after TBI. Key instruments have been translated into up to 20 languages and linguistically validated, and are now internationally available for clinical and research use. TBI affects multiple domains of functioning, and outcomes are affected by personal characteristics and life-course events, consistent with a multifactorial bio-psycho-socio-ecological model of TBI, as presented in the US National Academies of Sciences, Engineering, and Medicine (NASEM) 2022 report. Multidimensional assessment is desirable and might be best based on measurement of global functional impairment. More work is required to develop and implement recommendations for multidimensional assessment. Prediction of outcome is relevant to patients and their families, and can facilitate the benchmarking of quality of care. InTBIR studies have identified new building blocks (eg, blood biomarkers and quantitative CT analysis) to refine existing prognostic models. Further improvement in prognostication could come from MRI, genetics, and the integration of dynamic changes in patient status after presentation. Neurotrauma researchers traditionally seek translation of their research findings through publications, clinical guidelines, and industry collaborations. However, to effectively impact clinical care and outcome, interactions are also needed with research funders, regulators, and policy makers, and partnership with patient organisations. Such interactions are increasingly taking place, with exemplars including interactions with the All Party Parliamentary Group on Acquired Brain Injury in the UK, the production of the NASEM report in the USA, and interactions with the US Food and Drug Administration. More interactions should be encouraged, and future discussions with regulators should include debates around consent from patients with acute mental incapacity and data sharing. Data sharing is strongly advocated by funding agencies. From January 2023, the US National Institutes of Health will require upload of research data into public repositories, but the EU requires data controllers to safeguard data security and privacy regulation. The tension between open data-sharing and adherence to privacy regulation could be resolved by cross-dataset analyses on federated platforms, with the data remaining at their original safe location. Tools already exist for conventional statistical analyses on federated platforms, however federated machine learning requires further development. Support for further development of federated platforms, and neuroinformatics more generally, should be a priority. This update to the 2017 Commission presents new insights and challenges across a range of topics around TBI: epidemiology and prevention (section 1); system of care (section 2); clinical management (section 3); characterisation of TBI (section 4); outcome assessment (section 5); prognosis (Section 6); and new directions for acquiring and implementing evidence (section 7). Table 1 summarises key messages from this Commission and proposes recommendations for the way forward to advance research and clinical management of TBI.