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Item Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome(AHA, 2017-07) Kowalski, Robert G.; Haarbauer-Krupa, Juliet K.; Bell, Jeneita M.; Corrigan, John D.; Hammond, Flora M.; Torbey, Michel T.; Hofmann, Melissa C.; Dams-O'Connor, Kristen; Miller, A. Cate; Whiteneck, Gale G.; Physical Medicine and Rehabilitation, School of MedicineBackground and Purpose—Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods—A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results—Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3–2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1–23.4; P<0.001). Conclusions—Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events.Item The Feasibility of Telephone-Administered Cognitive Testing in Individuals 1 and 2 Years after Inpatient Rehabilitation for Traumatic Brain Injury(Mary Ann Liebert, 2018-05-15) Dams-O'Connor, Kristen; Sy, Karla Therese L.; Landau, Alexandra; Bodien, Yelena; Dikmen, Sureyya; Felix, Elizabeth R.; Giacino, Joseph T.; Gibbons, Laura; Hammond, Flora M.; Hart, Tessa; Johnson-Greene, Doug; Lengenfelder, Jeannie; Lequerica, Anthony; Newman, Jody; Novack, Thomas; O'Neil-Pirozzi, Therese M.; Whiteneck, Gale; Physical Medicine and Rehabilitation, School of MedicineTraumatic brain injury (TBI) often results in cognitive impairment, and trajectories of cognitive functioning can vary tremendously over time across survivors. Traditional approaches to measuring cognitive performance require face-to-face administration of a battery of objective neuropsychological tests, which can be time- and labor-intensive. There are numerous clinical and research contexts in which in-person testing is undesirable or unfeasible, including clinical monitoring of older adults or individuals with disability for whom travel is challenging, and epidemiological studies of geographically dispersed participants. A telephone-based method for measuring cognition could conserve resources and improve efficiency. The objective of this study is to examine the feasibility and usefulness of the Brief Test of Adult Cognition by Telephone (BTACT) among individuals who are 1 and 2 years post-moderate-to-severe TBI. A total of 463 individuals participated in the study at Year 1 post-injury, and 386 participated at Year 2. The sample was mostly male (73%) and white (59%), with an average age of (mean ± standard deviation) 47.9 ± 20.9 years, and 73% experienced a duration of post-traumatic amnesia (PTA) greater than 7 days. A majority of participants were able to complete the BTACT subtests (61-69% and 56-64% for Years 1 and 2 respectively); score imputation for those unable to complete a test due to severity of cognitive impairment yields complete data for 74-79% of the sample. BTACT subtests showed expected changes between Years 1-2, and summary scores demonstrated expected associations with injury severity, employment status, and cognitive status as measured by the Functional Independence Measure. Results indicate it is feasible, efficient, and useful to measure cognition over the telephone among individuals with moderate-severe TBI.Item Improving Transition from Inpatient Rehabilitation following Traumatic Brain Injury: Protocol for the BRITE Pragmatic Comparative Effectiveness Trial(Elsevier, 2021-05) Fann, Jesse R.; Hart, Tessa; Ciol, Marcia A.; Moore, Megan; Bogner, Jennifer; Corrigan, John D.; Dams-O'Connor, Kristen; Driver, Simon; Dubiel, Rosemary; Hammond, Flora M.; Kajankova, Maria; Watanabe, Thomas K.; Hoffman, Jeanne M.; Physical Medicine and Rehabilitation, School of MedicineModerate to severe traumatic brain injury (TBI) is a common cause of long-term disability. Due to challenges that include inconsistent access to follow-up care, persons with TBI being discharged from inpatient rehabilitation facilities (IRFs) are at risk for rehospitalization, poor reintegration into the community, family stress, and other unfavorable outcomes resulting from unmet needs. In a six-center randomized pragmatic comparative effectiveness study, the BRITE trial (Brain Injury Rehabilitation: Improving the Transition Experience, ClinicalTrials.gov NCT03422276), we compare the effectiveness of two existing methods for transition from IRF to community living or long-term nursing care. The Rehabilitation Discharge Plan (RDP) includes patient/family education and referrals for continued care. The Rehabilitation Transition Plan (RTP) provides RDP plus individualized, manualized care management via phone or videoconference, for 6 months. Nine hundred patients will be randomized (1:1) to RDP or RTP, with caregivers also invited to participate and contribute caregiver-reported outcomes. Extensive stakeholder input, including active participation of persons with TBI and their families, has informed all aspects of trial design and implementation planning. We hypothesize that RTP will result in better patient- and caregiver-reported outcomes (societal participation, quality of life, caregiver well-being) and more efficient use of healthcare resources at 6-months (primary outcome) and 12-months post-discharge, compared to RDP alone. Planned analyses will explore which participants benefit most from each transition model. With few exclusion criteria and other pragmatic features, the findings of this trial are expected to have a broad impact on improving transitions from inpatient TBI rehabilitation.Item The Longitudinal Effects of Comorbid Health Burden on Functional Outcomes for Adults With Moderate to Severe Traumatic Brain Injury(Wolters Kluwer, 2020) Kumar, Raj G.; Ketchum, Jessica M.; Corrigan, John D.; Hammond, Flora M.; Sevigny, Mitch; Dams-O'Connor, Kristen; Physical Medicine and Rehabilitation, School of MedicineObjective: To evaluate the impact of physical, mental, and total health condition burden on functional outcome and life satisfaction up to 10 years after moderate to severe traumatic brain injury (TBI). Setting: Six TBI Model Systems centers. Participants: Three hundred ninety-three participants in the TBI Model Systems National Database. Design: Retrospective cohort study. Main measures: Self-reported physical and mental health conditions at 10 years postinjury. Functional Independence Measure Motor and Cognitive subscales and the Satisfaction With Life Scale measured at 1, 2, 5, and 10 years. Results: In 10-year longitudinal individual growth curve models adjusted for covariates and inverse probability weighted to account for selection bias, greater physical and mental health comorbidity burden was negatively associated with functional cognition and life satisfaction trajectories. Physical, but not mental, comorbidity burden was negatively associated with functional motor trajectories. Higher total health burden was associated with poorer functional motor and cognitive trajectories and lower life satisfaction. Conclusions: This study offers evidence that comorbidity burden negatively impacts longitudinal functional and life satisfaction outcomes after TBI. The findings suggest that better identification and treatment of comorbidities may benefit life satisfaction, functional outcome, reduce healthcare costs, and decrease reinjury. Specific guidelines are needed for the management of comorbidities in TBI populations.Item Longitudinal Effects of Medical Comorbidities on Functional Outcome and Life Satisfaction After Traumatic Brain Injury: An Individual Growth Curve Analysis of NIDILRR Traumatic Brain Injury Model System Data(Wolters Kluwer, 2019-09-01) Malec, James F.; Ketchum, Jessica M.; Hammond, Flora M.; Corrigan, John D.; Dams-O'Connor, Kristen; Hart, Tessa; Novack, Thomas; Dahdah, Marie; Whiteneck, Gale G.; Bogner, Jennifer; Physical Medicine and Rehabilitation, School of MedicineObjective: To explore associations of specific physical and neuropsychiatric medical conditions to motor and cognitive functioning and life satisfaction over the first 10 years following traumatic brain injury (TBI). Setting: Telephone follow-up through six TBI Model System centers. Participants: 404 individuals or proxies with TBI enrolled in the TBI Model System longitudinal study participating in 10 year follow-up. Design: Individual growth curve analysis. Main Measures: FIM™ Motor and Cognitive subscales, Life Satisfaction Scales, Medical and Mental Health Co-Morbidities Interview. Results: Hypertension, diabetes, cancers, rheumatoid arthritis, and anxiety negatively affected the trajectory of motor functioning over time. Diabetes, cancers, chronic bronchitis, anxiety, and depression negatively impacted cognitive functioning. Numerous neuropsychiatric conditions (sleep disorder, alcoholism, drug addiction, anxiety, panic attacks, PTSD, depression, bipolar disorder), as well as hypertension, liver disease, and cancers diminished life satisfaction. Other medical conditions had a negative effect on functioning and satisfaction at specific follow-up periods. Conclusion: Natural recovery after TBI may include delayed onset of functional decline or early recovery followed by progressive deterioration and is negatively affected by medical comorbidities. Results contribute to the growing evidence that TBI is most appropriately treated as a chronic medical condition complicated by a variety of comorbid conditions.Item Prevalence of Medical and Psychiatric Comorbidities Following Traumatic Brain Injury(Wolters Kluwer, 2019-08-01) Hammond, Flora M.; Corrigan, John D.; Ketchum, Jessica M.; Malec, James F.; Dams-O'Connor, Kristen; Hart, Tessa; Novack, Thomas A.; Bogner, Jennifer; Dahdah, Marie N.; Whiteneck, Gale G.; Physical Medicine and Rehabilitation, School of MedicineObjective: To examine the prevalence of selected medical and psychiatric comorbidities that existed prior to, or up to 10 years following, traumatic brain injury (TBI) requiring acute rehabilitation. Design: Retrospective cohort. Setting: Six TBI Model Systems centers. Participants: 404 participants in the TBI Model System National Database who experienced TBI 10 years prior. Interventions: Not applicable. Main Outcome Measure: Self-reported medical and psychiatric comorbidities and the onset time of each endorsed comorbidity. Results: At 10 years post-injury, the most common comorbidities developing post-injury, in order, were: back pain, depression, hypertension, anxiety, fractures, high blood cholesterol, sleep disorders, panic attacks, osteoarthritis, and diabetes. Comparing those 50 years and older to those less than 50 years, diabetes (OR = 3.54; p = 0.0016), high blood cholesterol (OR = 2.04; p = 0.0092), osteoarthritis (OR = 2.02; p = 0.0454), and hypertension (OR = 1.84; p = 0.0175) were significantly more prevalent in the older cohort while panic attacks (OR = 0.33; p = 0.0022) were significantly more prevalent in the younger cohort. No significant differences in prevalence rates between the older and younger cohorts were found for back pain, depression, anxiety, fractures, or sleep disorders. Conclusions: People with moderate-severe TBI experience other medical and mental health comorbidities during the long-term course of recovery and life after injury. The findings can inform further investigation into comorbidities associated with TBI and the role of medical care, surveillance, prevention, lifestyle, and healthy behaviors in potentially modifying their presence and/or prevalence over the life span.Item Prior history of traumatic brain injury among persons in the Traumatic Brain Injury Model Systems National Database(Elsevier, 2013-10) Corrigan, John D.; Bogner, Jennifer; Mellick, Dave; Bushnik, Tamara; Dams-O'Connor, Kristen; Hammond, Flora M.; Hart, Tessa; Kolakowsky-Hayner, Stephanie; Physical Medicine and Rehabilitation, School of MedicineOBJECTIVE: To determine the association between demographic, psychosocial, and injury-related characteristics and traumatic brain injury (TBI) occurring prior to a moderate or severe TBI requiring rehabilitation. DESIGN: Secondary data analysis. SETTING: TBI Model System inpatient rehabilitation facilities. PARTICIPANTS: Persons (N=4464) 1, 2, 5, 10, 15, or 20 years after TBI resulting in participation in the TBI Model System National Database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: History of TBI prior to the TBI Model System Index injury, pre-Index injury demographic and behavioral characteristics, Index injury characteristics, post-Index injury behavioral health and global outcome. RESULTS: Twenty percent of the cohort experienced TBIs preceding the TBI Model System Index injury-80% of these were mild and 40% occurred before age 16. Pre- and post-Index injury behavioral issues, especially substance abuse, were highly associated with having had a prior TBI. Greater severity of the pre-Index injury as well as occurrence before age 6 often showed stronger associations. Unexpectedly, pre-Index TBI was associated with less severe Index injuries and better functioning on admission and discharge from rehabilitation. CONCLUSIONS: Findings suggest that earlier life TBI may have important implications for rehabilitation after subsequent TBI, especially for anticipating behavioral health issues in the chronic stage of recovery. Results provide additional evidence for the potential consequences of early life TBI, even if mild.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.