A simple heuristic for allocating opioid settlement funding to reduce overdose mortality in the United States.

As resolution for opioid-related claims and litigation against pharmaceutical manufacturers and other stakeholders, state and local governments are newly eligible for millions of dollars of settlement funding to address the overdose crisis in the United States. To inform effective use of opioid settlement funds, we propose a simple framework that highlights the principal determinants of overdose mortality: the number of people at risk of overdose each year, the average annual number of overdoses per person at risk, and the average probability of death per overdose event. We assert that the annual number of overdose deaths is a function of these three determinants, all of which can be modified through public health intervention. Our proposed heuristic depicts how each of these drivers of drug-related mortality - and the corresponding interventions designed to address each term - operate both in isolation and in conjunction. We intend for this framework to be used by policymakers as a tool for identifying and evaluating public health interventions and funding priorities that will most effectively address the structural forces shaping the overdose crisis and reduce overdose deaths.

Knowledge, Attitudes, and Beliefs About Opioid Use Disorder Treatment in Primary Care.

This survey study assesses the US public's perception and awareness regarding medication for opioid use disorder and its availability in primary care settings.

Adjuvant Delivery Method and Nanoparticle Charge Influence Peptide Amphiphile Micelle Vaccine Bioactivity.

Vaccines are an indispensable public health measure that have enabled the eradication, near elimination, and prevention of a variety of pathogens. As research continues and our understanding of immunization strategies develops, subunit vaccines have emerged as exciting alternatives to existing whole vaccine approaches. Unfortunately, subunit vaccines often possess weak antigenicity, requiring delivery devices and adjuvant supplementation to improve their utility. Peptide amphiphile micelles have recently been shown to function as both delivery devices and self-adjuvanting systems that can be readily associated with molecular adjuvants to further improve vaccine-mediated host immunity. While promising, many "design rules" associated with the plethora of underlying adjustable parameters in the generation of a peptide amphiphile micelle vaccine have yet to be uncovered. This work explores the impact micellar adjuvant complexation method and incorporated antigen type have on their ability to activate dendritic cells and induce antigen specific responses. Interestingly, electrostatic complexation of CpG to micelles resulted in improved in vitro dendritic cell activation over hydrophobic association and antigen|adjuvant co-localization influenced cell-mediated, but not antibody-mediated immune responses. These exciting results complement those previously published to build the framework of a micelle vaccine toolbox that can be leveraged for future disease-specific formulations.

Behavioral Assays Dissecting NMDA Receptor Function in Zebrafish.

Zebrafish are a powerful system to study brain development and to dissect the activity of complex circuits. One advantage is that they display complex behaviors, including prey capture, learning, responses to photic and acoustic stimuli, and social interaction (Dreosti et al., Front Neural Circuits 9:39, 2015; Bruckner et al., PLoS Biol 20:e3001838, 2022; Zoodsma et al., Mol Autism 13:38, 2022) that can be probed to assess brain function. Many of these behaviors are easily assayed at early larval stages, offering a noninvasive and high-throughput readout of nervous system function. Additionally, larval zebrafish readily uptake small molecules dissolved in water making them ideal for behavioral-based drug screens. Together, larval zebrafish and their behavioral repertoire offer a means to rapidly dissect brain circuitry and can serve as a template for high-throughput small molecule screens.NMDA receptor subunits are highly conserved in zebrafish compared to mammals (Zoodsma et al., Mol Autism 13:38, 2022; Cox et al., Dev Dyn 234:756-766, 2005; Zoodsma et al., J Neurosci 40:3631-3645, 2020). High amino acid and domain structure homology between humans and zebrafish underlie conserved functional similarities. Here we describe a set of behavioral assays that are useful to study the NMDA receptor activity in brain function.

Attitudes of Black American Christian church leaders toward Opioid Use Disorder, overdoses, and harm reduction: a qualitative study.

Introduction: Black American Christian church leaders are trusted community members and can be invaluable leaders and planners, listeners, and counselors for Opioid Use Disorder (OUD) sufferers in the opioid overdose crisis disproportionately affecting the Black community. This qualitative study examines the extent to which the knowledge, attitudes, practices, and beliefs of Black American church leaders support medical and harm reduction interventions for people with OUD. Methods: A semi-structured interview guide was used to conduct in-depth interviews of 30 Black Rhode Island church leaders recruited by convenience and snowball sampling. Results: Thematic analysis of the interviews identified four themes: Church leaders are empathetic and knowledgeable, believe that hopelessness and inequity are OUD risk factors, are committed to helping people flourish beyond staying alive, and welcome collaborations between church and state. Conclusion: Black American Christian church leaders are a critical resource in providing innovative and culturally sensitive strategies in the opioid overdose crisis affecting the Black American communities. As such, their views should be carefully considered in OUD policies, collaborations, and interventions in the Black American community.

Mental and physical health morbidity among people in prisons: an umbrella review.

BACKGROUND: People who experience incarceration are characterised by poor health profiles. Clarification of the disease burden in the prison population can inform service and policy development. We aimed to synthesise and assess the evidence regarding the epidemiology of mental and physical health conditions among people in prisons worldwide. METHODS: In this umbrella review, five bibliographic databases (Web of Science, PubMed, PsycINFO, Embase, and Global Health) were systematically searched from inception to identify meta-analyses published up to Oct 31, 2023, which examined the prevalence or incidence of mental and physical health conditions in general prison populations. We excluded meta-analyses that examined health conditions in selected or clinical prison populations. Prevalence data were extracted from published reports and study authors were contacted for additional information. Estimates were synthesised and stratified by sex, age, and country income level. The robustness of the findings was assessed in terms of heterogeneity, excess significance bias, small-study effects, and review quality. The study protocol was pre-registered with PROSPERO, CRD42023404827. FINDINGS: Our search of the literature yielded 1909 records eligible for screening. 1736 articles were excluded and 173 full-text reports were examined for eligibility. 144 articles were then excluded due to not meeting inclusion criteria, which resulted in 29 meta-analyses eligible for inclusion. 12 of these were further excluded because they examined the same health condition. We included data from 17 meta-analyses published between 2002 and 2023. In adult men and women combined, the 6-month prevalence was 11·4% (95% CI 9·9-12·8) for major depression, 9·8% (6·8-13·2) for post-traumatic stress disorder, and 3·7% (3·2-4·1) for psychotic illness. On arrival to prison, 23·8% (95% CI 21·0-26·7) of people met diagnostic criteria for alcohol use disorder and 38·9% (31·5-46·2) for drug use disorder. Half of those with major depression or psychotic illness had a comorbid substance use disorder. Infectious diseases were also common; 17·7% (95% CI 15·0-20·7) of people were antibody-positive for hepatitis C virus, with lower estimates (ranging between 2·6% and 5·2%) found for hepatitis B virus, HIV, and tuberculosis. Meta-regression analyses indicated significant differences in prevalence by sex and country income level, albeit not consistent across health conditions. The burden of non-communicable chronic diseases was only examined in adults aged 50 years and older. Overall, the quality of the evidence was limited by high heterogeneity and small-study effects. INTERPRETATION: People in prisons have a specific pattern of morbidity that represents an opportunity for public health to address. In particular, integrating prison health within the national public health system, adequately resourcing primary care and mental health services, and improving linkage with post-release health services could affect public health and safety. Population-based longitudinal studies are needed to clarify the extent to which incarceration affects health. FUNDING: Research Foundation-Flanders, Wellcome Trust, National Institutes of Health.

Developmental loss of NMDA receptors results in supernumerary forebrain neurons through delayed maturation of transit-amplifying neuroblasts.

Developmental neurogenesis is a tightly regulated spatiotemporal process with its dysregulation implicated in neurodevelopmental disorders. NMDA receptors are glutamate-gated ion channels that are widely expressed in the early nervous system, yet their contribution to neurogenesis is poorly understood. Notably, a variety of mutations in genes encoding NMDA receptor subunits are associated with neurodevelopmental disorders. To rigorously define the role of NMDA receptors in developmental neurogenesis, we used a mutant zebrafish line (grin1-/-) that lacks all NMDA receptors yet survives to 10 days post-fertilization, offering the opportunity to study post-embryonic neurodevelopment in the absence of NMDA receptors. Focusing on the forebrain, we find that these fish have a progressive supernumerary neuron phenotype confined to the telencephalon at the end of embryonic neurogenesis, but which extends to all forebrain regions during postembryonic neurogenesis. This enhanced neuron population does not arise directly from increased numbers or mitotic activity of radial glia cells, the principal neural stem cells. Rather, it stems from a lack of timely maturation of transit-amplifying neuroblasts into post-mitotic neurons, as indicated by a decrease in expression of the ontogenetically-expressed chloride transporter, KCC2. Pharmacological blockade with MK-801 recapitulates the grin1-/- supernumerary neuron phenotype, indicating a requirement for ionotropic signaling. Thus, NMDA receptors are required for suppression of indirect, transit amplifying cell-driven neurogenesis by promoting maturational termination of mitosis. Loss of suppression results in neuronal overpopulation that can fundamentally change brain circuitry and may be a key factor in pathogenesis of neurodevelopmental disorders caused by NMDA receptor dysfunction.

Pharmacy-based expansion of buprenorphine access.

INTRODUCTION: Access to evidence-based medication treatment is a challenge for most Americans with opioid use disorder. New models of collaborative care that actively incorporate pharmacists are being trialed. METHODS: We author a commentary based on our experiences providing clinical care as part of a randomized controlled trial of pharmacy-based addiction care. RESULTS: This commentary describes some of the experiences of working with a Collaborative Practice Agreement between pharmacists and physicians to provide pharmacy-based, low-threshold buprenorphine access. CONCLUSION: Given that 87 % of Americans with opioid use disorder are not getting access to buprenorphine or methadone, establishing a pharmacy-based buprenorphine treatment program is a promising strategy to address that gap and should be explored promptly.

Closing the Gap in Direct Admissions: A Quality Improvement Project.

BACKGROUND AND OBJECTIVES: Direct admissions (DAs) are nonemergent admissions to the inpatient unit that bypass the emergency department. Our institution lacked a standardized DA process, which resulted in postponement of prompt patient care. The purpose of the present study was to review and modify the existing DA process and to decrease the time between patient arrival for DA and placement of initial clinician orders. METHODS: A team was assembled and tasked with using quality improvement tools (eg, Define-Measure-Analyze-Improve-Control, fishbone diagrams, process mapping) to streamline the DA process to decrease average time between patient arrival for DA and initial clinician orders, from 84.4 minutes in July 2018 to 60 minutes or less by June 2019, without negatively affecting patient admission loyalty questionnaire scores. RESULTS: In a standardized and streamlined DA process, average time between patient arrival and provider order placement decreased to less than 60 minutes. This reduction was achieved without substantially affecting patient loyalty questionnaire scores. CONCLUSION: By using a quality improvement methodology, we developed a standardized DA process that resulted in prompt care for patients without decreasing admission loyalty scores.

Reimbursing incarcerated individuals for participation in research: A scoping review.

BACKGROUND: Little is known about global practices regarding the provision of reimbursement for the participation of people who are incarcerated in research. To determine current practices related to the reimbursement of incarcerated populations for research, we aimed to describe international variations in practice across countries and carceral environments to help inform the development of more consistent and equitable practices. METHODS: We conducted a scoping review by searching PubMed, Cochrane library, Medline, and Embase, and conducted a grey literature search for English- and French-language articles published until September 30, 2022. All studies evaluating any carceral-based research were included if recruitment of incarcerated participants occurred inside any non-juvenile carceral setting; we excluded studies if recruitment occurred exclusively following release. Where studies failed to indicate the presence or absence of reimbursement, we assumed none was provided. RESULTS: A total of 4,328 unique articles were identified, 2,765 were eligible for full text review, and 426 were included. Of these, 295 (69%) did not offer reimbursement to incarcerated individuals. A minority (n = 13; 4%) included reasons explaining the absence of reimbursement, primarily government-level policies (n = 7). Among the 131 (31%) studies that provided reimbursement, the most common form was monetary compensation (n = 122; 93%); five studies (4%) offered possible reduced sentencing. Reimbursement ranged between $3-610 USD in total and 14 studies (11%) explained the reason behind the reimbursements, primarily researchers' discretion (n = 9). CONCLUSIONS: The majority of research conducted to date in carceral settings globally has not reimbursed incarcerated participants. Increased transparency regarding reimbursement (or lack thereof) is needed as part of all carceral research and advocacy efforts are required to change policies prohibiting reimbursement of incarcerated individuals. Future work is needed to co-create international standards for the equitable reimbursement of incarcerated populations in research, incorporating the voices of people with lived and living experience of incarceration.

Perfluorooctane Sulfonate (PFOS) Negatively Impacts Prey Capture Capabilities in Larval Zebrafish.

Per- and polyfluoroalkyl substances (PFAS) are widely used in many industrial and domestic applications, which has resulted in unintentional human exposures and bioaccumulation in blood and other organs. Perfluorooctane sulfonate (PFOS) is among the most prevalent PFAS in the environment and has been postulated to affect brain functions in exposed organisms. However, the impacts of PFOS in early neural development have not been well described. We used zebrafish larvae to assess the effects of PFOS on two fundamental complex behaviors, prey capture and learning. Zebrafish exposed to PFOS concentrations ranging from 2 to 20 µM for differing 48-h periods were viable through early larval stages. In addition, PFOS uptake was unaffected by the presence of a chorion. We employed two different experimental paradigms; first we assessed the impacts of increasing organismal PFOS bioaccumulation on prey capture and learning, and second, we probed stage-specific sensitivity to PFOS by exposing zebrafish at different developmental stages (0-2 vs. 3-5 days post fertilization). Following both assays we measured the amount of PFOS present in each larva and found that PFOS levels varied in larvae from different groups within each experimental paradigm. Significant negative correlations were observed between larval PFOS accumulation and percentage of captured prey, whereas nonsignificant negative correlations were observed between PFOS accumulation and experienced-induced prey capture learning. These findings suggest that PFOS accumulation negatively affects larval zebrafish's ability to perform complicated multisensory behaviors and highlights the potential risks of PFOS exposure to animals in the wild, with implications for human health. Environ Toxicol Chem 2024;43:847-855. © 2023 SETAC.

Cruel and Unusual: Reforming Carceral Systems to Protect and Affirm Transgender and Gender-Diverse Communities.

Transgender and gender-diverse communities are disproportionately incarcerated in the USA. Incarcerated gender minority populations are detained within carceral systems constructed around a cisgender (gender identity matches sex assigned at birth) binary (only male and female identities recognized) understanding of gender. This leads to marginalizing experiences while perpetuating the extreme vulnerability individuals experience in the community. In order to address this cruel and unusual experience, carceral systems should undergo "whole-setting" reforms to protect and affirm transgender and gender-diverse populations. This includes ensuring access to gender-affirming clinical care that aligns with community health standards recommended by medical professional associations. Implementing gender-affirming reforms reduces security issues and will likely improve health outcomes providing mutual benefit for both correctional staff and gender minority populations. Given the current divisive political and social environment for gender minority populations in the USA, evidence-based person-centered reforms in corrections are needed now more than ever.

Loss of NMDA receptor function during development results in decreased KCC2 expression and increased neurons in the zebrafish forebrain.

Developmental neurogenesis is a tightly regulated spatiotemporal process with its dysregulation implicated in neurodevelopmental disorders. NMDA receptors are glutamate-gated ion channels that are widely expressed in the early nervous system, yet their contribution to neurogenesis is poorly understood. Notably, a variety of mutations in genes encoding NMDA receptor subunits are associated with neurodevelopmental disorders. To rigorously define the role of NMDA receptors in developmental neurogenesis, we used a mutant zebrafish line ( grin1 -/- ) that lacks all NMDA receptors yet survives to 10 days post-fertilization, offering the opportunity to study post-embryonic neurodevelopment in the absence of NMDA receptors. Focusing on the forebrain, we find that these fish have a progressive supernumerary neuron phenotype confined to the telencephalon at the end of embryonic neurogenesis, but which extends to all forebrain regions during postembryonic neurogenesis. This enhanced neuron population does not arise directly from increased numbers or mitotic activity of radial glia cells, the principal neural stem cells. Rather, it stems from a lack of timely maturation of transit-amplifying neuroblasts into post-mitotic neurons, as indicated by a decrease in expression of the ontogenetically-expressed chloride transporter, KCC2. Pharmacological blockade with MK-801 recapitulates the grin1 -/- supernumerary neuron phenotype, indicating a requirement for ionotropic signaling. Thus, NMDA receptors are required for suppression of indirect, transit amplifying cell-driven neurogenesis by promoting maturational termination of mitosis. Loss of suppression results in neuronal overpopulation that can fundamentally change brain circuitry and may be a key factor in pathogenesis of neurodevelopmental disorders caused by NMDA receptor dysfunction.

Prescribe to Save Lives: An Intervention to Increase Naloxone Prescribing Among HIV Clinicians.

OBJECTIVES: Overdose is a major cause of preventable death among persons living with HIV. This study aimed to increase HIV clinicians' naloxone prescribing, which can reduce overdose mortality. METHODS: We enrolled 22 Ryan White-funded HIV practices and implemented onsite, peer-to-peer training, posttraining academic detailing, and pharmacy peer-to-peer contact around naloxone prescribing in a nonrandomized stepped wedge design. Human immunodeficiency virus clinicians completed surveys to assess attitudes toward prescribing naloxone at preintervention and 6 and 12 months postintervention. Aggregated electronic health record data measured the number of patients with HIV prescribed and the number of HIV clinicians prescribing naloxone by site over the study period. Models controlled for calendar time and clustering of repeated measures among individuals and sites. RESULTS: Of 122 clinicians, 119 (98%) completed a baseline survey, 111 (91%) a 6-month survey, and 93 (76%) a 12-month survey. The intervention was associated with increases in self-reported "high likelihood" to prescribe naloxone (odds ratio [OR], 4.1 [1.7-9.4]; P = 0.001). Of 22 sites, 18 (82%) provided usable electronic health record data that demonstrated a postintervention increase in the total number of clinicians who prescribed naloxone (incidence rate ratio, 2.9 [1.1-7.6]; P = 0.03) and no significant effects on sites having at least one clinician who prescribed naloxone (OR, 4.1 [0.7-23.8]; P = 0.11). The overall proportion of all HIV patients prescribed naloxone modestly increased from 0.97% to 1.6% (OR, 2.2 [0.7-6.8]; P = 0.16). CONCLUSION: On-site, practice-based, peer-to-peer training with posttraining academic detailing was a modestly effective strategy to increase HIV clinicians' prescribing of naloxone.

Integrating long-acting injectable treatment to improve medication adherence among persons living with HIV and opioid use disorder: study protocol.

BACKGROUND: Oral antiretroviral therapy (ART) has been effective at reducing mortality rates of people with HIV. However, despite its effectiveness, people who use drugs face barriers to maintaining ART adherence. Receipt of opioid agonist treatment, in the context of HIV care, is associated with medication adherence and decreased HIV viral loads. Recent pharmacological advancements have led to the development of novel long-acting, injectable, medications for both HIV (cabotegravir co-administered with rilpivirine) and OUD (extended-release buprenorphine). These therapies have the potential to dramatically improve adherence by eliminating the need for daily pill-taking. Despite the extensive evidence base supporting long-acting injectable medications for both HIV and OUD, and clinical guidelines supporting integrated care provision, currently little is known about how these medications may be optimally delivered to this population. This paper presents the study design for the development of a clinical protocol to guide the delivery of combined treatment for HIV and OUD using long-acting injectable medications. METHODS: The study aims are to: (1) develop a clinical protocol to guide the delivery of combined LAI for HIV and OUD by conducting in-depth interviews with prospective patients, clinical content experts, and other key stakeholders; and (2) conduct This single group, open pilot trial protocol to assess feasibility, acceptability, and safety among patients diagnosed with HIV and OUD. Throughout all phases of the study, information on patient-, provider-, and organizational-level variables will be collected to inform future implementation. DISCUSSION: Findings from this study will inform the development of a future study to conduct a fully-powered Hybrid Type 1 Effectiveness-Implementation design.

Intersection and Considerations for Patient-Centered Care, Patient Experience, and Medication Experience in Pharmacogenomics.

As healthcare continues to embrace the concept of person- and patient-centered care, pharmacogenomics, patient experience, and medication experience will continue to play an increasingly important role in care delivery. This review highlights the intersection between these concepts and provides considerations for patient-centered medication and pharmacogenomic experiences. Elements at the patient, provider, and system level can be considered in the discussion, supporting the use of pharmacogenomics, with components of the patient and medication experience contributing to the mitigation of barriers surrounding patient use and the valuation of pharmacogenomic testing.

Assessing pharmacogenomic literacy in China through validation of the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy.

Pharmacogenomics (PGx) implementation into clinical care is rapidly increasing in China. However, the extent to which the public understands PGx testing and important knowledge domains requiring patient education or counseling remains unclear. To address this, we created and validated the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL-CTM ). The MAPL-C was developed by translating the English MAPL to Chinese following cross-cultural translation guidelines. An online survey validated the MAPL-C and assessed Chinese individuals' PGx literacy. Validation analyses were performed and associations of PGx literacy with participants' characteristics were quantified. Of 959 high-quality responses, the majority of respondents were Han Chinese (96.3%), men (54.5%), aged 18-29 years (70.9%), residing in China (97.3%), and had received college or higher education (95.0%). Out of 15 starting items developed to query specific predefined knowledge domains, two uninformative items were excluded, resulting in a 13-item MAPL-C. Chinese participants' MAPL-C performance was best explained by a three-factor model, encompassing PGx concepts and function, testing limitations, and privacy. Higher MAPL-C performance was associated with younger age, higher education, and previous genetic testing experience. Correct response rates for questions related to testing limitations were lower than those in other domains. The creation and validation of the MAPL-C fills a gap in determining PGx knowledge among Chinese speakers, quantifying PGx literacy within a Chinese cohort, and identifying response patterns and knowledge gaps. The MAPL-C can be useful in clinical practice to guide patient counseling, assess PGx education interventions, and quantify PGx knowledge in relation to outcomes in research studies involving Chinese participants.

Overdose Detection Technologies-A New Frontier in Preventing Solitary Drug Overdose Deaths.

This Viewpoint examines current opioid overdose detection technologies and their utility in detecting potential drug overdose episodes and preventing solitary overdose deaths in the US.