Executive Impairment Determines ADHD Medication Response: Implications for Academic Achievement

2011 ◽  
Vol 44 (2) ◽  
pp. 196-212 ◽  
Author(s):  
James B. Hale ◽  
Linda A. Reddy ◽  
Margaret Semrud-Clikeman ◽  
Lisa A. Hain ◽  
James Whitaker ◽  
...  

Methylphenidate (MPH) often ameliorates attention-deficit/hyperactivity disorder (ADHD) behavioral dysfunction according to indirect informant reports and rating scales. The standard of care behavioral MPH titration approach seldom includes direct neuropsychological or academic assessment data to determine treatment efficacy. Documenting “cool” executive-working memory (EWM) and “hot” self-regulation (SR) neuropsychological impairments could aid in differential diagnosis of ADHD subtypes and determining cognitive and academic MPH response. In this study, children aged 6 to 16 with ADHD inattentive type (IT; n = 19) and combined type ( n = 33)/hyperactive-impulsive type ( n = 4) (CT) participated in double-blind placebo-controlled MPH trials with baseline and randomized placebo, low MPH dose, and high MPH dose conditions. EWM/ SR measures and behavior ratings/classroom observations were rank ordered separately across conditions, with nonparametric randomization tests conducted to determine individual MPH response. Participants were subsequently grouped according to their level of cool EWM and hot SR circuit dysfunction. Robust cognitive and behavioral MPH response was achieved for children with significant baseline EWM/SR impairment, yet response was poor for those with adequate EWM/ SR baseline performance. Even for strong MPH responders, the best dose for neuropsychological functioning was typically lower than the best dose for behavior. Findings offer one possible explanation for why long-term academic MPH treatment gains in ADHD have not been realized. Implications for academic achievement and medication titration practices for children with behaviorally diagnosed ADHD will be discussed.

2000 ◽  
Vol 5 (4) ◽  
pp. 312-325 ◽  
Author(s):  
Gadi Maoz ◽  
Daniel Stein ◽  
Sorin Meged ◽  
Larisa Kurzman ◽  
Joseph Levine ◽  
...  

Psychopharmacological interventions for managing aggression in schizophrenia have thus far yielded inconsistent results. This study evaluates the antiaggressive efficacy of combined haloperidol-propranolol treatment. Thirty-four newly admitted schizophrenic patients were studied in a controlled double-blind trial. Following a 3-day drug-free period and 7 days of haloperidol treatment, patients were randomly assigned to receive either haloperidol-propranolol or haloperidol-placebo for eight consecutive weeks. Doses of medications were adjusted as necessary; biperiden was administered if required. Rating scales were applied to assess aggression, anger, psychosis, depression, anxiety and extrapyramidal symptoms. The mean daily dose of haloperidol was 21 mg (SD = 6.4) in the research group and 29 mg (SD = 6.9) in the controls. Mean and maximal daily doses of propranolol were 159 mg (SD = 61) and 192 mg (SD = 83), and of placebo, 145 mg (SD = 50) and 180 mg (SD = 70), respectively. Compared with the controls, the scores for the research patients decreased significantly from baseline, particularly after 4 weeks of treatment, for some dimensions of anger, psychosis, anxiety, and neuroleptic-induced parkinsonism. A tendency for reduced aggression was shown in the combined haloperidol-propranolol group for some dimensions but not others. These patients also required significantly less biperiden. The tendency toward elevated antiaggressive effect of combined haloperidol-propranolol treatment compared to haloperidol alone may be explained by a simultaneous decrease in aggression, psychotic symptomatology, and anxiety.


1985 ◽  
Vol 30 (12) ◽  
pp. 999-999
Author(s):  
Gerald S. Wasserman

2021 ◽  
pp. 107429562110206
Author(s):  
Michele L. Moohr ◽  
Kinga Balint-Langel ◽  
Jonté C. Taylor ◽  
Karen L. Rizzo

The term self-regulation (SR) refers to a set of specific cognitive skills necessary for students to independently manage, monitor, and assess their own academic learning and behavior. Students with and at risk for emotional and behavioral disorders (EBD) often lack these skills. This article provides educators with step-by-step procedures and information on three research- or evidence-based SR strategies they can implement in their classrooms: self-regulated strategy development, self-monitoring, and strategy instruction.


2021 ◽  
Vol 58 ◽  
pp. 101050
Author(s):  
Rebecca Distefano ◽  
Amanda Grenell ◽  
Alyssa R. Palmer ◽  
Kerry Houlihan ◽  
Ann S. Masten ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 213
Author(s):  
Lauren A. Roach ◽  
Mitchell K. Byrne ◽  
Steven J. Howard ◽  
Stuart J. Johnstone ◽  
Marijka Batterham ◽  
...  

Self-regulation, the regulation of behaviour in early childhood, impacts children’s success at school and is a predictor of health, wealth, and criminal outcomes in adulthood. Self-regulation may be optimised by dietary supplementation of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs). The aim of the “Omega Kid” study is to investigate the feasibility of a protocol to investigate whether n-3 LCPUFA supplementation enhances self-regulation in preschool-aged children. The protocol assessed involved a double-blind, randomised, placebo-controlled trial of 12 weeks duration, with an intervention of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day (0.3 g EPA and 1.3 g DHA) in a microencapsulated powder compared to placebo. Children (n = 78; 40 boys and 38 girls) aged 3–5 years old were recruited and randomly allocated to the treatment (n = 39) or placebo group (n = 39). The HS–Omega-3 Index® served as a manipulation check on the delivery of either active (n-3 LCPUFAs) or placebo powders. Fifty-eight children (76%) completed the intervention (28–30 per group). Compliance to the study protocol was high, with 92% of children providing a finger-prick blood sample at baseline and high reported-adherence to the study intervention (88%). Results indicate that the protocol is feasible and may be employed in an adequately powered clinical trial to test the hypothesis that n-3 LCPUFA supplementation will improve the self-regulation of preschool-aged children.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S612-S613
Author(s):  
Shawn Flanagan ◽  
Christopher M Rubino ◽  
Taylor Sandison

Abstract Background Rezafungin is a novel echinocandin antifungal in development for treatment as well as prevention (prophylaxis) of invasive fungal infections. STRIVE (NCT02734862) is a global, randomized, double-blind, placebo-controlled, Phase 2 trial evaluating safety and efficacy of IV rezafungin once weekly (QWk) for treatment of candidemia and/or invasive candidiasis compared with standard-of-care (IV caspofungin once daily with optional oral stepdown). Here we report pharmacokinetic (PK) data from the completed STRIVE trial analyzed by patient demographics at baseline. Methods Rezafungin Day 8 trough (Cmin) concentrations from patients treated with rezafungin were summarized categorically by race (black or white), sex (male or female), and geographic region (North America [NA], or Europe [EU]), or plotted versus continuous variables of age, body weight, body mass index (BMI), and body surface area (BSA). As the first dose of rezafungin was 400 mg for all rezafungin-treated patients, data from both dose groups (Group 1: 400 mg QWk; Group 2: 400 mg in Week 1 followed by 200 mg QWk) were combined in this analysis. Results Rezafungin mean Cmin (SD) values were 1.8 (0.7) and 2.3 (1.2) in black and white patients, 1.9 (1.0) and 2.6 (1.2) in males and females, and 1.9 (0.6) and 2.4 (1.3) in patients from NA and EU. There were small differences in point estimates between the groups, but there was a great deal of overlap and the differences are not expected to be clinically meaningful (Figure). Similarly, no trends in Cmin values were observed across a range of ages (20-80 years), weights (~40-155 kg), BMI (~15-65 kg/m2), and BSA (~1.4-2.4 m2). Figure Conclusion No meaningful differences in rezafungin Cmin values were observed in patients grouped by sex, race, or geographic region, or across a wide range of patient factors, including age and body weight and size. These findings indicate that a single rezafungin dose regimen can be expected to provide consistent PK across diverse patient populations. Disclosures Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Christopher M. Rubino, PharMD, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)


2016 ◽  
Vol 42 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Stephanie L. Day ◽  
Carol McDonald Connor

Children with stronger self-regulation skills generally demonstrate greater overall success in school both academically and socially. However, there are few valid and reliable measures of self-regulation in middle elementary school. Such a measure could help identify whether a child is truly having difficulties. Thus, the Remembering Rules and Regulation Picture Task (RRRP) was developed. The aim of this study was to develop scoring systems for the RRRP and then to examine the associations between RRRP and independent measures of self-regulation and academic achievement in mathematics and reading. Children ( N = 282) from 34 third-grade classrooms in Florida participated in this study. Results revealed that the RRRP captured three constructs: working memory, attentional flexibility, and inhibitory control. Hierarchical linear modeling (HLM) demonstrated that the RRRP was significantly and positively associated with other measures of self-regulation. The RRRP was significantly and positively associated with mathematics and reading as well. The RRRP appears to be a promising measure of children’s self-regulation skills.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.


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