Acceptance and commitment therapy delivered in a dyad after a severe traumatic brain injury: a feasibility study

Objective: There is a high prevalence of complex psychological distress after a traumatic brain injury but limited evidence of effective interventions. We examined the feasibility of Acceptance and Commitment Therapy after a severe traumatic brain injury using the criteria, investigating a therapeutic effect, and reviewing the acceptability of measures, treatment protocol, and delivery method (in a dyad of two clients and a therapist). Method: Two male outpatients with severe traumatic brain injury and associated psychological distress jointly engaged in a seven session treatment program based on Acceptance and Commitment Therapy principles. Pre- and post-treatment measures of mood, psychological flexibility, and participation were taken in addition to weekly measures. Results: The intervention showed a therapeutic effect with one participant, and appeared to be acceptable for both participants with regard to program content, measures, and delivery mode by in a dyad. One participant showed both significant clinical and reliable change across several outcome measures including measures of mood and psychological flexibility. The second participant did not show a reduction in psychological inflexibility, but did show a significant drop in negative affect. Significant changes pre- to post-treatment for measures of participation were not indicated. Qualitatively, both participants engaged in committed action set in accordance with their values. Conclusions: This study suggests that Acceptance and Commitment Therapy may be feasible to be delivered in a dyad with individuals who have a severe traumatic brain injury. A further test of its potential efficacy in a phase II clinical trial is recommended

Cytotoxic edema associated with hemorrhage predicts poor outcome after traumatic brain injury

Magnetic resonance imaging (MRI) is rarely used in the acute evaluation of traumatic brain injury (TBI), but may identify findings of clinical importance not detected by computed tomography (CT). We aimed to characterize the association of cytotoxic edema and hemorrhage, including traumatic microbleeds, on MRI obtained within hours of acute head trauma and investigated the relationship to clinical outcomes. Patients prospectively enrolled in the Traumatic Head Injury Neuroimaging Classification study (NCT01132937) with evidence of diffusion-related findings or hemorrhage on neuroimaging were included. Blinded interpretation of MRI for diffusion-weighted imaging and hemorrhage was conducted, with subsequent quantification of apparent diffusion coefficient (ADC) values. Of 161 who met criteria, 82 patients had conspicuous hyperintense lesions on diffusion-weighted imaging (DWI) with corresponding regions of hypointense ADC in proximity to hemorrhage. Median time from injury to MRI was 21 (10-30) hours. Median ADC values per patient grouped by time from injury to MRI were lowest within 24 hours after injury. ADC values associated with hemorrhagic lesions are lowest early after injury, with an increase in diffusion during the subacute period, suggesting transformation from cytotoxic to vasogenic edema during the subacute post-injury period. Of 118 patients with outcome data, 60 had Glasgow Outcome Scale Extended <6 at 30/90 days post-injury. Cytotoxic edema on MRI (OR 2.91 [1.32-6.37], P=0.008) and TBI severity (OR 2.51 [1.32-4.74], P=0.005) were independent predictors of outcome. These findings suggest that in TBI patients with findings of hemorrhage on CT, patients with DWI/ADC lesions on MRI are more likely to do worse

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Abstracts from the NIHR INVOLVE Conference 2017

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Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Exploring the relationship between cognitive flexibility and psychological flexibility after acquired brain injury

Abstract presented at the Tenth World Congress on Brain Injury, 19-22 March 2014, San Francisco, United State

Digital divide among individuals with acquired brain injury: a scoping review protocol

OBJECTIVE: This scoping review will identify literature pertaining to individuals with an acquired brain injury and digital divide; specifically, examining personal access and use of internet-enabled information and communication technologies. The review will identify the information and communication technologies used by individuals with an acquired brain injury as well as the determinants of technology use. The review will also identify and create a taxonomy of information and communication technologies utilized in relation to cognitive and psychosocial outcomes for individuals with an acquired brain injury in community and outpatient settings. INTRODUCTION: Internet-enabled technologies are increasingly central to all aspects of living, including health care and community participation; however, gaps in the access to and use of information and communication technologies among individuals with an acquired brain injury may limit the utility of a digitalized society. INCLUSION CRITERIA: Studies that focus on access to or use of internet-enabled information and communication technologies among individuals with an acquired brain injury (including stroke, infection, tumor, disease, hypoxia, or traumatic brain injury) will be considered in this review. METHODS: Primary peer-reviewed studies published in English from 2001 onward will be considered for inclusion. Six electronic databases will be searched: Embase, MEDLINE, Web of Science Core Collection, Google Scholar, CINAHL, and APA PsycINFO. Gray literature searches for government and nongovernment organization reports and data, and dissertation theses will be conducted via advanced Google searches. Two reviewers will independently screen titles, abstracts, and full texts of articles based on the population, concept, context inclusion criteria. Relevant data will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR)

Validating measures of psychological flexibility in a population with acquired brain injury

This study presents preliminary validation data on both the Acceptance and Action Questionnaire—Acquired Brain Injury (AAQ-ABI) and the Acceptance and Action Questionnaire—II (AAQ-II). Data from 150 participants with ABI was subject to exploratory factor analysis on the AAQ-ABI (15 items). A subset of 75 participants with ABI completed a larger battery of measures to test construct validity for the AAQ-ABI and to undertake a confirmatory factor analysis (CFA) on the AAQ-II (7 items). Three meaningful factors were identified on the AAQ-ABI: Reactive Avoidance, Denial, and Active Acceptance. Reactive Avoidance demonstrated good internal and test–retest consistency (α = .89) and correlated in expected directions with other related measures including the AAQ-II. CFA of the AAQ-II did not provide a good fit but did have similar correlations with measures of psychological distress as found in prior non-ABI samples. The results suggest both measures can be used with individuals following an ABI but they index different facets of psychological flexibility. The AAQ-ABI appears to measure psychological flexibility about the thoughts and feelings relating to the brain injury itself while the AAQ-II measures psychological flexibility around general psychological distress. Future research could explore the additional 2 factors of the AAQ-ABI and use these measures in outcome studies that promote psychological flexibility in individuals with an ABI