Infantile spasms (IS) are early childhood seizures with potentially devastating consequences. Standard therapies (adrenocorticotropic hormone ACTH, high-dose prednisolone, and vigabatrin) are ...strongly recommended as the first treatment for IS. Although this recommendation comes without preference for one standard therapy over another, early remission rates are higher with hormone therapy (ACTH and high-dose prednisolone) when compared with vigabatrin. Using quality improvement (QI) methodology that included hormone therapy as the first treatment, we sought to increase the percentage of children with new-onset nontuberous sclerosis complex (TSC)-associated IS achieving 3-month electroclinical remission from a mean of 53.8% to ≥70%.
This was an observational consecutive sample cohort study at a single academic tertiary care hospital that compared a prospective intervention cohort (May 2019-January 2022, N = 57) with a retrospective baseline cohort (November 2015-April 2019, N = 67). Our initiative addressed key drivers such as the routine use of vigabatrin over hormone therapy as first treatment and the common initiation of a second treatment after 14 days for initial nonresponders. We included consecutive children without TSC presenting with new-onset IS diagnosed and treated between ages 2 and 24 months. We displayed our primary outcome and process measures as control charts in which the centerline is the quarterly (previous 3 months) mean based on statistical process control methodology.
QI interventions that included the standardization of hormone therapy as the first treatment resulted in higher rates of 3-month remission, rising from 53.8% (baseline cohort) to 75.9% (intervention cohort). Process measure results included an increased rate of children receiving hormone therapy as first treatment (mean, 44.6%-100%) and a decreased number of days to both clinical follow-up after first treatment (mean, of 16.3-12.6 days) and starting a second treatment within 14 days for initial nonresponders (mean, 36.3-17.2 days).
For children with IS, improved rates of 3-month electroclinical remission can be achieved with QI methodology. Implementation of similar QI initiatives at other centers may likewise improve local remission rates.
Epilepsy and seizures represent a frequent cause of emergency department (ED) visits for patients. By implementing quality improvement (QI) methodology, we planned to decrease ED visits for children ...and adolescents with epilepsy.
In 2016, a multidisciplinary team was created to implement QI methodology to address ED visits for patients with epilepsy. Based on previous successes, further ED visit reduction was deemed possible. Our aim statement was to decrease the number of ED visits, per 1000 established patients with epilepsy, from 13.03 to 11.6, by December 2019 and sustain for 1 year.
We successfully decreased ED visits for seizure-related care in patients with epilepsy from 13.03% to 10.2% per 1,000 patients, which resulted in a centerline shift.
Using QI methodology, we improved the outcome measure of decreasing ED visits for children with epilepsy. Implementations of these interventions can be considered at other institutions that may lead to similar results.
To evaluate the efficacy and tolerability of atomoxetine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in 5- and 6-year-old children.
This was an 8-week, double-blind, ...placebo-controlled randomized clinical trial of atomoxetine in 101 children with ADHD. Atomoxetine or placebo was flexibly titrated to a maximum dose of 1.8 mg/kg per day. The pharmacotherapist reviewed psychoeducational material on ADHD and behavioral-management strategies with parents during each study visit.
Significant mean decreases in parent (P = .009) and teacher (P = .02) ADHD-IV Rating Scale scores were demonstrated with atomoxetine compared with placebo. A total of 40% of children treated with atomoxetine met response criteria (Clinical Global Impression-Improvement Scale indicating much or very much improved) compared with 22% of children on placebo, which was not significant (P = .1). Decreased appetite, gastrointestinal upset, and sedation were significantly more common with atomoxetine than placebo. Although some children demonstrated a robust response to atomoxetine, for others the response was more attenuated. Sixty-two percent of subjects who received atomoxetine were moderately, markedly, or severely ill according to the Clinical Global Impression-Severity Scale at study completion.
To our knowledge, this is the first randomized controlled trial of atomoxetine in children as young as 5 years. Atomoxetine generally was well tolerated and reduced core ADHD symptoms in the children on the basis of parent and teacher reports. Reductions in the ADHD-IV Rating Scale scores, however, did not necessarily translate to overall clinical and functional improvement, as demonstrated on the Clinical Global Impression-Severity Scale and the Clinical Global Impression-Improvement Scale. Despite benefits, the children in the atomoxetine group remained, on average, significantly impaired at the end of the study.
Allosteric modulation is a general feature of nicotinic acetylcholine receptors, yet the structural components and movements important for conversions among functional states are not well understood. ...In this study, we examine the communication between the binding sites for agonist and the modulator morantel (Mor) of neuronal α3β2 receptors, measuring evoked currents of receptors expressed in Xenopus oocytes with the two-electrode voltage-clamp method. We hypothesized that movement along an interface of β sheets connecting the agonist and modulator sites is necessary for allosteric modulation. To address this, we created pairs of substituted cysteines that span the cleft formed where the outer β sheet meets the β sheet constituting the (−)-face of the α3 subunit; the three pairs were L158C-A179C, L158C-G181C and L158C-K183C. Employing a disulfide trapping approach in which bonds are formed between neighboring cysteines under oxidation conditions, we found that oxidation treatments decreased the amplitude of currents evoked by either the agonist (ACh) or co-applied agonist and modulator (ACh + Mor), by as much as 51%, consistent with the introduced bond decreasing channel efficacy. Reduction treatment increased evoked currents up to 89%. The magnitude of the oxidation effects depended on whether agonists were present during oxidation and on the cysteine pair. Additionally, the cysteine mutations themselves decreased Mor potentiation, implicating these residues in modulation. Our findings suggest that these β sheets in the α3 subunit move with respect to each other during activation and modulation, and the residues studied highlight the contribution of this intramolecular allosteric pathway to receptor function.
•Double cysteine substitution and disulfide trapping perturb neuronal nAChR function.•Oxidation and reduction of mutant receptors alter efficacy.•Effects depend on residue position in α3 subunit and functional state of receptor.•Communication between modulator and agonist sites possibly disrupted.
Local newspapers are an important source of information for rural residents but often lack accurate or helpful nutrition-related information. To improve the quantity and quality of nutrition stories ...in rural, local newspapers, it is important to understand the perspective of editors. An online survey of 51 rural Midwest editors was conducted to assess attitudes toward writing nutrition stories, sources of information, perceived challenges, and interest in learning more about writing such stories. Of respondents, 49% were female, and 63% had at least a 4-year college degree. Through a mix of closed- and open-ended questions, the majority indicated positive attitudes toward nutrition stories, were confident in their abilities to write them, and expressed interest in learning more. Challenges cited include lack of print space, small staff, lack of specific requests from readers for nutrition stories, and the need to avoid offending local agricultural businesses. Results should be useful in planning an educational intervention for editors. Meanwhile, public health practitioners should provide concise press releases to their local newspapers about their activities. Also, greater expressions of appreciation from public health professionals and other readers may lead to higher prioritization of nutrition-related stories, and ultimately to an environment more supportive of healthy eating.
Background/Objective
Pediatric neurocritical care survivorship is frequently accompanied by functional impairments. Lack of prognostic biomarkers is a barrier to early identification and management ...of impairment. We explored the association between blood biomarkers and functional impairment in children with acute acquired brain injury.
Methods
This study is a secondary analysis of a randomized control trial evaluating early versus usual care rehabilitation in the pediatric intensive care unit (PICU). Forty-four children (17 39% female, median age 11 interquartile range 6–13 years) with acute acquired brain injury admitted to the PICU were studied. A single center obtained serum samples on admission days 0, 1, 3, 5, and the day closest to hospital discharge. Biomarkers relevant to brain injury (neuron specific enolase NSE, S100b), inflammation (interleukin IL-6, C-reactive protein), and regeneration (brain-derived neurotrophic factor BDNF, vascular endothelial growth factor VEGF) were collected. Biomarkers were analyzed using a Luminex® bioassay. Functional status scale (FSS) scores were abstracted from the medical record. New functional impairment was defined as a (worse) FSS score at hospital discharge compared to pre-PICU (baseline). Individual biomarker fluorescence index (FI) values for each sample collection day were correlated with new functional impairment using Spearman rank correlation coefficient (
ρ
). Trends in repeated measures of biomarker FI over time were explored graphically, and the association between repeated measures of biomarker FI and new functional impairment was analyzed using covariate adjusted linear mixed-effect models.
Results
Functional impairment was inversely correlated with markers of regeneration and plasticity including BDNF at day 3 (
ρ
= − 0.404,
p
= .015), day 5 (
ρ
= − 0.549,
p
= 0.005) and hospital discharge (
ρ
= − 0.420,
p
= 0.026) and VEGF at day 1 (
ρ
= − 0.282,
p
= 0.008) and hospital discharge (
ρ
= − 0.378,
p
= 0.047), such that lower levels of both markers at each time point were associated with greater impairment. Similarly, repeated measures of BDNF and VEGF were inversely correlated with new functional impairment (
B
= − 0.001,
p
= 0.001 and
B
= − 0.001,
p
= 0.003, respectively). NSE, a biomarker of acute brain injury, showed a positive correlation between day 0 levels and new functional impairment (
ρ
= 0.320,
p
= 0.044).
Conclusions
Blood-based biomarkers of regeneration and plasticity may hold prognostic utility for functional impairment among pediatric patients with neurocritical illness and warrant further investigation.
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