Cognitive Behavioral Therapy for Sleep Disturbance and Fatigue Following Acquired Brain Injury: Predictors of Treatment Response.

OBJECTIVE: To identify factors associated with treatment response to cognitive behavioral therapy for sleep disturbance and fatigue (CBT-SF) after acquired brain injury (ABI). SETTING: Community dwelling. PARTICIPANTS: Thirty participants with a traumatic brain injury or stroke randomized to receive CBT-SF in a parent randomized controlled trial. DESIGN: Participants took part in a parallel-groups, parent randomized controlled trial with blinded outcome assessment, comparing an 8-week CBT-SF program with an attentionally equivalent health education control. They were assessed at baseline, post-treatment, 2 months post-treatment, and 4 months post-treatment. The study was completed either face-to-face or via telehealth (videoconferencing). Following this trial, a secondary analysis of variables associated with treatment response to CBT-SF was conducted, including: demographic variables; injury-related variables; neuropsychological characteristics; pretreatment sleep disturbance, fatigue, depression, anxiety and pain; and mode of treatment delivery (face-to-face or telehealth). MAIN MEASURES: Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). RESULTS: Greater treatment response to CBT-SF at 4-month follow-up was associated with higher baseline sleep and fatigue symptoms. Reductions in fatigue on the FSS were also related to injury mechanism, where those with a traumatic brain injury had a more rapid and short-lasting improvement in fatigue, compared with those with stroke, who had a delayed but longer-term reduction in fatigue. Mode of treatment delivery did not significantly impact CBT-SF outcomes. CONCLUSION: Our findings highlight potential differences between fatigue trajectories in traumatic brain injury and stroke, and also provide preliminary support for the equivalence of face-to-face and telehealth delivery of CBT-SF in individuals with ABI.

Residues in Transmembrane Segments of the P2X4 Receptor Contribute to Channel Function and Ethanol Sensitivity.

Mouse models of alcohol use disorder (AUD) revealed purinergic P2X4 receptors (P2X4Rs) as a promising target for AUD drug development. We have previously demonstrated that residues at the transmembrane (TM)-ectodomain interface and within the TM1 segment contribute to the formation of an ethanol action pocket in P2X4Rs. In the present study, we tested the hypothesis that there are more residues in TM1 and TM2 segments that are important for the ethanol sensitivity of P2X4Rs. Using site-directed mutagenesis and two electrode voltage-clamp electrophysiology in Xenopus oocytes, we found that arginine at position 33 (R33) in the TM1 segment plays a role in the ethanol sensitivity of P2X4Rs. Molecular models in both closed and open states provided evidence for interactions between R33 and aspartic acid at position 354 (D354) of the neighboring TM2 segment. The loss of ethanol sensitivity in mixtures of wild-type (WT) and reciprocal single mutants, R33D:WT and D354R:WT, versus the WT-like response in R33D-D354R:WT double mutant provided further support for this interaction. Additional findings indicated that valine at TM1 position 49 plays a role in P2X4R function by providing flexibility/stability during channel opening. Collectively, these findings identified new activity sites and suggest the importance of TM1-TM2 interaction for the function and ethanol sensitivity of P2X4Rs.

Cognitive behavioural therapy for post-stroke fatigue and sleep disturbance: a pilot randomised controlled trial with blind assessment.

The objective of this study was to evaluate the effectiveness of individual cognitive behavioural therapy (CBT) for post-stroke fatigue and sleep disturbance compared to treatment as usual (TAU). In a parallel two-group pilot randomised controlled trial of 15 participants, nine were allocated to eight weekly sessions of adapted CBT and six continued usual care rehabilitation. The primary outcome was the Fatigue Severity Scale (FSS-7) at two and four months from baseline. Secondary outcomes included measures of sleep, mood and quality of life. Outcomes were assessed by a rater who was blind to group membership. At the four-month endpoint, the CBT group demonstrated significantly reduced fatigue relative to TAU (FSS-7 mean difference: 1.92, 95% CI: 0.24 to 3.60). Significant group differences also emerged for sleep quality and depression, favouring the CBT group. Insomnia and physical quality of life improved immediately post-therapy but were no longer superior to TAU at follow-up. Overall, CBT is a promising treatment for improving post-stroke fatigue, sleep quality and depression. Gains were maintained for two months after therapy cessation and represented large treatment effects. These findings highlight the feasibility of the intervention and warrant extension to a phase III clinical trial.

Cognitive Behavior Therapy to Treat Sleep Disturbance and Fatigue After Traumatic Brain Injury: A Pilot Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of adapted cognitive behavioral therapy (CBT) for sleep disturbance and fatigue in individuals with traumatic brain injury (TBI). DESIGN: Parallel 2-group randomized controlled trial. SETTING: Outpatient therapy. PARTICIPANTS: Adults (N=24) with history of TBI and clinically significant sleep and/or fatigue complaints were randomly allocated to an 8-session adapted CBT intervention or a treatment as usual (TAU) condition. INTERVENTIONS: Cognitive behavior therapy. MAIN OUTCOME MEASURES: The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) posttreatment and at 2-month follow-up. Secondary measures included the Insomnia Severity Index, Fatigue Severity Scale, Brief Fatigue Inventory (BFI), Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. RESULTS: At follow-up, CBT recipients reported better sleep quality than those receiving TAU (PSQI mean difference, 4.85; 95% confidence interval [CI], 2.56-7.14). Daily fatigue levels were significantly reduced in the CBT group (BFI difference, 1.54; 95% CI, 0.66-2.42). Secondary improvements were significant for depression. Large within-group effect sizes were evident across measures (Hedges g=1.14-1.93), with maintenance of gains 2 months after therapy cessation. CONCLUSIONS: Adapted CBT produced greater and sustained improvements in sleep, daily fatigue levels, and depression compared with TAU. These pilot findings suggest that CBT is a promising treatment for sleep disturbance and fatigue after TBI.

Cognitive behavioural therapy versus health education for sleep disturbance and fatigue after acquired brain injury: A pilot randomised trial.

BACKGROUND: Sleep disturbance and fatigue are highly prevalent after acquired brain injury (ABI) and are associated with poor functional outcomes. Cognitive behavioural therapy (CBT) is a promising treatment for sleep and fatigue problems after ABI, although comparison with an active control is needed to establish efficacy. OBJECTIVES: We compared CBT for sleep disturbance and fatigue (CBT-SF) with a health education (HE) intervention to control for non-specific therapy effects. METHODS: In a parallel-group, pilot randomised controlled trial, 51 individuals with traumatic brain injury (n = 22) and stroke (n = 29) and clinically significant sleep and/or fatigue problems were randomised 2:1 to 8 weeks of a CBT-SF (n = 34) or HE intervention (n = 17), both adapted for cognitive impairments. Participants were assessed at baseline, post-treatment, and 2 and 4 months post-treatment. The primary outcome was the Pittsburgh Sleep Quality Index; secondary outcomes included measures of fatigue, sleepiness, mood, quality of life, activity levels, self-efficacy and actigraphy sleep measures. RESULTS: The CBT-SF led to significantly greater improvements in sleep quality as compared with HE, during treatment and at 2 months [95% confidence interval (CI) -24.83; -7.71], as well as significant reductions in fatigue maintained at all time points, which were not evident with HE (95% CI -1.86; 0.23). HE led to delayed improvement in sleep quality at 4 months post-treatment and in depression (95% CI -1.37; -0.09) at 2 months post-treatment. CBT-SF led to significant gains in self-efficacy (95% CI 0.15; 0.53) and mental health (95% CI 1.82; 65.06). CONCLUSIONS: CBT-SF can be an effective treatment option for sleep disturbance and fatigue after ABI, over and above HE. HE may provide delayed benefit for sleep, possibly by improving mood. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12617000879369 (registered 15/06/2017) and ACTRN12617000878370 (registered 15/06/2017).

Factors associated with persistent post-concussion symptoms following mild traumatic brain injury in adults.

OBJECTIVES: Debate regarding factors associated with persistent symptoms following mild traumatic brain injury continues. Nested within a trial aiming to change practice in emergency department management of mild traumatic brain injury, this study investigated the nature of persistent symptoms, work/study outcomes, anxiety and quality of life and factors associated with persistent symptoms following injury, including the impact of receiving information about mild traumatic brain injuries in the emergency department. METHODS: A total of 343 individuals with mild traumatic brain injury completed the Rivermead Post-Concussion Symptom Questionnaire, Hospital Anxiety Depression Scale - Anxiety Scale, and Quality of Life - Short Form in average 7 months post-injury. RESULTS: Overall, 18.7% of participants reported 3 or more post-concussional symptoms, most commonly fatigue (17.2%) and forgetfulness (14.6%). Clinically significant anxiety was reported by 12.8%, and was significantly associated with symptom reporting, as were mental and physical quality of life scores. Significant predictors of post-concussional symptoms at follow-up were pre-injury psychological issues, experiencing loss of consciousness, and having no recall of receiving information about brain injury in the emergency department. CONCLUSION: This study confirms that loss of consciousness and pre-injury psychological issues are associated with persistent symptom reporting. Not receiving injury information in the emergency department may also negatively influence symptom reporting.

Exploring predictors of treatment outcome in cognitive behavior therapy for sleep disturbance following acquired brain injury.

PURPOSE: To identify predictors of treatment response to cognitive behavior therapy (CBT) for sleep disturbance following acquired brain injury (ABI). METHODS: Classification and regression tree (CART) analysis was conducted on individual patient data from two pilot randomized controlled trials (RCTs): one in traumatic brain injury (TBI), the other in stroke. The combined sample comprised 32 participants; 15 receiving CBT and 17 allocated to treatment as usual (TAU). The outcome was reliable improvement on the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Study group was a statistically significant predictor of outcome, with CBT participants more likely to achieve reliable improvements than TAU (OR = 4.88, p = 0.042). Study group (CBT vs. TAU) exhibited an area under the ROC curve (AUROC) of 69%. In separate CART analyzes, verbal memory (CVLT-II >45.5), age (<47.5) and baseline depression (HADS-D > 6) predicted positive outcomes in CBT recipients. Each of these variables added a small (∼5%) but not statistically significant amount to AUROC over study group. CONCLUSIONS: In this ABI sample, better memory, younger age, and higher baseline depression were associated with positive treatment response to CBT although individually these variables were not better than group alone in predicting outcomes. The present findings generate hypotheses for further investigation in future studies. Implications for rehabilitation Cognitive behavior therapy improves sleep quality over treatment as usual in persons with acquired brain injury. Individuals who are younger in age with better memory and co-morbid symptoms of depression are more likely to respond to the treatment. These findings are based on a small sample and can be considered hypothesis generating for future clinical studies.

Parental cognitive appraisals and coping behaviours following child's epilepsy diagnosis: a qualitative study.

Management of childhood epilepsy places significant demands and increased stress on the family unit. How parents adjust to this illness-related stress is believed to be shaped by their cognitive appraisals of the situation and the coping behaviours that are employed (Wallander & Varni, 1992). We investigated the cognitive and behavioural strategies that regulated psychological symptomatology in mothers following an epilepsy diagnosis of their child. Twenty-one mothers participated in this qualitative study. Interview data was analyzed using theory-driven thematic analysis. The analysis revealed common effective cognitive appraisals that include maintaining a positive outlook, re-structuring expectations and finding meaning from their experiences. Problem-solving, emotional venting, time to self and speaking with parents in similar situations were behaviours that buffered against carer strain. The coping strategies identified in this study can be seen as sources of resilience and therefore provide a guide for improving parent outcomes in the context of pediatric illness. Implications for clinical services are discussed in this paper.