This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury.

203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8–18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1–11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (∼4 months) phase.

Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not.

The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children).

To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.

To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490).

Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs.

Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe.

GXR was effective and well tolerated in children and adolescents with ADHD.

GXR, a selective α2A-adrenergic agonist, is a non-stimulant ADHD treatment approved in the USA for children and adolescents, and in Canada for children.

To evaluate long-term maintenance of efficacy of GXR in children and adolescents with ADHD who respond to an initial open-label, short-term trial.

To determine if there is a higher rate of treatment failure for placebo vs GXR during the double-blind randomised-withdrawal phase (RWP) (NCT01081145).

Patients (6–17 years) meeting DSM-IV-TR criteria for ADHD, baseline ADHD Rating Scale-IV (ADHD-RS-IV) ≥32 and Clinical Global Impressions-Severity (CGI-S) ratings ≥4 were enrolled. Following 7-week dose optimization and 6-week maintenance periods on open-label GXR (1–7 mg/day), eligible patients entered a 26-week, double-blind, RWP with GXR or placebo. The primary endpoint was rate of treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in CGI-S at two consecutive visits, compared to the RWP baseline). The key secondary endpoint was time-to-treatment failure. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs.

Of 528 patients enrolled, 316 (60.0%) entered the RWP. At study end, 49.3% (GXR) and 64.9% (placebo) (95%CI; −26.6, −4.5, p<0.01) of patients had relapsed (Figure). Time-to-treatment failure was 56 days (placebo) versus 218 days (GXR), p=0.003. During the RWP, the most common GXR TEAEs (≥5% patients) were headache, somnolence and nasopharyngitis.

GXR demonstrated long-term maintenance of efficacy versus placebo in children and adolescents with ADHD.