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Pioneering longitudinal studies of boys with hyperactivity by Satterfield et al. 1 indicated that one of the most deleterious outcomes associated with attention-deficit/hyperactivity disorder (ADHD) is later antisocial behaviors. This risk grows when ADHD is accompanied by severe behavior problems.2 Though most children with ADHD will not go on to engage in criminal behavior, dimensional measures of externalizing behavior problems as well as categorical diagnoses of oppositional defiant disorder and conduct disorder have strong associations with ADHD. Moreover, cross-sectional studies of incarcerated adults indicate that 20% to 30% meet diagnostic criteria for ADHD.3 These associations between childhood ADHD, oppositional defiant disorder, and conduct disorder and later criminal behavior beg the question of whether treatment of ADHD can reduce the severity of, or in some cases prevent, criminal behavior. [ABSTRACT FROM AUTHOR]

Poor school readiness and high rates of expulsion from preschool or day care are common in very young children with attention-deficit/hyperactivity disorder (ADHD), while in cases of severe impulsivity and inadequate monitoring there is real danger of injury to the child and others. Compared to older children, preschool-age children with ADHD have more frequent and often severe ADHD symptoms and high rates of psychiatric and developmental comorbidity.1 As pediatricians are now routinely screening for ADHD in children as young as 4 years of age,2 identification will likely increase. However, once identified, far less is known about treating ADHD.3. [ABSTRACT FROM AUTHOR]

There is a robust literature of predominantly cross-sectional studies demonstrating an association between attention-deficit/hyperactivity disorder (ADHD) and sleep quality in childhood and adolescence, measured by subjective as well as objective measures, dimensional and categorical variables, and controlling for a wide range of confounders such as other disorders.1 Moreover, ADHD symptoms and sleep problems are independently associated with adverse functional outcome and quality of life.2 As a result, these are viewed as common and mutually exacerbating conditions, likely mediated by common neuropathways.3-5. [ABSTRACT FROM AUTHOR]

Abstract Children with complex medical problems who require anesthesia are known to be at risk for acute adverse physiologic events related to anesthesia. The risks of anesthesia include short- and long-term psychological and neurobehavioral issues. Magnetic resonance imaging (MRI) has emerged as the standard of care for diagnosis and follow-up of many conditions, and more children are being subjected to anesthesia to ensure acceptable motion-free image quality of the MRI scans. The aim of this study was to evaluate the effectiveness of an anesthesia-free patient- and family-centered intervention through an analysis of MRI quality, health-care costs, and operational efficiency as compared with other approaches. This study retrospectively reviewed patient data extracted from electronic medical records of children aged 3-17 years, who underwent outpatient MRI at an urban academic medical center from 2015 to 2016. A total matched sample size of 500 children, 125 per group, was used to investigate the outcome variables including the quality of magnetic resonance image, health-care cost, and procedural time. The groups included are as follows: (1) intervention group, patient- and family-centered preparation of the child, and no anesthesia given (PFC/NA); (2) comparison group, no structured preparation, and no anesthesia given (SC/NA); (3) comparison group, certified child life specialist preparation, and anesthesia given (CCLS/A); (4) comparison group, no structured preparation, anesthesia given (SC/A). The PFC/NA intervention group was found to have significantly lower costs (p <.0001) and shorter procedure times (p <.0001), and 96.8% of the MRI images were of acceptable or better quality than those of the SC/A and CCLS/A groups. The PFC approach provides a way for children to undergo outpatient diagnostic MRI without the need for anesthesia, thus reducing risk, costs, and procedure time. Highlights • The Intervention dispels the notion children need anesthesia to remain still for MRI. • The Intervention allows children to undergo MRI without the need for anesthesia. • The Intervention group had lower costs than the anesthesia groups (p < 0.001). • The Intervention group had shorter procedure time than anesthesia groups (p < 0.001). • In the Intervention group, 96.8% of MRIs were of acceptable quality or better. [ABSTRACT FROM AUTHOR]

We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. [ABSTRACT FROM AUTHOR]

Objective: To examine the efficacy and tolerability of guanfacine extended release (GXR) administered in the morning or evening in children with attention-deficit/hyperactivity disorder (ADHD). Method: In this multicenter, double-blind, placebo-controlled, dose-optimization study, children 6 to 12 years of age with ADHD were randomized to receive GXR (1-4 mg/d) in the morning and placebo in the evening (GXR AM), placebo in the morning and GXR in the evening (GXR PM), or twice-daily placebo. The primary efficacy measure was the ADHD Rating Scale-IV (ADHD-RS-IV). Results: A total of 333 child participants received study drug in the following cohorts: GXR AM (n = 107), GXR PM (n = 114), or placebo (n = 112). Mean (standard deviation) changes from baseline to week 8 (visit 10 or last observation carried forward) in ADHD-RS-IV total scores were significant for both GXR treatment groups combined (GXR all-active: -20.0 [12.97]) and separately (GXR AM: -19.8 [12.95]; GXR PM: -20.1 [13.04]) compared with placebo (-11.0 [12.93]; p < .001 for all). Most spontaneously-elicited treatment-emergent adverse events were mild or moderate in severity; the most common was somnolence (GXR all-active: 44.3%; GXR AM: 46.7%; GXR PM: 42.1%; placebo: 12.5%). Conclusions: GXR administered either in the morning or evening was associated with significant and clinically meaningful improvements in ADHD symptoms. The levels of response and tolerability observed with GXR were similar regardless of time of dosing (morning versus evening), indicating that once-daily GXR monotherapy is effective whether administered in the morning or evening. Clinical trial registration information--Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity Disorder (ADHD) (The ADHD Tempo Study); http://clinicaltrials.gov/; NCT00997984. [ABSTRACT FROM AUTHOR]

ADHD, sleep, and ADHD treatments are highly interrelated. In this review, we describe the effects of stimulants and non stimulant medications on sleep in children, adolescents, and adults with ADHD. Clinical predictors of sleep problems during pharmacotherapy include age, sleep problems prior to initiating treatment, and dose and dosing schedule. As yet, we have little understanding of the biological or genetic factors related to individual variation in drug response and sleep. [ABSTRACT FROM AUTHOR]

Background: Thyroid abnormalities have been associated with attention deficit/hyperactivity disorder (ADHD) and with other childhood psychiatric disorders. The goal of this study was to determine the relationships between thyroid hormone concentrations, neurocognitive functioning, and psychiatric diagnosis in children. Methods: Free thyroxine index (FT4I) and thyroid stimulating hormone (TSH) were obtained, along with diagnostic and descriptive information for 338 children referred to a clinic specializing in learning and behavior problems. Results: Thyroid abnormalities were uncommon in children referred for ADHD. After excluding children with thyroid disease, there was a greater proportion with low concentrations of normal FT4I for ADHD–Predominantly Inattentive type (ratio=7.0), but not for ADHD–Combined Type. High concentrations of normal FT4I were associated with mood lability, preoccupations, and lower ratings of attention problems. Thyroxine concentrations within the normal range were differentially associated with ADHD–Combined Type compared to ADHD–Predominantly Inattentive, mood disorders, and pervasive developmental disorders. Conclusion: Thyroxine concentrations were associated with mood symptoms and unusual behaviors, and were less strongly related to attentional functioning. Thyroxine concentrations were not related to hyperactivity. [Copyright &y& Elsevier]

Persistent and early-onset externalizing behavior problems are associated with a wide range of impairments.1 Parent management training (PMT) is frequently recommended as either a prevention strategy in at-risk children, or as first -line treatment. Although several group-based and individually based models of PMT have demonstrated efficacy in reducing preschool behavior problems, there is a paucity of comparative effectiveness studies to help guide treatment selection. [ABSTRACT FROM AUTHOR]

Objective: To identify patient- and treatment-level factors that predict intervention engagement and outcome for adolescents with attention-deficit/hyperactivity disorder (ADHD), guiding efforts to enhance care.Method: Integrative data analysis was used to pool data from 4 randomized controlled trials of adolescent ADHD treatment with participants (N = 854) receiving various evidence-based behavioral therapy packages in 5 treatment arms (standard [STANDARD], comprehensive [COMP], engagement-focused [ENGAGE]), community-based usual care (UC), or no treatment (NOTX). Participants also displayed varying medication use patterns (negligible, inconsistent, consistent) during the trial. Regression and latent growth curve analyses examined treatment- and patient-level predictors of engagement and outcome.Results: Compared with COMP, ENGAGE was associated with higher parent engagement in behavioral therapy (d = 1.35-1.73) when delivered in university, but not community, clinics. Under some conditions, ENGAGE also predicted youth engagement in behavioral therapy (d = 1.21) and lower likelihood of negligible medication use (odds ratio = 0.49 compared with NOTX). UC was associated with poorer parent engagement compared with COMP (d = -0.59) and negligible medication use (odds ratio = 2.29) compared with NOTX. Compared with COMP, ENGAGE (in university settings) was consistently associated with larger ADHD symptom improvements (d = 0.41-0.83) at 6-month follow-up and sometimes associated with larger grade point average (d = 0.68) and parent-teen conflict (d = 0.41) improvements. Consistent medication use during behavioral therapy was associated with larger improvements in ADHD symptoms (d = 0.28) and parent-teen conflict (d = 0.25-0.36). An ADHD+internalizing clinical profile predicted larger improvements in grade point average (d = 0.45). Family adversity predicted poorer parent and youth engagement (rate ratio = 0.90-0.95), negligible medication use (odds ratio = 1.22), and smaller improvements in grade point average (d = -0.23). African American race predicted smaller improvements in parent-teen conflict (d = -0.49).Conclusion: Engagement-focused behavioral therapy and consistent medication use most frequently predicted stronger clinical engagement and outcomes for adolescents with ADHD. Youths who are African American or who experience family adversity may demonstrate treatment-related disparities for certain outcomes; youths with ADHD+internalizing symptoms may demonstrate excellent academic outcomes following behavioral therapy.Data Sharing: The full ADHD TIDAL dataset is publicly available through the National Data Archive (https://nda.nih.gov), including a data dictionary. The study protocol is also publicly available: https://doi.org/10.1186/s12888-020-02734-6. [ABSTRACT FROM AUTHOR]

ADHD is common in parents of children with ADHD, and little is known about how to select, sequence, or combine treatments in multiplex families in which both a child and a parent have ADHD. Over a 3-year period, 35 dyads consisting of a child aged 3-8 years with ADHD symptoms not yet treated with stimulant medications and a mother with ADHD were first randomized to receive 8 weeks of behavioral parent training (BPT) or individually titrated maternal stimulant medication (MSM). [Extracted from the article]

The goal of this session is to increase the understanding of the effects of ADHD medications on sleep in youth with ADHD by reviewing previous studies and a recent comparative effectiveness study [Methylphenidate-Atomoxetine Crossover (MACRO) Study]. The most common sleep problems reported at baseline were as follows: 1) takes >30 minutes to fall asleep (23.9%); 2) grinds teeth (19.3%); 3) snores (16.4%); 4) too much energy to sleep (13.4%); 5) talks in sleep (11.7%); and 6) excessive movements in sleep (10.5%). [Extracted from the article]

Background: Subcutaneous immunoglobulin (IGSC) replacement therapy for primary immunodeficiency (PI) is equally efficacious to intravenous immunoglobulin (IGIV), induces fewer systemic reactions, and may be self-infused. Limited SC infusion volumes and reduced bioavailability, however, necessitate multiple infusion sites, more frequent treatment, and dose adjustment to achieve pharmacokinetic equivalence. Recombinant human hyaluronidase (rHuPH20) increases SC tissue permeability and facilitates dispersion and absorption, enabling administration of monthly doses in one site. Objective: This study investigated the efficacy and tolerability of rHuPH20-facilitated IGSC (IGHy) in patients with PI. Methods: In this open-label, multicenter phase III study, 87 patients with PI aged ≥2 years received 10% IGIV for 3 months, then IGHy (n = 83) for approximately 14 to 18 months at 108% of the IGIV dose. IGHy infusions began weekly, increasing to 3- or 4-week intervals. Results: The majority (94.0%) of IGHy infusions were administered every 3 or 4 weeks, using one site (median, 1.09/month), with a mean volume of 292.2 mL. The bioavailability of IGHy measured by area under the concentration versus time curve was 93.3% of IGIV, which is pharmacokinetically equivalent. Systemic reactions were less frequent with IGHy than with IGIV (8.3% vs 25.0% of infusions). Local reactions to IGHy were generally mild to moderate, with a rate of 0.203 per infusion. The acute serious bacterial infection rate per subject-year for IGHy was low (0.025; upper 99% CI limit, 0.046). Overall infection rates per subject-year were 2.97 for IGHy and 4.51 for IGIV. Conclusion: IGHy was effective, safe, and pharmacokinetically equivalent to IGIV at the same administration intervals, but it caused fewer systemic reactions. Tolerability was good despite high infusion volumes and rates. [ABSTRACT FROM AUTHOR]

Objective: To conduct a phase II trial of the combination of carboplatin, prednisone, and everolimus in metastatic castrate-resistant prostate cancer (mCRPC) as mTOR inhibition can overcome resistance to chemotherapy in prostate cancer.Methods: Patients with progressive mCRPC pretreated with docetaxel-based regimen were eligible. Performance status of 0-1 and adequate bone marrow, renal, and liver function were required. Primary end point was time to progression. Treatment consisted of carboplatin (starting dose equal to area under the curve (AUC of 5) intravenously every 21 days along with oral everolimus 5 mg once daily and prednisone 5 mg twice daily.Results: Twenty-six patients were enrolled with median age of 69 years with 8 patients of African American origin. Grade 3 or 4 thrombocytopenia or neutropenia in 4 of 6 initial patients required dose adjustment of carboplatin to AUC of 4 for subsequent patients. There were no pharmacokinetic interactions between carboplatin and everolimus. The median time to progression was 2.5 months (90% confidence interval [CI], 1.8-4.3 months), and median overall survival was 12.5 months (90% CI, 7.7-18.7 months). Of 10 patients, 8 that demonstrated positive nuclear phosphorylated AKT (pAKT) staining on immunohistochemistry progressed within 9 weeks, whereas 2 patients with negative staining continued without progression for prolonged durations of 30 and 48 weeks. TSC1 gene mutations did not correlate with clinical outcome.Conclusion: The addition of the mTOR inhibitor everolimus to carboplatin demonstrated minimal clinical efficacy in metastatic prostate cancer. pAKT testing warrants further evaluation as a predictive marker of response to everolimus therapy. [ABSTRACT FROM AUTHOR]

Background: It has been posited that glutamate dysregulation contributes to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Modulation of glutamate neurotransmission may provide alternative therapeutic options. The novel 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor positive allosteric modulator Org 26576 was investigated with a translational approach including preclinical and clinical testing. Methods: Neonatal rat 6-hydroxydopamine lesion-induced hyperactivity was used as preclinical model. Seventy-eight ADHD adults entered a multicenter, double-blind, placebo-controlled, two-period crossover trial. After 1 week placebo lead-in, 67 subjects were randomized into one of four treatment sequences: sequence A (n = 15) Org 26576 (100 mg b.i.d.) for 3 weeks, followed by a 2-week placebo crossover and 3 weeks placebo; sequence B (n = 16) 5 weeks placebo followed by 3 weeks Org 26576 (100 mg b.i.d.); sequence C (n = 18) Org 26576 flexible dose (100–300 mg b.i.d.) for 3 weeks, then 5 weeks placebo; sequence D (n = 18) 5 weeks placebo followed by 3 weeks Org 26576 (100–300 mg b.i.d.). The Adult ADHD Investigator Symptom Rating Scale was used to assess changes in ADHD symptomatology. Results: Org 26576 (1, 3, 10 mg/kg intraperitoneal) produced dose-dependent inhibition of locomotor hyperactivity in 6-hydroxydopamine-lesioned rats. Org 26576 (100 mg b.i.d.) was superior to placebo in treating symptoms of adult ADHD subjects. The primary Adult ADHD Investigator Symptom Rating Scale results were supported by some secondary analyses. However, Org 26576 (100–300 mg b.i.d.) did not confirm these results. Most frequently reported adverse events were nausea, dizziness, and headache. Conclusions: These preclinical and clinical findings suggest that Org 25676 may have utility in the treatment of ADHD. [ABSTRACT FROM AUTHOR]