Pediatric Clinical Samples Research Articles

B-171 Iohexol Mass Spectrometry Method Validation and Comparison in Clinical Pediatric Laboratory

Abstract Background Accurate assessment of kidney function is important yet challenging in pediatric patients due to changing muscle mass affecting serum creatinine. There are several key methods to assess kidney function in this population, including estimated glomerular filtration rate (eGFR) from serum creatinine, urine creatinine clearance, and eGFR from serum iohexol clearance, which often provides a more reliable estimate. Iohexol is a non-ionic iodinated contrast agent filtered freely through the glomeruli without tubular secretion, making it an ideal GFR marker.In this study, we validated the LC-MS/MS method to quantitatively measure iohexol in clinical pediatric plasma and serum samples. The clinical performance was compared with the novel Verispray method. Methods A series of iohexol standards (Caymen Chemical) were prepared at 10, 100, 500, 1000 µg/mL in serum (UTAK). The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and Verispray method were developed to quantitatively measure iohexol concentrations in spiked pediatric specimens. The internal standard (IS) solution was prepared with Iohexol-D5 (Cayman Chemical) at 9 µg/mL in UPLC grade methanol. Specimen or calibration/QC (50 µL) were mixed with IS solution (450 µL), and then centrifuged at 14,000xg for 3 minutes. The supernatants were analyzed. For LC-MS/MS, 3 µL supernatants were chromatographed on a AccucoreTM Vanquish C18 50 x 2.1mm (Thermo Scientific) using a gradient of water with 0.1% formic acid (FA) against methanol with 0.1% FA. Iohexol and IS were measured by multiple reaction monitoring using a TSQ Quantis Plus Mass Spectrometer (ThermoFisher). For Verispray, 10 µL supernatants were loaded on the Verispray sample plate (ThermoFisher) without LC portion. The samples were extracted from the plate paper using 95% acetonitrile with 5% water and 0.1% FA before directly injected into the mass spectrometer. The LC-MS/MS method was evaluated for linearity, patient comparison, carryover, matrix effect, and stability. 40 patients were analyzed between methods. Results Linearity was assessed over 5 days at 4 calibrator levels, the coefficient of variation (CV) ranged from 3.46 - 5.99%. The patient comparison of 40, 20 serum and plasma respectively, was conducted with Mayo Clinics, and good concordance was observed. Matrix effects were evaluated with spiked samples prepared with 50% mobile phase A and B, the ion enhancement was at 10.7%, within the allowable limits. No significant carryover was seen. The samples were stable at room temperature for 48 hours and 4oC for 7 days. Freezing is not recommended. The comparison between Verispray and LC-MS/MS showed significant bias between and within the performing personnel, the deviation can be up to 40% comparing to LC-MS/MS method. Conclusions The LC-MS/MS method demonstrated stable and consistent analytical performance for iohexol measurement. However, the Verispray method showed significant inter- and intra-user variabilities. As the Verispray sample spot can only be used once, respotting is required for any additional measurement, reducing reproductivity. It is highly recommended to duplicate all samples when using Verispray, to limit preparation to one user per patient run. Overall, our validation indicates the LC-MS/MS method provides reliable performance as a useful alternative to other complex gold standard pediatric tests of kidney function.

Gas chromatography-mass spectrometry determination of nicotine and cotinine in urine: A study of the effect of passive smoking.

Recent data suggest that passive smoking has a risk comparable to active smoking. Passive smoking is considered dangerous in children and is suspected as a cause of asthma. However, some reports are opposing such claims, indicating the need for solid results and large-scale studies. This scientific work aims to develop a method for the determination of nicotine (NCOT) and major nicotine's metabolite cotinine (COT) in urine samples, using gas chromatography-mass spectrometry (GC-MS). Analysis was performed using a gas chromatograph Agilent Technologies 7890A with an MS 5975C inert XL, EI/CI MSD with Triple-Axis detector. For sample preparation, liquid-liquid extraction was applied after an optimization study with different extraction media. Eventually, 1 mL of dichloromethane was selected for the extraction of 0.5mL of urine. Suitable chromatographic conditions were found for the rapid and accurate determination of NCOT and COT. Injection of 2μL was performed using GC-MS, and selected ion monitoring (SIM) analysis was performed with the following ions (m/z): 162 (quantifier ion) and 84, 133, 161 qualifier ions for NCOT, and 176 (quantifier ion) and 98, 118, 119, 147 qualifier ions for COT. Nicotine-D4 (NCOT-D4) and cotinine-D3 (COT-D3) were used as internal standards with quantifier ions 101 and 166, respectively. The retention time (Rt) for NCOT was 7.557 min and 9.743 min for COT. The method was validated following international principles, assessing characteristics such as absolute recovery, carryover, linearity, specificity, selectivity, accuracy, precision, and stability. The method showed a linear dynamic range from 0.5 to 50 ng/mL, and the limits of detection and quantification were for both NCOT and COT 0.2 and 0.5 ng/mL, respectively. Validation results were found satisfactory.Finally, the method was applied to the analysis of 60 clinical pediatric samples obtained from Aristotle University's pediatric clinic to check for possible exposure to smoke. Concentration levels ranged between 0.5 and 16.2ng/mL for NCOT and between 1.0 and 25.1ng/mL for COT. A rapid, sensitive, accurate, and simple method was developed and used as a tool for the confirmation of passive smoking in children. It is the first method applied to the analysis of such samples belonging to nonsmokers of young age. The total runtime of the GC-MS analysis was short (20 min), and the pretreatment protocol was simple, giving the ability for analysis of a large number of samples on a daily routine basis.

Screening and Identification of Neutrophil Extracellular Trap-related Diagnostic Biomarkers for Pediatric Sepsis by Machine Learning.

Neutrophil extracellular trap (NET) is released by neutrophils to trap invading pathogens and can lead to dysregulation of immune responses and disease pathogenesis. However, systematic evaluation of NET-related genes (NETRGs) for the diagnosis of pediatric sepsis is still lacking. Three datasets were taken from the Gene Expression Omnibus (GEO) database: GSE13904, GSE26378, and GSE26440. After NETRGs and differentially expressed genes (DEGs) were identified in the GSE26378 dataset, crucial genes were identified by using LASSO regression analysis and random forest analysis on the genes that overlapped in both DEGs and NETRGs. These crucial genes were then employed to build a diagnostic model. The diagnostic model's effectiveness in identifying pediatric sepsis across the three datasets was confirmed through receiver operating characteristic curve (ROC) analysis. In addition, clinical pediatric sepsis samples were collected to measure the expression levels of important genes and evaluate the diagnostic model's performance using qRT-PCR in identifying pediatric sepsis in actual clinical samples. Next, using the CIBERSORT database, the relationship between invading immune cells and diagnostic markers was investigated in more detail. Lastly, to evaluate NET formation, we measured myeloperoxidase (MPO)-DNA complex levels using ELISA. A group of five important genes (MME, BST1, S100A12, FCAR, and ALPL) were found among the 13 DEGs associated with NET formation and used to create a diagnostic model for pediatric sepsis. Across all three cohorts, the sepsis group had consistently elevated expression levels of these five critical genes as compared to the normal group. Area under the curve (AUC) values of 1, 0.932, and 0.966 indicate that the diagnostic model performed exceptionally well in terms of diagnosis. Notably, when applied to the clinical samples, the diagnostic model also showed good diagnostic capacity with an AUC of 0.898, outperforming the effectiveness of traditional inflammatory markers such as PCT, CRP, WBC, and NEU%. Lastly, we discovered that children with high ratings for sepsis also had higher MPO-DNA complex levels. In conclusion, the creation and verification of a five-NETRGs diagnostic model for pediatric sepsis performs better than established markers of inflammation.

78. Daily Dynamics of Mood and Inhibitory Control in a Clinical Pediatric Sample: Naturalistic Sampling via Mobile-Based Applications

78. Daily Dynamics of Mood and Inhibitory Control in a Clinical Pediatric Sample: Naturalistic Sampling via Mobile-Based Applications

Screening for High-Risk Human Papillomavirus Reveals HPV52 and HPV58 among Pediatric and Adult Patient Saliva Samples.

Previous research has demonstrated that the human papillomavirus (HPV) can infect a wide range of human tissues, including those within the oral cavity. High-risk oral HPV strains have been associated with the development and progression of oral cancers, including oral squamous cell carcinomas. Although many studies have examined the prevalence of the high-risk strains HPV16 and HPV18, far fewer have assessed the prevalence of other high-risk HPV strains. An approved study protocol was used to identify HPV52 and HPV58 among clinical samples (n = 87) from a saliva biorepository. Quantitative polymerase chain reaction (qPCR) and validated primers for HPV52 and HPV58 were used to facilitate this screening. This screening demonstrated that a total of n = 4/45 or 8.9% of adult saliva samples harbored high-risk HPV52, and n = 2/45 or 4.4% tested positive for high-risk HPV58. In addition, a total of n = 6/42 or 14.3% of the pediatric saliva samples tested positive for high-risk HPV, including n = 5/42 or 11.9% with HPV52 and n = 3/42 or 7.1% for HPV58. These data demonstrate the presence of the high-risk oncogenic HPV52 and HPV58 strains among both adult and pediatric clinical patient samples. More detailed longitudinal research must be conducted to determine whether this prevalence may be increasing or decreasing over time. In addition, these data strongly support public health prevention efforts, such as knowledge and awareness of the nine-valent HPV vaccine covering additional high-risk strains, including HPV52 and HPV58.

Sleepless nights, sour moods: daily sleep-irritability links in a pediatric clinical sample.

Sleep, or a lack thereof, is strongly related to mood dysregulation. Although considerable research uses symptom scales to examine this relation, few studies use longitudinal, real-time methods focused on pediatric irritability. This study leveraged an ecological momentary assessment (EMA) protocol, assessing bidirectional associations between momentary irritability symptoms and daily sleep duration in a transdiagnostic pediatric sample enriched for irritability. A total of N = 125 youth (Mage = 12.58 years, SD = 2.56 years; 74% male; 68.8% White) completed digital, in vivo surveys three times a day for 7 days. For a subset of youth, their parents also completed the EMA protocol. Trait irritability was measured using youth-, parent-, and clinician-report to test its potential moderating effect on the association between sleep duration and momentary irritability. Results from multilevel modeling dynamically linked sleep to irritability. Specifically, according to youth- and parent-report, decreased sleep duration was associated with increased morning irritability (bs ≤ -.09, ps < .049). A bidirectional association between parent-reported nightly sleep duration and anger was found-increased evening anger related to decreased nightly sleep duration, and decreased sleep duration related to increased morning anger (bs ≤ -.17, ps < .019). Trait irritability moderated this association, which was stronger for more irritable youth (b = -.03, p < .027). This study adds to the literature and suggests sleep-irritability dynamics as a potential treatment target.

Evaluation of the Garmin Vivofit 4 for assessing sleep in youth experiencing sleep disturbances.

Wearable monitors are increasingly used to assess sleep. However, validity is unknown for certain monitors and populations. We tested the Garmin Vivofit 4 in a pediatric clinical sample. Participants (n = 25) wore the monitor on their nondominant wrist during an overnight polysomnogram. Garmin and polysomnography were compared using 95% equivalence testing, mean absolute error, and Bland-Altman analysis. On average (mean ± SD), the Garmin predicted later sleep onset (by 0.84 ± 1.60 hours) and earlier sleep offset (by 0.34 ± 0.70 hours) than polysomnography. The resulting difference for total sleep time was -0.55 ± 1.21 hours. Sleep onset latency was higher for Garmin than polysomnography (77.4 ± 100.9 and 22.8 ± 20.0 minutes, respectively), while wake after sleep onset was lower (5.2 ± 9.3 and 43.2 ± 37.9 minutes, respectively). Garmin sleep efficiency averaged 3.3% ± 13.8% lower than polysomnography. Minutes in light sleep and deep sleep (the latter including rapid eye movement) were within ±3.3% of polysomnography (both SDs = 14.9%). No Garmin means were significantly equivalent with polysomnography (adjusted p > 0.99). Mean absolute errors were 0.47 to 0.95 hours for time-based variables (sleep onset, offset, and latency, plus total sleep time and wake after sleep onset), and 8.9% to 21.2% for percentage-based variables (sleep efficiency and sleep staging). Bland-Altman analysis showed systematic bias for wake after sleep onset, but not other variables. The Vivofit 4 showed consistently poor individual-level validity, while group-level validity was better for some variables (total sleep time and sleep efficiency) than others.

Administration of Clinical COVID-19 Mouthwashing Protocol and Potential Modulation of Pediatric Oral Bacterial Prevalence of Selenomonas noxia: A Pilot Study.

Dental office protocols to combat the SARS-CoV-2 (COVID-19) pandemic include mouth washing for an extended 60 s, thereby reducing detectable oral virus. However, it is unclear whether this protocol has any effects on the newly identified periodontal pathogen and obesity-related bacterium often found among pediatric patients, Selenomonas noxia. To determine if the mouthwash protocol has any measurable effect on S. noxia amongst pediatric patients, clinical pediatric saliva samples were obtained from pediatric patients during routine visits for clinical care and treatment. Using an approved protocol, two saliva samples were collected on the same visit before and after chlorhexidine mouthwash (Sample A, Sample B). The third sample (Sample C) was taken at the recall appointment-usually between two and eight weeks later. A total of n = 97 pre-mouthwash samples, and an equal number of matching post-mouthwash samples (n = 97) were collected, with a small number of matching recall samples (n = 36) that were subsequently collected and identified. The demographic composition of the study sample was analyzed using Chi square statistics. Sample DNA from the matching pre-, post-, and recall collections (Sample A, Sample B, and Sample C) was isolated and screened using qPCR and validated primers, which revealed that 11.1% (n = 4/36) from Sample A tested positive for S. noxia with 0% (n = 0/36) of Sample B testing positive and 13.9% (n = 5/36) of the recall (Sample C) testing positive. In addition, comparative analysis of the qPCR cycle threshold data revealed relatively lower expression (quantity) of S. noxia DNA among the recall samples, as determined by two-tailed t-tests (p=0.004). These data and results provide new evidence for the oral prevalence of S. noxia among pediatric patients, while also demonstrating that the COVID-19 protocol of mouth washing prior to clinical treatment for periods extending up to 60 s may be sufficient to reduce the levels of detectable S. noxia-at least temporarily. More research will be needed to determine whether these effects may be limited to the short- or may exhibit more lasting effects in the long-term.

A comparison of MVP and MSVT performance among a diverse clinical pediatric sample

The Memory Validity Profile (MVP) and Medical Symptom Validity Test (MSVT) are performance validity tests (PVTs) used to identify potential noncredible test performance during psychological evaluations. This study sought to examine the agreement between MVP and MSVT pass rates, as well as to determine if there are differences in MVP pass rates when using the cutoff score in the MVP professional manual compared with the experimental cutoff score of <31. Via retrospective review of records, 106 clients at a private neuropsychological clinic who had been given the MVP and the MSVT were identified. Results indicated that only one client met the manual cutoff scores, compared to 20 clients who failed the MSVT, raising concerns regarding the sensitivity of the MVP. Utilizing the receiver operator characteristic (ROC), curve analyses indicated fair discriminability of the MVP for the 106 participants (AUC = .717) with acceptable sensitivity (.50) and specificity (.92) for an MVP total score cutoff of <31. These findings support the utility of the experimental cut score in improving the sensitivity while maintaining adequate specificity in a clinically mixed population.

Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders

BackgroundExternalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs.MethodsMulti-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6–18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined.ResultsNo significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results.ConclusionsThe current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations.

27.2 Examining the Psychometric Properties and Clinical Utility of the Toronto Obsessive-Compulsive Scale (TOCS) in a Pediatric Clinical Sample

This session aims to examine the psychometric properties and establish clinical cutoffs for the parent-report version of the Toronto Obsessive-Compulsive Scale (TOCS), a 21-item screening tool that examines obsessive-compulsive traits. Participants had a primary diagnosis of OCD (n = 350; 50% female; ages 6-20 years), ADHD (n = 835; 25% female; ages 5-20 years), autism spectrum disorder (ASD; n = 805; 22% female; ages 2-21 years), or were typically developing controls (n = 398; 51% female; ages 3-21 years). Data were collected from 2 tertiary care clinics as well as from the Province of Ontario Neurodevelopmental Disorders (POND) Network. Confirmatory factor analyses, internal consistency, and convergent and divergent validity of the TOCS were examined in the OCD group. Receiver operating characteristic (ROC) analyses were used to establish a clinical cutoff by splitting the OCD and control groups into a discovery sample (166 OCD cases, 164 controls) and a validation sample (184 OCD cases, 234 controls). TOCS scores were compared across clinical groups using multivariate analysis of variance (MANOVA). The 6-factor structure of the TOCS was confirmed (χ2 [137] = 596.60; CFI = 0.90; RMSEA = 0.09; 90% CI, 0.09-0.10; SRMR = 0.06) with each factor demonstrating strong reliability (α range 0.71-0.92) and validity (eg, r = 0.40 with existing OCD measure). ROC analyses indicated excellent diagnostic discrimination of OCD cases from controls (area under the curve ≥ 0.95), with excellent sensitivity (77%-92%) and specificity (92%-98%) in both the discovery and validation samples. The OCD group scored significantly higher on all TOCS dimensions than the ADHD and ASD groups (all p < 0.001), with the exception of hoarding. The TOCS is a reliable and valid screening tool for pediatric OCD, with a strong ability to discriminate OCD cases. It is a multipurpose quantitative OCD measure that is useful not only for research (including genome-wide association studies), but also as a clinical screening tool.

The Impact of the COVID-19 Epidemic During the Lockdown on Children With the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANDAS/PANS): The Importance of Environmental Factors on Clinical Conditions.

Introduction: In March 2020, SARS-CoV-2 declared a pandemic by the World Health Organization. Restrictive isolation measures have also brought psychological distress to the pediatric population. Building on the syndrome's characteristics, the present study explored the impact of lockdown on the clinical course of young people with PANDAS/PANS. The initial hypothesis considered both the reduced exposure to viral agents and the strategies of the parents and other containment actions as protective factors against the worsening of symptoms.Methods: One hundred and eight children, adolescents, and young adults were recruited according to the multicenter PANDAS/PANS research program. Parents participated in a web-based survey. Results: contrary to our hypothesis, the study results show an increase in symptoms during the block in 71% of the sample. Psychometric analyzes allowed us to exclude a relationship between the main symptoms of PANDAS and the increase in symptoms or the presence of symptoms before the block and their increase over time. The increase in symptoms is best explained by the presence of sleep disturbances and emotional lability. The exacerbation also appears to be linked to the onset of new symptoms in children and adolescents with depressed moods and eating problems. Furthermore, irritability and oppositionality are significant predictors of acute exacerbation. Equally statistically significant is the factor linked to the effects of pandemic stress, such as the fear of contracting the virus. No significant associations for symptom reduction have been identified between parental strategies or other parent-initiated actions, but the study demonstrates that caregiver perceived efficacy on the strategies used can reduce the risk of exacerbation.Conclusion: This preliminary study highlights the importance of studying the causes of increased symptoms in children with PANDAS/PANS. Life events can exacerbate the clinical condition or generate new symptoms in young patients. In particular, environmental, family, and social changes in the course of clinical symptoms in PANDAS/PANS patients should be investigated. It highlights the importance of emotional and behavioral management, which can be improved by enhancing coping strategies in young people with PANDAS/PANS and their caregivers through a combination treatment in which CBT and PMT are included, in line with guidelines.Limits: An experimental proxy-report questionnaire not yet standardized and validated on the PANS/PANDAS pediatric clinical sample was used for the exploratory study. There is also a small sample size (N = 108) and the absence of a control group (pre-lockdown or children without PANDAS/PANS). It would be interesting to evaluate the exact long-term dimensions to see the course of symptoms after covid and conduct a new study focusing on the impact of stressful events on the clinical course of the syndrome.

The Impact of Learning and Memory on Performance Validity Tests in a Mixed Clinical Pediatric Population.

This study examined the degree to which verbal and visuospatial memory abilities influence performance validity test (PVT) performance in a mixed clinical pediatric sample. Data from 252 consecutive clinical pediatric cases (Mage=11.23 years, SD=4.02; 61.9% male) seen for outpatient neuropsychological assessment were collected. Measures of learning and memory (e.g., The California Verbal Learning Test-Children's Version; Child and Adolescent Memory Profile [ChAMP]), performance validity (Test of Memory Malingering Trial 1 [TOMM T1]; Wechsler Intelligence Scale for Children-Fifth Edition [WISC-V] or Wechsler Adult Intelligence Scale-Fourth Edition Digit Span indices; ChAMP Overall Validity Index), and intellectual abilities (e.g., WISC-V) were included. Learning/memory abilities were not significantly correlated with TOMM T1 and accounted for relatively little variance in overall TOMM T1 performance (i.e., ≤6%). Conversely, ChAMP Validity Index scores were significantly correlated with verbal and visual learning/memory abilities, and learning/memory accounted for significant variance in PVT performance (12%-26%). Verbal learning/memory performance accounted for 5%-16% of the variance across the Digit Span PVTs. No significant differences in TOMM T1 and Digit Span PVT scores emerged between verbal/visual learning/memory impairment groups. ChAMP validity scores were lower for the visual learning/memory impairment group relative to the nonimpaired group. Findings highlight the utility of including PVTs as standard practice for pediatric populations, particularly when memory is a concern. Consistent with the adult literature, TOMM T1 outperformed other PVTs in its utility even among the diverse clinical sample with/without learning/memory impairment. In contrast, use of Digit Span indices appear to be best suited in the presence of visuospatial (but not verbal) learning/memory concerns. Finally, the ChAMP's embedded validity measure was most strongly impacted by learning/memory performance.

406 Clinical Validation of AI Scoring in Adult and Pediatric Clinical PSG Samples Compared to Prospective, Double-Blind Scoring Panel

Abstract Introduction Despite an appreciable rise in sleep wellness and sleep medicine A.I. research publications, public data corpuses, institutional support, and health A.I. research funding opportunities, the availability of controlled-retrospective, hybrid-retrospective-prospective, and prospective-RCT quality clinical validation study evidence is limited with respect to their potential clinical impact. Furthermore, only a few practical examples of A.I. technologies are validated, in use today clinically, and widely adopted, to assist in sleep diagnoses and treatment. In this study, we contribute to this growing body of clinical A.I. validation evidence and experimental design methodologies with an interoperable A.I. scoring engine in Adult and Pediatric populations. Methods Stratified random sampling with proportionate allocation was applied to a database of N&amp;gt;10,000 retrospective diagnostic clinical polysomnography (PSG), selected by evidence grading standards, with controls applied for OSA severity, diagnoses; sleep, psychiatric, neurologic, neurodevelopmental, cardiac, pulmonary, metabolic disorders, medications; benzodiazepines, antidepressants, stimulants, opiates, sleep aids, demographic groups of interest; sex, adult age, pediatric age, BMI, weight, height, and patient-reported sleepiness, to establish representative N=100 Adult and N=100 Pediatric samples. Double Blinded scoring was prospectively collected for each sample by 3 experienced RPSGT certified sleep technologists randomized from a pool of 9 scorers. Sensitivity (PA), Specificity (NA), Accuracy (OA), Kappa (K), and 95% Bootstrap CI’s are presented for sleep stages, OSA/CSA, hypopnea 3%/4%, arousals, limb movements, Cheyenne-Stokes respiration, periodic breathing, atrial fibrillation, and other events, and normative, mild, moderate, and severe OSA categories for global-AHI and REM-AHI. Results for Sleep Staging and OSA Severity Diagnostic Accuracy are summarized. Results A.I. scoring performance meet but in most cases exceeded initial clinical validation study (N=72 Adults, 2017) PA, NA, OA, K point-estimates and confidence-interval results for the 26 event types and 8 AHI-categories evaluated. The Adult sample showed 87%/94% Sensitivity/Specificity across all stages (Wake/N1/N2/N3/REM) and 94%/96% Sensitivity/Specificity for AHI&amp;gt;=15. The Pediatric sample showed 87%/93% Sensitivity/Specificity staging, 89%/98% Sensitivity/Specificity AHI&amp;gt;=15. Observed Accuracy was &amp;gt;90% for Adults and Pediatrics all 26 events and 7 AHI-categories analyzed, except REM-AHI&amp;gt;=5 (85%/82% Adults/Pediatrics). Conclusion We provide clinical validation evidence that demonstrates interoperable A.I. scoring performance in representative Adult and Pediatric patient clinical PSG samples when compared to prospective, double-blind scoring panel. Support (if any):

A-171 A Factor Analytic Investigation of the Behavior Rating Inventory of Executive Function, Second Edition in a Pediatric Clinical Sample

Abstract Objective The parent-report Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) is a widely used measure in pediatric clinical neuropsychology. Unfortunately, despite notable changes from its predecessor, few studies to date have examined its internal factor structure (comprised of Behavioral Regulation [BRI], Emotion Regulation [ERI], and Cognitive Regulation [CRI]). Thus, this study sought to investigate the dimensionality of the parent-report BRIEF-2 in a mixed clinical sample. Method Two hundred two (202) outpatient pediatric neuropsychology examinees (M age = 9.90; 68% males; 53.5% with diagnosis of autism spectrum disorder) with complete data for the parent-report BRIEF-2 were extracted from an archival dataset. The sample was randomly split for confirmatory and exploratory factor analyses (CFA and EFA; ns = 101). Results Descriptive results revealed elevated scores across BRIEF-2 scales (Global Executive Composite M T = 70.16). CFA revealed that the theoretical three-factor model described by the BRIEF-2’s authors provided generally poor fit (root mean square error of approximation [RMSEA] = .12). Also, the three-factor model did not provide statistically significantly nor relatively better fit than a simpler two-factor model (RMSEA = .12), which merged BRI and ERI (consistent with the original BRIEF), identified via EFA. Conclusion(s) A two-factor structure (CRI and BRI/ERI) for the BRIEF-2 may be a more parsimonious and preferred model compared to the theoretical three-factor model in heavily neurodevelopmental clinical samples with high levels of reported executive dysfunction. Implications of these findings in context of previous literature, limitations of the present study, and appropriate directions for future inquiry are noted.

Reliability of multimodal MRI brain measures in youth at risk for mental illness.

IntroductionA new generation of large‐scale studies is using neuroimaging to investigate adolescent brain development across health and disease. However, imaging artifacts such as head motion remain a challenge and may be exacerbated in pediatric clinical samples. In this study, we assessed the scan–rescan reliability of multimodal MRI in a sample of youth enriched for risk of mental illness.MethodsWe obtained repeated MRI scans, an average of 2.7 ± 1.4 weeks apart, from 50 youth (mean age 14.7 years, SD = 4.4). Half of the sample (52%) had a diagnosis of an anxiety disorder; 22% had attention‐deficit/hyperactivity disorder (ADHD). We quantified reliability with the test–retest intraclass correlation coefficient (ICC).ResultsGray matter measurements were highly reliable with mean ICCs as follows: cortical volume (ICC = 0.90), cortical surface area (ICC = 0.89), cortical thickness (ICC = 0.82), and local gyrification index (ICC = 0.85). White matter volume reliability was excellent (ICC = 0.98). Diffusion tensor imaging (DTI) components were also highly reliable. Fractional anisotropy was most consistently measured (ICC = 0.88), followed by radial diffusivity (ICC = 0.84), mean diffusivity (ICC = 0.81), and axial diffusivity (ICC = 0.78). We also observed regional variability in reconstruction, with some brain structures less reliably reconstructed than others.ConclusionsOverall, we showed that developmental MRI measures are highly reliable, even in youth at risk for mental illness and those already affected by anxiety and neurodevelopmental disorders. Yet, caution is warranted if patterns of results cluster within regions of lower reliability.

They’re not just little adults: The utility of adult performance validity measures in a mixed clinical pediatric sample

Performance validity tests (PVTs) have become a standard part of adult neuropsychological practice; however, they are less widely used in pediatric testing. The current study aimed to obtain a better understanding of the application of PVTs within a mixed clinical pediatric sample with a wide range of diagnosis, IQ, and age. Cross-sectional data were analyzed from 130 consecutive pediatric patients evaluated as part of clinical care and diagnosed with a variety of medical/neurological, developmental, and psychiatric disorders. Patients were administered a battery of neuropsychological tests; results of intellectual functioning measures (i.e., Wechsler Intelligence Scale for Children-Fifth Edition [WISC-V] or Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV]), and PVTs (i.e., Test of Memory Malingering [TOMM] and Digit Span [DS] subtests of the WISC-V/WAIS-IV) were analyzed to assess PVT performance across the sample as well as age- and Full-Scale IQ-related (FSIQ) effects on pass rate. Results suggested that the TOMM is an effective validity test for youth, as the TOMM adult cutoff score was also valid for children (88% pass rate on TOMM trial 1 cut-score ≥41, 71% pass rate on TOMM trial 1 cut-score ≥45). In contrast, Reliable Digit Span (RDS) was less accurate (34% failed RDS [cut-score ≤6], 54% failed RDS-r [cut-score ≤10], and 25% failed DS ACSS [cut-score ≤5]) using standard adult cutoffs. Notably, although TOMM scores were not strongly influenced by IQ, DS scores increased as IQ increased. Overall, further analysis of PVTs can champion new standards of practice through additional research establishing PVT accuracy within pediatric populations.

0764 The Diagnostic Conundrum Posed By Antidepressant Medications While Conducting The Pediatric Mslt

Research examining the influence of antidepressants on multiple sleep latency test (MSLT) parameters in pediatric populations is limited. We examined the impact of rapid eye movement (REM)-suppressant antidepressant medications and other clinical, actigraphy and polysomnography (PSG) characteristics on mean sleep latency (MSL) and sleep-onset REM episodes (SOREMs) in a large pediatric clinical sample. This was a retrospective chart review. We identified 164 MSLTs performed in patients aged <18 years. All of the data were manually abstracted. Correlations between clinical, actigraphy and PSG characteristics and MSL as well as SOREMs were examined using univariate and regression analyses. Mean age of the sample was 11.9 years (SD 4.19); 62% were female, 28 (17%) were on REM-suppressant antidepressants (48% of whom were able to discontinue these prior to MSLT) and mean pediatric daytime sleepiness score was 21.7 (SD 6.1). MSL was 11.27 min (SD=5.77) and mean number of SOREMs was 0.55 (1.04). Twelve patients met criteria for narcolepsy and 40 for idiopathic hypersomnia. In the overall sample, MSL positively correlated with average time in bed on actigraphy, sleep-onset latency on PSG, and negatively correlated with age, use of REM-suppressant antidepressants and number of SOREMs (all p<0.05). The number of SOREMs positively correlated with age, BMI and arousal index and negatively correlated with use of REM-suppressant antidepressants, time in bed and total sleep time on actigraphy as well as self-reported sleep duration (all p<0.05). Similar findings were noted in the narcolepsy and idiopathic hypersomnia groups. In regression analyses accounting for factors significant in univariate analyses and sex, MSL and SOREMs continued to be associated with the use of REM-suppressant antidepressants (p=0.008 and 0.003 respectively). Further analyses examining the impact of tapering these medications in the weeks prior to MSLT did not change these associations. Clinicians should account for REM-suppressant antidepressant use while interpreting the results of MSLT. Future studies examining the impact, if any, and the precise timing of the discontinuation of these medications to reduce the likelihood of spurious results are required. None

On defining irritability and its relationship to affective traits and social interpretations

Irritability has gained recognition as a clinically significant trait in youth and adults that when persistent and severe, predicts poor outcomes throughout life. However, its definition, measurement, and relationship to similar constructs remain poorly understood. In a community sample of adults (N = 458; 19–74 years; M = 40.5), we sought to identify a unitary irritability factor from independently constructed self-reported measures of irritability distinct from the related constructs of aggression, depression, and anxiety, and whether it was associated with face emotion identification deficits and hostile interpretation biases previously established in clinical pediatric samples. The three measures of irritability generated a common factor characterized by a rapid, angry response to provocation. This irritability factor had unique associations with tendencies to judge ambiguous stimuli as reflecting hostility, but not with face emotion identification performance. These findings clarify the nature of irritability and its associations with neurocognitive phenomenon.

Novel insights from actigraphy: Anxiety is associated with sleep quantity but not quality during childhood.

Anxiety and sleep function change dynamically across development, and sleep dysfunction has emerged as a correlate and predictor of anxiety in pediatric clinical samples. Despite this, previous research has not investigated how associations between qualitative and quantitative measures of sleep function change with anxiety across development, specifically from childhood to adolescence. The present study used actigraphy collection to examine whether associations between quantitative and qualitative sleep function and anxiety differed as a function of developmental stage in a community pediatric sample (8-17 years old; N = 92). Age moderated the association between anxiety and sleep quantity, but not sleep quality. Contrary to hypotheses, higher anxiety was related to increased sleep for children, but not adolescents. Results suggest age-related changes in the association between sleep function and anxiety across development, with implications for targeting sleep-related interventions for youth with anxiety.