Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.

This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].

No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).

Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.

The Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database Project is a multisite collaborative that includes neuropsychological evaluations of children presenting for epilepsy surgery. There is some evidence for specific neuropsychological phenotypes within epilepsy (Hermann et al, 2016); however, this is less clear in pediatric patients. As a first step, we applied an empirically-based subtyping approach to determine if there were specific profiles using indices from the Wechsler scales [Verbal IQ (VIQ), Nonverbal IQ (NVIQ), Processing Speed Index (PSI), Working Memory Index (WMI)]. We hypothesized that there would be at least four profiles that are distinguished by slow processing speed and poor working memory as well as profiles with significant differences between verbal and nonverbal reasoning abilities.

Our study included 372 children (M=12.1 years SD=4.1; 77.4% White; 48% male) who completed an age-appropriate Wechsler measure, enough to render at least two index scores. Epilepsy characteristics included 84.4% with focal epilepsy (evenly distributed between left and right focus) and 13.5% with generalized or mixed seizure types; mean age of onset = 6.7 years, SD = 4.5; seizure frequency ranged from daily to less than monthly; 53% had structural etiology; 71% had an abnormal MRI; and mean number of antiseizure medications was two. Latent profile analysis was used to identify discrete underlying cognitive profiles based on intellectual functioning. Demographic and epilepsy characteristics were compared among profiles.

Based on class enumeration procedures, a 3-cluster solution provided the best fit for the data, with profiles characterized by generally Average, Low Average, or Below Average functioning. 32.8% were in the Average profile with mean index scores ranging from 91.7-103.2; 47.6% were in the Low Average profile with mean index ranging from 80.7 to 84.5; and 19.6% were in the Below Average profile with mean index scores ranging from 55.0-63.1. Across all profiles, the lowest mean score was the PSI, followed by WMI. VIQ and NVIQ represented relatively higher scores for all three profiles. Mean discrepancy between indices within a profile was as large as 11.5 IQ points. No demographics or epilepsy characteristics were significantly different across cognitive phenotypes.

Latent cognitive phenotypes in a pediatric presurgical cohort were differentiated by general level of functioning; however, across profiles, processing speed was consistently the lowest index followed by working memory. These findings across phenotypes suggest a common relative weakness which may result from a global effect of antiseizure medications and/or the widespread impact of seizures on neural networks even in a largely focal epilepsy cohort; similar to adult studies with temporal lobe epilepsy (Hermann et al, 2007). Future work will use latent profile analysis to examine phenotypes across other domains relevant to pediatric epilepsy including attention, naming, motor, and memory functioning. These findings are in line with collaborative efforts towards cognitive phenotyping which is the aim of our PERC Epilepsy Surgery Database Project that has already established one of the largest pediatric epilepsy surgery cohorts.

Children with epilepsy are at greater risk of lower academic achievement than their typically developing peers (Reilly and Neville, 2015). Demographic, social, and neuropsychological factors, such as executive functioning (EF), mediate this relation. While research emphasizes the importance of EF skills for academic achievement among typically developing children (e.g., Best et al., 2011; Spiegel et al., 2021) less is known among children with epilepsy (Ng et al., 2020). The purpose of this study is to examine the influence of EF skills on academic achievement in a nationwide sample of children with epilepsy.

Participants included 427 children with epilepsy (52% male; MAge= 10.71), enrolled in the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database who had been referred for surgery and underwent neuropsychological testing. Academic achievement was assessed by performance measures (word reading, reading comprehension, spelling, and calculation and word-based mathematics) and parent-rating measures (Adaptive Behavior Assessment System (ABAS) Functional Academics and Child Behavior Checklist (CBCL) School Performance). EF was assessed by verbal fluency measures, sequencing, and planning measures from the Delis Kaplan Executive Function System (DKEFS), NEPSY, and Tower of London test. Rating-based measures of EF included the 'Attention Problems’ subscale from the CBCL and 'Cognitive Regulation’ index from the Behavior Rating Inventory of Executive Function (BRIEF-2). Partial correlations assessed associations between EF predictors and academic achievement, controlling for fullscale IQ (FSIQ; A composite across intelligence tests). Significant predictors of each academic skill or rating were entered into a two-step regression that included FSIQ, demographics, and seizure variables (age of onset, current medications) in the first step with EF predictors in the second step.

Although zero-order correlations were significant between EF predictors and academic achievement (.29 < r’s < .63 for performance; -.63 < r’s < -.50 for rating measures), partial correlations controlling for FSIQ showed fewer significant relations. For performance-based EF, only letter fluency (DKEFS Letter Fluency) and cognitive flexibility (DKEFS Trails Condition 4) demonstrated significant associations with performance-based academic achievement (r’s > .29). Regression models for performance-based academic achievement indicated that letter fluency (ß = .22, p = .017) and CBCL attention problems (ß = -.21, p =.002) were significant predictors of sight-word reading. Only letter fluency (ß = .23, p =.006) was significant for math calculation. CBCL Attention Problems were a significant predictor of spelling performance (ß = -.21, p = .009) and reading comprehension (ß = -.18, p =.039). CBCL Attention Problems (ß = -.38, p <.001 for ABAS; ß = -.34, p =.002 for CBCL School) and BRIEF-2 Cognitive Regulation difficulties (ß = -.46, p < .001 for ABAS; ß = -.46, p =.013 for CBCL School) were significant predictors of parent-rated ABAS Functional Academics and CBCL School Performance.

Among a national pediatric epilepsy dataset, performance-based and ratings-based measures of EF predicted performance academic achievement, whereas only ratings-based EF predicted parent-rated academic achievement, due at least in part to shared method variance. These findings suggest that interventions that increase cognitive regulation, reduce symptoms of attention dysfunction, and promote self-generative, flexible thinking, may promote academic achievement among children with epilepsy.

Pediatric patients with frontal lobe epilepsy (FLE) have higher rates of attention deficit hyperactivity disorder (ADHD), as well as executive functioning (EF) and fine motor (FM) challenges. Relations between these constructs have been established in youth with ADHD and are supported by FM and EF skill involvement in frontal-subcortical systems. Still, they are not well understood in pediatric FLE. We hypothesized that poorer FM performance would be related to greater executive dysfunction and ADHD symptomatology in this group.

47 children and adolescents with FLE (AgeM=12.47, SD=5.18; IQM=84.07; SD=17.56; Age of Seizure OnsetM=6.85, SD=4.64; right-handed: n=34; left-handed: n=10; Unclear: n=3) were enrolled in the Pediatric Epilepsy Research Consortium dataset as part of their phase I epilepsy surgical evaluation. Participants were selected if they had unifocal FLE and completed the Lafayette Grooved Pegboard (GP). Seizure lateralization (left-sided: n=19; right-sided: n=26; bilateral: n=2) and localization were established via data (e.g., EEG, MRI) presented at a multidisciplinary team case conference. Patients completed neuropsychological measures of FM, attention, and EF. Parents also completed questionnaires inquiring about their child’s everyday EF and ADHD symptomatology. Correlational analyses were conducted to examine FM, EF, and ADHD relations.

Dominant hand (DH) manual dexterity (GP) was related to parent-reported EF (Behavior Rating Inventory of Executive Function, Second Edition [BRIEF-2]-Global Executive Composite [GEC]: r(15) =-.70, p<.01, d=1.96). While not statistically significant, medium to large effect sizes were found for GP DH and parent-reported inattention (Behavior Assessment System for Children, Third Edition [BASC-3]-Attention Problems: r(12)=-.39, p=.17, d=.85) and hyperactivity/impulsivity (BASC-3-Hyperactivity: r(11)= -.44, p=.13, d=.98), as well as performance-based attention (Conners Continuous Performance Test, Third Edition -Omission Errors: r(12)=-.35, p=.22, d=.41), working memory (Wechsler Intelligence Scale for Children - Fifth Edition [WISC-V]-Digit Span [DS]: r(19)=.38, p=.09, d=.82) and cognitive flexibility (Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Category Switching: r(13)=.46, p=.08, d=1.04); this suggests that these relations may exist but that our study was underpowered to detect them. Non-dominant hand (NDH) manual dexterity was related to performance-based working memory (WISC-V-DS: r(19)=.50, p<.01, d=1.12) and cognitive flexibility (D-KEFS-Trails Making Test Number-Letter Switching: r(17)=.64, p<.01, d=1.67). Again, while underpowered, medium to large effect sizes were found for GP NDH and parent-reported EF (BRIEF-2 GEC: r(15) =-.45, p=.07, d=1.01) and performance-based phonemic fluency (D-KEFS-Letter Fluency: r(13)=.31, p=.20, d=.65).

Our findings suggest that FM, EF, and ADHD are related in youth with FLE; however, these relations appear to vary by skill and hand. We posit that our findings are due in part to the frontal-cerebellar networks given their anatomic proximity between frontal motor areas and the dorsolateral prefrontal cortex - as well as their shared functional involvement in these networks. Future studies should evaluate the predictive validity of initial FM skills for later executive dysfunction and ADHD symptomatology in FLE. If such relations emerge, contributions of early FM interventions on EF development should be examined. Further replication of these findings with a larger sample is warranted.

Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.

To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.

We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.

The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.

In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

COVID-19 has markedly impacted the provision of neurodevelopmental care. In response, the Cardiac Neurodevelopmental Outcome Collaborative established a Task Force to assess the telehealth practices of cardiac neurodevelopmental programmes during COVID-19, including adaptation of services, test protocols and interventions, and perceived obstacles, disparities, successes, and training needs.

A 47-item online survey was sent to 42 Cardiac Neurodevelopmental Outcome Collaborative member sites across North America within a 3-week timeframe (22 July to 11 August 2020) to collect cross-sectional data on practices.

Of the 30 participating sites (71.4% response rate), all were providing at least some clinical services at the time of the survey and 24 sites (80%) reported using telehealth. All but one of these sites were offering new telehealth services in response to COVID-19, with the most striking change being the capacity to offer new intervention services for children and their caregivers. Only a third of sites were able to carry out standardised, performance-based, neurodevelopmental testing with children and adolescents using telehealth, and none had completed comparable testing with infants and toddlers. Barriers associated with language, child ability, and access to technology were identified as contributing to disparities in telehealth access.

Telehealth has enabled continuation of at least some cardiac neurodevelopmental services during COVID-19, despite the challenges experienced by providers, children, families, and health systems. The Cardiac Neurodevelopmental Outcome Collaborative provides a unique platform for sharing challenges and successes across sites, as we continue to shape an evidence-based, efficient, and consistent approach to the care of individuals with CHD.

To assess the quality and quantity of foods and beverages provided to children aged 0–5 years in family day care and identify structural and sociodemographic factors associated with the nutritional quality of food provided.

A cross-sectional study measured the food and beverages provided to children using weighed food records. The number of serves from different food groups was calculated according to the Australian Guide to Healthy Eating, and a healthy food provision index score was created. Associations between structural and sociodemographic factors and healthy food provision index scores were analysed using linear mixed models.

Family day care services in two large geographic areas in New South Wales, Australia.

One hundred and four children in thirty-three family day care services.

During attendance at childcare, most children met recommended servings of fruit but not dairy, vegetables, lean meat and meat alternatives and wholegrains. Discretionary foods exceeded recommendations. Children’s age, socio-economic status and the type of main meal provided were significantly associated with the healthy food provision index score.

Foods provided to children in family day care are aligned with dietary recommendations for fruit but not vegetables, dairy, lean meat and meat alternatives, wholegrains or discretionary foods. Interventions to promote healthy eating are needed to support families and educators to improve the nutritional quality of food provided to children.

Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke.

We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery.

We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone.

Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%.

The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.

Perinatal mood and anxiety disorders (PMADs) are the most common complication of pregnancy and have been found to have long-term implications for both mother and child. In vulnerable patient populations such as those served at Denver Health, a federally qualified health center the prevalence of PMADs is nearly double the nationally reported rate of 15–20%. Nearly 17% of women will be diagnosed with major depression at some point in their lives and those numbers are twice as high in women who live in poverty. Women also appear to be at higher risk for depression in the child-bearing years. In order to better address these issues, an Integrated Perinatal Mental Health program was created to screen, assess, and treat PMADs in alignment with national recommendations to improve maternal–child health and wellness. This program was built upon a national model of Integrated Behavioral Health already in place at Denver Health.

A multidisciplinary team of physicians, behavioral health providers, public health, and administrators was assembled at Denver Health, an integrated hospital and community health care system that serves as the safety net hospital to the city and county of Denver, CO. This team was brought together to create a universal screen-to-treat process for PMAD’s in perinatal clinics and to adapt the existing Integrated Behavioral Health (IBH) model into a program better suited to the health system’s obstetric population. Universal prenatal and postnatal depression screening was implemented at the obstetric intake visit, a third trimester prenatal care visit, and at the postpartum visit across the clinical system. At the same time, IBH services were implemented across our health system’s perinatal care system in a stepwise fashion. This included our women’s care clinics as well as the family medicine and pediatric clinics. These efforts occurred in tandem to support all patients and staff enabling a specially trained behavioral health provider (psychologists and L.C.S.W.’s) to respond immediately to any positive screen during or after pregnancy.

In August 2014 behavioral health providers were integrated into the women’s care clinics. In January 2015 universal screening for PMADs was implemented throughout the perinatal care system. Screening has improved from 0% of women screened at the obstetric care intake visit in August 2014 to >75% of women screened in August 2016. IBH coverage by a licensed psychologist or licensed clinical social worker exists in 100% of perinatal clinics as of January 2016. As well, in order to gain sustainability, the ability to bill same day visits as well as to bill, and be reimbursed for screening and assessment visits, continues to improve and provide for a model that is self-sustaining for the future.

Implementation of a universal screening process for PMADs alongside the development of an IBH model in perinatal care has led to the creation of a program that is feasible and has the capacity to serve as a national model for improving perinatal mental health in vulnerable populations.

Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators.

Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps.

Forty-eight competency statements in 8 domains were developed.

Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.

The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel.

In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized.

This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP.

We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.