The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).

The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were "roundtable" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.

When stroke survivors' self-ratings are inconsistent with the ratings of others: a cohort study examining biopsychosocial factors associated with impaired self-awareness of functional abilities.

Background Stroke survivors' self-ratings of functional abilities are often inconsistent with ratings assigned by others (e.g. clinicians), a phenomenon referred to as 'impaired self-awareness' (ISA). There is limited knowledge of the biopsychosocial contributors and consequences of post-stroke ISA measured across the rehabilitation journey. This multi-site cohort study explored biopsychosocial correlates of ISA during subacute rehabilitation (inpatient) and at 4 months post-discharge (community-dwelling). Methods Forty-five subacute stroke survivors participated (Age M (s.d.) = 71.5 (15.6), 56% female), and 38 were successfully followed-up. Self-assessments were compared to those of an independent rater (occupational therapist, close other) to calculate ISA at both time points. Survivors and raters completed additional cognitive, psychological and functional measures. Results Multivariate regression (multiple outcomes) identified associations between ISA during inpatient admission and poorer outcomes at follow-up, including poorer functional cognition, participation restriction, caregiver burden, and close other depression and anxiety. Regression models applied cross-sectionally, including one intended for correlated predictors, indicated associations between ISA during inpatient admission and younger age, male sex, poorer functional cognition, poorer rehabilitation engagement and less frequent use of non-productive coping (adjusted R 2 = 0.60). ISA at community follow-up was associated with poorer functional cognition and close other anxiety (adjusted R 2 = 0.66). Conclusions Associations between ISA and poorer outcomes across the rehabilitation journey highlight the clinical importance of ISA and the value of assessment and management approaches that consider the potential influence of numerous biological and psychosocial factors on ISA. Future studies should use larger sample sizes to confirm these results and determine the causal mechanisms of these relationships.

Co-developing 'The CyberABIlity Scale' to assess vulnerability to cyberscams for people with acquired brain injury: Delphi and cognitive interviews with clinicians and people with acquired brain injury.

Background Although individuals with acquired brain injury (ABI) may be vulnerable to cyberscams, the lack of existing measures documenting cybersafety behaviours in people with ABI limits our understanding of ABI-specific risk factors, the frequency of this problem, and the ability to evaluate evidence-based interventions. The CyberABIlity Scale was developed to assess vulnerability in people with ABI via self-rated statements and practical scam-identification tasks. This study aimed to develop and refine The CyberABIlity Scale through feedback from clinicians and people with ABI. Methods Scale feedback was collected via three rounds of clinician surveys (n = 14) using Delphi methods and two rounds of cognitive interviews with participants with ABI (n = 8). Following each round, feedback was quantitatively and qualitatively summarised, and revisions were made accordingly. Results Key revisions included removing 12 items deemed irrelevant. Instructions and rating scales were revised to improve clarity. Cognitive interviews identified 15 comprehension errors, with further revisions made to support response clarity for participants with ABI. Clinicians and participants with ABI endorsed the content and face validities of The CyberABIlity Scale . Conclusions Following further validation, The CyberABIlity Scale has the potential to be an effective screening measure for online vulnerability for people with ABI within clinical and research settings.

Co-designing for behavioural change: understanding barriers and enablers to addressing sexuality after traumatic brain injury and mapping intervention strategies in a multi-disciplinary rehabilitation unit.

Background Persistent changes in sexuality often follow traumatic brain injury (TBI). However, health professionals remain reticent about discussing sexuality and have reported barriers including uncertainties around whose role it is and limited educational and institutional support. This study employed a co-design and implementation process, aiming to promote team-wide behavioural change, whereby health professionals at a TBI rehabilitation unit would attempt to address sexuality with patients routinely. Methods Focus group sessions with multidisciplinary health professionals were conducted to identify barriers and enablers to behavioural change, identify areas for development, and co-design intervention options. Implementation deliverables were then finalised and provided to the team. The Theoretical Domains Framework was used to map factors influencing behaviours and the Behaviour Change Wheel was used to map interventions. Thematic analysis was used to further analyse barrier themes. Results Thirty-five barriers and eight enablers falling within 12 theoretical domains to behavioural change were identified. Thematic analysis revealed highly correlated barriers in initiating and sustaining change. Nine co-designed intervention options aligned with five intervention functions of the Behaviour Change Wheel, resulting in six final implementation deliverables. Conclusions Barriers were highly interrelated, influencing the approach to implementation deliverables. Simultaneously addressing multiple barriers could potentially alleviate discomfort associated with discussing sexuality. Concerns around initiating change were related to confidence in achieving sustainable changes. Achieving change requires organisational and team-level environmental restructuring and enablement. The next step involves evaluating the effectiveness of the co-design and implementation process in driving behavioural change and potential impacts on patient satisfaction and sexuality outcomes.

Co-designing positive behaviour support (PBS+PLUS) training resources: a qualitative study of people with ABI, close-others, and clinicians' experiences.

Background Challenging behaviours are often a significant difficulty faced following acquired brain injury (ABI), for which PBS+PLUS (a Positive Behaviour Support framework) is an effective intervention. Clinicians report experiencing a range of barriers to supporting behaviour change for individuals with ABI and require tailored resources to support the implementation of PBS+PLUS. This study aimed to describe the process of co-designing a PBS+PLUS intervention guidebook and podcast series together with individuals with ABI, close-others, and clinicians, and qualitatively examine co-design experiences. Methods The Knowledge-To-Action Framework was followed to support the translation of PBS+PLUS into clinical practice. Participants with ABI (n = 4), close-others (n = 7), and clinicians (n = 3) participated in focus groups contributing to the development of a PBS+PLUS intervention guidebook and podcast series. Following completion of the groups, qualitative interviews were conducted to understand participants' perspectives of the co-design experience. Transcripts were analysed using reflexive thematic analysis. Results Co-design processes are described, and participants provided practical suggestions for co-design and the dissemination of developed resources. Two core themes encapsulating four sub-themes were identified. Firstly, 'Esteeming Experiences ' described the person-driven approach of co-design whereby participants felt supported and connected with other contributors and facilitators through sharing their perspectives. Secondly, 'Empowerment ' reflected participants' increased confidence and skills in applying PBS+PLUS. Conclusions Overall, participants endorsed the therapeutic benefits of co-design engagement and high utility of PBS+PLUS resources. This study adds to the growing literature supporting the use of co-design methodology within clinical implementation, and is inclusive of individuals with ABI, close-others, and clinicians.

"It's Not Only the Injury but Also the Kind of Head." Factors Influencing Outcome After Traumatic Brain Injury.

OBJECTIVE: Given the high variability in traumatic brain injury (TBI) outcomes and relative lack of examination of the influence of noninjury factors on outcome, this study aimed to examine factors associated with functional outcome at 1 and 2 years after moderate to severe TBI, including both preinjury and injury-related factors. DESIGN: Observational cohort study. SETTING: Inpatient hospital recruitment with outpatient follow-up at 1 and 2 years post injury. PARTICIPANTS: Individuals with moderate to severe TBI were recruited prospectively into a Longitudinal Head Injury Outcome Study. Of the eligible 3253 individuals who were eligible, 1899 participants consented to the study (N=1899). MAIN OUTCOME MEASURE: Functional outcome was measured using the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: 1476 participants (73.6% males) and 1365 participants (73% males) completed the GOS-E at 1 and 2 years post injury. They had a mean age at injury of 40 years and mean duration of post-traumatic amnesia (PTA) of 26 days. Good recovery, representing return to previous activities on the GOS-E (score 7-8), was present in 31% of participants at 1 year post injury and 33.5% at 2 years post injury. When predictor variables were entered into regression together, good outcome was significantly associated with not being from a culturally and linguistically diverse background and not having preinjury mental health or alcohol treatment, shorter PTA duration, and absence of limb injuries at both 1 and 2 years; higher education was also a significant predictor at 1 year post injury. CONCLUSIONS: Alongside consideration of injury severity, consideration of preinjury factors is important to inform prognostication and rehabilitation planning.

The impact of age on outcome 2 years after traumatic brain injury: Case control study.

BACKGROUND: Age is associated with outcome after traumatic brain injury (TBI). However, there are mixed findings across outcome domains and most studies lack controls. OBJECTIVES: This cross-sectional study examined the association between age group (15-24 years, 25-34 years, 35-44 years, 45-54 years, 55-64 years, and 65 years or more) and outcomes 2 years after TBI in independence in daily activities, driving, public transportation use, employment, leisure activities, social integration, relationships and emotional functioning, relative to healthy controls. It was hypothesized that older individuals with TBI would have significantly poorer outcomes than controls in all domains except anxiety and depression, for which it was expected they would show better outcomes. Global functional outcome (measured using the Glasgow Outcome Scale-Extended) was also examined, and we hypothesized that older adults would have poorer outcomes than younger adults. METHODS: Participants were 1897 individuals with TBI (mean, SD age 36.7, 17.7 years) who completed measures 2 years post-injury and 110 healthy controls (age 38.3, 17.5 years). RESULTS: Compared to controls, individuals with TBI were less independent in most activities of daily living, participated less in leisure activities and employment, and were more socially isolated, anxious and depressed (p < 0.001). Those who were older in age were disproportionately less likely to be independent in light domestic activities, shopping and driving; and participated less in occupational activities relative to controls. Functional outcome was significantly higher in the youngest age group than in all older age groups (p < 0.001), but the younger groups were more likely to report being socially isolated (p < 0.001), depressed (p = 0.005) and anxious (p = 0.02), and less likely to be married or in a relationship (p < 0.001). CONCLUSION: A greater focus is needed on addressing psychosocial issues in younger individuals with TBI, whereas those who are older may require more intensive therapy to maximise independence in activities of daily living and return to employment.

The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.

The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.

The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.

Altered grey matter structural covariance in chronic moderate-severe traumatic brain injury.

Traumatic brain injury (TBI) alters brain network connectivity. Structural covariance networks (SCNs) reflect morphological covariation between brain regions. SCNs may elucidate how altered brain network topology in TBI influences long-term outcomes. Here, we assessed whether SCN organisation is altered in individuals with chronic moderate-severe TBI (≥ 10 years post-injury) and associations with cognitive performance. This case-control study included fifty individuals with chronic moderate-severe TBI compared to 75 healthy controls recruited from an ongoing longitudinal head injury outcome study. SCNs were constructed using grey matter volume measurements from T1-weighted MRI images. Global and regional SCN organisation in relation to group membership and cognitive ability was examined using regression analyses. Globally, TBI participants had reduced small-worldness, longer characteristic path length, higher clustering, and higher modularity globally (p < 0.05). Regionally, TBI participants had greater betweenness centrality (p < 0.05) in frontal and central areas of the cortex. No significant associations were observed between global network measures and cognitive ability in participants with TBI (p > 0.05). Chronic moderate-severe TBI was associated with a shift towards a more segregated global network topology and altered organisation in frontal and central brain regions. There was no evidence that SCNs are associated with cognition.

Providing rehabilitation services to major traumatic injury survivors in rural Australia: perspectives of rehabilitation practitioners and compensation claims managers.

PURPOSE: The delivery of healthcare services in rural locations can be challenging. From the perspectives of rural rehabilitation practitioners and compensation claims managers, this study explored the experience of providing and coordinating rehabilitation services for rural major traumatic injury survivors. MATERIALS AND METHODS: Semi-structured interviews with 14 rural rehabilitation practitioners and 10 compensation claims managers were transcribed, and reflexive thematic analysis was conducted. RESULTS: Six themes were identified (1) Challenges finding and connecting with rural services, (2) Factors relating to insurance claims management, (3) Managing the demand for services, (4) Good working relationships, (5) Limited training and support, and (6) Client resilience and community. System-related barriers included a lack of available search resources to find rural rehabilitation services, limited service/clinician availability and funding policies lacking the flexibility to meet rehabilitation needs in a rural context. Strong peer and interdisciplinary relationships were viewed as crucial facilitators, which rural practitioners were particularly adept at developing. CONCLUSIONS: Greater consideration of unique needs within rural contexts is required when developing service delivery models. Specifically, flexible and equitable funding policies; facilitating interdisciplinary connections, support and training for rehabilitation practitioners and compensation claims managers; and harnessing clients' resilience may improve the delivery of rural services.IMPLICATIONS FOR REHABILITATIONRural survivors of major traumatic injury often have ongoing health and rehabilitation needs and struggle to access required treatment services.Rehabilitation providers and compensation claims managers highlighted areas for improvement in rural areas, including resources for locating available services, funding the additional costs of rural service delivery, and greater service choice for clients.Building rural workforce capacity for treatment of major traumatic injury is needed, including improved clinician access to specialist training and support.Developing good working relationships between clients and clinicians, including interdisciplinary collaborations, and supporting client resilience and self-management should be promoted in future service delivery models.

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.

The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.

The Australian Traumatic Brain Injury Initiative: Single Data Dictionary to Predict Outcome for People With Moderate-Severe Traumatic Brain Injury.

In this series of eight articles, the Australian Traumatic Brain Injury Initiative (AUS-TBI) consortium describes the Australian approach used to select the common data elements collected acutely that have been shown to predict outcome following moderate-severe traumatic brain injury (TBI) across the lifespan. This article presents the unified single data dictionary, together with additional measures chosen to facilitate comparative effectiveness research and data linkage. Consultations with the AUS-TBI Lived Experience Expert Group provided insights on the merits and considerations regarding data elements for some of the study areas, as well as more general principles to guide the collection of data and the selection of meaningful measures. These are presented as a series of guiding principles and themes. The AUS-TBI Aboriginal and Torres Strait Islander Advisory Group identified a number of key points and considerations for the project approach specific to Aboriginal and Torres Strait Islander peoples, including key issues of data sovereignty and community involvement. These are outlined in the form of principles to guide selection of appropriate methodologies, data management, and governance. Implementation of the AUS-TBI approach aims to maximize ongoing data collection and linkage, to facilitate personalization of care and improved outcomes for people who experience moderate-severe TBI.

Reduced total number of enlarged perivascular spaces in post-traumatic epilepsy patients with unilateral lesions - a feasibility study.

BACKGROUND: We investigated the value of automated enlarged perivascular spaces (ePVS) quantification to distinguish chronic traumatic brain injury (TBI) patients with post-traumatic epilepsy (PTE+) from chronic TBI patients without PTE (PTE-) in a feasibility study. METHODS: Patients with and without PTE were recruited and underwent an MRI post-TBI. Multimodal auto identification of ePVS algorithm was applied to T1-weighted MRIs to segment ePVS. The total number of ePVS was calculated and corrected for white matter volume, and an asymmetry index (AI) derived. RESULTS: PTE was diagnosed in 7 out of the 99 participants (male=69) after a median time of less than one year since injury (range 10-22). Brain lesions were observed in all 7 PTE+ cases (unilateral=4, 57%; bilateral=3, 43%) as compared to 40 PTE- cases (total 44%; unilateral=17, 42%; bilateral=23, 58%). There was a significant difference between PTE+ (M=1.21e-4, IQR [8.89e-5]) and PTE- cases (M=2.79e-4, IQR [6.25e-5]) in total corrected numbers of ePVS in patients with unilateral lesions (p=0.024). No differences in AI, trauma severity and lesion volume were seen between groups. CONCLUSION: This study has shown that automated quantification of ePVS is feasible and provided initial evidence that individuals with PTE with unilateral lesions may have fewer ePVS compared to TBI patients without epilepsy. Further studies with larger sample sizes should be conducted to determine the value of ePVS quantification as a PTE-biomarker.

Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as predictors of intracranial lesions on CT after mild traumatic brain injury (mTBI). However, most cases with mTBI are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. In this study, we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults younger than 50 years presenting to an emergency department within 6 hours of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post-traumatic amnesia (LOC/PTA), and delayed presentation affected classification performance. METHODS: Blood samples, symptom questionnaires, and cognitive tests were prospectively conducted for participants with mTBI recruited from The Alfred Hospital Level 1 Emergency & Trauma Center and uninjured controls. Follow-up testing was conducted at 7 days. Simoa quantified plasma GFAP, UCH-L1, tau, neurofilament light chain (NfL), interleukin (IL)-6, and IL-1ß. Area under the receiver operating characteristic (AUC) analysis assessed classification accuracy for diagnosed mTBI, and logistic regression models identified optimal biomarker combinations. RESULTS: Plasma IL-6 (AUC 0.91, 95% CI 0.86-0.96), GFAP (AUC 0.85, 95% CI 0.78-0.93), and UCH-L1 (AUC 0.79, 95% CI 0.70-0.88) best differentiated mTBI (n = 74) from controls (n = 44) acutely (<6 hours), with NfL (AUC 0.81, 95% CI 0.72-0.90) the only marker to have such utility subacutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP: AUC 0.71, 95% CI 0.55-0.88; IL-6: AUC 0.71, 95% CI 0.55-0.87) and in those with LOC/PTA (GFAP: AUC 0.73, 95% CI 0.59-0.86; IL-6: AUC 0.71, 95% CI 0.57-0.84). Acute IL-6 (R 2 = 0.50, 95% CI 0.34-0.64) outperformed GFAP and UCH-L1 combined (R 2 = 0.35, 95% CI 0.17-0.50), with the best acute model featuring GFAP and IL-6 (R 2 = 0.54, 95% CI 0.34-0.68). DISCUSSION: These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults younger than 50 years. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best-performing acute markers, subacute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility.

Experience of adapted cognitive behaviour therapy to address sexuality problems after traumatic brain injury: A qualitative study.

Although sexuality has been shown to be negatively impacted in up to half of individuals who sustain traumatic brain injury (TBI), few studies have sought to evaluate the efficacy of targeted interventions. Gaining insight into the participant experience of undergoing treatment for post-TBI sexuality changes is a crucial aspect of intervention evaluation. This study aimed to investigate participants with TBI experience of undergoing eight sessions of a novel CBT intervention designed to help both couples and singles improve sexual wellbeing after TBI. Eight participants (50% male) with moderate-severe TBI, and a mean age of 46.38-years (SD = 13.54), completed a qualitative interview. A six-phase reflexive thematic analysis approach was used. Despite variability in participant characteristics, the findings suggested that participants with TBI experience reflected that of a positive treatment journey characterized by high levels of enjoyment and satisfaction. Key themes identified included contextual factors that preceded treatment, factors that facilitated treatment engagement, outcomes derived from the treatment experience, and feedback provided on reflection. The results not only provide an enriched understanding of the client experience of the intervention but provide corroborating preliminary evidence of efficacy for this novel CBT intervention in addressing complex and persistent sexuality problems after TBI.

Traumatic brain injury alters the relationship between brain structure and episodic memory.

BACKGROUND: Focal and diffuse pathology resulting from traumatic brain injury (TBI) often disrupts brain circuitry that is critical for episodic memory, including medial temporal lobe and prefrontal regions. Prior studies have focused on unitary accounts of temporal lobe function, associating verbally learned material and brain morphology. Medial temporal lobe structures, however, are domain-sensitive, preferentially supporting different visual stimuli. There has been little consideration of whether TBI preferentially disrupts the type of visually learned material and its association with cortical morphology following injury. Here, we investigated whether (1) episodic memory deficits differ according to the stimulus type, and (2) the pattern in memory performance can be linked to changes in cortical thickness. METHODS: Forty-three individuals with moderate-severe TBI and 38 demographically similar healthy controls completed a recognition task in which memory was assessed for three categories of stimuli: faces, scenes, and animals. The association between episodic memory accuracy on this task and cortical thickness was subsequently examined within and between groups. RESULTS: Our behavioral results support the notion of category-specific impairments: the TBI group had significantly impaired accuracy for memory for faces and scenes, but not animals. Moreover, the association between cortical thickness and behavioral performance was only significant for faces between groups. CONCLUSION: Taken together, these behavioral and structural findings provide support for an emergent memory account, and highlight that cortical thickness differentially affects episodic memory for specific categories of stimuli.

Associations of Enlarged Perivascular Spaces With Brain Lesions, Brain Age, and Clinical Outcomes in Chronic Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Enlarged perivascular spaces (ePVS) have been identified as a key signature of glymphatic system dysfunction in neurologic conditions. The incidence and clinical implications of ePVS after traumatic brain injury (TBI) are not yet understood. We investigated whether individuals with chronic moderate-to-severe TBI had an increased burden of ePVS and whether ePVS burden is modulated by the presence of focal lesions, older brain age, and poorer sleep quality. We examined whether an increased burden of ePVS was associated with poorer cognitive and emotional outcomes. METHODS: Using a cross-sectional design, participants with a single moderate-to-severe chronic TBI (sustained ≥10 years ago) were recruited from an inpatient rehabilitation program. Control participants were recruited from the community. Participants underwent 3T brain MRI, neuropsychological assessment, and clinical evaluations. ePVS burden in white matter was quantified using automated segmentation. The relationship between the number of ePVS, group membership, focal lesions, brain age, current sleep quality, and outcome was modeled using negative binomial and linear regressions. RESULTS: This study included 100 participants with TBI (70% male; mean age = 56.8 years) and 75 control participants (54.3% male; mean age = 59.8 years). The TBI group had a significantly greater burden of ePVS (prevalence ratio rate [PRR] = 1.29, p = 0.013, 95% CI 1.05-1.57). The presence of bilateral lesions was associated with greater ePVS burden (PRR = 1.41, p = 0.021, 95% CI 1.05-1.90). There was no association between ePVS burden, sleep quality (PRR = 1.01, p = 0.491, 95% CI 0.98-1.048), and sleep duration (PRR = 1.03, p = 0.556, 95% CI 0.92-1.16). ePVS was associated with verbal memory (ß = -0.42, p = 0.006, 95% CI -0.72 to -0.12), but not with other cognitive domains. The burden of ePVS was not associated with emotional distress (ß = -0.70, p = 0.461, 95% CI -2.57 to 1.17) or brain age (PRR = 1.00, p = 0.665, 95% CI 0.99-1.02). DISCUSSION: TBI is associated with a greater burden of ePVS, especially when there have been bilateral brain lesions. ePVS was associated with reduced verbal memory performance. ePVS may indicate ongoing impairments in glymphatic system function in the chronic postinjury period.