Browsing by Author "Okonkwo, David"

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    Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study
    (American Medical Association, 2021-03-01) Brett, Benjamin L.; Kramer, Mark D.; Whyte, John; McCrea, Michael A.; Stein, Murray B.; Giacino, Joseph T.; Sherer, Mark; Markowitz, Amy J.; Manley, Geoffrey T.; Nelson, Lindsay D.; TRACK-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Boase, Kim; Barber, Jason; Bodien, Yelena; Bullock, M. Ross; Chesnut, Randall; Corrigan, John D.; Crawford, Karen; Diaz-Arrastia, Ramon; Dikmen, Sureyya; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Jain, Sonia; Keene, C. Dirk; Korley, Frederick K.; Kramer, Joel; Kreitzer, Natalie; Levin, Harvey; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Mukherjee, Pratik; Ngwenya, Laura B.; Noel, Florence; Okonkwo, David; Palacios, Eva; Puccio, Ava; Rabinowitz, Miri; Robertson, Claudia; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Taylor, Sabrina; Temkin, Nancy; Toga, Arthur; Valadka, Alex; Vassar, Mary; Wang, Kevin; Yue, John K.; Yuh, Esther; Zafonte, Ross; Psychiatry, School of Medicine
    Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, setting, and participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures: TBI. Main outcomes and measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.
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    A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
    (Springer, 2019-12-01) Hawryluk, Gregory W. J.; Aguilera, Sergio; Buki, Andras; Bulger, Eileen; Citerio, Giuseppe; Cooper, D. Jamie; Arrastia, Ramon Diaz; Diringer, Michael; Figaji, Anthony; Gao, Guoyi; Geocadin, Romergryko; Ghajar, Jamshid; Harris, Odette; Hoffer, Alan; Hutchinson, Peter; Joseph, Mathew; Kitagawa, Ryan; Manley, Geoffrey; Mayer, Stephan; Menon, David K.; Meyfroidt, Geert; Michael, Daniel B.; Oddo, Mauro; Okonkwo, David; Patel, Mayur; Robertson, Claudia; Rosenfeld, Jeffrey V.; Rubiano, Andres M.; Sahuquillo, Juan; Servadei, Franco; Shutter, Lori; Stein, Deborah; Stocchetti, Nino; Taccone, Fabio Silvio; Timmons, Shelly; Tsai, Eve; Ullman, Jamie S.; Vespa, Paul; Videtta, Walter; Wright, David W.; Zammit, Christopher; Chesnut, Randall M.; Neurological Surgery, School of Medicine
    Background Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.
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    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 Medicine
    Traumatic 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.