Faculty Bibliography

It is unclear if impairments in social functioning and peer relationships significantly differ across common developmental conditions such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and associated callous-unemotional traits (CU traits). The current study explored sex differences and symptoms of parent- and teacher-reported psychopathology on peer relationships and prosocial behaviour in a sample of 147 referred children and adolescents (aged 5-17 years; 120 m). The results showed that increases in parent-reported ADHD Inattentive symptoms and teacher-reported ADHD Hyperactive-Impulsive symptoms, CD, ODD, and CU traits were significantly associated with peer relationship problems across sex. At the same time, teacher-reported symptoms of ODD and both parent- and teacher-reported CU traits were related to difficulties with prosocial behaviour, for both boys and girls, with sex explaining additional variance. Overall, our findings show a differential association of the most common disruptive behaviours to deficits in peer relationships and prosocial behaviour. Moreover, they highlight that different perspectives of behaviour from parents and teachers should be taken into account when assessing social outcomes in disruptive behaviours. Given the questionable separation of conduct problem-related constructs, our findings not only point out the different contribution of those aspects in explaining peer relationships and prosocial behaviour, but furthermore the variance from different informants about those aspects of conduct problems.

Neonatal brain lesions cause deficits in structure and function of the cerebral cortex that sometimes are not fully expressed until adolescence. To better understand the onset and persistence of changes caused by postnatal day 7 (P7) ethanol treatment, we examined neocortical cell numbers, volume, surface area and thickness from neonatal to post-adolescent ages. In control mice, total neuron number decreased from P8 to reach approximately stable levels at about P30, as expected from normal programmed cell death. Cortical thickness reached adult levels by P14, but cortical volume and surface area continued to increase from juvenile (P20-30) to post-adolescent (P54-93) ages. P7 ethanol caused a reduction of total neurons by P14, but this deficit was transient, with later ages having only small and non-significant reductions. Previous studies also reported transient neuron loss after neonatal lesions that might be partially explained by an acute acceleration of normally occurring programmed cell death. GABAergic neurons expressing parvalbumin, calretinin, or somatostatin were reduced by P14, but unlike total neurons the reductions persisted or increased in later ages. Cortical volume, surface area and thickness were also reduced by P7 ethanol. Cortical volume showed evidence of a transient reduction at P14, and then was reduced again in post-adolescent ages. The results show a developmental sequence of neonatal ethanol effects. By juvenile ages the cortex overcomes the P14 deficit of total neurons, whereas P14 GABA cell deficits persist. Cortical volume reductions were present at P14, and again in post-adolescent ages.

Regulatory agencies are increasingly taking on the important issue of effective risk assessment, risk stratification, and treatment planning for youth with psychiatric illness.¹ The Joint Commission mandates a suicide assessment for patients "who exhibit suicidal behavior or who have screened positive for suicidal ideation" followed by risk stratification: after "this assessment, patients should be classified as high, medium or low risk of suicide."² We anticipate that just as screening for depression and suicidality was initially restricted to emergency departments and inpatient units before being rolled out across all care settings, so risk stratification requirements will roll out to these other settings as well.

BACKGROUND:Caregivers of children with primary immunodeficiency disorders (PIDs) experience significant psychological distress during their child's hematopoietic cell transplantation (HCT) process. OBJECTIVES:This study aims to understand caregiver challenges and identify areas for health care system-level improvements to enhance caregiver well-being. METHODS:In this mixed-methods study caregivers of children with PIDs were contacted in August to November 2017 through online and electronic mailing lists of rare disease consortiums and foundations. Caregivers were invited to participate in an online survey assessing sociodemographic variables, the child's medical characteristics, psychosocial support use, and the World Health Organization-5 Well-Being Index. Open-ended questions about health care system improvements were included. Descriptive statistics and linear multivariate regression analyses were conducted. A modified content analysis method was used to code responses and identify emergent themes. RESULTS:Among the 80 caregiver respondents, caregivers had a median age of 34 years (range, 23-62 years) and were predominantly female, white, and married with male children given a diagnosis of severe combined immune deficiency. In the adjusted regression model lower caregiver well-being was significantly associated with lower household income and medical complications. Challenges during HCT include maintaining relationships with partners and the child's healthy sibling or siblings, managing self-care, and coping with feelings of uncertainty. Caregivers suggested several organizational-level solutions to enhance psychosocial support, including respite services, online connections to other PID caregivers, and bedside mental health services. CONCLUSIONS:Certain high-risk subpopulations of caregivers might need more targeted psychosocial support to reduce the long-term effect of the HCT experience on their well-being. Caregivers suggested several organizational-level solutions for provision of this support.

Short duration of marriage (DoM) is a risk factor for preeclampsia that is also related to the risk for schizophrenia. This analysis examined the risk for schizophrenia associated with DoM and its independence from parental psychiatric disorders, parental ages and fathers' age at marriage.

Identify correlates of nicotine dependence [lifetime (l) and ongoing (o)] in adults with attention-deficit/hyperactivity disorder (ADHD) in childhood. We conducted a 33-year prospective follow-up of boys (mean age 8) with combined type ADHD (n = 135/207, 65% original sample). Correlates of nicotine dependence in adulthood were selected from characteristics obtained in childhood and adolescence. Among selected childhood features, only immature behavior was significantly related to nicotine dependence (OR(o) = 0.29, p = 0.02), indexing decreased risk. In contrast, several adolescent variables significantly correlated (p < 0.01) with nicotine dependence at mean age 41, including alcohol substance use disorder (SUD, OR(l) = 4.97), non-alcohol SUD (OR(o) = 4.33/OR(l) = 10.93), parental antisocial personality disorder (OR(l) = 4.42), parental SUD (OR(l) = 3.58), dropped out of school (OR(l) = 2.29), impulsivity (OR(o) = 1.53/OR(l) = 1.59), hyperactivity (OR(o) = 1.38), and number of antisocial behaviors (OR(o) = 1.10/OR(l) = 1.14). Results highlight the role of adolescent psychopathology in the development of nicotine dependence, motivating prospective longitudinal efforts to better define the developmental trajectories of risk and protection.

Background: The full-thickness resection device (FTRD)was recently introduced in the US and has made endoscopic resection of difficult lesions and those with deep wall origin/infiltration possible using non-exposure resection technique. Although initial studies were promising, outcome results of FTRD in the literature are scarce.
Aim(s): To study the feasibility, effciacy, and safety of FTRD for the resection of colonic lesions.
Method(s): Patients who underwent endoscopic full-thickness resection (EFTR)using the FTRD for lower GI lesions at 24 U.S. tertiary-care centers between 10/17 and 10/18 were included in this retrospective study. Outcomes were technical success (defined as en-block resection)and R0 histologic margin. Chi square test was used to assess the association between lesion type, size, and location with the two outcomes.
Result(s): A total of 79 patients (mean age 65 yr, 39.2% F)underwent resection of colonic lesions using the FTRD. The most common indication was difficult adenoma (defined as non-lifting, recurrent, residual or involving appendiceal orifice/diverticular opening)in 48 (60.8 %)patients, followed by adenocarcinoma in 17 (21.5%), and sub-epithelial lesions in 10 (12.7 %). Lesion location was in the proximal colon in 46 (58.2%)patients, followed by distal colon in 17 (21.5%), and rectum in 16 (20.3%). Mean pre-resection lesion diameter and total procedure time were 15.3 +/- 6.5 mm and 63 +/-32 min, respectively. Majority of patients underwent MAC sedation and received no prophylactic antibiotics. Most patients, 72.2%, were discharged post-procedurally. Technical success was achieved in 67 (84.8 %)patients. For the 12 patients with technical failure, 5 underwent hot snare resection, 2 endoscopic submucosal dissection, 1 was managed surgically, while 4 had no further interventions. R0 resection was achieved in 88.9% of patients. A total of 9 (11.4%)adverse events occurred. Mild, moderate, and severe AE had a frequency of 6 (7.6%), 1 (1.3%), and 2 (2.5%), respectively. Most common AE was FTRD mechanical failure in 5 cases (6.3%), with one leading to perforation requiring surgery (severe event). Bleeding was reported in 3 cases (3.8%), with one case requiring endoscopic intervention 2-days post-procedure. One patient, despite being on pre and post procedure antibiotics, developed appendicitis 10-days post-procedure and was managed surgically (severe event). Technical success and R0 resection were not significantly associated with lesion type, size, or location.
Conclusion(s): Results from this first U.S multicenter study suggest that EFTR is a feasible, safe, and effective technique for EFTR of difficult colonic lesions. Surgical management can be avoid in the vast majority of cases. Although adverse events are not uncommon, severe complications are rare. [Figure presented][Figure presented]
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OBJECTIVE:Parental age at birth has been shown to affect the rates of a range of neurodevelopmental disorders, but the understanding of the mechanisms through which it mediates different outcomes is still lacking. A population-based cohort was used to assess differential effects of parental age on estimates of risk across pediatric-onset neuropsychiatric disorders: autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and Tourette's disorder/chronic tic disorder (TD/CT). METHOD:The study cohort included all singleton births in Denmark from 1980 through 2007 with full information on parental ages (N = 1,490,745) and was followed through December 31, 2013. Cases of ASD, ADHD, OCD, and TD/CT were identified in the Danish Psychiatric Central Register and the National Patient Register. Associations with parental age were modeled using a stratified Cox regression, allowing for changes in baseline diagnostic rates across time. RESULTS:Younger parental age was significantly associated with increased estimates of risk for ADHD and TD/CT, whereas older parental age was associated with ASD and OCD. Except for OCD, no evidence for differential effects of parental ages on male versus female offspring was observed. CONCLUSION:This study provides novel evidence for the association between age at parenthood and TD/CT and OCD and for the first time shows in a population-based sample that parental age confers differential risk rates for pediatric-onset psychiatric disorders. These results are consistent with a model of shared and unshared risk architecture for pediatric-onset neuropsychiatric conditions, highlighting unique contributions of maternal and paternal ages.

The Child Behavior Checklist (CBCL) is widely used to assess behavioral and emotional problems in youth. The CBCL Diagnostic and Statistical Manual (DSM)-Oriented Anxiety Problems subscale (CBCL-AP) was developed for the identification of DSM-IV anxiety disorders. Using data from 298 youth aged 6- to 18, the CBCL-AP scale was examined to determine its ability to differentially predict, via Receiver Operating Characteristics (ROC) analysis, the presence of (a) generalized anxiety disorder (GAD), (b) separation anxiety disorder (SAD), (c) specific phobia (SPPH), or (d) the presence of any of these disorders. Independent Evaluators (IEs) administered the Anxiety Disorders Interview Schedule for Children (ADIS-C/P) to determine the presence of an anxiety disorder. The ability of the CBCL-AP to predict to anxiety disorders was compared to the ability of the CBCL Anxious/Depressed (CBCL-A/D) scale and the seven empirically derived CBCL syndrome subscales and five DSM-Oriented subscales to predict anxiety disorder diagnoses. Results revealed that CBCL-AP scores significantly predicted all diagnoses. CBCL-A/D scores significantly predicted SAD (AUC = 0.67), GAD (AUC = 0.69), and the presence of any of the three disorders (AUC = 0.72), but not the presence of SPPH (AUC = 0.52). Although the CBCL-AP scale may not be a substitute for extensive diagnostics, it has demonstrated utility as an instrument for assessing anxiety and can serve to identify anxious youth in need of mental health services.

Background: Prior data from Asian countries showed comparable outcomes of endoscopic submucosal dissection (ESD)vs surgery in patients with early gastric cancer (EGC)meeting standard and expanded criteria. Data from comparative studies using strict criteria in North American population are lacking.
Method(s): We conducted a multicenter retrospective study from 16 North American centers. All patient underwent ESD and/or gastrectomy for EGC between 12/2004 and 2/2018, with follow-up until 10/2018. Patients who did not meet either standard or expanded criteria, those with evidence of lymph node or distant metastasis at time of diagnosis, those without curative resection, and those with follow-up time of less than 6 months were excluded. Primary outcomes were overall survival (OS), cancer-specific survival (CSS)and recurrence-free survival (RFS). Kaplan-Meier using log-rank analysis was used to compare outcomes between ESD and surgery groups. Factors associated with outcomes were analyzed using Cox hazards regression and linear regression analyses.
Result(s): There were 393 patients with EGC who underwent ESD or gastrectomy from 14 US and 2 Canadian centers. Of these, 318 patients were excluded due to unfulfilled standard or expanded criteria (n=254), evidence of lymph node metastasis (n=1), no data on lymphovascular invasion (n=1), non-R0 resection (n=17)and follow-up time of less than 6 months (n=45). A total of 75 patients were analyzed (38 treated with ESD and 37 treated with surgery). Patients treated with surgery had a higher proportion of pedunculated lesions (P=0.02), undifferentiated tumors (P =0.01), EGCs fulfilling expanded criteria (P <0.0001)and longer follow-up time (P=0.0004)(Table 1). OS (P= 1.00), CSS (P=1.00)and RFS (P=1.00)were not statistically different between ESD vs surgery groups. There was no subsequent nodal or distant metastasis in either group. A single patient in the surgery group died of an etiology not related to gastric cancer at 7.9 years after gastrectomy. There were no deaths in the ESD group. One patient with moderately differentiated adenocarcinoma in the gastric antrum, treated with curative ESD, developed a gastric cardiac neuroendocrine tumor at 7.2 years (Table 2). The metachronous lesion was treated with a repeat curative endoscopic resection. There was no demographic, procedural or histological factor associated with OS, CSS or RFS.
Conclusion(s): The standard and expanded criteria for gastric ESD are clinically applicable to a North American population. ESD provides comparable oncologic outcomes and is thus an alternative treatment option to surgery. Recurrence after ESD is uncommon, and can be managed successfully using follow-up and repeat endoscopic treatment. [Figure presented][Figure presented]
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