Traumatic Brain Injury-Related Attention Deficits in Children: A Controlled Treatment Trial with Lisdexamfetamine Dimesylate (Vyvanse)

Attention deficits are among the most common and persistent impairments resulting from traumatic brain injury (TBI). This study was the first to examine the effects of lisdexamfetamine dimesylate (LDX, Vyvanse) in treating TBI-related attention deficits in children. It was an extension of a previous controlled trial with adults. This was a 12-week, randomized, double-blind, placebo-controlled, dose-titration, crossover trial. In addition to weekly safety monitoring, there were assessments on a broad range of neuropsychological and behavioral measures at baseline, 6-weeks, and 12-weeks. A total of 20 carefully selected children were enrolled, ranging from 10 to 16 years of age. The sample consisted of cases with mainly mild TBI (based on the known details regarding their injuries), but they had persisting attention deficits and other post-concussion symptoms lasting from 2 to 29 months by the time of enrollment. A total of 16 children completed the trial. One of the children withdrew due to a mild anxiety reaction while on LDX. There were no other adverse effects. Positive treatment results were found on both formal testing of sustained attention and in terms of parent ratings of attention, emotional status, behavioral controls, and various aspects of executive functioning. The findings also served to highlight broader insights into the nature of attention deficits and their treatment in children with TBI

Traumatic Brain Injury-Related Attention Deficits in Children: A Controlled Treatment Trial with Lisdexamfetamine Dimesylate (Vyvanse)

Attention deficits are among the most common and persistent impairments resulting from traumatic brain injury (TBI). This study was the first to examine the effects of lisdexamfetamine dimesylate (LDX, Vyvanse) in treating TBI-related attention deficits in children. It was an extension of a previous controlled trial with adults. This was a 12-week, randomized, double-blind, placebo-controlled, dose-titration, crossover trial. In addition to weekly safety monitoring, there were assessments on a broad range of neuropsychological and behavioral measures at baseline, 6-weeks, and 12-weeks. A total of 20 carefully selected children were enrolled, ranging from 10 to 16 years of age. The sample consisted of cases with mainly mild TBI (based on the known details regarding their injuries), but they had persisting attention deficits and other post-concussion symptoms lasting from 2 to 29 months by the time of enrollment. A total of 16 children completed the trial. One of the children withdrew due to a mild anxiety reaction while on LDX. There were no other adverse effects. Positive treatment results were found on both formal testing of sustained attention and in terms of parent ratings of attention, emotional status, behavioral controls, and various aspects of executive functioning. The findings also served to highlight broader insights into the nature of attention deficits and their treatment in children with TBI

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study

BACKGROUND: and Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors. METHODS: This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis. RESULTS: 947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p \u3c 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p \u3c 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings. CONCLUSION: Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study

BACKGROUND: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; =0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; =0.02). CONCLUSIONS: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study.

BACKGROUND and Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors. METHODS This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis. RESULTS 947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de-novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings. CONCLUSION Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

BACKGROUND A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies