"Make yourself un-NIMBY-able": stakeholder perspectives on strategies to mobilize public and political support for overdose prevention centers in the United States of America.

BACKGROUND: Overdose prevention centers (OPCs), also known as supervised injection facilities and safe consumption sites, are evidenced-based interventions for preventing overdose deaths and drug-related morbidities. The pathways to legalizing OPCs in the USA have confronted multiple social, political, and legal obstacles. We conducted a multi-site, qualitative study to explore heterogeneities in these pathways in four jurisdictions, as well as to understand stakeholder perspectives on valuable strategies for galvanizing political and public support for OPCs. METHODS: From July 2022 to February 2023, we conducted 17 semi-structured, in-depth interviews with OPC policymakers, service providers, advocates, and researchers from California, New York City, Philadelphia, and Rhode Island, where efforts have been undertaken to authorize OPCs. Using inductive thematic analysis, we identified and compared contextually relevant, salient approaches for increasing support for OPCs. RESULTS: Participants described several strategies clustering around five distinct domains: (1) embedding OPC advocacy into broader overdose prevention coalitions to shape policy dialogs; (2) building rapport with a plurality of powerbrokers (e.g., lawmakers, health departments, law enforcement) who could amplify the impact of OPC advocacy; (3) emphasizing specific benefits of OPCs to different audiences in different contexts; (4) leveraging relationships with frontline workers (e.g., emergency medicine and substance use treatment providers) to challenge OPC opposition, including 'NIMBY-ism,' and misinformation; and (5) prioritizing transparency in OPC decision-making to foster public trust. CONCLUSION: While tailored to the specific socio-political context of each locality, multiple OPC advocacy strategies have been deployed to cultivate support for OPCs in the USA. Advocacy strategies that are multi-pronged, leverage partnerships with stakeholders at multiple levels, and tailor communications to different audiences and settings could yield the greatest impact in increasing support for, and diffusing opposition to, future OPC implementation.

High-dose naloxone formulations are not as essential as we thought.

Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review investigates the adequacy of two doses of standard IM or IN naloxone in reversing fentanyl overdoses compared to newer high-dose naloxone formulations. Moreover, our initiative incorporates the experiences of people who use drugs, enabling a more practical and contextually-grounded analysis. The evidence indicates that the vast majority of fentanyl overdoses can be successfully reversed using two standard IM or IN dosages. Exceptions include cases of carfentanil overdose, which necessitates ≥ 3 doses for reversal. Multiple studies documented the risk of precipitated withdrawal using ≥ 2 doses of naloxone, notably including the possibility of recurring overdose symptoms after resuscitation, contingent upon the half-life of the specific opioid involved. We recommend distributing multiple doses of standard IM or IN naloxone to bystanders and educating individuals on the adequacy of two doses in reversing fentanyl overdoses. Individuals should continue administration until the recipient is revived, ensuring appropriate intervals between each dose along with rescue breaths, and calling emergency medical services if the individual is unresponsive after two doses. We do not recommend high-dose naloxone formulations as a substitute for four doses of IM or IN naloxone due to the higher cost, risk of precipitated withdrawal, and limited evidence compared to standard doses. Future research must take into consideration lived and living experience, scientific evidence, conflicts of interest, and the bodily autonomy of people who use drugs.

Supervised Inhalation Sites: Preventing Overdose and Reducing Health Inequities among People Who Use Drugs.

Policy and research on the implementation of services for people who inhale drugs lag behind similar efforts for people who inject drugs, limiting access to adequate harm reduction resources for people who inhale drugs. This commentary considers why supervised inhalation sites (SIS) are needed, highlights operational characteristics of four existing services, and advocates for future SIS research. Our hope is to encourage the expansion of SIS worldwide for overdose prevention and reduction of health inequities. Given the limited literature regarding SIS, more extensive study of these programs is warranted to incorporate inhalation into the implementation of supervised consumption sites to provide fair opportunities for all people who use drugs to do so safely without fear of stigma and overdose.

Cannabis use and episodic memory performance among adolescents: Moderating effects of depression symptoms and sex.

OBJECTIVE: Cannabis use has been linked to poorer episodic memory. However, little is known about whether depression and sex may interact as potential moderators of this association, particularly among adolescents. The current study addresses this by examining interactions between depression symptoms and sex on the association between cannabis use and episodic memory in a large sample of adolescents. METHOD: Cross-sectional data from 360 adolescents (M age = 17.38, SD = .75) were analyzed at the final assessment wave of a two-year longitudinal study. We used the Drug Use History Questionnaire to assess for lifetime cannabis use, and the Computerized Diagnostic Interview Schedule for Children, Fourth edition to assess the number of depression symptoms in the past year. Subtests from the Wechsler Memory Scale, Fourth Edition and the California Verbal Learning Test, Second Edition were used to assess episodic memory performance. RESULTS: The effect of the three-way interaction among cannabis use, depression symptoms, and sex did not have a significant impact on episodic memory performance. However, follow-up analyses revealed a significant effect of the two-way interaction of cannabis use and depression symptoms on episodic memory, such that associations between cannabis use and episodic memory were only significant at lower and average levels of depression symptoms. CONCLUSIONS: Contrary to our hypotheses, we found that as depression symptoms increased, the negative association between cannabis use and episodic memory diminished. Given the use of a predominantly subsyndromic sample, future studies should attempt to replicate findings among individuals with more severe depression.

Evaluating the Impact of Brave Technology Co-op's Novel Drug Overdose Detection and Response Devices in North America: a Retrospective Study.

Assess the preliminary impact of Brave Technology Co-op's overdose detection devices that have been implemented in housing, medical, social service facilities, and several private settings in North America. Administrative data was collected by Brave on their Buttons and Sensors during several proof-of-concept projects and full installations in Canada and United States (US) between December 2018 and July 2022. Data analyzed provided insights on the number of overdoses detected and reversed (averted overdose deaths) using Brave Sensors and Buttons, along with other programmatic and session-specific indicators. Implementation of 486 Brave Buttons and 148 Brave Sensors in Canada has detected and prevented 108 overdose deaths (100 using Buttons and 8 using Sensors) whereas implementation of 170 Buttons in the US has averted 2 overdose deaths to date, with the potential to save many more lives. Brave's devices hold promise for increasing rates of overdose detection and preventing overdose deaths.

Childhood adversity and co-occurring post-traumatic stress and externalizing symptoms among a predominantly low-income, African American sample of early adolescents.

Although there is strong evidence supporting the association between childhood adversity and symptomatology during adolescence, the extent to which adolescents present with distinct patterns of co-occurring post-traumatic stress (PTS) and externalizing symptoms remains unclear. Additionally, prior research suggests that experiencing nonviolent, negative life events may be more salient risk factors for developing some forms of psychopathology than exposure to violence. The current study used latent profile analysis to identify subgroups of early adolescents with distinct patterns of PTS, physical aggression, delinquency, and substance use, and examined subgroup differences in exposure to three forms of violent and nonviolent childhood adversity. Participants were a predominantly low-income, African American sample of 2,722 urban middle school students (M age = 12.9, 51% female). We identified four symptom profiles: low symptoms (83%), some externalizing (8%), high PTS (6%), and co-occurring PTS and externalizing symptoms (3%). A higher frequency of witnessing violence was associated with increased odds of membership in subgroups with externalizing symptoms, whereas a higher frequency of nonviolent, negative life events was associated with increased odds of membership in subgroups with PTS symptoms. Interventions aimed to address childhood adversity may be most effective when modules addressing both PTS and externalizing symptoms are incorporated.

Associations between potentially traumatic events and psychopathology among preadolescents in the Adolescent Brain and Cognitive Development Study®.

The current cross-sectional study aimed to extend the literature on childhood adversity by examining the unique associations between potentially traumatic events (PTEs) and a range of mental health concerns, including domain-specific versus comorbid concerns. Participants were 11,877 preadolescents (47.8% female, 15.0% Black, 20.3% Hispanic/Latinx, Mage  = 9.5 years) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study® . The Kiddie Schedule for Affective Disorders and Schizophrenia was used to measure PTEs and caregiver- and child-reported mental health concerns. Adjusted odds ratios (aORs) were used for the outcomes of interest. Overall, PTEs were consistently associated with increased odds of experiencing comorbid posttraumatic stress disorder (PTSD), internalizing disorders, and externalizing disorders, significant AORs = 1.34-4.30, after accounting for children's experiences of other PTEs and polyvictimization. In contrast, PTEs were generally not associated with meeting the criteria for diagnoses within only one domain (i.e., internalizing-only or externalizing-only diagnoses). We also found PTEs to be differentially related to the various mental health outcomes. In particular, witnessing domestic violence was consistently associated with children's psychopathology. Other PTEs, such as witnessing community violence, were not associated with children's psychopathology in the final model. Associations between PTEs and mental health concerns did not differ as a function of sex. Overall, the results support the notion that PTEs are associated with comorbid concerns rather than individual disorders. These findings have important implications for the screening of PTEs, continued research on the conceptualization of traumatic stress, and the importance of accounting for comorbidities across mental health domains.

What We Have Heard: Next Steps for Long-Term Care Pandemic Preparedness in Canada.

In this concluding article, Healthcare Excellence Canada and the Canadian Institutes of Health Research reflect upon and respond to the lessons learned from the contributing articles in the special issue and summarize key takeaways for the next steps in evidence-informed pandemic preparedness in long-term care in Canada. The implications of their cross-organizational partnership for achieving collective impact now and in the future are also discussed.

S054: incidence and management of jejunojejunal intussusception after Roux-en-Y gastric bypass: a large case series.

INTRODUCTION: Jejunojejunal intussusception after Roux-en-Y gastric bypass (RYGBP) for morbid obesity is a rare but potentially catastrophic complication. There are limited data regarding the incidence of intussusception and the different surgical options for management of this disease. METHODS: This is a retrospective review of all patients that underwent RYGBP and subsequently developed intussusception at the jejunojejunostomy. Data were collected between 1/1/2008 and 5/31/2018 and included demographics, details related to the index procedure, presentation, and management of intussusception. Perioperative outcomes and complications were also collected. RESULTS: 665 patients underwent RYGBP. A total of 34 patients developed intussusception, with 31 (4.7%) of them having undergone RYGBP in our hospital. Demographics included age, gender, and BMI at both the index surgery and at the time of intussusception. The jejunojejunostomy was created during RYGBP using a linear stapler in all patients with 64.5% of them achieving a length of 90 mm. All intussuscepted patients presented acutely with abdominal pain. All but one patient required surgical intervention. 42.4% of the patients were found to have intraoperative intussusception which appeared to be retrograde in 78.6% of them. Reduction followed by enteropexy or just enteropexy was performed in 20 patients (60.6%) that required surgery. No immediate post-operative complications were noted but 8 patients (26.5%) had recurrence of intussusception requiring another surgical intervention. In the reoperated group, 75% of the patients were treated with reduction followed by enteropexy or just enteropexy. CONCLUSIONS: This is the largest case series describing jejunojejunal intussusception following RYGBP. All patients that developed intussusception had jejunojejunostomy length greater than 60 mm. The most commonly performed surgical repair was reduction of the intussuscepted segment (if present) followed by enteropexy. Jejunojejunostomy length greater than 60 mm might be associated with the occurrence of intussusception and could explain the higher incidence noted in our series. Minimal intervention with enteropexy can offer effective treatment for most patients.

Deviant Peer Factors During Early Adolescence: Cause or Consequence of Physical Aggression?

This study investigated reciprocal relations between adolescents' physical aggression and their perceptions of peers' deviant behaviors and attitudes. Analyses were conducted on four waves of data from 2,290 adolescents (ages 10-16) from three urban middle schools. Autoregression models revealed reciprocal relations between peer factors (i.e., friends' problem behavior, peer pressure for fighting, friends' support for fighting) and adolescents' reporting of their aggressive behavior. Bidirectional relations were also found between peer pressure for fighting and adolescents' frequency of physical aggression based on teacher ratings. Findings were consistent across sex, grade, and time. Findings suggest that multiple dimensions of peers' behaviors uniquely play a role in the development of adolescents' aggression and have important implications for interventions to reduce problem behaviors.

Bidirectional Relations between Witnessing Violence, Victimization, Life Events, and Physical Aggression among Adolescents in Urban Schools.

Although there is empirical evidence supporting associations between exposure to violence and engaging in physically aggressive behavior during adolescence, there is limited longitudinal research to determine the extent to which exposure to violence is a cause or a consequence of physical aggression, and most studies have not addressed the influence of other negative life events experienced by adolescents. This study examined bidirectional relations between physical aggression, two forms of exposure to violence-witnessing violence and victimization, and other negative life events. Participants were a sample of 2568 adolescents attending three urban public middle schools who completed measures of each construct every 3 months during middle school. Their mean age was 12.76 (SD = 0.98); 52% were female. The majority were African American (89%); 17% were Hispanic or Latino/a. Cross-lagged regression analyses across four waves of data collected within the same grade revealed bidirectional relations between witnessing violence and physical aggression, and between witnessing violence and negative life events. Although physical aggression predicted subsequent changes in victimization, victimization predicted changes in physical aggression only when witnessing violence was not taken into account. Findings were consistent across sex and grades. Overall, these findings highlight the need for interventions that break the connection between exposure to violence and aggression during adolescence.

Biophysical Characterization of a Disabled Double Mutant of Soybean Lipoxygenase: The "Undoing" of Precise Substrate Positioning Relative to Metal Cofactor and an Identified Dynamical Network.

Soybean lipoxygenase (SLO) has served as a prototype for understanding the molecular origin of enzymatic rate accelerations. The double mutant (DM) L546A/L754A is considered a dramatic outlier, due to the unprecedented size and near temperature-independence of its primary kinetic isotope effect, low catalytic efficiency, and elevated enthalpy of activation. To uncover the physical basis of these features, we herein apply three structural probes: hydrogen-deuterium exchange mass spectrometry, room-temperature X-ray crystallography and EPR spectroscopy on four SLO variants (wild-type (WT) enzyme, DM, and the two parental single mutants, L546A and L754A). DM is found to incorporate features of each parent, with the perturbation at position 546 predominantly influencing thermally activated motions that connect the active site to a protein-solvent interface, while mutation at position 754 disrupts the ligand field and solvation near the cofactor iron. However, the expanded active site in DM leads to more active site water molecules and their associated hydrogen bond network, and the individual features from L546A and L754A alone cannot explain the aggregate kinetic properties for DM. Using recently published QM/MM-derived ground-state SLO-substrate complexes for WT and DM, together with the thorough structural analyses presented herein, we propose that the impairment of DM is the combined result of a repositioning of the reactive carbon of linoleic acid substrate with regard to both the iron cofactor and a catalytically linked dynamic region of protein.

Longitudinal relations between trauma-related psychological distress and physical aggression among urban early adolescents.

There is convincing evidence that trauma-related psychological distress and aggressive behavior are highly related among adolescents. The evidence is less clear regarding the direction of this relation. OBJECTIVE: The purpose of this study was to examine reciprocal longitudinal relations between trauma-related distress and physical aggression. METHOD: A predominantly African American sample of early adolescents (N = 2,271; mean age = 12.9) living in an urban, under-resourced community participated in this investigation. The current study used autoregressive cross-lagged models to examine changes across four waves of data within each grade of middle school. RESULTS: Support was found for trauma-related distress uniquely predicting increased levels of physical aggression. This effect was consistent across gender and within and across middle school grades. Conversely, physical aggression did not predict changes in trauma-related distress. CONCLUSIONS: Violence prevention efforts should routinely screen for trauma-related distress.

Victimization, Aggression, and Other Problem Behaviors: Trajectories of Change Within and Across Middle School Grades.

This study examined trajectories of victimization and problem behaviors within and across three grades of middle school. Participants were 2,166 adolescents from three urban middle schools in the United States who completed measures of victimization, physical and relational aggression, substance use, and delinquent behavior. Latent curve analyses modeled changes in each construct across 12 waves collected every 3 months. In each case, the best-fitting model required separate linear slopes to represent changes within each grade and a factor representing decreases in the summers. Positive cross-construct correlations were found for intercepts, linear slopes, and measures within waves. The findings suggest strong associations among victimization and problem behaviors, and individual differences in their patterns of change both within and across grades.

Correction to: Dimensions of Peer Influences and Their Relationship to Adolescents' Aggression, Other Problem Behaviors and Prosocial Behavior.

Correction to: J Youth Adolescence (2017) 46:1351-1369. 10.1007/s10964-016-0601-4.

Dimensions of Peer Influences and Their Relationship to Adolescents' Aggression, Other Problem Behaviors and Prosocial Behavior.

Although peers are a major influence during adolescence, the relative importance of specific mechanisms of peer influence on the development of problem behavior is not well understood. This study investigated five domains of peer influence and their relationships to adolescents' problem and prosocial behaviors. Self-report and teacher ratings were obtained for 1787 (53 % female) urban middle school students. Peer pressure for fighting and friends' delinquent behavior were uniquely associated with aggression, drug use and delinquent behavior. Friends' prosocial behavior was uniquely associated with prosocial behavior. Friends' support for fighting and friends' support for nonviolence were not as clearly related to behavior. Findings were generally consistent across gender. This study highlights the importance of studying multiple aspects of peer influences on adolescents' behavior.

Pharmacologic treatment of type 2 diabetes: oral medications.

OBJECTIVE: To review the oral and injectable pharmacologic treatment options for type 2 diabetes. DATA SOURCES: A literature search was conducted using PubMed electronic database for studies published in English between 1993 and September 2014. Search terms included diabetes mellitus, type 2 diabetes, and the individual name for each antidiabetic medication reviewed. In addition, manual searches were performed for cross-references from publications. Package inserts, United States Food and Drug Administration (FDA) Web site, Institute for Safe Medication Practices Web site, American Diabetes Association Web site and scientific session poster presentations, and individual drug company Web pages were also reviewed. STUDY SELECTION AND DATA EXTRACTION: This review focused on information elucidated over the past 10 years to assist prescribers in choosing optimal therapy based on individual patient characteristics. Studies leading to the approval of or raising safety concerns for the antidiabetic medications reviewed in this article were included. DATA SYNTHESIS: In the past 10 years, there have been 4 novel oral antidiabetic medication classes and 9 new injectable agents and insulin products approved by the FDA for the treatment of type 2 diabetes as well as new information regarding the safety and use of several older antidiabetic medication classes. The distinctions were reviewed for each individual agent, and a comparison was completed if there was more than one agent in a particular therapeutic class. Using current information available, select investigational agents in phase III trials or those with a pending new drug application were highlighted. CONCLUSION: There are now 9 distinct oral pharmacologic classes and a variety of insulin and noninsulin injectable medications available for the treatment of type 2 diabetes. Metformin remains the first-line treatment option for most patients. When considering options for alternative or additional treatment, prescribers must weigh the benefits and risks using individual patient characteristics.

Pharmacologic treatment of type 2 diabetes: injectable medications.

OBJECTIVE: To review the oral and injectable pharmacologic treatment options for type 2 diabetes. DATA SOURCES: A literature search was conducted using PubMed electronic database for studies published in English between 1993 and September 2014. Search terms included diabetes mellitus, type 2 diabetes, and the individual name for each antidiabetic medication reviewed. In addition, manual searches were performed for cross-references from publications. Package inserts, United States Food and Drug Administration (FDA) Web site, Institute for Safe Medication Practices Web site, American Diabetes Association Web site and scientific session poster presentations, and individual drug company Web pages were also reviewed. STUDY SELECTION AND DATA EXTRACTION: This review focused on information elucidated over the past 10 years to assist prescribers in choosing optimal therapy based on individual patient characteristics. Studies leading to the approval of or raising safety concerns for the antidiabetic medications reviewed in this article were included. DATA SYNTHESIS: In the past 10 years, there have been 4 novel oral antidiabetic medication classes and 10 new injectable agents and insulin products approved by the FDA for the treatment of type 2 diabetes as well as new information regarding the safety and use of several older antidiabetic medication classes. The distinctions were reviewed for each individual agent, and a comparison was completed if there was more than one agent in a particular therapeutic class. Using current information available, select investigational agents in phase III trials or with a pending new drug application were highlighted. CONCLUSION: There are now 9 distinct oral pharmacologic classes and a variety of insulin and noninsulin injectable medications available for the treatment of type 2 diabetes. Metformin remains the first-line treatment option for most patients. When considering options for alternative or additional treatment, prescribers must weigh the benefits and risks using individual patient characteristics.

Enrichment of core competencies to maximize health system impact: An analysis of an embedded research training program.

Introduction: The Health System Impact (HSI) Fellowship is an embedded research training program that aims to prepare doctoral trainees and postdoctoral fellows for stronger career readiness and greater impact as emerging leaders within and beyond the academy, including in learning health systems (LHS). The program supports fellows to develop 10 leadership and research competencies that comprise the Enriched Core Competency Framework in Health Services and Policy Research through a combination of experiential learning, mentorship, and professional development training. This study tracks competency development of HSI fellows over time and examines fellows' perspectives on which program design elements support their competency development. Methods: A competency assessment tool developed for the program was independently completed by 95 postdoctoral and 36 doctoral fellows (self-assessments) and their respective 203 dyad (academic and health system) supervisors in the 2017 to 2019 program cohorts, who independently rated the strength of fellows' 10 competencies at baseline and several points thereafter. Competency strength ratings were analyzed to understand change over time and differences in ratings across groups (between fellows' sex, supervisor type, and supervisor vs. fellow). Program design element ratings were examined to understand perspectives on their contribution toward fellows' competency development. Results: Fellows' competency strength significantly improved in all 10 domains over time, based on independent assessments by the fellows and their dyad supervisors. Supervisors tended to rate the fellows' competency strength higher than the fellows did. Differences in competency ratings between male and female fellows (self-assessments) and between academic and health system supervisors were either negligble or not significant. Fellows identified all nine program design elements as enriching their competency development. Conclusion: The HSI Fellowship provides an opportunity for fellows to develop the full suite of enriched core competencies and to prepare a cadre of emerging leaders with the skills and experience to contribute to the advancement of LHS.

"Politics Versus Policy": Qualitative Insights on Stigma and Overdose Prevention Center Policymaking in the United States.

BACKGROUND: Federal, state, and municipal governments in the United States have been reluctant to authorize overdose prevention centers (OPCs), which are evidence-based approaches for preventing overdose deaths and blood-borne pathogen transmission. METHODS: From July 2022 to February 2023, we explored how stigma manifests in OPC policymaking by conducting in-depth interviews with 17 advocates, legislators, service providers, and researchers involved with OPC advocacy and policymaking in Rhode Island, California, Pennsylvania, and New York. RESULTS: We found that although jurisdictions differed in their OPC policymaking experiences, stigma manifested throughout the process, from planning to authorization. Participants described OPCs as a tool for destigmatizing overdose and substance use, yet confronted institutionalized stigma and discriminatory attitudes toward people who use drugs (PWUD) and harm reduction from multiple sources (eg, politicians, media, and members of the public). Opposition toward OPCs and harm reduction approaches more broadly intersected with public discourse on crime, homelessness, and public disorder. Employed stigma-mitigation strategies included humanizing PWUD, publicizing the benefits of OPCs to the wider community, and strategically engaging media. CONCLUSION: These findings illustrate the importance of understanding stigma at different stages of the policymaking process to better facilitate authorization and eventual implementation of OPCs in the United States.