Objective: To evaluate the acute efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) vs placebo (PBO) in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD).Method: This phase 3, double-blind, fixed-dose study randomly assigned children (aged 4-5 years) with ADHD to 6 weeks of LDX (5, 10, 20, 30 mg) or PBO. The prespecified primary (change from baseline at week 6 in ADHD Rating Scale IV, Preschool version, total score [ADHD-RS-IV-PS-TS]) and key secondary (Clinical Global Impression-Improvement [CGI-I] score at week 6) efficacy endpoints were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and changes in pulse and blood pressure (BP).Results: The study comprised 199 participants randomly asigned 5:5:5:5:6 to receive 5, 10, 20, 30 mg LDX or PBO, respectively. Least squares (LS) mean (95% CI) treatment difference at week 6 between pooled LDX (10, 20, 30 mg) and PBO was statistically significant for ADHD-RS-IV-PS-TS change (-5.9 [-11.01, -0.78], p = .0242; effect size [ES], -0.43). CGI-I scores improved (ie, 1-2 on CGI-I) in 41.7% for pooled LDX and 24.3% for PBO (p = .0857). The LS mean (95% CI) treatment difference between pooled LDX and PBO for CGI-I score at week 6 was -0.6 (-1.03, -0.16; p = .0074; ES, -0.52). Frequency of TEAEs was 46.6% across all 4 LDX doses vs 42.2% with PBO; the most frequent TEAEs were decreased appetite (13.7% vs 8.9%, respectively) and irritability (9.6% vs 0%). Discontinuations because of TEAEs were 5.5% for all LDX doses and 4.4% for PBO. Mean & PLUSMN; SD pulse/BP changes from baseline at week 6/early termination were numerically greater with LDX vs PBO (pulse beats/min: 2.7 & PLUSMN; 10.79 vs 1.2 & PLUSMN; 9.90; systolic BP, mm Hg: 1.0 & PLUSMN; 7.51 vs 0.3 & PLUSMN; 6.06; diastolic BP, mm Hg: 1.7 & PLUSMN; 5.90 vs 0.0 & PLUSMN; 6.88).Conclusion: In children aged 4 to 5 years with ADHD, LDX was more efficacious than PBO in reducing symptoms. The observed ES for change in ADHD-RS-IV-PS-TS appears to be smaller in magnitude than has been reported for studies of LDX conducted in older children and adolescents. LDX was generally well tolerated, and no new safety signals were identified.Clinical trial registration information: Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-Deficit/Hyperactivity Disorder; http://www.clinicaltrials.gov; NCT03260205.

Consistency in parenting infants has positive developmental outcomes. Yet, the role of socioeconomic status (SES) in consistency of maternal behaviors is not well understood. We investigated individual-order continuity of maternal smile and laughter and positive vocalization from 6 to 12 months of age in 82 mother-infant dyads. Overall, individual differences in maternal smile and laughter, and positive vocalization were consistent across time. A multidimensional measure of SES moderated the association of maternal smile and laughter from 6 to 12 months, such that infants from lower SES families were vulnerable to unpredictable parenting - experiencing a lack of consistency in maternal smiles and laughter.

Aim: Two separate LC-MS/MS assays were developed to quantitate sulfatides and lysosulfatide in human cerebrospinal fluid (CSF). Materials & methods: Lysosulfatide and the 15 most abundant sulfatide species were quantitated by LC-MS/MS using artificial CSF as surrogate matrix to prepare calibration curves. Results: Validation criteria were met (linear range: 0.02-1.00 μg/ml sulfatides [0.02-1.00 ng/ml lysosulfatide]); accuracy/precision were within ±15%. CSF from 21 children with metachromatic leukodystrophy had significantly higher sulfatide and lysosulfatide concentrations than CSF from 60 healthy children (p < 0.0001). Worse motor function correlated with higher CSF sulfatide (p = 0.0087) and lysosulfatide (p = 0.0034) levels. Conclusion: These assays, validated in patients with metachromatic leukodystrophy, may aid the clinical assessment of therapeutic responses.