Faculty Bibliography

BACKGROUND:Approximately 70% of Black/African American family members report no contact with mental health providers prior to initial diagnosis and the receipt of services for early psychosis. Black families often encounter barriers and experience delays on the pathway to coordinated specialty care programmes for early psychosis. METHODS AND ANALYSIS:This mixed-methods study will (1) develop and refine a family peer navigator (FPN) for Black families designed to increase access and engagement in coordinated specialty care and (2) pilot-test FPN for Black families with 40 family members with loved ones at risk for psychosis in a randomised trial to assess the acceptability and feasibility. Families will be randomised to FPN (n=20) or a low-intensive care coordination (n=20). Other outcomes include proposed treatment targets (eg, knowledge, social connectedness), preliminary impact outcomes (time to coordinated specialty care programmes, initial family engagement), and implementation outcomes (acceptability, feasibility, appropriateness). ETHICS AND DISSEMINATION:Ethics approval has been obtained from Washington State University Institutional Review Board and informed consent will be obtained from all participants. This study will establish an innovative culturally responsive FPN programme and implementation strategy, and generate preliminary data to support a larger hybrid effectiveness-implementation trial. Study findings will be presented at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER:NCT05284721.

IMPORTANCE:Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. OBJECTIVE:To characterize neurological, psychological, and quality of life sequelae after MIS-C. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. EXPOSURE:Diagnosis of MIS-C. MAIN OUTCOMES AND MEASURES:A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. RESULTS:Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. CONCLUSIONS AND RELEVANCE:In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

OBJECTIVE:To examine diet quality and diet-related factors among male adults of reproductive age with and without disabilities. DESIGN/METHODS:Cross-sectional data from the National Health and Nutrition Examination Surveys, 2013-2018. SETTING/METHODS:Disability was reported as serious difficulty hearing, seeing, concentrating, walking, dressing and/or running errands due to physical, mental or emotional conditions. Diet quality was assessed by the Healthy Eating Index (HEI)-2015 and diet-related factors included self-rated diet healthfulness, food security and food assistance programmes. Multivariable linear regression estimated differences in HEI-2015 scores. Multivariable Poisson regression estimated adjusted prevalence ratios (aPR) and 95 % CI for diet-related factors. PARTICIPANTS/METHODS:In total, 3249 males, 18-44 years; of whom, 441 (13·4 %) reported having disabilities. RESULTS:Compared with males without disabilities, those with disabilities had a 2·69-point (95 % CI: -4·18, -1·20) lower mean total HEI-2015 score and approximately one-third to half of a point lower HEI-2015 component scores for greens and beans, total protein foods, seafood and plant proteins, fatty acids and added sugars. Males with any disabilities were more likely to have low food security (aPR = 1·57; 95 % CI: 1·28, 2·92); household participation in food assistance programmes (aPR = 1·61; 95 % CI: 1·34, 1·93) and consume fast food meals during the previous week (1-3 meals: aPR = 1·11; 95 % CI: 1·01-1·21 and 4 or more meals: aPR = 1·18; 95 % CI: 1·01-1·38) compared with males with no disabilities. CONCLUSIONS:Factors affecting diet and other modifiable health behaviours among male adults of reproductive age with disabilities require further investigation. Health promotion strategies that are adaptive to diverse populations within the disability community are needed.

We conducted the first scientometric analysis to quantitatively assess the scientific contribution of researchers from Italian institutions in the field of pediatric sleep medicine. We searched Science Citation Index Expanded from Web of Science (WOS) Science Citation up to November 3rd, 2022. Bibliometrix R packages (3.1.4) and CiteSpace (6.0.R2) were used to extract and analyze co-citation reference networks, co-occurring keyword networks, co-authorship network, co-cited institutions, and co-cited journals. We retrieved a total of 2499 documents, published between 1975 and 2022. Co-cited reference networks showed four main clusters of highly cited topics: evidence synthesis of publications on sleep disorders in children and adolescents, sleep and neurological disorders, non-pharmacological treatments of sleep disturbances, and sleep and Covid-19 in youth. Co-occurring keyword networks showed an earlier focus on the neurophysiology of sleep/neurological disorders, followed by a trend on the association of sleep disturbances to neurodevelopmental disorders and behavioral aspects. Co-authorship network showed that Italian researchers in the field of pediatric sleep medicine tend to be highly collaborative internationally. Overall, Italian researchers have provided a crucial contribution to pediatric sleep medicine across a number of specific topics, spanning from neurophysiology to treatment, and from neurological to behavioral/psychopathological aspects.

Prefrontal cortical and striatal areas have been identified by inactivation or lesion studies to be required for behavioral flexibility, including selecting and processing of different types of information. In order to identify these networks activated selectively during the acquisition of new reward contingency rules, rats were trained to discriminate orientations of bars presented in pseudorandom sequence on two video monitors positioned behind the goal sites on a T-maze with return arms. A second group already trained in the visual discrimination task learned to alternate left and right goal arm visits in the same maze while ignoring the visual cues still being presented. In each experimental group, once the rats reached criterion performance, the brains were prepared after a 90-min delay for later processing for c-fos immunohistochemistry. While both groups extinguished a prior strategy and acquired a new rule, they differed by the identity of the strategies and previous learning experience. Among the 28 forebrain areas examined, there were significant increases in the relative density of c-fos immunoreactive cell bodies after learning the second rule in the prefrontal cortex cingulate, the prelimbic and infralimbic areas, the dorsomedial striatum and the core of the nucleus accumbens, the ventral subiculum, and the central nucleus of the amygdala. These largely correspond to structures previously identified in inactivation studies, and their neurons fire synchronously during learning and strategy shifts. The data suggest that this dynamic network may underlie reward-based selection for action-a type of cognitive flexibility.

Interest in neurostimulation interventions has significantly grown in recent decades, yet a scientometric analysis objectively mapping scientific knowledge and recent trends remains unpublished. Using relevant keywords, we conducted a search in the Web of Science Core Collection on September 23, 2022, retrieving a total of 47,681 documents with 987,979 references. We identified two prominent research trends: 'noninvasive brain stimulation' and 'invasive brain stimulation.' These methods have interconnected over time, forming a cluster focused on evidence synthesis. Noteworthy emerging research trends encompassed 'transcutaneous auricular vagus nerve stimulation,' 'DBS/epilepsy in the pediatric population,' 'spinal cord stimulation,' and 'brain-machine interface.' While progress has been made for various neurostimulation interventions, their approval as adjuvant treatments remains limited, and optimal stimulation parameters lack consensus. Enhancing communication between experts of both neurostimulation types and encouraging novel translational research could foster further development. These findings offer valuable insights for funding agencies and research groups, guiding future directions in the field.

A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.

BACKGROUND:Despite evidence of the long-term implications of unrelieved pain during infancy, it is evident that infant pain is still under-managed and unmanaged. Inadequately managed pain in infancy, a period of exponential development, can have implications across the lifespan. Therefore, a comprehensive and systematic review of pain management strategies is integral to appropriate infant pain management. This is an update of a previously published review update in the Cochrane Database of Systematic Reviews (2015, Issue 12) of the same title. OBJECTIVES:To assess the efficacy and adverse events of non-pharmacological interventions for infant and child (aged up to three years) acute pain, excluding kangaroo care, sucrose, breastfeeding/breast milk, and music. SEARCH METHODS:= 74%, substantial heterogeneity), based on low- to moderate-certainty evidence. Of these five interventions most studied, only two studies observed adverse events, specifically vomiting (one preterm neonate) and desaturation (one full-term neonate hospitalised in the NICU) following the non-nutritive sucking intervention. The presence of considerable heterogeneity limited our confidence in the findings for certain analyses, as did the preponderance of evidence of very low to low certainty based on GRADE judgements. AUTHORS' CONCLUSIONS:Overall, non-nutritive sucking, facilitated tucking, and swaddling may reduce pain behaviours in preterm born neonates. Non-nutritive sucking may also reduce pain behaviours in full-term neonates. No interventions based on a substantial body of evidence showed promise in reducing pain behaviours in older infants. Most analyses were based on very low- or low-certainty grades of evidence and none were based on high-certainty evidence. Therefore, the lack of confidence in the evidence would require further research before we could draw a definitive conclusion.