The Longitudinal Effects of Comorbid Health Burden on Functional Outcomes for Adults With Moderate to Severe Traumatic Brain Injury.
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ABSTRACT: Objective
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.
SUBMITTER: Kumar RG
PROVIDER: S-EPMC7335323 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceModerate 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.ObjectiveTo prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI.Design, setting, and participantsThis 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.ExposuresModerate or severe TBI.Main outcomes and measuresThe 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.ResultsA 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 relevanceIn 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.
| S-EPMC8261688 | biostudies-literature
Project description:ObjectivesAfter traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome.DesignPost hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as "ictal-interictal continuum"; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures.SettingTwenty U.S. level I trauma centers.PatientsPatients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4-12 were included.InterventionsNone.Measurements and main resultsAmong 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30-9.09), absence of N2 sleep transients (3.69; 1.69-8.20), predominant delta activity (2.82; 1.32-6.10), and discontinuous background (5.33; 2.28-12.96) within the first 72 hours of monitoring.ConclusionsSevere ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.
| S-EPMC6639805 | biostudies-literature
Project description:IntroductionIn order to augment the certainty of the radiological interpretation of "possible microbleeds" after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI.MethodsStandardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up.ResultsOf the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations.ConclusionsOur findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.
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Project description:OBJECTIVES:To characterize admission patterns, treatments, and outcomes among patients with moderate traumatic brain injury. DESIGN:Retrospective cohort study. SETTING:National Trauma Data Bank. PATIENTS:Adults (age > 18 yr) with moderate traumatic brain injury (International Classification of Diseases, Ninth revision codes and admission Glasgow Coma Scale score of 9-13) in the National Trauma Data Bank between 2007 and 2014. INTERVENTIONS:None. MEASUREMENT AND MAIN RESULTS:Demographics, mechanism of injury, hospital course, and facility characteristics were examined. Admission characteristics associated with discharge outcomes were analyzed using multivariable Poisson regression models. Of 114,066 patients, most were white (62%), male (69%), and had median admission Glasgow Coma Scale score of 12 (interquartile range, 10-13). Seventy-seven percent had isolated traumatic brain injury. Concussion, which accounted for 25% of moderate traumatic brain injury, was the most frequent traumatic brain injury diagnosis. Fourteen percent received mechanical ventilation, and 66% were admitted to ICU. Over 50% received care at a community hospital. Seven percent died, and 32% had a poor outcome, including those with Glasgow Coma Scale score of 13. Compared with patients 18-44 years, patients 45-64 years were twice as likely (adjusted relative risk, 1.97; 95% CI, 1.92-2.02) and patients over 80 years were five times as likely (adjusted relative risk, 4.66; 95% CI, 4.55-4.76) to have a poor outcome. Patients with a poor discharge outcome were more likely to have had hypotension at admission (adjusted relative risk, 1.10; 95% CI, 1.06-1.14), lower admission Glasgow Coma Scale (adjusted relative risk, 1.37; 95% CI, 1.34-1.40), higher Injury Severity Score (adjusted relative risk, 2.97; 95% CI, 2.86-3.09), and polytrauma (adjusted relative risk, 1.05; 95% CI, 1.02-1.07), compared with those without poor discharge outcomes. CONCLUSIONS:Many patients with moderate traumatic brain injury deteriorate, require neurocritical care, and experience poor outcomes. Optimization of care and outcomes for this vulnerable group of patients are urgently needed.
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Project description:We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant ?-amyloid neuritic and cored plaques, diffuse ?-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.
| S-EPMC5939622 | biostudies-literature
Project description:Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow-up period, as well as to changes in memory performance, prior to multiple comparison correction. In conclusion, traumatic brain injury results in progressive loss of brain tissue volume, which continues for many years post-injury. Atrophy is most prominent in the white matter, but is also more pronounced in cortical sulci compared to gyri. These findings suggest the Jacobian determinant provides a method of quantifying brain atrophy following a traumatic brain injury and is informative in determining the long-term neurodegenerative effects after injury. Power calculations indicate that Jacobian determinant images are an efficient surrogate marker in clinical trials of neuroprotective therapeutics.
| S-EPMC5837530 | biostudies-literature
Project description:OBJECTIVE: To evaluate the hypothesis that educational attainment, a marker of cognitive reserve, is a predictor of disability-free recovery (DFR) after moderate to severe traumatic brain injury (TBI). METHODS: Retrospective study of the TBI Model Systems Database, a prospective multicenter cohort funded by the National Institute on Disability and Rehabilitation Research. Patients were included if they were admitted for rehabilitation after moderate to severe TBI, were aged 23 years or older, and had at least 1 year of follow-up. The main outcome measure was DFR 1 year postinjury, defined as a Disability Rating Scale score of zero. RESULTS: Of 769 patients included, 214 (27.8%) achieved DFR at 1 year. In total, 185 patients (24.1%) had <12 years of education, while 390 (50.7%) and 194 patients (25.2%) had 12 to 15 years and ?16 years of education, respectively. DFR was achieved by 18 patients (9.7%) with <12 years, 120 (30.8%) with 12 to 15 years, and 76 (39.2%) with ?16 years of education (p < 0.001). In a logistic regression model controlling for age, sex, and injury- and rehabilitation-specific factors, duration of education of ?12 years was independently associated with DFR (odds ratio 4.74, 95% confidence interval 2.70-8.32 for 12-15 years; odds ratio 7.24, 95% confidence interval 3.96-13.23 for ?16 years). CONCLUSION: Educational attainment was a robust independent predictor of 1-year DFR even when adjusting for other prognostic factors. A dose-response relationship was noted, with longer educational exposure associated with increased odds of DFR. This suggests that cognitive reserve could be a factor driving neural adaptation during recovery from TBI.
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Project description:Patient outcomes are variable following severe traumatic brain injury (TBI); however, the biological underpinnings explaining this variability are unclear. Mitochondrial dysfunction after TBI is well documented, particularly in animal studies. The aim of this study was to investigate the role of mitochondrial polymorphisms on mitochondrial function and patient outcomes out to 1 year after a severe TBI in a human adult population. The Human MitoChip V2.0 was used to evaluate mitochondrial variants in an initial set of n=136 subjects. SNPs found to be significantly associated with patient outcomes [Glasgow Outcome Scale (GOS), Neurobehavioral Rating Scale (NRS), Disability Rating Scale (DRS), in-hospital mortality, and hospital length of stay] or neurochemical level (lactate:pyruvate ratio from cerebrospinal fluid) were further evaluated in an expanded sample of n=336 subjects. A10398G was associated with DRS at 6 and 12 months (p=0.02) and a significant time by SNP interaction for DRS was found (p=0.0013). The A10398 allele was associated with greater disability over time. There was a T195C by sex interaction for GOS (p=0.03) with the T195 allele associated with poorer outcomes in females. This is consistent with our findings that the T195 allele was associated with mitochondrial dysfunction (p=0.01), but only in females. This is the first study associating mitochondrial DNA variation with both mitochondrial function and neurobehavioral outcomes after TBI in humans. Our findings indicate that mitochondrial DNA variation may impact patient outcomes after a TBI potentially by influencing mitochondrial function, and that sex of the patient may be important in evaluating these associations in future studies.
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Project description:IntroductionFew studies account for prehospital deaths when estimating incidence and mortality rates of moderate and severe traumatic brain injury (msTBI). In a population-based study, covering both urban and rural areas, including also prehospital deaths, the aim was to estimate incidence and mortality rates of msTBI. Further, we studied the 30-day and 6-month case-fatality proportion of severe TBI in relation to age.MethodsAll patients aged ≥17 years who sustained an msTBI in Central Norway were identified by three sources: (1) the regional trauma center, (2) the general hospitals, and (3) the Norwegian Cause of Death Registry. Incidence and mortality rates were standardized according to the World Health Organization's world standard population. Case-fatality proportions were calculated by the number of deaths from severe TBI at 30 days and 6 months, divided by all patients with severe TBI.ResultsThe overall incidence rates of moderate and severe TBI were 4.9 and 6.7 per 100,000 person-years, respectively, increasing from age 70 years. The overall mortality rate was 3.4 per 100,000 person-years, also increasing from age 70 years. Incidence and mortality rates were highest in men. The case-fatality proportion in people with severe TBI was 49% in people aged 60-69 years and 81% in people aged 70-79 years.ConclusionThe overall incidence and mortality rates for msTBI in Central Norway were low but increased from age 70 years, and among those ≥80 years of age with severe TBI, nearly all died. Overall estimates are strongly influenced by high incidence and mortality rates in the elderly, and studies should therefore report age-specific estimates, for better comparison of incidence and mortality rates.
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