Internet-Guided Cognitive Behavioral Therapy for Insomnia Among Patients With Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Many military service members and veterans report insomnia after sustaining traumatic brain injury (TBI). Limitations of first-line treatment, cognitive-behavioral therapy for insomnia (CBT-I), include availability of qualified clinicians, low completion rates, and cost. Objective: To investigate the feasibility and efficacy of internet-guided CBT-I (eCBT-I) in military service members and veterans with insomnia and a history of TBI. Design, Setting, and Participants: This randomized clinical trial of fully remote internet-based interventions and evaluations was conducted from September 1, 2020, to June 30, 2021, with 3 months of follow-up. Participants included a volunteer sample of military service members and veterans aged 18 to 64 years with a history of mild TBI/concussion and at least moderately severe insomnia defined as an insomnia severity index (ISI) score of greater than 14 and Pittsburgh Sleep Quality Index of greater than 4. Self-reported race, ethnicity, and educational level were generally representative of the US military. Data were analyzed from October 21, 2021, to April 29, 2024. Intervention: Internet-based CBT-I delivered over 6 weekly lesson modules with assigned homework activities. Main Outcomes and Measures: The prespecified primary outcome measure was change in ISI score over time. Prespecified secondary outcome measures included self-reported measures of depression symptoms, posttraumatic stress disorder (PTSD) symptoms, sleep quality, migraine impact, and fatigue. Results: Of 204 people screened, 125 were randomized 3:1 to eCBT-I vs online sleep education, and 106 completed baseline evaluations (83 men [78.3%]; mean [SD] age, 42 [12] years). Of these, 22 participants (20.8%) were Hispanic or Latino and 78 (73.6%) were White. Fifty participants completed postintervention evaluations, and 41 completed the 3-month follow-up. Baseline mean (SD) ISI scores were 19.7 (4.0) in those randomized to eCBT-I and 18.9 (5.0) in those randomized to sleep education. After intervention, mean (SD) ISI scores were 13.7 (5.6) in those randomized to eCBT-I and 16.6 (5.7) in those randomized to sleep education. The difference in the extent of reduction in ISI scores between groups was 3.5 (95% CI,-6.5 to -0.4 [P = .03]; Cohen d, -0.32 [95% CI, -0.70 to -0.04]). In the eCBT-I group, the extent of insomnia improvement correlated with the extent of depressive symptom improvement (Spearman ρ = 0.68 [P < .001]), PTSD symptoms (ρ = 0.36 [P = .04]), sleep quality (ρ = 0.54 [P = .001]), and fatigue impact (ρ = -0.58 [P < .001]) but not migraine-related disability. Conclusions and Relevance: The findings of this randomized clinical trial suggest that fully remote eCBT-I was moderately feasible and effective for self-reported insomnia and depression symptoms in military service members and veterans with a history of TBI. There is great potential benefit for eCBT-I due to low availability and cost of qualified CBT-I clinicians, although optimization of completion rates remains a challenge. Future studies may use home-based objective sleep assessments and should increase study retention. Trial Registration: ClinicalTrials.gov Identifier: NCT04377009.

A pilot study of volumetric and density tumor analysis of ACC patients treated with vorinostat in a phase II clinical trial.

Rationale and objectives: Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. The vast majority of clinical trials evaluating systemic therapy efficacy in solid tumors use the Response Evaluation Criteria in Solid Tumors (RECIST) to measure response that is limited to 2 dimensional only evaluations, not taking volume or density into account. The indolent behavior ACC represents a challenge toward an appropriate evaluation of therapy response. Objectives: 1) To describe and contrast volumetric and density changes at each time-point, including changes noted from baseline to best response, to currently used 2 dimensional-only criteria (RECIST) and 2) To report the coefficient of variation in volume measurement among three reviewers on a subset of ACC patients. Materials and methods: We retrospectively assessed a cohort of 18 prospectively treated patients with ACC in a phase 2 trial with vorinostat using a volumetric (viable tumor volume, VTV) and density criteria. Three independent and blinded observers segmented target lesions across a sample of randomly selected computed tomography (CT) exams to examine inter-observer variation. Results: We found that the average coefficient of variation among observers for all target lesions was 16.1%, with lung lesions displaying a smaller variation at 14.0% (p-value >0.17). We describe examples of decrease in volume and density in several lesions despite stable disease by RECIST. Conclusion: This pilot study demonstrates that two-dimensional criteria such as RECIST may not be the best criteria to assess response to therapy, especially with evolving tools within picture archiving and communication system (PACS) that can assess volumetric size, density and texture, however, this should be prospectively studied.