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The objective of this study was to determine the diagnostic yield of continuous video electroencephalographic (EEG) monitoring in critically ill neonates in the setting of a novel, university-based Neonatal Neurocritical Care Service. Patient demographic characteristics, indication for seizure monitoring, and presence of electrographic seizures were obtained by chart review. Among 595 patients cared for by the Neonatal Neurocritical Care Service, 400 (67%) received continuous video EEG. The median duration of continuous video EEG monitoring was 49 (interquartile range = 22-87) hours. Electrographic seizures were captured in 105 of 400 (26% of monitored patients) and of those, 25 of 105 (24%) had no clinical correlate. In addition, 52 of 400 subjects (13%) were monitored due to paroxysmal events concerning for seizures, but never had electrographic seizures. Continuous video EEG monitoring helped confirm or rule out ongoing seizures in more than one-third of the cases. This finding helps to support the use of continuous video EEG in critically ill neonates.

This case report examined the effectiveness of a home program using neuromuscular electrical stimulation (NMES) during voluntary task-oriented exercise to achieve functional and impairment improvements for an individual with primarily proximal arm paresis after a stroke. The subject initially achieved a Fugl-Meyer Assessment (FMA) score of 58/66, but she reported minimal functional use of her involved, dominant arm. The 6-wk intervention consisted of NMES-assisted task practice involving repetitive reaching for and manipulation of small objects for three daily 15-min sessions. The subject applied NMES to the deltoid and triceps brachii muscles to augment shoulder flexion and abduction and elbow extension during task practice. Outcome measures included the FMA, the Action Research Arm Test (ARAT), and the Motor Activity Log Quality of Movement subscale (MAL-QOM). The FMA remained unchanged, but the ARAT and MAL-QOM showed improvements, from the beginning to the conclusion of the intervention, that were maintained at 6-wk follow-up. [ABSTRACT FROM AUTHOR]

Video-EEG (VEEG) monitoring is now commonly used in children. When designing a pediatric video-EEG monitoring unit, there are many issues that need to be considered to take full advantage of this technology. Topics such as the physical layout of the VEEG unit, VEEG equipment, networking, staffing, and lines of communication regarding referrals and VEEG interpretation must be considered. Only after careful consideration of these issues, can video-EEG monitoring be successful and provide safe, state of the art clinical care in an efficient manner. [ABSTRACT FROM AUTHOR]

Several cytokines have been reported to have hepatoprotective properties in animal models of acetaminophen toxicity. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood samples were collected from patients following acute ingestions of acetaminophen. Samples for cytokine analysis were collected at the time of routine clinical monitoring in 111 patients (90 females; mean age 13.6 years). Plasma concentrations of interleukin 6, interleukin 8, interleukin 10, and monocyte chemoattractant protein 1 were analyzed by enzyme-linked immunosorbent assay. Patients were stratified by toxicity severity, defined by the maximal values of hepatic transaminase elevation. Levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 were higher in patients with serum alanine aminotransferase > 1000 IU/L, and monocyte chemoattractant protein 1 had the strongest association with toxicity. Monocyte chemoattractant protein 1 values were higher in patients with greater delays in N-acetylcysteine treatment and in patients with higher values of prothrombin time. Monocyte chemoattractant protein 1 elevation in acetaminophen overdose may represent an innate, immunomodulary response of the liver to earlier events in the toxicity. An understanding of the role of cytokine responses in acetaminophen overdose may be relevant to the future development of new therapies for acetaminophen toxicity. [ABSTRACT FROM AUTHOR]

Abstract Background Auditory brainstem responses (ABRs) are used to study auditory acuity in animal-based medical research. ABRs are evoked by acoustic stimuli, and consist of an electrical signal resulting from summated activity in the auditory nerve and brainstem nuclei. ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Traditionally, threshold has been assessed by visual estimation of a series of ABRs evoked by different sound intensities. Here we develop an automated threshold detection method that eliminates the variability and subjectivity associated with visual estimation. Results The automated method is a robust computational procedure that detects the sound level at which the peak amplitude of the evoked ABR signal first exceeds four times the standard deviation of the baseline noise. Implementation of the procedure was achieved by evoking ABRs in response to click and tone stimuli, under normal and experimental conditions (adult stem cell transplantation into cochlea). Automated detection revealed that the threshold shift from pre- to post-surgery hearing levels was similar in mice receiving stem cell transplantation or sham injection for click and tone stimuli. Visual estimation by independent observers corroborated these results but revealed variability in ABR threshold shifts and significance levels for stem cell-transplanted and sham-injected animals. Conclusion In summary, the automated detection method avoids the subjectivity of visual analysis and offers a rapid, easily accessible http://axograph.com/source/abr.html approach to measure hearing threshold levels in auditory brainstem response.

Abstract Background In order to establish a consistent method for brachial artery reactivity assessment, we analyzed commonly used approaches to the test and their effects on the magnitude and time-course of flow mediated dilation (FMD), and on test variability and repeatability. As a popular and noninvasive assessment of endothelial function, several different approaches have been employed to measure brachial artery reactivity with B-mode ultrasound. Despite some efforts, there remains a lack of defined normal values and large variability in measurement technique. Methods Twenty-six healthy volunteers underwent repeated brachial artery diameter measurements by B-mode ultrasound. Following baseline diameter recordings we assessed endothelium-dependent flow mediated dilation by inflating a blood pressure cuff either on the upper arm (proximal) or on the forearm (distal). Results Thirty-seven measures were performed using proximal occlusion and 25 with distal occlusion. Following proximal occlusion relative to distal occlusion, FMD was larger (16.2 ± 1.2% vs. 7.3 ± 0.9%, p < 0.0001) and elongated (107.2 s vs. 67.8 s, p = 0.0001). Measurement of the test repeatability showed that differences between the repeated measures were greater on average when the measurements were done using the proximal method as compared to the distal method (2.4%; 95% CI 0.5–4.3; p = 0.013). Conclusion These findings suggest that forearm compression holds statistical advantages over upper arm compression. Added to documented physiological and practical reasons, we propose that future studies should use forearm compression in the assessment of endothelial function.

Abstract Background The mechanism behind the triggering effect of fine particulate matter (PM) air pollution on cardiovascular events remains elusive. We postulated that elevated levels of PM would be associated with increased blood levels of inflammatory and thrombotic markers in elderly individuals. We also hypothesized that elevated PM would increase levels of cytokines in individuals with heart disease. Methods We measured these blood markers in 47 elderly individuals with (23) and without (16 COPD and 8 healthy) cardiovascular disease (CVD) on 2 or 3 mornings over a 5 or 10-day period between February 2000 and March 2002. Blood measures were paired with residence level outdoor PM measured by nephelometry. Analyses determined the within-individual effect of 24-hour averaged outdoor PM on blood measures. Results Analyses found no statistically significant effect of a same day 10 ug/m3 increase in fine PM on log transformed levels of CRP 1.21 fold-rise [95% CI: 0.86, 1.70], fibrinogen 1.02 fold-rise [95% CI: 0.98, 1.06], or D-dimer 1.02 fold-rise [95% CI: 0.88, 1.17] in individuals with CVD. One-day lagged analyses in the CVD subgroup found similar null results. These same models found no change in these blood markers at the same-day or 1-day lag in the group without CVD. In 21 individuals with CVD, a 10 μg/m3 increase in same-day PM was associated with a 1.3 fold-rise [95% CI: 1.1, 1.7] in the level of monocyte chemoattractant protein-1. Conclusion We did not find consistent effects of low ambient levels of PM on blood measures of inflammation or thrombosis in elderly individuals.

Objective: To describe the association between electrographically detected seizures and brain injury evaluated by magnetic resonance imaging in newborns treated with hypothermia.Study Design: A total of 56 newborns treated with hypothermia were monitored using video electroencephalography through cooling and rewarming, and then imaged at a median of 5 days. The electroencephalograms were reviewed for indications of seizure and status epilepticus. Moderate-severe injury detected on magnetic resonance imaging was measured using a classification scheme similar to one predicting abnormal outcome in an analogous population.Results: Seizures were recorded in 17 newborns (30%), 5 with status epilepticus. Moderate-severe injury was more common in newborns with seizures (relative risk, 2.9; 95% CI, 1.2-4.5; P=.02), and was present in all 5 newborns with status epilepticus. Newborns with moderate-severe injury had seizures that were multifocal and of later onset, and they were more likely to experience recurrent seizures after treatment with 20 mg/kg phenobarbital. Newborns with only subclinical seizures were as likely to have injury as those with seizures with a clinical correlate (57% vs 60%).Conclusion: Seizures represent a risk factor for brain injury in the setting of therapeutic hypothermia, especially in neonates with status epilepticus, multifocal-onset seizures, and a need for multiple medications. However, 40% of our neonates were spared from brain injury, suggesting that the outcome after seizures is not uniformly poor in children treated with therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Examines the psychological sequelae of early-treated phenylketonuria (PKU) with emphasis on the impact of dietary control on functioning. Psychological profile associated with PKU; Emotional and behavioral disturbances prevalent in PKU-affected individuals; Factors and processes that may influence emotional and behavioral functioning in PKU.

Background: Significant barriers to advancing pediatric drug development continue despite federal incentives to expedite pediatric drug development. There is an urgent need to improve how clinical trials are designed, implemented, and conducted to increase the number of approved therapeutic interventions for children., Methods: The Pediatric Improvement Collaborative for Clinical Trials & Research was created to measure timelines and address delays in the pediatric clinical trials process. This multi-site collaborative prospectively monitored sixteen time points in industry-sponsored pediatric clinical drug trials, including times to budget approval, contract execution, ancillary protocol review, Institutional Review Board approval, Site Initiation Visit, and first patient consented., Results: Twenty-four sites contributed data on 330 industry-sponsored pediatric drug studies. The average duration to final study budget approval was 121 (range 3-585) days, to final study Institutional Review Board (IRB) approval was 51 (range 1-205) days, to Site Initiation Visit was 204 (range 23-600) days, and to first patient consented was 239 (range 30-534) days., Conclusion: Significant study start-up delays were noted in industry-sponsored clinical drug trials among a large group of pediatric sites. Delays and wide variation in all steps of the study process indicate multiple opportunities for improvement., Competing Interests: Declaration of competing interest Angie Price is an IACT4C employee. Dr. Steven Steiner serves as an Advisory Chair consultant for the PICTR program. Hannah Simmons is a Quality Improvement consultant for the PICTR program. Emily Gehring is the Data Science consultant for the PICTR program. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This report highlights a case of PEA arrest which mimicked a tonic seizure and was discovered using electroencephalogram recordings., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: Accurate perception of tactile stimuli is essential for performing and learning activities of daily living. Through this scoping review, we sought to summarize existing examination approaches for identifying tactile deficits at the upper extremity in individuals with stroke. The goal was to identify current limitations and future research needs for designing more comprehensive examination tools., Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute methodological framework and the PRISMA for Scoping Reviews (PRISMA-ScR) guidelines. A database search for tactile examination approaches at the upper extremity of individuals with stroke was conducted using Medline (Ovid), The Cochrane Library (Wiley), CINAHL Plus with Full Text (Ebsco), Scopus (Elsevier), PsycInfo (Ebsco), and Proquest Dissertations and Theses Global. Original research and review articles that involved adults (18 years or older) with stroke, and performed tactile examinations at the upper extremity were eligible for inclusion. Data items extracted from the selected articles included: if the examination was behavioral in nature and involved neuroimaging, the extent to which the arm participated during the examination, the number of possible outcomes of the examination, the type(s) of tactile stimulation equipment used, the location(s) along the arm examined, the peripheral nerves targeted for examination, and if any comparison was made with the non-paretic arm or with the arms of individuals who are neurotypical., Results: Twenty-two articles met the inclusion criteria and were accepted in this review. Most examination approaches were behavioral in nature and involved self-reporting of whether a tactile stimulus was felt while the arm remained passive (i.e., no volitional muscle activity). Typically, the number of possible outcomes with these behavioral approaches were limited (2-3), whereas the neuroimaging approaches had many more possible outcomes ( > 15 ). Tactile examinations were conducted mostly at the distal locations along the arm (finger or hand) without targeting any specific peripheral nerve. Although a majority of articles compared paretic and non-paretic arms, most did not compare outcomes to a control group of individuals who are neurotypical., Discussion: Our findings noted that most upper extremity tactile examinations are behavioral approaches, which are subjective in nature, lack adequate resolution, and are insufficient to identify the underlying neural mechanisms of tactile deficits. Also, most examinations are administered at distal locations of the upper extremity when the examinee's arm is relaxed (passive). Further research is needed to develop better tactile examination tools that combine behavioral responses and neurophysiological outcomes, and allow volitional tactile exploration. Approaches that include testing of multiple body locations/nerves along the upper extremity, provide higher resolution of outcomes, and consider normative comparisons with individuals who are neurotypical may provide a more comprehensive understanding of the tactile deficits occurring following a stroke., (© 2024. The Author(s).)

Purpose: The aim of this study was to investigate the effect of alterations in muscle length of the biceps in various elbow postures during shoulder elevation and muscle activation., Methods: Participants aged 5 years and older with a birth brachial plexus injury were asked to perform elevation shoulder (abduction and flexion) in 7 elbow conditions. Surface electromyography was applied to bilateral biceps and triceps., Results: Peak shoulder elevation was present in the immobilized 20° elbow posture. Muscle activity of the triceps and biceps was impacted by the elbow posture via immobilization., Conclusions: Elbow postures in elongated postures, via immobilization, may result in higher shoulder elevation due to increased passive forces when there is an altered muscle state of the biceps in this population. Clinicians should consider the optimal elbow joint posture (<30°) to improve overhead reaching in this population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Background/purpose: The Upper Extremity Fugl-Meyer Assessment (UEFMA, maximum 66) is widely used in clinics and research studies to examine poststroke upper extremity (UE) impairment. This study aimed to develop and provide pilot data to support the validity of a remote version of the UEFMA to examine UE impairment after stroke through telerehabilitation., Methods: Team members developed a remote version of the UEFMA for telerehabilitation (tUEFMA, maximum 44) using subscales II to IV and VII of the UEFMA. Twenty-two participants with moderate to severe arm impairment (UEFMA, median = 19) and chronic stroke (>1 year post) were evaluated using the UEFMA (face-to-face) and the tUEFMA (remotely). A prediction equation was used to identify the function to predict the UEFMA based on the tUEFMA. Intraclass correlation (ICC) was used to test the absolute agreement between the subscales included in the UEFMA and the tUEFMA, and between their 2 normalized total scores., Results: A strong and significant agreement was found between the total scores of the UEFMA and the projected value based on the tUEFMA (ICC = 0.79, P < 0.05). The ICC test also reported a good agreement in subscales II to IV and a poor agreement in subscale VII between the UEFMA and the tUEFMA using a real-time video link., Discussion and Conclusions: The study findings suggest that the tUEFMA is a promising tool to remotely examine UE impairment in individuals with chronic stroke and moderate to severe arm impairment. Future research should evaluate additional psychometric properties and clinical utility of the tUEFMA across stroke participants with a broad range of arm impairments.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A441 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published byWolters Kluwer Health, Inc. on behalf of Academy of Neurologic Physical Therapy, APTA.)

Bacterial bloodstream infections (BSIs) resulting in late-onset sepsis affect up to half of extremely preterm infants and have substantial morbidity and mortality. Bacterial species associated with BSIs in neonatal intensive care units (NICUs) commonly colonize the preterm infant gut microbiome. Accordingly, we hypothesized that the gut microbiome is a reservoir of BSI-causing pathogenic strains that increase in abundance before BSI onset. We analyzed 550 previously published fecal metagenomes from 115 hospitalized neonates and found that recent ampicillin, gentamicin, or vancomycin exposure was associated with increased abundance of Enterobacteriaceae and Enterococcaceae in infant guts. We then performed shotgun metagenomic sequencing on 462 longitudinal fecal samples from 19 preterm infants (cases) with BSI and 37 non-BSI controls, along with whole-genome sequencing of the BSI isolates. Infants with BSI caused by Enterobacteriaceae were more likely than infants with BSI caused by other organisms to have had ampicillin, gentamicin, or vancomycin exposure in the 10 days before BSI. Relative to controls, gut microbiomes of cases had increased relative abundance of the BSI-causing species and clustered by Bray-Curtis dissimilarity according to BSI pathogen. We demonstrated that 11 of 19 (58%) of gut microbiomes before BSI, and 15 of 19 (79%) of gut microbiomes at any time, harbored the BSI isolate with fewer than 20 genomic substitutions. Last, BSI strains from the Enterobacteriaceae and Enterococcaceae families were detected in multiple infants, indicating BSI-strain transmission. Our findings support future studies to evaluate BSI risk prediction strategies based on gut microbiome abundance in hospitalized preterm infants.

Background and Purpose: Fear of falling (FoF) is highly prevalent in community-dwelling older adults and is associated with low health-related quality of life (QoL). Low QoL is associated with increased health care utilization and is a predictor of future falls, but few studies have examined the relationship between high-level balance and dynamic gait performance and QoL in community-dwelling older adults. The purpose of this cross-sectional study was to determine whether there is a relationship between FoF avoidance behaviors, balance confidence, performance on measures of high-level mobility, and QoL in community-dwelling older adults. The secondary purpose was to determine whether older adults who fall have a different QoL than older adults who have not fallen in the past year., Methods: Eighty-nine community-dwelling older adults (76.33 ± 6.84 years, 54 female, 34 fallers) completed the World Health Organization Quality of Life-BREF (WHOQOL-BREF), Activities-specific Balance Confidence Scale (ABC), Fear of Falling Avoidance Behavior Questionnaire (FFABQ), Functional Gait Assessment (FGA), and Community Balance and Mobility Scale (CB&M). Correlation and multiple regression analyses were calculated to determine the relationship between the outcome measures and domains on the WHOQOL-BREF., Results and Discussion: Significant correlations were observed between the WHOQOL-BREF physical health domain and the ABC, FFABQ, FGA, and CB&M (ρ= 0.524, -0.509, 0.348, and r = 0.423, respectively), the WHOQOL-BREF psychological domain and the ABC (ρ= 0.284) and FFABQ (ρ=-0.384), and the WHOQOL-BREF environment domain and the ABC (ρ= 0.343) and FFABQ (ρ=-0.406). No correlations were found between WHOQOL-BREF domain scores and a history of falls., Conclusions: Performance-based outcome measures that measure high-level mobility such as the CB&M and FGA, and patient-reported outcome measures for balance confidence and FoF avoidance behavior such as the ABC and FFABQ, are correlated with the physical health QoL domain on the WHOQOL-BREF. The ABC and FFABQ are correlated with psychological and environment QoL. Fall history was not correlated with QoL. Interventions to decrease FoF or improve high-level mobility may improve QoL in community-dwelling older adults., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

Background: Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children., Methods: We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score., Results: Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity., Conclusions: We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease., Competing Interests: Potential conflicts of interest. A. G. R. reports receiving reagents to her institution from Illumina Inc for work outside of this project. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The purpose of this study was to evaluate changes to acute pediatric surgical needs during the early phase of the SARS-Cov2 (COVID-19) pandemic., Methods: We performed a retrospective cohort study of all in-hospital pediatric surgery consultations placed through the consult paging system at a single institution. We compared both median and absolute differences for emergency department (ED), operative, and hospital outcomes between March, April, and May of 2019 versus 2020., Results: There were 225 in-hospital pediatric surgery consults in 2019 and 123 in 2020. Overall, mean age was 8.4-y (standard deviation = 6.4) and 60% were male. Initial vitals were similar between years and a similar proportion of patients underwent laboratory and imaging tests. In 2020, children spent a median of 1.1-h fewer in the ED (95% confidence interval = -2.2, -0.1) and 0.9-h fewer in the ED before surgical consultation (95% confidence interval = -1.5, -0.3) compared to 2019. Patients required significantly more procedures in the ED in 2020 (n = 16, 14.3%) than 2019 (n = 13, 6.2%) (P = 0.02), most commonly laceration repairs. In 2019, 46 children (20.4% of all consults in 2019) presented with appendicitis and 27 children (22.0% of all consults in 2020) in 2020. Complicated appendicitis was more common in 2020 (n = 12, 44.4%) than 2019 (n = 9, 19.6%) (P = 0.02). Two children (7.4%) were managed nonoperatively with a drain in 2020 compared to none in 2019 (P = 0.13). Median time from surgical consultation to surgery, median operative time, and median time to discharge was similar for children with appendicitis in both years., Conclusions: The early phase of the pandemic was associated with more efficient triaging in the ED, but more ED procedures and more complex surgical pathology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy., Objective: To evaluate the efficacy and safety of fenfluramine in patients with LGS., Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration. Patients were enrolled at 65 study sites in North America, Europe, and Australia. Included patients were aged 2 to 35 years with confirmed diagnosis of LGS and experienced 2 or more drop seizures per week during the 4-week baseline. Using a modified intent-to-treat method, data analysis was performed from November 27, 2017, to October 25, 2019. The database lock date was January 30, 2020, and the date of final report was September 11, 2021., Interventions: Patients were randomized to receive either a 0.7-mg/kg/d or 0.2-mg/kg/d (maximum 26 mg/d) dose of fenfluramine or placebo. After titration (2-week period), patients were taking their randomized dose for 12 additional weeks., Main Outcomes and Measures: Primary efficacy end point was percentage change from baseline in drop seizure frequency in patients who received 0.7 mg/kg/d of fenfluramine vs placebo., Results: A total of 263 patients (median [range] age, 13 [2-35] years; 146 male patients [56%]) were randomized to the 0.7-mg/kg/d fenfluramine group (n = 87), 0.2-mg/kg/d fenfluramine group (n = 89), or placebo group (n = 87). The median percentage reduction in frequency of drop seizures was 26.5 percentage points in the 0.7-mg/kg/d fenfluramine group, 14.2 percentage points in the 0.2-mg/kg/d fenfluramine group, and 7.6 percentage points in the placebo group. The trial met its primary efficacy end point: patients in the 0.7-mg/kg/d fenfluramine group achieved a -19.9 percentage points (95% CI, -31.0 to -8.7 percentage points; P = .001) estimated median difference in drop seizures from baseline vs placebo. More patients in the 0.7-mg/kg/d fenfluramine group achieved a 50% or greater response (22 of 87 [25%]; P = .02) vs placebo (9 of 87 [10%]). Site investigators and caregivers gave a much improved or very much improved rating on the Clinical Global Impression of Improvement scale to more patients in the 0.7-mg/kg/d fenfluramine group than patients in the placebo group (21 [26%] vs 5 [6%]; P = .001). The seizure subtype that appeared most responsive to fenfluramine was generalized tonic-clonic seizure (120 of 263 [46%]), with a decrease in frequency of 45.7% in the 0.7-mg/kg/d fenfluramine group and 58.2% in the 0.2-mg/kg/d fenfluramine group compared with an increase of 3.7% in the placebo group. Most common treatment-emergent adverse events included decreased appetite (59 [22%]), somnolence (33 [13%]), and fatigue (33 [13%]). No cases of valvular heart disease or pulmonary arterial hypertension were observed., Conclusions and Relevance: Results of this trial showed that, in patients with LGS, fenfluramine compared with placebo provided a significantly greater reduction in drop seizures and may be a particularly advantageous choice in patients who experience generalized tonic-clonic seizures., Trial Registration: ClinicalTrials.gov Identifier: NCT03355209.

Objective: Kentucky ranks among the highest in the nation for attention-deficit/hyperactivity disorder (ADHD) prevalence in children aged 4 to 17 years. In 2011, the American Academy of Pediatrics (AAP) released a clinical practice guideline based on the DSM-IV. A guideline revision based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) was released in October 2019. In this study, we assess and describe pediatric providers' ADHD practices using the 2011 guideline and DSM-5 diagnostic criteria., Methods: This was a cross-sectional, survey-based descriptive study. Kentucky Chapter of the AAP (KY AAP) members were anonymously surveyed. The results were examined for trends in routine practice., Results: Fifty-eight general pediatricians and pediatric residents responded to the survey, yielding a 38% (58/154) response rate. Among respondents performing routine diagnosis of ADHD (N = 51), 73% (37/51) used DSM-5 criteria. Most providers usually or always initially assessed for coexisting behavioral conditions (96%; 49/51), developmental conditions (78%; 39/51), and adverse childhood experiences (73%; 37/51). Among respondents performing routine management of ADHD (N = 55), only 11% (6/55) of respondents indicated that they titrated stimulant medications every 3 to 7 days. After initiation of medication, 78% of providers scheduled a follow-up visit within 2 to 4 weeks. During subsequent visits, only half indicated discussing behavioral interventions, screening for coexisting conditions, and reviewing follow-up teacher-rated ADHD scales., Conclusion: Pediatricians in the KY AAP adhere to the DSM-5 criteria for diagnosing ADHD. Pediatric providers' practices would benefit from education in improvements in pharmacotherapy titration, surveillance of coexisting conditions associated with ADHD, discussion of psychosocial interventions, and school support strategies., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Traumatic brain injury is a major public health concern with a rising incidence in the United States. Prior studies have looked at associations between insurance status and traumatic brain injury, but none have focused specifically on traumatic subdural hematomas (SDH). It is important to evaluate whether insurance and/or other social determinants of health play a role in treatment and outcomes of traumatic SDH., Methods: A retrospective analysis of the National Trauma Data Bank was conducted from 2012 to 2016 to look at associations between insurance status and management of SDH with surgery versus intracranial pressure (ICP)/EVD monitoring. Secondary outcomes of interest were emergency department (ED) length of stay (LOS), hospital LOS, ICU admission, ICU LOS, and mortality., Results: We identified 68,687 adult patients with a single diagnosis of subdural hematoma. Overall, self-pay patients with SDH were younger, predominately male, and more likely to be non-white compared to patients with public or private health insurance.  More specifically, Black/African American SDH patients made up a large percentage of the self-pay category (15.5%; P < 0.001) compared to publicly and privately insured (7.5% and 8.0%, respectively). After adjusting for age, sex, injury severity score (ISS), Glasgow Coma Scale, alcohol intoxication, and trauma center level, publicly insured patients were 1.86 (95% CI 1.36-2.55, P < 0.001) times more likely to undergo a craniotomy or craniectomy compared to self-pay patients. However, insurance status did not appear to impact whether a patient received ICP/EVD monitoring (OR 0.52; 95% CI 0.24-1.18, P = 0.118). There was no statistically significant difference in ED LOS, Hospital LOS, and ICU LOS between insurance categories., Conclusions: Publicly insured patients have higher odds of undergoing surgical management for traumatic SDH compared to self-pay patients. Further studies evaluating this association are warranted., (Copyright © 2021. Published by Elsevier Inc.)

Rationale: A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available., Objective: To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility., Design: The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to., Methods: Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence., Results: The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements., Conclusions: The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision., Competing Interests: Drs. Smith and Berkenbosch were responsible for the adjudication of any conflicts of interest for this guideline. The following relevant disclosures were provided for consideration. Dr. Srinivasan authored “Conversion from prolonged intravenous fentanyl infusion to enteral methadone in critically ill children,” World Journal of Clinical Pediatrics (May 2017). Dr. Almgren authored “Pharmacological Strategies for Decreasing Opioid Therapy and Management of Side Effects From Chronic Use”, Children (2018) and “Multidisciplinary Pain Management for Pediatric Patients with Acute and Chronic Pain: A Foundational Treatment Approach When Prescribing Opioids,” Children (2019). Dr. Grant was a lead author for the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Study Investigators (2016) and for “Dexmedetomidine Use in Critically-Ill Children with Acute Respiratory Failure,” Pediatric Critical Care Medicine. Dr. deAlmeida was a contributing author on “Delirium in Critically Ill Children: An International Point Prevalence Study,” Critical Care Medicine (2017). Dr. Simone is a lead author for “Analgesia, Sedation, Paralytics, and Opioid Syndrome (2021); Pediatric Acute Care. A Guide for Interprofessional Practice, second Edition (2019); Delirium and Pharmacologic Treatment in Critically Ill Children: A Retrospective Matched Cohort Study,” Journal of Pediatric Pharmacologic and Therapeutics (2017). “Implementation of an ICU Bundle: An Interprofessional Quality Improvement Project to Enhance Delirium Management and Monitor Delirium Prevalence in a Single PICU,” Pediatric Critical Care Medicine (2017). Dr. Su was a lead author for “Pharmacokinetics of Dexmedetomidine in Infants and Children After Orthotopic Liver Transplantation,” Anesthesia Analog (2018). Dr. Traube was a lead author on “Detection and Management of Delirium in the Neonatal Unit: A Case Series,” Pediatrics (2016); “Prospective Study to Establish the German version of the CAPD for the Assessment of Delirium in Children Undergoing Intensive Care” (German), Monatsschrift Kinderheilkunde (2016); “Cost Associated With Pediatric Delirium in the ICU,” Critical Care Medicine (2016); “Validity of the Richmond Agitation-Sedation Scale (RASS) in Critically Ill Children,” Journal of Intensive Care (2016); “Sedation, Analgesia, and Paralysis During Mechanical Ventilation of Premature Infants,”(2017), “Patterns of Postoperative Delirium in Children,” Pediatric Critical Care Medicine (2017); “Delirium in Children After Cardiac Bypass Surgery,” Pediatric Critical Care Medicine (2017); “Delirium in Critically Ill Children: An International Point Prevalence Study,”Critical Care Medicine (2017); “Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium,” Critical Care Medicine (2017); “Iatrogenic Withdrawal Syndrome or Undiagnosed Delirium?,” Critical Care Medicine (2017); “‘The Times They Are A-Changin’: Universal Delirium Screening in Pediatric Critical Care,” Pediatric Critical Care Medicine (2017); “Quality Improvement Initiative to Reduce Pediatric Intensive Care Unit Noise Pollution With the Use of a Pediatric Delirium Bundle,” Journal of Intensive Care Medicine (2017); “Delirium in Pediatric Critical Care,” Pediatric Clinics of North America (2017); “Delirium in the Pediatric Cardiac Extracorporeal Membrane Oxygenation Patient Population: A Case Series,” Pediatric Critical Care Medicine (2017); “Delirium in Hospitalized Children with Cancer: Incidence and Associated Risk Factors,” The Journal of Pediatrics (2017); “Provider Beliefs Regarding Early Mobilization in the Pediatric Intensive Care Unit,” Journal of Pediatric Nursing (2018); “Identify Delirium, Then Investigate for Underlying Etiology,” Pediatric Critical Care Medicine (2018); “Consensus Report by PALISI and PBMTC Joint Working Committees, Supportive Care Guidelines for Management of VOD in Children and Adolescents; Part 3: Focus on Cardio-Respiratory Dysfunction, Infections, Liver Dysfunction and Delirium,” Biology of Blood and Marrow Transplantation (2018); “Delirium is a Common and Early Finding in Patients in the Pediatric Cardiac Intensive Care Unit,” The Journal of Pediatrics (2018); “Delirium Upon Presentation to the Pediatric Emergency Department: A Case Series,” Pediatric Emergency Care (2018); “Benzodiazepines and Development of Delirium in Critically Ill Children: Estimating the Causal Effect,” Critical Care Medicine (2018); “Association Between Transfusion of RBCs and Subsequent Development of Delirium in Critically Ill Children,” Pediatric Critical Care Medicine (2018); “All Delirium May Not Be Created Equal: Consideration of Differential Effects of Delirium Based Upon Underlying Etiology,” Pediatric Critical Care Medicine (2018); “Risk Factors for the Development of Postoperative Delirium in Pediatric Intensive Care Patients,” Pediatric Critical Care Medicine (2018); “Management Guidelines For Paediatric Patients Receiving Chimeric Antigen Receptor T Cell Therapy,” Nature Reviews Clinical Oncology (2019); and “A Systematic Approach to Family Engagement: Feasibility Pilot of a Pediatric Delirium Management And Prevention Toolkit,” Palliative and Supportive Care (2019). Stacey Williams was lead author for “The Preschool Confusion Assessment Method for the ICU: Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children,” Critical Care Medicine(2016). The remaining authors have disclosed that they do not have any potential conflicts of interest. Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as “strong” with “we recommend” or “conditional” with “we suggest.” Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Medication administration errors that take place in the home are common, especially when liquid preparations are used and complex medication schedules with multiple medications are involved; children with chronic conditions are disproportionately affected. Parents and other caregivers with low health literacy and/or limited English proficiency are at higher risk for making errors in administering medications to children in their care. Recommended strategies to reduce home medication errors relate to provider prescribing practices; health literacy-informed verbal counseling strategies (eg, teachback and showback) and written patient education materials (eg, pictographic information) for patients and/or caregivers across settings (inpatient, outpatient, emergency care, pharmacy); dosing-tool provision for liquid medication measurement; review of medication lists with patients and/or caregivers (medication reconciliation) that includes prescription and over-the-counter medications, as well as vitamins and supplements; leveraging the medical home; engaging adolescents and their adult caregivers; training of providers; safe disposal of medications; regulations related to medication dosing tools, labeling, packaging, and informational materials; use of electronic health records and other technologies; and research to identify novel ways to support safe home medication administration., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Yin reports a National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. research relationship; Dr Paul reports an expert panel relationship with Denver Health, advisory board relationships with Pfizer, Consumer Healthcare Produce Association, and Johnson & Johnson, and a consulting relationship with Merck and Evidera; and Dr Neuspiel has indicated he has no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: Adults living with intellectual and developmental disability (IDD) and epilepsy (IDD-E) face challenges in addition to those faced by the general population of adults with epilepsy, which may be associated with distinct priorities for improving health-related quality of life (HR-QOL). This study sought to (1) conduct a survey of HR-QOL priorities identified by adults with IDD-E and caregivers, and (2) perform an exploratory cross-sectional comparison to adults with epilepsy who do not have IDD., Methods: This cross-sectional study recruited 65 adults with IDD-E and 134 adults with epilepsy without IDD and caregivers. Using a three-step development process, 256 items from existing quality-of-life scales recommended by the American Academy of Neurology (AAN) were rated by patients/caregivers for their importance as HR-QOL priorities. HR-QOL items identified as critical to the majority of the sample of adults with IDD-E were reported. Health-related quality of life priorities were compared between adults with IDD-E and adults with epilepsy without IDD., Results: Health-related quality of life was significantly lower in adults with IDD-E. Health-related quality of life domains identified as critical priorities by adults with IDD-E included seizure burden, anti-seizure medication side effects, seizure unpredictability, and family impact. Priorities for improving HR-QOL differed between adults with and without IDD-E, with concerns about family impact, difficulty finding appropriate living conditions, inadequate assistance, and difficulty transitioning from pediatric-to-adult care valued significantly more among those with IDD-E., Significance: Intellectual and developmental disability is an important determinant of HR-QOL among adults with epilepsy. We report HR-QOL priorities identified by adults with IDD-E and their caregivers. These results may help epilepsy clinicians and researchers develop tailored strategies to address priorities of the patient with IDD-E/caregiver community., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies., Methods: A population PK model was developed using opportunistically collected plasma samples. For each dosing strategy, model-based probability of target attainment (PTA) estimates were computed for study participants using empirical Bayes estimates. In addition, the effects of body size and renal function on PTA were evaluated using stochastic model simulations with virtually generated subjects., Results: Twenty-nine participants, 24 of whom were obese, contributed data towards the analysis. The median (range) age, body weight, and body mass index of participants were 12.2 years (2.3-20.6), 59.2 kg (8.4-121), and 25.2 kg/m 2 (13.8-42.9), respectively. Administration of 50 mg/kg intravenously (IV) every 8 hours (q8h; max 6 g/day) or 40 mg/kg IV q6h (max 6 g/day) resulted in PTA values of ≥ 90% (minimum inhibitory concentration 8 mg/L) for the subset of obese participants with estimated glomerular filtration rates (GFR) ≥ ~ 80 mL/min/1.73 m 2 . However, for both regimens, stochastic model simulations denoted lower PTA values (< 90%) with increasing body weight for virtual subjects with GFR ≥ 120 mL/min/1.73 m 2 . Alternatively, permitting for a maximum daily dose of 8 g/day using a 40 mg/kg IV q6h regimen provided PTA values that were near or above target (90%) for virtual subjects between 10 to 120 kg with GFR ≥ 80 mL/min/1.73 m 2 ., Conclusion: Our analysis suggests administration of 40 mg/kg IV q6h (max 8 g/day) maximizes PTA in children and adolescents with obesity and GFR ≥ 80 mL/min/1.73 m 2 ., Trial Registration: Clinicaltrials.gov Identifier: NCT01431326., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Objectives: The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the National Institutes of Health sponsor research on off-patent drugs important to pediatric therapeutics. Failing to enroll cohorts that reflect the pediatric population at large restricts the generalizability of such studies. In this investigation, we evaluate racial and ethnic minority representation among participants enrolled in BPCA-sponsored studies., Methods: Data were obtained for all participants enrolled in 33 federally funded studies of drugs and devices conducted from 2008 through June 2020. Observed racial and ethnic distributions were compared with expected distributions by sampling Census data at the same geographic frequency as in the studies. Racial and ethnic enrollment was examined by demography, geography, study type, study burden, and expected bias. Standard descriptive statistics, χ 2 , generalized linear models, and linear regression were applied., Results: A total of 10 918 participants (51% male, 6.6 ± 8.2 years) were enrolled across 46 US states and 4 countries. Studies ranged from treatment outcome reviews to randomized, placebo-controlled trials. Minority enrollment was comparable to, or higher than, expected (+0.1% to +2.6%) for all groups except Asian Americans (-3.7%, P < .001). American Indian and Alaskan Native and multiracial enrollment significantly increased over the evaluation period ( P < .01). There were no significant differences in racial distribution as a function of age or sex, although differences were observed on the basis of geography, study type, and study burden., Conclusions and Relevance: This study revealed no evidence of racial and ethnic bias in enrollment for pediatric studies conducted with funding from BPCA, fulfilling the legislation's expectation to ensure adequate representation of all children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Abdel-Rahman, Ms Delmore, and Drs Hornik, Paul, Sullivan, Wade, and Zimmerman serve as members of the steering committee for the Pediatric Trials Network, which receives Best Pharmaceuticals for Children Act funding from the Eunice Kennedy Shriver National Institute for Child Health and Human Development. Dr Benjamin serves as the PI of the Pediatric Trials Network. At the time of writing Dr Sharma was employed by the Best Pharmaceuticals for Children Act data coordinating center., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: To examine (1) correlates of religious coping, and (2) associations of religious coping at baseline with evaluation of treatment acceptability and depressive symptom severity outcomes of short-term psychotherapeutic depression treatments among 277 low-income homebound older adults (70% female; 41% non-Hispanic White, 30% African American, and 29% Hispanic) who participated in a treatment effectiveness trial., Method: Religious coping was measured with a 2-item subscale of the Brief COPE. Treatment acceptability was measured with the 11-item Treatment Evaluation Inventory (TEI). Depressive symptoms were measured with the 24-item Hamilton Rating Scale for Depression (HAMD). We used linear regression modeling to examine correlates of religious coping at baseline and to examine associations of religious coping with treatment acceptability and depression outcome at 12 weeks., Results: Being female and being African American predicted higher religious coping. Additionally, active coping, emotional support coping, and clergy consultation on depression were significantly associated with higher religious coping. Religious coping was not significantly associated with TEI and HAMD scores at 12 weeks., Conclusion: The findings show that once these older adults participate in depression treatment, they find it highly acceptable and benefit from treatment, regardless of their religious coping, and that psychotherapeutic treatment is a highly acceptable and effective addition to those with religious-oriented coping.

Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included a priori in the model. Using the final model, the steady-state maximum concentrations (C ss,max ) and the area under the metoclopramide plasma concentration-time curve at steady state from 0 to 6 hours (AUC ss,0-6h ) were simulated following 0.1 or 0.15 mg/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two-compartment model with first-order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01-19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (> 12 years). Body weight was the only covariate included in the final model. For > 75% of virtual patients, simulated C ss,max and AUC ss,0-6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients < 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society of Clinical Pharmacology and Therapeutics.)

The National Institutes of Health's Environmental Influences on Child Health Outcomes (ECHO) program aims to study high-priority and high-impact pediatric conditions. This broad-based health initiative is unique in the National Institutes of Health research portfolio and involves 2 research components: (1) a large group of established centers with pediatric cohorts combining data to support longitudinal studies (ECHO cohorts) and (2) pediatric trials program for institutions within Institutional Development Awards states, known as the ECHO Institutional Development Awards States Pediatric Clinical Trials Network (ISPCTN). In the current presentation, we provide a broad overview of the ISPCTN and, particularly, its importance in enhancing clinical trials capabilities of pediatrician scientists through the support of research infrastructure, while at the same time implementing clinical trials that inform future health care for children. The ISPCTN research mission is aligned with the health priority conditions emphasized in the ECHO program, with a commitment to bringing state-of-the-science trials to children residing in underserved and rural communities. ISPCTN site infrastructure is critical to successful trial implementation and includes research training for pediatric faculty and coordinators. Network sites exist in settings that have historically had limited National Institutes of Health funding success and lacked pediatric research infrastructure, with the initial funding directed to considerable efforts in professional development, implementation of regulatory procedures, and engagement of communities and families. The Network has made considerable headway with these objectives, opening two large research studies during its initial 18 months as well as producing findings that serve as markers of success that will optimize sustainability., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Aim: Parents' role as end-of-life decision-makers for their child has become largely accepted Western health-care practice. How parents subsequently view and live with the end-of-life decision (ELD) they made has not been extensively examined. To help extend understanding of this phenomenon and contribute to care, as a part of a study on end-of-life decision-making, bereaved parents were asked about the aftermath of their decision-making., Methods: A qualitative methodology was used. Semi-structured interviews were conducted with parents who had discussed ELDs for their child who had a life-limiting condition and had died. Data were thematically analysed., Results: Twenty-five bereaved parents participated. Results indicate that parents hold multi-faceted views about their decision-making experiences. An ELD was viewed as weighty in nature, with decisions judged against the circumstances that the child and parents found themselves in. Despite the weightiness, parents reflected positively on their decisions, regarding themselves as making the right decision. Consequently, parents' comments demonstrated being able to live with their decision. When expressed, regret related to needing an ELD, rather than the actual decision. The few parents who did not perceive themselves as their child's decision-maker subsequently articulated negative reactions. Enduring concerns held by some parents mostly related to non-decisional matters, such as the child's suffering or not knowing the cause of death., Conclusion: Results suggest that parents can live well with the ELDs they made for their child. End-of-life decision-making knowledge is confirmed and extended, and clinical support for parents informed., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Importance: When working with clients who have experienced spinal cord injury (SCI), occupational therapy practitioners can face challenges in achieving desired results during functional activity when using electrical stimulation (ES) interventions. In an effort to understand current practice, a survey study was conducted., Objective: For people with SCI, ES elicits positive physiological effects; however, no implementation guidelines exist for upper extremity application of ES for this population. Therefore, we surveyed occupational therapy practitioners about their use of ES with clients who have cervical-level SCI., Design: A 33-item, 20-min online survey was used., Participants and Setting: We queried 57 occupational therapy practitioners with active caseloads in regional rehabilitation centers specializing in SCI, both outpatient and inpatient., Results: For clients with SCI, occupational therapy practitioners used ES most often for grasp-and-release, reaching, and grip or pinch activities using a broad range of parameter settings. Among respondents, 43% did not use a specific treatment protocol; 27% used research evidence to guide selection of parameters., Conclusions and Relevance: Findings suggest that ES treatment parameters are not uniformly applied, introducing potential unknown effects on client outcomes and undermining treatment fidelity., What This Article Adds: Our survey of occupational therapy practitioners regarding their practice and use of ES interventions with this population revealed variation in application of ES treatment parameters. Understanding different treatment approaches and justification used when applying ES to clients with SCI is an important first step in unifying and promoting best practice and maximizing patient outcomes., (Copyright © 2020 by the American Occupational Therapy Association, Inc.)

Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (C ss ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving C ss within target; however, the risk of achieving C ss > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving C ss within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target C ss in children of varying weights., (© 2019, The American College of Clinical Pharmacology.)

Epilepsy is a common disorder in children and adults that causes significant morbidity and affects many aspects of a patient's lives. Two-thirds of patients with epilepsy are controlled with established antiseizure medications, leaving a significant number of patients searching for other options. The purpose of this review is to provide an overview of recent advancements in the management of treatment-resistant epilepsy in pediatric patients. Recent publications have shown the efficacy of new pharmaceutical options such as fenfluramine and cannabidiol, some of which have been tested specifically in patients with childhood-onset epilepsy syndromes such as Dravet's syndrome and Lennox-Gastaut's syndrome. Furthermore, recent approval by the U.S. Food and Drug Administration of stiripentol has made available a previously difficult-to-obtain option for patients with Dravet's syndrome. Finally, implanted responsive neurostimulation devices for direct cortical stimulation and deep brain stimulation have shown efficacy in adult patients and may represent a thrilling new horizon for pediatric patients., Competing Interests: Dr. Sullivan reports grants from Zogenix and personal fees from Epygenix, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)