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Abstract Background Autoantibodies against self-antigens have been associated not only with autoimmune diseases, but also with cancer and are even found in healthy individuals. The mechanism causing the autoantibody response remains elusive for the majority of the immunogenic antigens. To deepen the understanding of autoantibody responses, we ask whether natural-occurring, autoimmunity-associated and tumor-associated antigens have structural or biological features related to the immune response. To this end, we have carried out the most comprehensive in-silicio study of different groups of autoantigens including large antigen sets identified by our groups combined with publicly available antigen sets. Results We found evidence for an enrichment of genes with a larger exon length increasing the probability of the occurrence of potential immunogenic features such as mutations, SNPs, immunogenic sequence patterns and structural epitopes, or alternative splicing events. While SNPs seem to play a more central role in autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated antigens. In addition, antigens of autoimmune diseases are different from other antigen sets in that they appear preferentially secreted, have frequently an extracellular location, and they are enriched in pathways associated with the immune system. Furthermore, for autoantibodies in general, we found enrichment of sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to proteins or nucleic acids including RNA and enrichment of proteins that are part of ribosome or spliceosome. Both, homologies to proteins of other species and an enrichment of ancient protein domains indicate that immunogenic proteins are evolutionary conserved and that mimicry might play a central role. Conclusions Our results provide evidence that proteins which i) are evolutionary conserved, ii) show specific sequence motifs, and iii) are part of cellular structures show an increased likelihood to become autoimmunogenic.

Processing social feedback optimistically may maintain positive self-beliefs and stable social relationships. Conversely, a lack of this optimistic bias in depression and social anxiety may perpetuate negative self-beliefs and maintain symptoms. Research investigating this mechanism is scarce, however, and the mechanisms by which depressed and socially anxious individuals respond to social evaluation may also differ. Using a range of computational approaches in two large datasets (mega-analysis of previous studies, n = 450; pre-registered replication study, n = 807), we investigated how depression (PHQ-9) and social anxiety (BFNE) symptoms related to social evaluation learning in a computerized task. Optimistic bias (better learning of positive relative to negative evaluations) was found to be negatively associated with depression and social anxiety. Structural equation models suggested this reflected a heightened sensitivity to negative social feedback in social anxiety, whereas in depression it co-existed with a blunted response to positive social feedback. Computational belief-based learning models further suggested that reduced optimism was driven by less positive trait-like self-beliefs in both depression and social anxiety, with some evidence for a general blunting in belief updating in depression. Recognizing such transdiagnostic similarities and differences in social evaluation learning across disorders may inform approaches to personalizing treatment., (© 2024. The Author(s).)

Objectives: In the United States, pediatric emergency department (ED) visits for behavioral health (BH) are increasing. We sought to determine ED-level characteristics associated with having recommended BH-related policies., Methods: We conducted a retrospective serial cross-sectional study of National Pediatric Readiness Project assessments administered to US EDs in 2013 and 2021. Changes in responses related to BH items over time were examined. Multivariable logistic regression models examined ED characteristics associated with the presence of specific BH-related policies in 2021., Results: Of 3554 EDs that completed assessments in 2021, 73.0% had BH-related policies, 66.5% had transfer guidelines for children with BH issues, and 38.6% had access to BH resources in a disaster. Of 2570 EDs that completed assessments in both 2013 and 2021, presence of specific BH-related policies increased from 48.6% to 72.0% and presence of appropriate transfer guidelines increased from 56.2% to 64.9%. The adjusted odd ratios (aORs) of having specific BH-related policies were lower in rural (aOR 0.73; 95% confidence interval [CI] 0.57, 0.92) and remote EDs (aOR 0.65; 95% CI 0.48, 0.88) compared to urban EDs; lower among EDs with versus without trauma center designation (aOR 0.80; 95% CI 0.67, 0.95); and higher among EDs with a nurse and physician pediatric emergency care coordinator (PECC) (aOR 1.89; 95% CI 1.54, 2.33) versus those without a PECC., Conclusion: Although pediatric readiness for BH conditions increased from 2013 to 2021, gaps remain, particularly among rural EDs and designated trauma centers. Having nurse and physician PECCs is a modifiable strategy to increase ED pediatric readiness pertaining to BH., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 The Author(s). Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: The COVID-19 pandemic adversely affected children's mental health (MH) and changed patterns of MH emergency department (ED) utilization. Our objective was to assess how pediatric MH ED visits during the COVID-19 pandemic differed from expected prepandemic trends., Methods: We retrospectively studied MH ED visits by children 5 to <18 years old at nine U.S. hospitals participating in the Pediatric Emergency Care Applied Research Network Registry from 2017 to 2022. We described visit length by time period: prepandemic (January 2017-February 2020), early pandemic (March 2020-December 2020), midpandemic (2021), and late pandemic (2022). We estimated expected visit rates from prepandemic data using multivariable Poisson regression models. We calculated rate ratios (RRs) of observed to expected visits per 30 days during each pandemic time period, overall and by sociodemographic and clinical characteristics., Results: We identified 175,979 pediatric MH ED visits. Visit length exceeded 12 h for 7.3% prepandemic, 8.4% early pandemic, 15.0% midpandemic, and 19.2% late pandemic visits. During the early pandemic, observed visits per 30 days decreased relative to expected rates (RR 0.80, 95% confidence interval [CI] 0.78-0.84), were similar to expected rates during the midpandemic (RR 1.01, 95% CI 0.96-1.07), and then decreased below expected rates during the late pandemic (RR 0.92, 95% CI 0.86-0.98). During the late pandemic, visit rates were higher than expected for females (RR 1.10, 95% CI 1.02-1.20) and for bipolar disorders (RR 1.83, 95% CI 1.38-2.75), schizophrenia spectrum disorders (RR 1.55, 95% CI 1.10-2.59), and substance-related and addictive disorders (RR 1.50, 95% CI 1.18-2.05)., Conclusions: During the late pandemic, pediatric MH ED visits decreased below expected rates; however, visits by females and for specific conditions remained elevated, indicating a need for increased attention to these groups. Prolonged ED visit lengths may reflect inadequate availability of MH services., (© 2024 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Importance: Many US children and adolescents with mental and behavioral health (MBH) conditions do not access MBH services. One contributing factor is limited insurance coverage, which is influenced by state MBH insurance parity legislation., Objective: To investigate the association of patient-level factors and the comprehensiveness of state MBH insurance legislation with perceived poor access to MBH care and perceived inadequate MBH insurance coverage for US children and adolescents., Design, Setting, and Participants: This retrospective cross-sectional study was conducted using responses by caregivers of children and adolescents aged 6 to 17 years with MBH conditions in the National Survey of Children's Health and State Mental Health Insurance Laws Dataset from 2016 to 2019. Data analyses were conducted from May 2022 to January 2024., Exposure: MBH insurance legislation comprehensiveness defined by State Mental Health Insurance Laws Dataset (SMHILD) scores (range, 0-7)., Main Outcomes and Measures: Perceived poor access to MBH care and perceived inadequacy of MBH insurance were assessed. Multivariable regression models adjusted for individual-level characteristics., Results: There were 29 876 caregivers of children and adolescents with MBH conditions during the study period representing 14 292 300 youths nationally (7 816 727 aged 12-17 years [54.7%]; 8 455 171 male [59.2%]; 292 543 Asian [2.0%], 2 076 442 Black [14.5%], and 9 942 088 White [69.6%%]; 3 202 525 Hispanic [22.4%]). A total of 3193 caregivers representing 1 770 492 children and adolescents (12.4%) perceived poor access to MBH care, and 3517 caregivers representing 1 643 260 of 13 175 295 children and adolescents (12.5%) perceived inadequate MBH insurance coverage. In multivariable models, there were higher odds of perceived poor access to MBH care among caregivers of Black (adjusted odds ratio [aOR], 1.35; 95% CI, 1.04-1.75) and Asian (aOR, 1.69; 95% CI, 1.01-2.84) compared with White children and adolescents. As exposures to adverse childhood experiences (ACEs) increased, the odds of perceived poor access to MBH care increased (aORs ranged from 1.68; 95%, CI 1.32-2.13 for 1 ACE to 4.28; 95% CI, 3.17-5.77 for ≥4 ACEs compared with no ACEs). Compared with living in states with the least comprehensive MBH insurance legislation (SMHILD score, 0-2), living in states with the most comprehensive legislation (SMHILD score, 5-7) was associated with lower odds of perceived poor access to MBH care (aOR, 0.79; 95% CI, 0.63-0.99), while living in states with moderately comprehensive legislation (score, 4) was associated with higher odds of perceived inadequate MBH insurance coverage (aOR, 1.23; 95% CI, 1.01-1.49)., Conclusions and Relevance: In this study, living in states with the most comprehensive MBH insurance legislation was associated with lower odds of perceived poor access to MBH care among caregivers for children and adolescents with MBH conditions. This finding suggests that advocacy for comprehensive mental health parity legislation may promote improved child and adolescent access to MBH services.

Importance: Suicide is a leading cause of death among US youths, and mental health disorders are a known factor associated with increased suicide risk. Knowledge about potential sociodemographic differences in documented mental health diagnoses may guide prevention efforts., Objective: To examine the association of documented mental health diagnosis with (1) sociodemographic and clinical characteristics, (2) precipitating circumstances, and (3) mechanism among youth suicide decedents., Design, Setting, and Participants: This retrospective, cross-sectional study of youth suicide decedents aged 10 to 24 years used data from the Centers for Disease Control and Prevention National Violent Death Reporting System from 2010 to 2021. Data analysis was conducted from January to November 2023., Exposures: Sociodemographic characteristics, clinical characteristics, precipitating circumstances, and suicide mechanism., Main Outcomes and Measures: The primary outcome was previously documented presence of a mental health diagnosis. Associations were evaluated by multivariable logistic regression., Results: Among 40 618 youth suicide decedents (23 602 aged 20 to 24 years [58.1%]; 32 167 male [79.2%]; 1190 American Indian or Alaska Native [2.9%]; 1680 Asian, Native Hawaiian, or Other Pacific Islander [4.2%]; 5118 Black [12.7%]; 5334 Hispanic [13.2%]; 35 034 non-Hispanic; 30 756 White [76.1%]), 16 426 (40.4%) had a documented mental health diagnosis and 19 027 (46.8%) died by firearms. The adjusted odds of having a mental health diagnosis were lower among youths who were American Indian or Alaska Native (adjusted odds ratio [aOR], 0.45; 95% CI, 0.39-0.51); Asian, Native Hawaiian, or Other Pacific Islander (aOR, 0.58; 95% CI, 0.52-0.64); and Black (aOR, 0.62; 95% CI, 0.58-0.66) compared with White youths; lower among Hispanic youths (aOR, 0.76; 95% CI, 0.72-0.82) compared with non-Hispanic youths; lower among youths aged 10 to 14 years (aOR, 0.70; 95% CI, 0.65-0.76) compared with youths aged 20 to 24 years; and higher for females (aOR, 1.64; 95% CI, 1.56-1.73) than males. A mental health diagnosis was documented for 6308 of 19 027 youths who died by firearms (33.2%); 1691 of 2743 youths who died by poisonings (61.6%); 7017 of 15 331 youths who died by hanging, strangulation, or suffocation (45.8%); and 1407 of 3181 youths who died by other mechanisms (44.2%). Compared with firearm suicides, the adjusted odds of having a documented mental health diagnosis were higher for suicides by poisoning (aOR, 1.70; 95% CI, 1.62-1.78); hanging, strangulation, and suffocation (aOR, 2.78; 95% CI, 2.55-3.03); and other mechanisms (aOR, 1.59; 95% CI, 1.47-1.72)., Conclusions and Relevance: In this cross-sectional study, 3 of 5 youth suicide decedents did not have a documented preceding mental health diagnosis; the odds of having a mental health diagnosis were lower among racially and ethnically minoritized youths than White youths and among firearm suicides compared with other mechanisms. These findings underscore the need for equitable identification of mental health needs and universal lethal means counseling as strategies to prevent youth suicide.

Objectives: Acute agitation during pediatric mental health emergency department (ED) visits presents safety risks to patients and staff. We previously convened multidisciplinary stakeholders who prioritized 20 proposed quality measures for pediatric acute agitation management. Our objectives were to assess feasibility of evaluating performance on these quality measures using electronic health record (EHR) data and to examine performance variation across 3 EDs., Methods: At a children's hospital and 2 nonchildren's hospitals, we assessed feasibility of evaluating quality measures for pediatric acute agitation management using structured EHR data elements. We retrospectively evaluated measure performance during ED visits by children 5 to 17 years old who presented for a mental health condition, received medication for agitation, or received physical restraints from July 2020 to June 2021. Bivariate and multivariable regression were used to examine measure performance by patient characteristics and hospital., Results: We identified 2785 mental health ED visits, 275 visits with medication given for agitation, and 35 visits with physical restraints. Performance was feasible to measure using EHR data for 10 measures. Nine measures varied by patient characteristics, including 4.87 times higher adjusted odds (95% confidence interval 1.28-18.54) of physical restraint use among children with versus without autism spectrum disorder. Four measures varied by hospital, with physical restraint use varying from 0.5% to 3.3% of mental health ED visits across hospitals., Conclusions: Quality of care for pediatric acute agitation management was feasible to evaluate using EHR-derived quality measures. Variation in performance across patient characteristics and hospitals highlights opportunities to improve care quality., (Copyright © 2024 by the American Academy of Pediatrics.)

Background and Objectives: Visits by youth to the emergency department (ED) with mental and behavioral health (MBH) conditions are increasing, yet use of psychotropic medications during visits has not been well described. We aimed to assess changes in psychotropic medication use over time, overall and by medication category, and variation in medication administration across hospitals., Methods: We conducted a retrospective cross-sectional study of ED encounters by youth aged 3-21 with MBH diagnoses using the Pediatric Health Information System, 2013-2022. Medication categories included psychotherapeutics, stimulants, anticonvulsants, antihistamines, antihypertensives, and other. We constructed regression models to examine trends in use over time, overall and by medication category, and variation by hospital., Results: Of 670 911 ED encounters by youth with a MBH diagnosis, 12.3% had psychotropic medication administered. The percentage of MBH encounters with psychotropic medication administered increased from 7.9% to16.3% from 2013-2022 with the odds of administration increasing each year (odds ratio, 1.09; 95% confidence interval, 1.05-1.13). Use of all medication categories except for antianxiety medications increased significantly over time. The proportion of encounters with psychotropic medication administered ranged from 4.2%-23.1% across hospitals (P < .001). The number of psychotropic medications administered significantly varied from 81 to 792 medications per 1000 MBH encounters across hospitals (P < .001)., Conclusions: Administration of psychotropic medications during MBH ED encounters is increasing over time and varies across hospitals. Inconsistent practice patterns indicate that opportunities are available to standardize ED management of pediatric MBH conditions to enhance quality of care., (Copyright © 2024 by the American Academy of Pediatrics.)

Background and Objectives: Approximately half of youth suicides involve firearms. The promotion of safe firearm storage in the home through lethal means counseling reduces suicide risk. We aimed to increase the documentation of firearm access and storage among children presenting to the emergency department (ED) with suicidal ideation or self-injury to 80% within 13 months., Methods: We conducted a multidisciplinary quality improvement initiative to improve the documentation of firearm access and storage among children <18 years old seen in the ED for suicidal ideation or self-injury. The baseline period was February 2020 to September 2021, and interventions occurred through October 2022. Interventions included adding a templated phrase about firearm access to psychiatric social work consult notes and the subsequent modification of the note to include all firearm storage elements (ie, locked, unloaded, separate from ammunition). Statistical process control and run charts were generated monthly to monitor the documentation of firearm access and storage, which was measured through a review of keyword snippets extracted from note text., Results: We identified 2158 ED encounters for suicidal ideation or self-injury during the baseline and intervention periods. Documentation of firearm access increased from 37.8% to 81.6%, resulting in a centerline shift. Among families who endorsed firearm access, the documentation of firearm storage practices increased from 50.0% to 78.0%, resulting in a centerline shift., Conclusions: The modification of note templates facilitated increased documentation of firearm access and storage practices for children with suicidal ideation in the ED. Future studies should assess whether improved documentation is associated with improved storage practices and reductions in firearm suicides after ED encounters., (Copyright © 2024 by the American Academy of Pediatrics.)

Suicide is a leading cause of death among youth, and the emergency department (ED) serves as the primary point of healthcare contact for many with suicidal ideation. As suicide-related presentations to the ED continue to rise, the implementation of time- and cost-effective care pathways becomes ever more critical. Evidence-based tools for the identification and stratification of suicide risk can aid in clinical decision-making and care linkage. This issue reviews best practices for suicide risk assessment of youth to guide evaluation, management, and disposition planning within the ED setting.

Background: Mental health visits to the emergency department (ED) by children are rising in the United States, and acute agitation during these visits presents safety risks to patients and staff., Objective: We sought to assess barriers and strategies for providing high-quality care to children who experience acute agitation in the ED., Methods: We conducted semistructured interviews with 6 ED physicians, 6 ED nurses, 6 parents, and 6 adolescents at high risk for developing agitation. We asked participants about their experiences with acute agitation care in the ED, barriers and facilitators to providing high-quality care, and proposed interventions. Interviews were coded and analyzed thematically., Results: Participants discussed identifying risk factors for acute agitation, worrying about safety and the risk of injury, feeling moral distress, and shifting the culture toward patient-centered, trauma-informed care. Barriers and facilitators included using a standardized care pathway, identifying environmental barriers and allocating resources, partnering with the family and child, and communicating among team members. Nine interventions were proposed: opening a behavioral observation unit with dedicated staff and space, asking screening questions to identify risk of agitation, creating personalized care plans in the electronic health record, using a standardized agitation severity scale, implementing a behavioral response team, providing safe activities and environmental modifications, improving the handoff process, educating staff, and addressing bias and inequities., Conclusions: Understanding barriers can inform solutions to improve care for children who experience acute agitation in the ED. The perspectives of families and patients should be considered when designing interventions to improve care., (Copyright © 2023 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Toll signaling is well known for its pivotal role in the host response against the invasion of external pathogens. Here, we investigate the potential involvement of Toll signaling in the intersection between the host and oncogenic cells. We show that loss of myeloid differentiation factor 88 (Myd88) leads to drastic fly death after the injection of RasV12-GFP oncogenic cells. Transcriptomic analyses show that challenging flies with oncogenic cells or bacteria leads to distinct inductions of Myd88-dependent genes. We note that downregulation of Myd88 in the tracheal system accounts for fly mortality, and ectopic tracheal complementation of Myd88 rescues the survival defect in Myd88 loss-of-function mutants following RasV12-GFP injection. Further, molecular and genetic evidence indicate that Toll signaling modulates fly resistance to RasV12-GFP cells through mediating airway function in a rolled-dependent manner. Collectively, our data indicate a critical role of Toll signaling in tracheal homeostasis and host survival after the injection of oncogenic cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Approximately 10% of emergency medical services (EMS) encounters in the United States are behavioral health related, but pediatric behavioral health EMS encounters have not been well characterized. We sought to describe demographic, clinical, and EMS system characteristics of pediatric behavioral health EMS encounters across the United States and to evaluate factors associated with sedative medication administration and physical restraint use during these encounters., Methods: We conducted a retrospective cross-sectional study of pediatric (<18 years old) behavioral health EMS encounters from 2019 to 2020 using the National Emergency Medical Services Information System. Behavioral health encounters were defined using primary or secondary impression codes. We used multivariable logistic regression to identify factors associated with sedative medication administration and physical restraint use., Results: Of 2,740,271 pediatric EMS encounters, 309,442 (11.3%) were for behavioral health. Of pediatric behavioral health EMS encounters, 85.2% of patients were 12-17 years old, 57.3% of patients were female, and 86.6% of encounters occurred in urban areas. Sedative medications and physical restraints were used in 2.2% and 3.0% of pediatric behavioral health EMS encounters, respectively. Sedative medication use was associated with the presence of developmental, communication, or physical disabilities relative to their absence (adjusted odds ratio [aOR] 3.38, 95% confidence interval [CI] 2.93-3.91) and with encounters in the West relative to the South (aOR 1.23, 95% CI 1.16-1.32). Physical restraint use was associated with encounters by patients 6-11 years old relative to those 12-17 years old (aOR 1.35, 95% CI 1.27-1.44), the West relative to the South (aOR 3.49, 95% CI 3.27-3.72), and private nonhospital EMS systems relative to fire departments (aOR 3.39, 95% CI 3.18-3.61)., Conclusions: Among pediatric prehospital behavioral health EMS encounters, the use of sedative medications and physical restraint varies by demographic, clinical, and EMS system characteristics. Regional variation suggests opportunities may be available to standardize documentation and care practices during pediatric behavioral health EMS encounters., (© 2023 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Importance: Febrile infants at low risk of invasive bacterial infections are unlikely to benefit from lumbar puncture, antibiotics, or hospitalization, yet these are commonly performed. It is not known if there are differences in management by race, ethnicity, or language., Objective: To investigate associations between race, ethnicity, and language and additional interventions (lumbar puncture, empirical antibiotics, and hospitalization) in well-appearing febrile infants at low risk of invasive bacterial infection., Design, Setting, and Participants: This was a multicenter retrospective cross-sectional analysis of infants receiving emergency department care between January 1, 2018, and December 31, 2019. Data were analyzed from December 2022 to July 2023. Pediatric emergency departments were determined through the Pediatric Emergency Medicine Collaborative Research Committee. Well-appearing febrile infants aged 29 to 60 days at low risk of invasive bacterial infection based on blood and urine testing were included. Data were available for 9847 infants, and 4042 were included following exclusions for ill appearance, medical history, and diagnosis of a focal infectious source., Exposures: Infant race and ethnicity (non-Hispanic Black, Hispanic, non-Hispanic White, and other race or ethnicity) and language used for medical care (English and language other than English)., Main Outcomes and Measures: The primary outcome was receipt of at least 1 of lumbar puncture, empirical antibiotics, or hospitalization. We performed bivariate and multivariable logistic regression with sum contrasts for comparisons. Individual components were assessed as secondary outcomes., Results: Across 34 sites, 4042 infants (median [IQR] age, 45 [38-53] days; 1561 [44.4% of the 3516 without missing sex] female; 612 [15.1%] non-Hispanic Black, 1054 [26.1%] Hispanic, 1741 [43.1%] non-Hispanic White, and 352 [9.1%] other race or ethnicity; 3555 [88.0%] English and 463 [12.0%] language other than English) met inclusion criteria. The primary outcome occurred in 969 infants (24%). Race and ethnicity were not associated with the primary composite outcome. Compared to the grand mean, infants of families that use a language other than English had higher odds of the primary outcome (adjusted odds ratio [aOR]; 1.16; 95% CI, 1.01-1.33). In secondary analyses, Hispanic infants, compared to the grand mean, had lower odds of hospital admission (aOR, 0.76; 95% CI, 0.63-0.93). Compared to the grand mean, infants of families that use a language other than English had higher odds of hospital admission (aOR, 1.08; 95% CI, 1.08-1.46)., Conclusions and Relevance: Among low-risk febrile infants, language used for medical care was associated with the use of at least 1 nonindicated intervention, but race and ethnicity were not. Secondary analyses highlight the complex intersectionality of race, ethnicity, language, and health inequity. As inequitable care may be influenced by communication barriers, new guidelines that emphasize patient-centered communication may create disparities if not implemented with specific attention to equity.

Background and Objective: Pediatric firearm injuries increased during the coronavirus disease 2019 pandemic, but recent trends in firearm injury emergency department (ED) visits are not well described. We aimed to assess how pediatric firearm injury ED visits during the pandemic differed from expected prepandemic trends., Methods: We retrospectively studied firearm injury ED visits by children <18 years old at 9 US hospitals participating in the Pediatric Emergency Care Applied Research Network Registry before (January 2017 to February 2020) and during (March 2020 to November 2022) the pandemic. Multivariable Poisson regression models estimated expected visit rates from prepandemic data. We calculated rate ratios (RRs) of observed to expected visits per 30 days, overall, and by sociodemographic characteristics., Results: We identified 1904 firearm injury ED visits (52.3% 15-17 years old, 80.0% male, 63.5% non-Hispanic Black), with 694 prepandemic visits and 1210 visits during the pandemic. Death in the ED/hospital increased from 3.1% prepandemic to 6.1% during the pandemic (P = .007). Firearm injury visits per 30 days increased from 18.0 prepandemic to 36.1 during the pandemic (RR 2.09, 95% CI 1.63-2.91). Increases beyond expected rates were seen for 10- to 14-year-olds (RR 2.61, 95% CI 1.69-5.71), females (RR 2.46, 95% CI 1.55-6.00), males (RR 2.00, 95% CI 1.53-2.86), Hispanic children (RR 2.30, 95% CI 1.30-9.91), and Black non-Hispanic children (RR 1.88, 95% CI 1.34-3.10)., Conclusions: Firearm injury ED visits for children increased beyond expected prepandemic trends, with greater increases among certain population subgroups. These findings may inform firearm injury prevention efforts., (Copyright © 2023 by the American Academy of Pediatrics.)

Introduction: CCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women., Material and Methods: In our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion., Results: Sixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73-0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2., Conclusion: Low maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance., Trial Registration Number (drks-Id): DRKS00010763, Registration date: September 02, 2016., (© 2023. The Author(s).)

Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Injection of OCs into adult male flies induces a strong transcriptomic response in the host flies featuring in particular genes encoding bona fide G coupled proteins, among which the gene for methuselah like 1 is prominent. The injection is followed after a 3-d lag period, by the proliferation of the oncogenic cells. We hypothesized that through the product of mthl1 the host might control, at least in part, this proliferation as a defense reaction. Through a combination of genetic manipulations of the mthl1 gene (loss of function and overexpression of mthl1 ), we document that indeed this gene has an antiproliferative effect. Parallel injections of primary embryonic Drosophila cells or of various microbes do not exhibit this effect. We further show that mthl1 controls the expression of a large number of genes coding for chemoreceptors and genes implicated in regulation of development. Of great potential interest is our observation that the expression of the mouse gene coding for the adhesion G-protein-coupled receptor E1 ( Adgre1, also known as F4/80 ), a potential mammalian homologue of mthl1 , is significantly induced by B16-F10 melanoma cell inoculation 3 d postinjection in both the bone marrow and spleen (nests of immature and mature myeloid-derived immune cells), respectively. This observation is compatible with a role of this GPCR in the early response to injected tumor cells in mice.

Background and Objectives: Pediatric mental health emergency department (ED) visits are rising in the United States, with more visits involving medication for acute agitation. Timely, standardized implementation of behavioral strategies and medications may reduce the need for physical restraint. Our objective was to standardize agitation management in a pediatric ED and reduce time in physical restraints., Methods: A multidisciplinary team conducted a quality improvement initiative from September 2020 to August 2021, followed by a 6-month maintenance period. A barrier assessment revealed that agitation triggers were inadequately recognized, few activities were offered during long ED visits, staff lacked confidence in verbal deescalation techniques, medication choices were inconsistent, and medications were slow to take effect. Sequential interventions included development of an agitation care pathway and order set, optimization of child life and psychiatry workflows, implementation of personalized deescalation plans, and adding droperidol to the formulary. Measures include standardization of medication choice for severe agitation and time in physical restraints., Results: During the intervention and maintenance periods, there were 129 ED visits with medication given for severe agitation and 10 ED visits with physical restraint use. Among ED visits with medication given for severe agitation, standardized medication choice (olanzapine or droperidol) increased from 8% to 88%. Mean minutes in physical restraints decreased from 173 to 71., Conclusions: Implementing an agitation care pathway standardized and improved care for a vulnerable and high-priority population. Future studies are needed to translate interventions to community ED settings and to evaluate optimal management strategies for pediatric acute agitation., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: To examine how timing of the first outpatient mental health (MH) visit after a pediatric firearm injury varies by sociodemographic and clinical characteristics., Methods: We retrospectively studied children aged 5 to 17 years with a nonfatal firearm injury from 2010 to 2018 using the IBM Watson MarketScan Medicaid database. Logistic regression estimated the odds of MH service use in the 6 months after injury, adjusted for sociodemographic and clinical characteristics. Cox proportional hazard models, stratified by previous MH service use, evaluated variation in timing of the first outpatient MH visit by sociodemographic and clinical characteristics., Results: After a firearm injury, 958 of 2613 (36.7%) children used MH services within 6 months; of these, 378 of 958 (39.5%) had no previous MH service use. The adjusted odds of MH service use after injury were higher among children with previous MH service use (adjusted odds ratio, 10.41; 95% confidence interval [CI], 8.45-12.82) and among non-Hispanic white compared with non-Hispanic Black children (adjusted odds ratio, 1.29; 95% CI, 1.02-1.63). The first outpatient MH visit after injury occurred sooner among children with previous MH service use (adjusted hazard ratio, 6.32; 95% CI, 5.45-7.32). For children without previous MH service use, the first MH outpatient visit occurred sooner among children with an MH diagnosis made during the injury encounter (adjusted hazard ratio, 2.72; 95% CI, 2.04-3.65)., Conclusions: More than 3 in 5 children do not receive MH services after firearm injury. Previous engagement with MH services and new detection of MH diagnoses during firearm injury encounters may facilitate timelier connection to MH services after injury., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: Acute agitation episodes in the emergency department (ED) can be distressing for patients, families, and staff and may lead to injuries. We aim to understand availability of ED resources to care for children with acute agitation, perceived staff confidence with agitation management, barriers to use of de-escalation techniques, and desired resources to enhance care., Methods: We conducted a survey of pediatric emergency care coordinators (PECCs) in EDs in Massachusetts, Rhode Island, and Los Angeles County, California., Results: PECCs from 63 of 102 (61.8%) EDs responded. PECCs reported that ED staff feel least confident managing agitation due to developmental delay (DD) or autism spectrum disorder (ASD) (52.4%). Few EDs had a separate space to care for children with mental health conditions (22.5%), a standardized agitation scale (9.6%), an agitation management guideline (12.9%), or agitation management training (24.2%). Modification of the environment was not perceived possible for 42% of EDs. Participants reported that a barrier to the use of the de-escalation techniques distraction and verbal de-escalation was perceived lack of effectiveness (22.6% and 22.6%, respectively). Desired resources to manage agitation included guidelines for medications (82.5%) and sample care pathways (57.1%)., Conclusions: ED PECCs report low confidence in managing agitation due to DD or ASD and limited pediatric resources to address acute agitation. Additional pediatric-specific resources and training, especially for children with DD or ASD, are needed to increase clinician confidence in agitation management and to promote high-quality, patient-centered care. Training programs can focus on the early identification of agitation and the effective use of non-invasive de-escalation strategies., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

People often overestimate the prevalence of unfavorable behavior. To explain these misperceptions, social sampling models propose that individuals infer the social norm from the behavior of their own social circle. We investigated this idea by asking a friendship network of college freshmen to report their own behavior and norm perceptions across eight domains at two timepoints (N = 104). Assessing this complete social network allows to directly test if sampling from the social circle shapes norm perception. Replicating previous findings, freshmen systematically misperceived the average social norm within their cohort. Yet, these misperceptions persisted even when individuals judged their own social circle, indicating that sampling from social circles does not fully explain normative biases. Moreover, cognitive modelling of norm perceptions suggested that individuals unlikely limited their search to their own social circle., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Giese, Hoffmann. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Government and commercial health insurers have recently enacted policies to discourage nonemergent emergency department (ED) visits by reducing or denying claims for such visits using retrospective claims algorithms. Low-income Black and Hispanic pediatric patients often experience worse access to primary care services necessary for preventing some ED visits, raising concerns about the uneven impact of these policies., Objective: To estimate potential racial and ethnic disparities in outcomes of Medicaid policies for reducing ED professional reimbursement based on a retrospective diagnosis-based claims algorithm., Design, Setting, and Participants: This simulation study used a retrospective cohort of pediatric ED visits (aged 0-18 years) for Medicaid-insured children and adolescents appearing in the Market Scan Medicaid database between January 1, 2016, and December 31, 2019. Visits missing date of birth, race and ethnicity, professional claims data, and Current Procedural Terminology codes of billing level of complexity were excluded, as were visits that result in admission. Data were analyzed from October 2021 to June 2022., Main Outcomes and Measures: Proportion of ED visits algorithmically classified as nonemergent and simulated per-visit professional reimbursement after applying a current reimbursement reduction policy for potentially nonemergent ED visits. Rates were calculated overall and compared by race and ethnicity., Results: The sample included 8 471 386 unique ED visits (43.0% by patients aged 4-12 years; 39.6% Black, 7.7% Hispanic, and 48.7% White), of which 47.7% were algorithmically identified as potentially nonemergent and subject to reimbursement reduction, resulting in a 37% reduction in ED professional reimbursement across the study cohort. More visits by Black (50.3%) and Hispanic (49.0%) children were algorithmically identified as nonemergent when compared with visits by White children (45.3%; P < .001). Modeling the impact of the reimbursement reductions across the cohort resulted in expected per-visit reimbursement that was 6% lower for visits by Black children and 3% lower for visits by Hispanic children relative to visits by White children., Conclusions and Relevance: In this simulation study of over 8 million unique ED visits, algorithmic approaches for classifying pediatric ED visits that used diagnosis codes identified proportionately more visits by Black and Hispanic children as nonemergent. Insurers applying financial adjustments based on these algorithmic outputs risk creating uneven reimbursement policies across racial and ethnic groups.

The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as the known Toll-regulated antimicrobial peptide (AMP) genes are active only against filamentous fungi and not against Gram-positive bacteria or yeasts. Besides AMPs, two families of peptides secreted in response to infectious stimuli that activate the Toll pathway have been identified, namely Bomanins and peptides derived from a polyprotein precursor known as Baramicin A (BaraA). Unexpectedly, the deletion of a cluster of 10 Bomanins phenocopies the Toll mutant phenotype of susceptibility to infections. Here, we demonstrate that BaraA is required specifically in the host defense against Enterococcus faecalis and against the entomopathogenic fungus Metarhizium robertsii , albeit the fungal burden is not altered in BaraA mutants. BaraA protects the fly from the action of distinct toxins secreted by these Gram-positive and fungal pathogens, respectively, Enterocin V and Destruxin A. The injection of Destruxin A leads to the rapid paralysis of flies, whether wild type (WT) or mutant. However, a larger fraction of wild-type than BaraA flies recovers from paralysis within 5 to 10 h. BaraAs' function in protecting the host from the deleterious action of Destruxin is required in glial cells, highlighting a resilience role for the Toll pathway in the nervous system against microbial virulence factors. Thus, in complement to the current paradigm, innate immunity can cope effectively with the effects of toxins secreted by pathogens through the secretion of dedicated peptides, independently of xenobiotics detoxification pathways.

Objectives: To examine how outpatient mental health (MH) follow-up after a pediatric MH emergency department (ED) discharge varies by patient characteristics and to evaluate the association between timely follow-up and return encounters., Methods: We conducted a retrospective study of 28 551 children aged 6 to 17 years with MH ED discharges from January 2018 to June 2019, using the IBM Watson MarketScan Medicaid database. Odds of nonemergent outpatient follow-up, adjusted for sociodemographic and clinical characteristics, were estimated using logistic regression. Cox proportional hazard models were used to evaluate the association between timely follow-up and risk of return MH acute care encounters (ED visits and hospitalizations)., Results: Following MH ED discharge, 31.2% and 55.8% of children had an outpatient MH visit within 7 and 30 days, respectively. The return rate was 26.5% within 6 months. Compared with children with no past-year outpatient MH visits, those with ≥14 past-year MH visits had 9.53 odds of accessing follow-up care within 30 days (95% confidence interval [CI], 8.75-10.38). Timely follow-up within 30 days was associated with a 26% decreased risk of return within 5 days of the index ED discharge (hazard ratio, 0.74; 95% CI, 0.63-0.91), followed by an increased risk of return thereafter., Conclusions: Connection to outpatient care within 7 and 30 days of a MH ED discharge remains poor, and children without prior MH outpatient care are at highest risk for poor access to care. Interventions to link to outpatient MH care should prioritize follow-up within 5 days of an MH ED discharge., (Copyright © 2023 by the American Academy of Pediatrics.)

Rationale: Preterm infants are at risk for ventilatory control instability that may be due to aberrant peripheral chemoreceptor activity. Although term infants have increasing peripheral chemoreceptor contribution to overall ventilatory drive with increasing postnatal age, how peripheral chemoreceptor contribution changes in preterm infants with increasing postmenstrual age is not known. Objectives: To evaluate peripheral chemoreceptor activity between 32 and 52 weeks postmenstrual age in preterm infants, using both quantitative and qualitative measures. Methods: Fifty-five infants born between 24 weeks, 0 days gestation and 28 weeks, 6 days gestation underwent hyperoxic testing at one to four time points between 32 and 52 weeks postmenstrual age. Quantitative [Formula: see text] decreases were calculated, and qualitative responses were categorized as apnea, continued breathing with a clear reduction in [Formula: see text], sigh breaths, and no response. Measurements and Main Results: A total of 280 hyperoxic tests were analyzed (2.2 ± 0.3 tests per infant at each time point). Mean peripheral chemoreceptor contribution to ventilatory drive was 85.2 ± 20.0% at 32 weeks and 64.1 ± 22.0% at 52 weeks. Apneic responses were more frequent at earlier postmenstrual ages. Conclusions: Among preterm infants, the peripheral chemoreceptor contribution to ventilatory drive was greater at earlier postmenstrual ages. Apnea was a frequent response to hyperoxic testing at earlier postmenstrual ages, suggesting high peripheral chemoreceptor activity. A clearer description of how peripheral chemoreceptor activity changes over time in preterm infants may help explain how ventilatory control instability contributes to apnea and sleep-disordered breathing later in childhood. Clinical trial registered with www.clinicaltrials.gov (NCT03464396).

Abstract: Hospital incident command systems (HICS) were implemented to expand mental and behavioral healthcare (MBHC) services during the COVID-19 pandemic. Data on patient census, nurse vacancies, staff injuries, and staff perceptions were analyzed to quantify issues and track progress toward HICS goals. Data, environment of care, staffing, staff support, staff education, and communication resources were developed. After HICS implementation, 84% of nurses reported confidence in providing care to youth with acute MBHC needs. Nurse leaders should consider HICS for addressing other crises., Competing Interests: Dr Jennifer Hoffmann receives grant support from the US Agency for Healthcare Research and Quality (#5K12HS026385-03). The funder had no role in the study design, analysis, decision to publish, or preparation of the manuscript. Otherwise, there are no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We have injected dish-cultured oncogenic RasV12 cells into adult male flies and analyzed by single cell transcriptomics their destiny within the host after 11 days. We identified in the preinjection samples and in the 11-day postinjection samples in all 16 clusters of cells, of which 5 disappeared during the experiment in the host. The other cell clusters expanded and expressed genes involved in the regulation of cell cycle, metabolism, and development. In addition, three clusters expressed genes related to inflammation and defense. Predominant among these were genes coding for phagocytosis and/or characteristic for plasmatocytes (the fly equivalent of macrophages). A pilot experiment indicated that the injection into flies of oncogenic cells, in which two of most strongly expressed genes had been previously silenced by RNA interference, into flies resulted in a dramatic reduction of their proliferation in the host flies as compared to controls. As we have shown earlier, the proliferation of the injected oncogenic cells in the adult flies is a hallmark of the disease and induces a wave of transcriptions in the experimental flies. We hypothesize that this results from a bitter dialogue between the injected cells and the host, while the experiments presented here should contribute to deciphering this dialogue., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Importance: Suicide is the second leading cause of death among US adolescents. Workforce shortages of mental health professionals in the US are widespread, but the association between mental health workforce shortages and youth suicides is not well understood., Objective: To assess the association between youth suicide rates and mental health professional workforce shortages at the county level, adjusting for county demographic and socioeconomic characteristics., Design, Setting, and Participants: This retrospective cross-sectional study included all US counties and used data of all US youlth suicides from January 2015, through December 31, 2016. Data were analyzed from July 1, 2021, through December 20, 2021., Exposures: County health-professional shortage area designation for mental health, assigned by the US Health Resources and Services Administration based on mental health professionals relative to the population, level of need for mental health services, and service availability in contiguous areas. Designated shortage areas receive a score from 0 to 25, with higher scores indicating greater workforce shortages., Main Outcomes and Measures: Suicides by youth aged 5 to 19 years from 2015 to 2016 were identified from the US Centers for Disease Control and Prevention's Compressed Mortality File. A multivariable negative binomial regression model was used to analyze the association between youth suicide rates and mental health workforce shortage designation, adjusting for the presence of a children's mental health hospital and county-level markers of health insurance coverage, education, unemployment, income, poverty, urbanicity, racial and ethnic composition, and year. Similar models were performed for the subgroups of (1) firearm suicides and (2) counties assigned a numeric shortage score., Results: During the study period, there were 5034 youth suicides (72.8% male and 68.2% non-Hispanic White) with an annual suicide rate of 3.99 per 100 000 youths. Of 3133 US counties, 2117 (67.6%) were designated as mental health workforce shortage areas. After adjusting for county characteristics, mental health workforce shortage designation was associated with an increased youth suicide rate (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.07-1.26) and an increased youth firearm suicide rate (aIRR, 1.27; 95% CI, 1.13-1.42). For counties with an assigned numeric workforce shortage score, the adjusted youth suicide rate increased 4% for every 1-point increase in the score (aIRR, 1.04; 95% CI, 1.02-1.06)., Conclusions and Relevance: In this cross-sectional study, US county mental health professional workforce shortages were associated with increased youth suicide rates. These findings may inform suicide prevention efforts.