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OBJECTIVE: To assess pre and postself-reported counseling outcomes for Safer: Storing Firearms Prevents Harm, an American Academy of Pediatrics universal firearm safe storage counseling training for pediatric clinicians providing health maintenance in outpatient settings. STUDY DESIGN: Safer was developed by a national multidisciplinary committee of firearm injury prevention experts with input from firearm-owning families and launched in June 2021. Pediatric clinicians completed baseline and 1-month posttraining surveys after signing up for the Pedialink course from February through June 2022. Primary outcomes included self-reported measures of counseling self-efficacy and frequency. Wilcoxon matched-pairs signed-rank tests compared outcome distributions at baseline and follow-up. Two adjusted, multilevel mixed-effects regression models were conducted. RESULTS: Of 230 clinicians who completed baseline surveys, 146 (64%) completed 1-month postsurveys. Regional representation included Southeast = 67 (46%), Northeast = 24 (16%), Midwest = 21 (14%), Pacific = 15 (10%), Southwest = 11 (8%), and Rocky Mountain = 8 (5%). At follow-up, there was significant improvement in both the distribution of self-efficacy (median [first Quartile-third Quartile = 50 [20-70] at baseline and 80 [60-85] at follow-up; P < .001) and self-reported counseling frequency (median [first Quartile-third Quartile] = 10 [0-50] at baseline and 50 [10-80] at follow-up; P < .001). Adjusted regression model results suggested that self-efficacy significantly improved from baseline to follow-up (time coefficient 25.3; 95% CI = [21.0, 29.5]; P < .001) as did counseling frequency (time coefficient 13.6; 95% CI = [9.2, 18.0]; P < .001). CONCLUSIONS: Significant improvement in self-reported counseling self-efficacy and frequency was demonstrated 1 month following Safer training.
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Armas de Fogo , Ferimentos por Arma de Fogo , Humanos , Criança , Estados Unidos , Segurança , Aconselhamento , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Easy firearm access increases injury risk among adolescents. We evaluated the acceptability and feasibility of improving knowledge of a 3 min safe firearm storage education video in the paediatric emergency department. METHODS: We conducted a single-centre block trial in a large paediatric emergency department (August 2020-2022). Participants were caregivers of adolescents (10-17 years) in firearm-owning households. First block participants (control) completed a baseline survey about child safety behaviours (including firearms). Second block participants (intervention) completed a baseline survey, watched the safe firearm storage video and evaluated acceptability. Participants completed a 3-month follow-up survey about firearm safety behaviours and knowledge recall. Demographic and clinical variables were compared between the intervention and control groups using Fisher's exact and χ2 tests. McNemar's test was used to compare firearm storage behaviours at the initial and 3-month visit within each group. RESULTS: Research staff approached 1264 caregivers; 371 consented to participate (29.4%) and 144 (38.8%) endorsed firearm ownership. There were 95 participants in the control group and 62 in the intervention group. Follow-up was lower in the intervention group (53.7% vs 37.1%, p=0.04). Among participants viewing the video, 80.3% liked the video and 50.0% felt they learnt something new from the video. CONCLUSIONS: Video-based firearm education in a paediatric emergency department is acceptable among a population of caregivers of adolescents with household firearms. This is a higher-risk group that may uniquely benefit from consistent education in the paediatric emergency department. Further study with larger populations is needed to evaluate intervention effectiveness. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT05168878).
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BACKGROUND: The Gun Shop Project aims to reduce firearm suicide and is widely implemented in the USA, yet little is known about the core firearm business practices and behaviours that might contribute to preventing firearm suicide. METHODS: Owners or managers of all firearm businesses identified as participants in Colorado's Gun Shop Project were invited to respond to a questionnaire. Data collection occurred from March to May 2021. Analyses included unweighted descriptive statistics with CIs and Pearson χ2 tests for categorical associations. RESULTS: 54 firearm businesses participated (response rate: 28%). Under half reported practices that are Gun Shop Project core aspects (range: 14%-45%). 22% of businesses frequently engaged customers on the importance of safe firearm storage in suicide prevention while 26% had denied a firearm sale and 14% had assisted with temporary secure storage in the past year with customers perceived to be in suicidal crisis. However, high proportions reported willingness to engage in these behaviours if a customer was in crisis: 74% were willing to refuse a sale of a firearm or ammunition, 70% were willing to discuss temporary secure storage options and 70% were willing to direct customers to mental health services. CONCLUSIONS: This study suggests that efforts to continue educating and involving firearm businesses may have an impact on the adoption of organisational suicide prevention practices and behaviours. Ongoing efforts are needed to understand core components of Gun Shop Project to inform standardised recommendations for effective firearm business practices that prevent firearm suicide.
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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.
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Bullying , Cyberbullying , Adolescente , Humanos , Feminino , Masculino , Psicometria , Violência/prevenção & controle , Fatores de RiscoRESUMO
STUDY OBJECTIVE: Safe firearm storage is protective against pediatric firearm injuries. We sought to compare a 3-minute versus 30-second safe firearm storage video in terms of acceptability of video content and use in the pediatric emergency department (PED). METHODS: We conducted a randomized controlled trial in a large PED (from March to September 2021). Participants were English-speaking caregivers of noncritically ill patients. Participants were surveyed about child safety behaviors (including firearm storage), then shown 1 of 2 videos. Both videos described safe storage principles; the 3-minute video included temporary firearm removal and a survivor testimonial. The primary outcome was acceptability, measured by responses on a 5-point Likert scale (strongly disagree to strongly agree). A survey at 3 months evaluated information recall. Baseline characteristics and outcomes were compared between groups using Pearson chi-squared, Fisher exact, and Wilcoxon Mann Whitney tests as appropriate. Absolute risk difference for categoric variables and mean difference for continuous variables are reported with 95% confidence interval (CI). RESULTS: Research staff screened 728 caregivers; 705 were eligible and 254 consented to participate (36%); 4 withdrew. Of 250 participants, most indicated acceptability in terms of setting (77.4%) and content (86.6%), and doctors discussing firearm storage (78.6%), with no difference between groups. More caregivers viewing the longer video felt the length appropriate (99.2%) compared with the shorter video (81.1%, difference 18.1%, 95% CI 11.1 to 25.1). CONCLUSIONS: We show that video-based firearm safety education is acceptable among study participants. This can provide consistent education to caregivers in PEDs and needs further study in other settings.
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Armas de Fogo , Ferimentos por Arma de Fogo , Humanos , Criança , Ferimentos por Arma de Fogo/prevenção & controle , Projetos Piloto , Cuidadores , Serviço Hospitalar de Emergência , SegurançaRESUMO
BACKGROUND AND OBJECTIVES: Youth violence is an alarming public health problem, yet, violence screening and interventions are not systematically offered in primary care (PC). This paper describes data from a pilot effectiveness-implementation trial of an efficacious youth violence prevention programme (SafERteens). METHODS: The study was conducted in two PC clinics: a university-affiliated satellite clinic and a community health centre. In phase 1, we obtained stakeholder feedback to customise the SafERteens package and enrolled a comparison group of adolescents (age 14-18) seeking care in two clinics. In phase 2, clinical staff delivered the SafERteens-PC intervention with adolescents, which is a single, behavioural health therapy session delivered one-on-one from clinic providers to youth patients, followed by text message (TM) reminders. In phase 3, we assessed planned maintenance. All participants reported past-year violent behaviour at intake and completed a 3-month follow-up assessment. RESULTS: Based on stakeholder interviews (n=13), we created a web-based SafERteens-PC programme package, including a three-item past-year violence screen, 30 min motivational interviewing-based brief intervention delivery tool, training videos and 2 months of TM boosters. We enrolled a comparison group (n=49) first, then an intervention group (n=61). Intervention delivery characteristics varied by clinic, including completion of intervention (75.9%; 62.5%), modality (100% delivered via telehealth; 60% via telehealth/40% in-person) and enrolment in TMs (81.8%; 55.0%); 91.8% completed the follow-up. Using an intention-to-treat approach, the intervention group showed significantly greater reductions in severe peer aggression (p<0.05), anxiety (p<0.05) and substance use consequences (p<0.05) relative to the comparison group. Participant and staff feedback were positive and identified challenges to long-term implementation, such as lack of availability of reimbursement for youth violence prevention. CONCLUSIONS: If these challenges could be addressed, routine provision of behavioural health services for violence prevention in PC could have high impact on health outcomes for adolescents.
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Comportamento do Adolescente , Entrevista Motivacional , Adolescente , Agressão , Ensaios Clínicos como Assunto , Humanos , Estudos Multicêntricos como Assunto , Projetos Piloto , Atenção Primária à Saúde , Violência/prevenção & controleRESUMO
Intentional and unintentional firearm injury is the second leading cause of death for youth, underscoring the need for effective primary prevention approaches that focus on increasing safe storage by caregivers and decreasing handling/carriage among youth. This article describes the state of the science for prevention of firearm injuries among children and adolescents. We applied PRISMA guidelines to present results from a scoping review using PubMed, Scopus, CINAHL, and CJ Abstracts for original research articles published between January 1, 1985 and March 1, 2018 in the U.S. focusing on primary screening or interventions for primary prevention of pediatric firearm injuries. In total, 46 articles met inclusion criteria: safe storage (23), screening (2), firearm handling/carriage/use (21). Across school, healthcare, and community settings, few evidenced-based programs exist, and data on firearm safety technologies are lacking. Programs have generally not employed rigorous designs, and/or assessed behavioral (e.g., carriage) or injury-related firearm outcomes. Evidenced-based prevention programs are needed to mitigate firearm morbidity and mortality among youth.
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Armas de Fogo/estatística & dados numéricos , Prevenção Primária/normas , Segurança/estatística & dados numéricos , Ferimentos por Arma de Fogo/prevenção & controle , Adolescente , Criança , Feminino , Humanos , Masculino , Programas de Rastreamento/normas , Medição de Risco , Instituições AcadêmicasRESUMO
Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (1011 unique small molecules) against multiple forms of the InhA enzyme in a multiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.
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Proteínas de Bactérias/antagonistas & inibidores , Mycobacterium tuberculosis/enzimologia , Oxirredutases/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Bibliotecas de Moléculas PequenasRESUMO
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.
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DNA/química , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Tirosina Quinase da Agamaglobulinemia , Sítios de Ligação , Linhagem Celular , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , DNA/metabolismo , Humanos , Cinética , Simulação de Acoplamento Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Estrutura Terciária de Proteína , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Bibliotecas de Moléculas Pequenas/metabolismoRESUMO
Youth violence is a major problem in the United States. It remains the third leading cause of death among youth between the ages of 10 and 24 years and the leading cause of death in Blacks between 10 and 24 years of age. In its effort to prevent youth violence, the Center for Disease Control and Prevention funds six Youth Violence Prevention Centers (YVPCs) to design, implement and evaluate community-based youth violence prevention programs. These Centers rely on surveillance data to monitor youth violence and evaluate the impact of their interventions. In public health, surveillance entails a systematic collection and analysis of data, typically within defined populations. In the case of youth violence, surveillance data may include archival records from medical examiners, death certificates, hospital discharges, emergency room visits, ambulance pickups, juvenile justice system intakes, police incident reports, and school disciplinary incidents and actions. This article illustrates the process the YVPCs used for collecting and utilizing youth violence surveillance data. Specifically, we will describe available surveillance data sources, describe community-level outcomes, illustrate effective utilization of the data, and discuss the benefits and limitations of each data source. Public health professionals should utilize local surveillance data to monitor and describe youth violence in the community. Further, the data can be used to evaluate the impact of interventions in improving community-level outcomes.
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Delinquência Juvenil/estatística & dados numéricos , Características de Residência , Violência/estatística & dados numéricos , Adolescente , Criança , Humanos , Avaliação de Resultados em Cuidados de Saúde , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
PURPOSE: There is limited evidence as to how to facilitate health care providers (HCPs) addressing firearm injury prevention during routine visits. The purpose of this project was to examine whether including a screening question about firearms in the home in the routine care template increases the screening of youth access to firearms. METHODS: A pre-post approach chart review was conducted for youth 12-21 years old. Outcomes included HCP documentation of screening for the presence of firearms and whether counseling caregivers on safer storage practices was delivered. RESULTS: HCPs documented screening adolescents for firearms 85% after the addition of the prompt compared to 25% prior to the change (p < .001). The presence of the screening prompt also led to an increase in the delivery of safe storage counseling (p = .035). DISCUSSION: Altering the EMR template increased HCP documentation of the presence of firearms in the home while also increasing firearm injury prevention counseling delivered to caregivers.
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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.
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Comportamento do Adolescente , Tentativa de Suicídio , Humanos , Adolescente , Estados Unidos/epidemiologia , Criança , Ideação Suicida , Fatores de Risco , Saúde Mental , Comportamento do Adolescente/psicologiaRESUMO
OBJECTIVE: 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. METHODS: This was a retrospective chart review of primary care well child visits occurring January-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, PHQ-9 scores, and assessed suicide risk. RESULTS: Of the 743 charts reviewed, firearms were discussed in 9% (n=66). Medical students were most likely to discuss firearms (15%), attending physicians were least likely (1%, p < 0.001). Providers did not discuss firearms more frequently among youth at elevated suicide risk. CONCLUSION: Though providers do not frequently discuss and document firearm discussions overall, the higher rates among medical students is 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. WHAT'S NEW: Pediatric providers have an opportunity to counsel families about the risk of firearm access. We found that trainees are most likely to counsel families about firearms, and that providers are not more likely to counsel youth at elevated suicide risk.
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Evasion of apoptosis is critical for the development and growth of tumors. The pro-survival protein myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family, associated with tumor aggressiveness, poor survival, and drug resistance. Development of Mcl-1 inhibitors implies blocking of protein-protein interactions, generally requiring a lengthy optimization process of large, complex molecules. Herein, we describe the use of DNA-encoded chemical library synthesis and screening to directly generate complex, yet conformationally privileged macrocyclic hits that serve as Mcl-1 inhibitors. By applying a conceptual combination of conformational analysis and structure-based design in combination with a robust synthetic platform allowing rapid analoging, we optimized in vitro potency of a lead series into the low nanomolar regime. Additionally, we demonstrate fine-tuning of the physicochemical properties of the macrocyclic compounds, resulting in the identification of lead candidates 57/59 with a balanced profile, which are suitable for future development toward therapeutic use.
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Antineoplásicos , Neoplasias , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Apoptose , Conformação Molecular , DNA , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
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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Armas de Fogo , Adolescente , Humanos , Registros Eletrônicos de Saúde , Segurança , Pessoal de Saúde , PaisRESUMO
The American Academy of Pediatrics and its members recognize the importance of improving the physician's ability to recognize intimate partner violence (IPV) and understand its effects on child health and development and its role in the continuum of family violence. Pediatricians are in a unique position to identify IPV survivors in pediatric settings, to evaluate and treat children exposed to IPV, and to connect families with available local and national resources. Children exposed to IPV are at increased risk of being abused and neglected and are more likely to develop adverse health, behavioral, psychological, and social disorders later in life. Pediatricians should be aware of these profound effects of exposure to IPV on children and how best to support and advocate for IPV survivors and their children.
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Maus-Tratos Infantis , Violência Doméstica , Violência por Parceiro Íntimo , Humanos , Criança , Violência por Parceiro Íntimo/psicologia , Maus-Tratos Infantis/psicologia , Pediatras , Saúde da CriançaRESUMO
OBJECTIVE: We compared the Patient Health Questionnaire (PHQ)-2 to the PHQ-9 and examined the implications of using various cutoff scores on the PHQ-2 to detect moderate or greater depressive symptoms on the PHQ-9. We hypothesized that a cutoff score of ≥2 would be optimal for detecting scores of ≥10 on the PHQ-9. METHODS: Demographic and depression screening data from 3,256 routine preventive visits for patients aged 12-25 years at the adolescent and young adult clinic at Children's Hospital Colorado between March 2017 and July 2019 were collected retrospectively. Patients completed routine depression screening at 2,183 visits which were included for analysis. PHQ-2 scores and PHQ-9 scores were calculated for each included patient visit. Associations between different PHQ-2 cutoff scores and moderate or greater depressive symptoms on the PHQ-9 (≥10) were evaluated. RESULTS: A PHQ-2 score ≥2 had a sensitivity of 89% and specificity of 83% for detecting patients with moderate or greater depressive symptoms on the PHQ-9. On a receiver operating characteristic curve, a PHQ-2 cutoff of ≥2 optimized sensitivity and specificity. Analysis of gender and ethnic/racial subgroups demonstrated the same optimal cutoff score for each group studied. For patients aged 21 years and older a PHQ-2 cutoff of ≥3 was most accurate. DISCUSSION: Lowering the positive PHQ-2 cutoff to ≥2 has several clinical advantages, including increased detection of moderate or greater depressive symptoms and depressive disorders. Providers may increase identification of depression by making this change particularly if they follow a positive PHQ-2 with a full PHQ-9.