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Item Characterizing Extreme Phenotypes for Pain Interference in Persons with Chronic Pain following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project(Wolters Kluwer, 2024) Hoffman, Jeanne M.; Ketchum, Jessica M.; Agtarap, Stephanie; Dams-O’Connor, Kristen; Hammond, Flora M.; Martin, Aaron M.; Sevigny, Mitch; Walker, William C.; Harrison-Felix, Cynthia; Zafonte, Ross; Nakase-Richardson, Risa; Physical Medicine and Rehabilitation, School of MedicineObjective: To define and characterize extreme phenotypes based on pain interference for persons with chronic pain following traumatic brain injury (TBI). Setting: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. Participants: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. Primary measures: The Brief Pain Inventory (BPI) interference scale, sociodemographic, injury, functional outcome, pain, and treatment characteristics. Results: Participants were predominantly male (73%), White (75%), middle-aged (mean 46 years), and who were injured in motor vehicle accidents (53%) or falls (20%). Extreme phenotypes were identified based on upper and lower 25th percentiles to create low-interference ( n = 441) and high-interference ( n = 431) extreme phenotypes. Bivariate comparisons found several sociodemographic, injury, function, pain, and treatment differences between extreme phenotype groups, including significant differences ( P < .001) on all measures of concurrent function with those in the low-interference extreme phenotype experiencing better function than those in the high-interference extreme phenotype. Lasso regression combined with logistic regression identified multivariable predictors of low- versus high-interference extreme phenotypes. Reductions in the odds of low- versus high-interference phenotypes were significantly associated with higher pain intensity (odds ratio [OR] = 0.33), having neuropathic pain (OR = 0.40), migraine headache (OR = 0.41), leg/feet pain (OR = 0.34), or hip pain (OR = 0.46), and more pain catastrophizing (OR = 0.81). Conclusion: Results suggest that for those who experience current chronic pain, there is high variability in the experience and impact of pain. Future research is needed to better understand how pain experience impacts individuals with chronic pain and TBI given that pain characteristics were the primary distinguishing factors between phenotypes. The use of extreme phenotypes for pain interference may be useful to better stratify samples to determine efficacy of pain treatment for individuals with TBI.Item Characterizing Extreme Phenotypes for Perceived Improvement from Treatment in Persons with Chronic Pain following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project(Wolters Kluwer, 2024) Hoffman, Jeanne M.; Ketchum, Jessica M.; Agtarap, Stephanie; Dams-O’Connor, Kristen; Hammond, Flora M.; Martin, Aaron M.; Sevigny, Mitch; Walker, William C.; Harrison-Felix, Cynthia; Zafonte, Ross; Nakase-Richardson, Risa; Physical Medicine and Rehabilitation, School of MedicineObjective: To define and characterize extreme phenotypes based on perceived improvement in pain for persons with chronic pain following traumatic brain injury (TBI). Setting: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. Participants: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. Primary measures: The Patient's Global Impression of Change (PGIC) related to pain treatment. Sociodemographic, injury, functional outcome, pain, and pain treatment characteristics. Results: Participants were mostly male (73%), White (75%), middle-aged (mean 46 years), injured in motor vehicle accidents (53%), or falls (20%). Extreme phenotypes were created for an extreme improvement phenotype ( n = 512, 29.8%) defined as "moderately better" or above on the PGIC and an extreme no-change group ( n = 290, 16.9%) defined as no change or worse. Least absolute shrinkage and selection operator (LASSO) regression combined with logistic regression identified multivariable predictors of improvement versus no-change extreme phenotypes. Higher odds of extreme improvement phenotype were significantly associated with being female (odds ratio [OR] = 1.85), married versus single (OR = 2.02), better motor function (OR = 1.03), lower pain intensity (OR = 0.78), and less frequent pain, especially chest pain (OR = 0.36). Several pain treatments were associated with higher odds of being in the extreme improvement versus no-change phenotypes including pain medication (OR = 1.85), physical therapy (OR = 1.51), yoga (OR = 1.61), home exercise program (OR = 1.07), and massage (OR = 1.69). Conclusion: Investigation of extreme phenotypes based on perceived improvement with pain treatment highlights the ability to identify characteristics of individuals based on pain treatment responsiveness. A better understanding of the biopsychosocial characteristics of those who respond and do not respond to pain treatments received may help inform better surveillance, monitoring, and treatment. With further research, the identification of risk factors (such as pain intensity and frequency) for treatment response/nonresponse may provide indicators to prompt changes in care for individuals with chronic pain after TBI.Item Development and Validation of a Functionally Relevant Comorbid Health Index in Adults Admitted to Inpatient Rehabilitation for Traumatic Brain Injury(Mary Ann Liebert, 2022) Kumar, Raj G.; Zhong, Xiaobo; Whiteneck, Gale G.; Mazumdar, Madhu; Hammond, Flora M.; Egorova, Natalia; Lercher, Kirk; Dams-O’Connor, Kristen; Physical Medicine and Rehabilitation, School of MedicineSeveral studies have characterized comorbidities among individuals with traumatic brain injury (TBI); however, there are few validated TBI comorbidity indices. Widely used indices (e.g., Elixhauser Comorbidity Index [ECI]) were developed in other patient populations and anchor to mortality or healthcare utilization, not functioning, and notably exclude conditions known to co-occur with TBI. The objectives of this study were to develop and validate a functionally relevant TBI comorbidity index (Fx-TBI-CI) and to compare prognostication of the Fx-TBI-CI with the ECI. We used data from the eRehabData database to divide the sample randomly into a training sample (N = 21,292) and an internal validation sample (N = 9166). We used data from the TBI Model Systems National Database as an external validation sample (N = 1925). We used least absolute shrinkage and selection operator (LASSO) regression to narrow the list of functionally relevant conditions from 39 to 12. In internal validation, the Fx-TBI-CI explained 14.1% incremental variance over an age and sex model predicting the Functional Independence Measure (FIM) Motor subscale at inpatient rehabilitation discharge, compared with 2.4% explained by the ECI. In external validation, the Fx-TBI-CI explained 4.9% incremental variance over age and sex and 3.8% over age, sex, and Glasgow Coma Scale score,compared with 2.1% and 1.6% incremental variance, respectively, explained by the ECI. An unweighted Sum Condition Score including the same conditions as the Fx-TBI-CI conferred similar prognostication. Although the Fx-TBI-CI had only modest incremental variance over demographics and injury severity in predicting functioning in external validation, the Fx-TBI-CI outperformed the ECI in predicting post-TBI function.Item Distal and Proximal Predictors of Rehospitalization Over 10 Years Among Survivors of TBI: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study(Wolters Kluwer, 2023) Lercher, Kirk; Kumar, Raj G.; Hammond, Flora M.; Zafonte, Ross D.; Hoffman, Jeanne M.; Walker, William C.; Verduzco-Gutierrez, Monica; Dams-O’Connor, Kristen; Physical Medicine and Rehabilitation, School of MedicineObjective: To describe the rates and causes of rehospitalization over a 10-year period following a moderate-severe traumatic brain injury (TBI) utilizing the Healthcare Cost and Utilization Project (HCUP) diagnostic coding scheme. Setting: TBI Model Systems centers. Participants: Individuals 16 years and older with a primary diagnosis of TBI. Design: Prospective cohort study. Main measures: Rehospitalization (and reason for rehospitalization) as reported by participants or their proxies during follow-up telephone interviews at 1, 2, 5, and 10 years postinjury. Results: The greatest number of rehospitalizations occurred in the first year postinjury (23.4% of the sample), and the rates of rehospitalization remained stable (21.1%-20.9%) at 2 and 5 years postinjury and then decreased slightly (18.6%) at 10 years postinjury. Reasons for rehospitalization varied over time, but seizure was the most common reason at 1, 2, and 5 years postinjury. Other common reasons were related to need for procedures (eg, craniotomy or craniectomy) or medical comorbid conditions (eg, diseases of the heart, bacterial infections, or fractures). Multivariable logistic regression models showed that Functional Independence Measure (FIM) Motor score at time of discharge from inpatient rehabilitation was consistently associated with rehospitalization at all time points. Other factors associated with future rehospitalization over time included a history of rehospitalization, presence of seizures, need for craniotomy/craniectomy during acute hospitalization, as well as older age and greater physical and mental health comorbidities. Conclusion: Using diagnostic codes to characterize reasons for rehospitalization may facilitate identification of baseline (eg, FIM Motor score or craniotomy/craniectomy) and proximal (eg, seizures or prior rehospitalization) factors that are associated with rehospitalization. Information about reasons for rehospitalization can aid healthcare system planning. By identifying those recovering from TBI at a higher risk for rehospitalization, providing closer monitoring may help decrease the healthcare burden by preventing rehospitalization.Item Factors Associated with the Remission of Insomnia After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study(Taylor & Francis, 2020) Lequerica, Anthony H.; Weber, Erica; Dijkers, Marcel P.; Dams-O’Connor, Kristen; Kolakowsky-Hayner, Stephanie A.; Bell, Kathleen R.; Bushnik, Tamara; Goldin, Yelena; Hammond, Flora M.; Physical Medicine and Rehabilitation, School of MedicineObjective: To examine the factors associated with the remission of insomnia by examining a sample of individuals who had insomnia within the first two years after traumatic brain injury (TBI) and assessing their status at a secondary time point. Design and Methods: Secondary data analysis from a multicenter longitudinal cohort study. A sample of 40 individuals meeting inclusion criteria completed a number of self-report scales measuring sleep/wake characteristics (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Insomnia Severity Index, Sleep Hygiene Index), fatigue and depression (Multidimensional Assessment of Fatigue, Patient Health Questionnaire-9), and community participation (Participation Assessment with Recombined Tools-Objective). One cohort was followed at 1 and 2 years post-injury (n = 19) while a second cohort was followed at 2 and 5 years post-injury (n = 21). Results: Remission of insomnia was noted in 60% of the sample. Those with persistent insomnia had significantly higher levels of fatigue and depression at their final follow-up and poorer sleep hygiene across both follow-up time-points. A trend toward reduced community participation among those with persistent insomnia was also found. Conclusion: Individuals with persistent post-TBI insomnia had poorer psychosocial outcomes. The chronicity of post-TBI insomnia may be associated with sleep-related behaviors that serve as perpetuating factors.Item Functional Outcome Trajectories following Inpatient Rehabilitation for TBI in the United States: A NIDILRR TBIMS and CDC Interagency Collaboration(Wolters Kluwer, 2020) Dams-O’Connor, Kristen; Ketchum, Jessica M.; Cuthbert, Jeff P.; Corrigan, John; Hammond, Flora M.; Haarbauer Krupa, Juliet; Kowalski, Robert G.; Miller, A. Cate; Physical Medicine and Rehabilitation, School of MedicineObjective: To describe trajectories of functioning up to 5 years after traumatic brain injury (TBI) that required inpatient rehabilitation in the United States using individual growth curve models conditioned on factors associated with variability in functioning and independence over time. Design: Secondary analysis of population-weighted data from a multicenter longitudinal cohort study. Setting: Acute inpatient rehabilitation facilities. Participants: A total of 4624 individuals 16 years and older with a primary diagnosis of TBI. Main outcome measures: Ratings of global disability and supervision needs as reported by participants or proxy during follow-up telephone interviews at 1, 2, and 5 years postinjury. Results: Many TBI survivors experience functional improvement through 1 and 2 years postinjury, followed by a decline in functioning and decreased independence by 5 years. However, there was considerable heterogeneity in outcomes across individuals. Factors such as older age, non-White race, lower preinjury productivity, public payer source, longer length of inpatient rehabilitation stay, and lower discharge functional status were found to negatively impact trajectories of change over time. Conclusions: These findings can inform the content, timing, and target recipients of interventions designed to maximize functional independence after TBI.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 Identification of Factors in Moderate-Severe TBI Related to a Functional Decline in Cognition Decades After Injury(Elsevier, 2023) LoBue, Christian; Schaffert, Jeff; Dams-O’Connor, Kristen; Taiwo, Zinat; Sander, Angelle; Venkatesan, Umesh M.; O’Neil-Pirozzi, Therese M.; Hammond, Flora M.; Wilmoth, Kristin; Ding, Kan; Bell, Kathleen; Cullum, C. Munro; Physical Medicine and Rehabilitation, School of MedicineObjective: To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury. Design: Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI. Setting: TBI Model Systems Centers. Participants: Included were 732 participants rated on the cognitive subscale of the Functional Independence Measure (FIM Cognitive), a metric for everyday cognitive skills, across 3 time points out to 20 years (visits at 2-, 10-, and 20-year follow-ups; N=732). Interventions: Not applicable. Main outcome measure(s): FIM Cognitive Scale. Injury characteristics such as timing and features pertaining to severity and health-related factors (eg, alcohol use, socioeconomic status) were examined to discriminate stable from declining participants on the FIM Cognitive Scale using logistic regression. Results: At 20 years post-injury, there was a low base rate of FIM Cognitive decline (11%, n=78), with most being stable or having meaningful improvement (89%, n=654). Older age at injury, longer duration of post-traumatic amnesia, and presence of repetitive seizures were significant predictors of FIM Cognitive decline in the final model (area under the curve=0.75), while multiple health-related factors that can represent independent co-morbidities or possible consequences of injury were not. Conclusion(s): The strongest contributors to reported functional decline in cognitive activities later-in-life were related to acute characteristics of m-sTBI and experiencing post-traumatic seizures. Future studies are needed integrating functional with performance-based cognitive assessments to affirm conclusions and identify the timeline and trajectory of cognitive decline.Item Mortality Secondary to Unintentional Poisoning after Inpatient Rehabilitation among Individuals with Moderate to Severe Traumatic Brain Injury(Mary Ann Liebert, Inc., 2020) Hammond, Flora M.; Ketchum, Jessica; Dams-O’Connor, Kristen; Corrigan, John D.; Miller, Cate; Haarbauer-Krupa, Juliet; Faul, Mark; Trexler, Lance E.; Harrison-Felix, Cynthia; Physical Medicine and Rehabilitation, School of MedicineStudies have shown reduced life expectancy following moderate-severe traumatic brain injury (TBI) with death from unintentional poisoning (UP) being 11 times higher following TBI than in the general population. The characteristics of those who die of unintentional poisoning are compared with the characteristics of those who die of other causes (OC) in a retrospective cohort who received inpatient rehabilitation following TBI and enrolled in the TBI Model Systems National Database between 1989 and 2017 (n = 15,835 cases with 2,238 deaths recorded). Seventy-eight cases (3.5%) of deaths were the result of UP, 76% were the result of OC, and 20.5% were from an unknown cause. Among the UP deaths, 90% involved drugs (of these, 67% involved narcotic drugs and 14% involved psychostimulants), and 8% involved alcohol. Age-adjusted risk for UP death was associated with: white/non-Hispanic race/ethnicity, living alone, non-institutionalization, pre- and post-injury illicit drug use and alcohol/drug problem use, any alcohol use at last follow-up, better Functional Independence MeasureTM (FIM) scores, history of arrest, moderate disability (vs. severe disability or good recovery), less supervision needed, and greater anxiety. Adults who receive inpatient rehabilitation for TBI who die from UP are distinguishable from those who die of OC. Factors such as pre-injury substance use in the context of functional independence may be regarded as targets for prevention and/or intervention to reduce substance use and substance-related mortality among survivors of moderate-severe TBI. The current findings may have implications for medical care, surveillance, prevention, and health promotion.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.