Suicide and Suicide Risk in Adolescents Hua, Liwei L; Lee, Janet; Rahmandar, Maria H ...
Pediatrics (Evanston),
2024-Jan-01, Letnik:
153, Številka:
1
Journal Article
Recenzirano
Suicide is the second leading cause of death for 10- to 24-year-olds in the United States and is a global public health issue, with a recent declaration of a National State of Emergency in Children's ...Mental Health by the American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, and Children's Hospital Association. This clinical report is an update to the previous American Academy of Pediatrics clinical report, "Suicide and Suicide Attempts in Adolescents." Because pediatricians and pediatric health care providers are at the front line of care for adolescents amid a child and adolescent mental health crisis, and because of the chronic and severe shortage of mental health specialists, it is important that pediatric health care providers become facile with recognizing risk factors associated with suicidality and at-risk populations, screening and further assessment of suicidality as indicated, and evidence-based interventions for patients with suicidal ideation and associated behaviors. Suicide risk can be mitigated by appropriate screening, bolstering of protective factors, indicated treatment, community resources, and referrals to mental health providers when available.
Youth violence continues to be widespread. Despite numerous evidence‐based programs that reduce youth violence, objective ways to identify youth in need of services is lacking. Few screening tools ...are available that enables practitioners or community organizations to predict who may perpetrate serious violence. The Violence Injury Protection and Risk Screen (VIPRS) is a previously validated screening tool providing a framework to address youth violence. The purpose of this study is to evaluate the psychometric properties of the VIPRS in a community sample for use in multiple settings. Youth participating in a community‐focused youth violence prevention intervention served as the study subjects. Households with youth ages 10−17 were eligible to participate. Study personnel verbally asked youth survey questions and recorded answers on a laptop. Multiple measures—including risk factors for violent behavior as well as, violence and delinquency scales, were asked. Eleven hundred youth participated. Mean age was 13.3; 53% female, 26% Black, 58% Hispanic, 11% more than 1 race. Twenty percent screened positive on the VIPRS—28% male versus 13% female (p = .000). Violence‐related behaviors were common: 33% were in a physical fight, 27% experienced cyberbullying victimization, and 9% perpetrated a minor assault. The VIPRS demonstrated robust criterion validity with significant correlation to multiple violence measures (0.3−0.6). Scoring positive on the VIPRS conveyed increased odds of reporting other violent behaviors, such as perpetrating physical aggression (OR: 7 95% CI: 5.1−11.5). Overall, the VIPRS performed well in a community sample of youth further validating its psychometric functioning while demonstrating the potential for use in settings beyond healthcare.
The activity of the secreted phosphodiesterase autotaxin produces the inflammatory signaling molecule LPA and has been associated with a number of human diseases including idiopathic pulmonary ...fibrosis (IPF). We screened a single DNA-encoded chemical library (DECL) of 225 million compounds and identified a series of potent inhibitors. Optimization of this series led to the discovery of compound 1 (X-165), a highly potent, selective, and bioavailable small molecule. Cocrystallization of compound 1 with human autotaxin demonstrated that it has a novel binding mode occupying both the hydrophobic pocket and a channel near the autotaxin active site. Compound 1 inhibited the production of LPA in human and mouse plasma at nanomolar levels and showed efficacy in a mouse model of human lung fibrosis. After successfully completing IND-enabling studies, compound 1 was approved by the FDA for a Phase I clinical trial. These results demonstrate that DECL hits can be readily optimized into clinical candidates.
DNA-encoded small molecule libraries (DELs) have enabled discovery of novel inhibitors for many distinct protein targets of therapeutic value. We demonstrate a new approach applying machine learning ...to DEL selection data by identifying active molecules from large libraries of commercial and easily synthesizable compounds. We train models using only DEL selection data and apply automated or automatable filters to the predictions. We perform a large prospective study (∼2000 compounds) across three diverse protein targets: sEH (a hydrolase), ERα (a nuclear receptor), and c-KIT (a kinase). The approach is effective, with an overall hit rate of ∼30% at 30 μM and discovery of potent compounds (IC50 < 10 nM) for every target. The system makes useful predictions even for molecules dissimilar to the original DEL, and the compounds identified are diverse, predominantly drug-like, and different from known ligands. This work demonstrates a powerful new approach to hit-finding.
A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates ...with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.
Safe firearm storage decreases self-inflicted and unintentional firearm injury in youth. Medical providers are well-positioned to discuss safe firearm storage with families. The primary objective of ...this study was to determine which providers are most likely to discuss firearms with their patients. Our secondary objective was to determine whether providers were more likely to discuss firearms with patients at elevated suicide risk.
This was a retrospective chart review of primary care well-child visits occurring January to December 2019 in a large, urban academic clinic. We documented provider type and training level (exposure); any documentation of firearms in the chart (counseling, screening) was considered as having a firearm discussion (outcome). We also collected demographics, patient mental health history, and Patient Health Questionnaire-9 scores and assessed suicide risk.
Of the 743 charts reviewed, firearms were discussed in 9% (n = 66). Medical students were most likely to discuss firearms (15%), and attending physicians were least likely (1%, P < 0.001). Providers did not discuss firearms more frequently among youth at elevated suicide risk.
Though providers do not frequently discuss and document firearm discussions overall, the higher rates among medical students are promising. Given the lethality of firearms in a suicide attempt, the lack of firearm safety discussions with those at elevated suicide risk was concerning. Further study should evaluate factors that facilitate discussions in this cohort and identify strategies to improve counseling among more senior providers.
We have identified and characterized novel potent inhibitors of Bruton's tyrosine kinase (BTK) from a single DNA-encoded library of over 110 million compounds by using multiple parallel selection ...conditions, including variation in target concentration and addition of known binders to provide competition information. Distinct binding profiles were observed by comparing enrichments of library building block combinations under these conditions; one enriched only at high concentrations of BTK and was competitive with ATP, and another enriched at both high and low concentrations of BTK and was not competitive with ATP. A compound representing the latter profile showed low nanomolar potency in biochemical and cellular BTK assays. Results from kinetic mechanism of action studies were consistent with the selection profiles. Analysis of the co-crystal structure of the most potent compound demonstrated a novel binding mode that revealed a new pocket in BTK. Our results demonstrate that profile-based selection strategies using DNA-encoded libraries form the basis of a new methodology to rapidly identify small molecule inhibitors with novel binding modes to clinically relevant targets.
The goal of this project was to determine whether screening youth and parents for firearm presence and imbedding those results in the electronic medical record (EMR) increased health care provider ...(HCP) documentation of firearms and subsequent delivery of a safe storage message. The study took place in a large adolescent medicine practice. Fifty-six dyads (40% of eligible) were randomized to usual care or the intervention, in which screening results for firearms were imbedded in the EMR. Health care providers delivered a safe storage message to 20% of controls and 51.2% in the intervention (P = .04). When HCPs documented the delivery of a safe storage message, 64% of parents recalled hearing it, compared with only 36% when there was no documentation (P = .012). Therefore, we found that incorporating firearm screening into the EMR increases the attention HCPs give to delivering a firearm safe storage message and correlates with parents recalling having heard a safe storage message.
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