A review of amphetamine extended release once-daily options for the management of attention-deficit hyperactivity disorder.

INTRODUCTION: Amphetamine preparations are one of the two categories of stimulant medications approved for the treatment of attention deficit hyperactivity disorder (ADHD). Optimal treatment of ADHD aims to reduce core symptoms for as much of the waking hours as possible, leading to longer-acting delivery formats. In addition, the pediatric population commonly has difficulty swallowing pills and manufacturers have developed a variety of options to facilitate this concern. These include chewable tablets, capsules that may be sprinkled on soft food, liquids and transdermal patches. AREAS COVERED: This article reviews the once-daily extended-release preparations currently available for amphetamine compounds, their pharmacodynamics, and common adverse effects. EXPERT OPINION: There is an extensive evidence base supporting use of amphetamine preparations in the treatment of ADHD. Rapid onset of action and a favorable side effect profile make these widely used. The availability of once-daily extended-release chewable tablets, capsules that can be opened and sprinkled, and liquid formulations provides clinicians with multiple options to meet the specific needs of patients with difficulty swallowing whole pills.

Descriptive Analysis of Documentation Time for the National Developmental-Behavioral Pediatric Physician Workforce Using a Commercial Electronic Health Record System.

OBJECTIVE: The national developmental-behavioral pediatric (DBP) workforce struggles to meet current service demands because of several factors. Lengthy and inefficient documentation processes are likely to contribute to service demand challenges, but DBP documentation patterns have not been sufficiently studied. Identifying clinical practice patterns may inform strategies to address documentation burden in DBP practice. METHODS: Nearly 500 DBP physicians in the United States use a single commercial electronic health record (EHR) system (EpicCare Ambulatory, Epic Systems Corporation, Verona WI). We evaluated descriptive statistics using the US Epic DBP provider data set. We then compared DBP documentation metrics against those of pediatric primary care and selected pediatric subspecialty providers who provide similar types of care. One-way analyses of variance (ANOVAs) were conducted to determine whether outcomes differed among provider specialties. RESULTS: We identified 4 groups for analysis from November 2019 through February 2020: DBP (n = 483), primary care (n = 76,423), pediatric psychiatry (n = 783), and child neurology (n = 8589). Post hoc pairwise comparisons revealed statistically significant differences between multiple outcome-specialty combinations. Time in notes per appointment and progress note length demonstrated the strongest evidence of an increased burden on DBP providers compared with other similar provider groups. CONCLUSION: DBP providers spend a significant amount of time documenting progress notes both during and outside of normal clinic hours. This preliminary analysis highlights the utility of using EHR user activity data to quantitatively measure documentation burden.

Caring for a child with an eating disorder: Understanding differences among mothers and fathers of adolescent and adult children.

OBJECTIVE: This study investigated treatment-engagement fears, self-efficacy, and accommodating and enabling in mothers and fathers of adolescent and adult children with eating disorders. METHODS: This study involved a secondary analysis of pre-treatment data from a subsample of 143 parents (95 mothers; 48 fathers) from a Canada-wide multi-site study. Parents completed the Caregiver Traps Scale, Parents Versus Anorexia Scale, and the Accommodation and Enabling Scale for Eating Disorders. Data were analysed using factorial Multivariate Analysis of Variance and mediation via multiple regression. RESULTS: Mothers reported higher levels of treatment-engagement fears than fathers. Among mothers, higher fear predicted lower self-efficacy and more accommodating and enabling behaviours. Among fathers, neither fear nor self-efficacy predicted accommodating and enabling. No differences in treatment-engagement fear or self-efficacy between parents of adolescent child and adult children were found at pre-treatment. CONCLUSIONS: Mothers' and fathers' experience different levels of fear related to their involvement in their ill-child's treatment at pre-treatment, and that fear is uniquely related to variables that impact treatment outcomes. There is a need to support parents even when their child is an adult. This study can inform family-based treatments vis-a-vis tailoring interventions for mothers and fathers and providing support to parents of children with eating disorders across the lifespan.

Unexplained regression in Down syndrome: 35 cases from an international Down syndrome database.

PURPOSE: An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease. METHODS: Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls. RESULTS: We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p < 0.001 for all but externalizing behaviors). Patients with regression had four times as many mental health concerns (p < 0.001), six times as many stressors (p < 0.001), and seven times as many depressive symptoms (p < 0.001). Tiered medical evaluation most often identified abnormalities in vitamin D 25-OH levels, polysomnograms, thyroid peroxidase antibodies, and celiac screens. Analysis of the subset of patients with nondiagnostic medical evaluations reinforced the proposed definition. CONCLUSIONS: Our case-control evidence supports a proposed definition of unexplained regression in Down syndrome. Establishing this clinical definition supports future research and investigation of an underlying mechanism.

The influence of carer fear and self-blame when supporting a loved one with an eating disorder.

Carers often feel disempowered and engage in behaviours that inadvertently enable their loved one's ED symptoms and yet little is known regarding these processes. This study examined the relationships among fear, self-blame, self-efficacy, and accommodating and enabling behaviours in 137 carers of adolescents and adults with ED. The results revealed that fear and self-blame predicted low carer self-efficacy in supporting their loved one's recovery as well as the extent to which carers reported engaging in recovery-interfering behaviours. The relevance of these findings are discussed in the context of family-oriented ED therapies and highlight the importance for clinicians to attend to and help to process strong emotions in carers, in order to improve their supportive efforts and, ultimately, ED outcomes.

Troponin.

Troponin T and I can be found within the myocardial filaments. Measuring these cardiac troponin levels in full-term newborns and premature infants has not become a common practice in the neonatal intensive care unit and newborn nurseries. Research studies are discovering that an elevation in troponin T and I levels can be directly correlated with the severity of the infant's illness, and it can be potentially prognostic of morbidity. This literature analysis discusses what can be considered normal cardiac troponin levels along with what elevated levels are and possible conditions associated with those elevations.

Exonic deletions in AUTS2 cause a syndromic form of intellectual disability and suggest a critical role for the C terminus.

Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3'AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future.

Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine.

Down syndrome (DS) patients have an increased risk of developing pulmonary hypertension (PH). Increased plasma levels of asymmetric dimethylarginine (ADMA) may contribute to vascular dysfunction in adults with idiopathic pulmonary hypertension. Our goal was to test the hypothesis that DS patients with PH have higher plasma levels of ADMA than DS patients without PH. DS patients with definitive PH (n = 6) and DS patients with no evidence of PH (n = 12) were studied. Plasma levels of arginine, ADMA, and nitrite/nitrate (NOx; stable metabolites of nitric oxide (NO)) were measured. Plasma arginine concentration was lower (p < 0.05) in PH patients (23 ± 11 µM) versus non-PH patients (46 ± 24 µM). Plasma ADMA concentration was higher (p < 0.005) in PH patients (18.0 ± 4.2 µM) versus non-PH patients (8.6 ± 5.9 µM). Plasma NOx was lower (p < 0.05) in PH patients (4.5 ± 1.7 µM) versus non-PH patients (8.5 ± 7.3 µM). These results are consistent with ADMA contributing to lower NO production in DS patients with PH and suggest that ADMA levels may be a potential biomarker for PH in DS patients.

Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children.

This study was designed to explore the placebo-controlled effects of risperidone on cognitive-motor processes, dyskinetic movements, and behavior in children receiving maintenance risperidone therapy. Sixteen children aged 4-14 years with disruptive behavior were randomly assigned to drug order in a crossover study of risperidone and placebo for 2 weeks each. Dependent measures included tests of sustained attention, memory, visual matching, tremor, seat activity, abnormal movements, and parent behavior ratings. Results were compared by repeated measures ANOVA. Fourteen boys and 2 girls with disruptive behavior and IQ

Umbilical catheters, placement, and complication management.

Umbilical arterial and venous catheter placement have become the standard of care in the neonatal intensive care unit. These catheters allow for rapid and reliable vascular access for the administration of fluids and medications, as well as a means for accurate laboratory determinations and invasive monitoring. Catheter placement and maintenance require training and education of all healthcare workers to prevent or minimize the associated risks.

Endothelial nitric oxide synthase polymorphisms associated with abnormal nitric oxide production are not over-represented in children with Down syndrome.

OBJECTIVE: Down syndrome patients are at increased risk for developing pulmonary hypertension (PHTN). Nitric oxide (NO) is an important factor for pulmonary vasoreactivity. Various endothelial nitric oxide synthase (eNOS) polymorphisms have been shown to affect NO. The goal of this study was to determine whether there was a difference in prevalence of eNOS polymorphisms between Down syndrome patients vs. non-Down syndrome patients. METHODS: Down syndrome patients were recruited as well as non-Down syndrome patients. Gene polymorphisms for eNOS-3 (GG, GT, TT), eNOS-4 (bb, ba, aa), and eNOS-P (TT, TC, CC) were determined. Three forms of the 3 genes were compared in cross-tabulation tables with Down syndrome patients vs. non-Down syndrome patients and Down syndrome patients with heart defects vs. those without defects. Association was tested with chi-square and significance was set at P < or = .05. RESULTS: Fifty-one Down syndrome patients and 411 controls were studied. Twenty-one Down syndrome patients had heart defects and 6 of these patients had documented PHTN. There was no difference in gender between Down syndrome patients (males 56.9%) and controls (males 50.4%), P = .38. Prevalence of eNOS polymorphisms between Down syndrome patients and controls was not different for the genes (eNOS-3, P = .94; eNOS-4, P = .40; eNOS-P, P = .18). There was no difference in gene polymorphisms between Down syndrome patients with heart defects vs. those without defects (eNOS-3, P = .19; eNOS-4, P = .29; eNOS-P, P = .99). CONCLUSION: Prevalence of various eNOS polymorphisms between Down syndrome patients and controls was not different. Other polymorphisms that are associated with PHTN should be studied to determine whether they may be the cause of the increased risk of PHTN in Down syndrome patients.

Acute and long-term safety and tolerability of risperidone in children with autism.

Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

Epidemiology and etiology of autistic spectrum disorders difficult to determine.

The epidemiology of the autistic spectrum disorders is changing. A clear increase in prevalence has been noted during the past 2 decades. What is less clear is the cause for this increase. Multiple factors appear to be responsible. The preponderance of evidence suggests most of the rise in incidence and prevalence is related to changes in diagnostic criteria and greater awareness on the part of both professionals and parents. Proposed theories of causation, which also seek to explain the increase in prevalence, have not been substantiated. Further research is needed to better determine the incidence and prevalence of these disorders and their etiologic factors.