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Caleb J Banta-Green,1– 3 Mandy D Owens,1,4 Jason R Williams,1 Anthony S Floyd,1 Wendy Williams-Gilbert,1 Susan Kingston1 1Addictions, Drug & Alcohol Institute, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington Seattle, Seattle, WA, USA; 2Department of Health Systems and Population Health, School of Public Health, University of Washington Seattle, Seattle, WA, USA; 3Department of Epidemiology, School of Public Health, University of Washington Seattle, Seattle, WA, USA; 4Department of Psychology, University of Washington, Seattle, WA, USACorrespondence: Caleb J Banta-Green, Addictions, Drug & Alcohol Institute, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, NE Pacific St Box 356560, Seattle, WA, 98195, USA, Email calebbg@uw.eduPurpose: A large treatment gap exists for people who could benefit from medications for opioid use disorder (MOUD). People OUD accessing services in harm reduction and community-based organizations often have difficulty engaging in MOUD at opioid treatment programs and traditional health care settings. We conducted a study to test the impacts of a community-based medications first model of care in six Washington (WA) State communities that provided drop-in MOUD access.Participants and Methods: Participants included people newly prescribed MOUD. Settings included harm reduction and homeless services programs. A prospective cohort analysis tested the impacts of the intervention on MOUD and care utilization. Intervention impacts on mortality were tested via a synthetic comparison group analysis matching on demographics, MOUD history, and geography using WA State agency administrative data.Results: 825 people were enrolled in the study of whom 813 were matched to state records for care utilization and outcomes. Cohort analyses indicated significant increases for days’ supply of buprenorphine, months with any MOUD, and months with any buprenorphine for people previously on buprenorphine (all results p< 0.05). Months with an emergency department overdose did not change. Months with an inpatient hospital stay increased (p< 0.05). The annual death rate in the first year for the intervention group was 0.45% (3 out of 664) versus 2.2% (222 out of 9893) in the comparison group in the 12 months; a relative risk of 0.323 (95% CI 0.11– 0.94).Conclusion: Findings indicated a significant increase in MOUD for the intervention group and a lower mortality rate relative to the comparison group. The COVID-19 epidemic and rapid increase in non-pharmaceutical-fentanyl may have lessened the intervention impact as measured in the cohort analysis. Study findings support expanding access to a third model of low barrier MOUD care alongside opioid treatment programs and traditional health care settings.Keywords: opioid use disorder, medications for opioid use disorder, multi-site study, low-barrier care, harm reduction

Caleb J Banta-Green,1,2 Anthony S Floyd,1,3 Kristin Vick,1 Jen Arthur,1 Theresa J Hoeft,4 Judith I Tsui5 1Alcohol and Drug Abuse Institute, University of Washington, Seattle, WA, USA; 2School of Public Health, Department of Health Services, University of Washington, Seattle, WA, USA; 3School of Public Health, Department of Epidemiology, University of Washington, Seattle, WA, USA; 4Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA; 5Department of Medicine, University of Washington, Seattle, WA, USACorrespondence: Caleb J Banta-GreenAlcohol and Drug Abuse Institute, University of Washington, 1107 NE 45th Street, Suite 120, Box 354805, Seattle, WA 98105-4631, USAEmail calebbg@uw.eduPurpose: Opioid use disorder (OUD) is a medical condition that is effectively treated with medications. A major challenge in breaking the cycle of OUD and related illegal activity is seamlessly introducing medications for opioid use disorder (MOUD) as individuals leave jail or prison. We examined the feasibility of a pilot intervention to link participants to ongoing MOUD and psychosocial supports following release from custody.Methods: The study enrolled adults with a history of OUD released from Washington State prisons to Department of Corrections (DOC) community supervision. Participants were randomized to the study intervention or comparison group. The intervention consisted of education on OUD and available treatments, support with individualized treatment decision making, and continued care navigation for 6 months to facilitate linkage to chosen treatments. Participants randomized to the control condition received referral to services in the community from their community corrections officers. A care navigation activity log documented intervention participants’ intervention engagement, service utilization, and needs. Follow-up interviews were conducted at 1 and 6 months to assess satisfaction with the intervention.Results: Fifteen participants were enrolled. All were male, most were white (86.6%) and the average age was 36.9 years. The majority (14 of 15 participants) were near-daily heroin users with severe OUD prior to incarceration. Of the seven intervention participants, two wished to start medications immediately. Three participants reported starting buprenorphine or methadone in the subsequent follow-up period, with or without social support and/or outpatient counseling, and three reported enrolling in social support and/or outpatient counseling without medications. Participants who received the intervention reported high satisfaction. We discuss barriers and facilitators to study implementation.Conclusion: An intervention to link participants to ongoing MOUD and psychosocial supports following release from prison had broad acceptability among participants and was feasible to implement among those recruited; however, enrollment was much lower than anticipated and the study intervention did not demonstrate the intended effect to facilitate use of MOUD immediately post-release in this small sample of participants. Given recent research showing benefits of pre-release medication initiation, the potential added benefits of this two-part intervention should be studied in systems that initiate MOUD prior to release.Keywords: opioid use disorder, opioids, intervention development, criminal justice, treatment, feasibility study

Robin A Pollini1, Caleb J Banta-Green2, Jazmine Cuevas-Mota3, Mitcheal Metzner3, Eyasu Teshale4, Richard S Garfein31Pacific Institute for Research and Evaluation, Calverton, MD; 2Alcohol and Drug Abuse Institute, University of Washington, Seattle, WA; 3Department of Medicine, University of California San Diego, La Jolla, CA; 4National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USABackground: Misuse of prescription-type opioids and related adverse health effects are increasing, but little is known about the role of these drugs as a precursor to heroin use. We conducted an exploratory study to determine the proportion of young heroin injectors reporting problematic use of prescription-type opioids prior to using heroin, and to describe the factors associated with prior problematic prescription-type opioid use.Methods: Between March 2009 and June 2010, we recruited injection drug users (IDUs) for a cross-sectional study of hepatitis C virus infection risk. Participants were aged 18–40 years and had injected illicit drugs within the previous six months. A computerized self-administered survey assessed sociodemographics, drug use history, human immunodeficiency virus (HIV)/hepatitis C virus risk behaviors and perceptions, and medical history. We added questions on prescription-type opioid use to the parent study in March 2010; heroin injectors who subsequently enrolled and reported problematic prescription-type opioid use prior to heroin initiation were compared with other heroin IDUs using univariate and multivariate regression methods.Results: Among 123 heroin IDUs, 49 (39.8%) reported problematic prescription-type opioid use prior to heroin initiation (“prescription-type opioid first injection drug users” (PTO-First IDUs)). PTO-First IDUs had higher odds of injecting with friends (adjusted odds ratio [AOR] 6.01; 95% confidence interval [CI] 1.90–19.07), getting new syringes from a spouse/family member/sex partner (AOR 23.0; 95% CI 2.33–226.0), knowing about the local syringe exchange program (AOR 7.28; 95% CI 1.17–45.05), using powder cocaine (AOR 3.75; 95% CI 1.43–9.86), and perceiving themselves as less likely than other IDUs to get HIV (AOR 4.32; 95% CI 1.26–14.77). They had lower odds of ever being tested for HIV (AOR 0.25; 95% CI 0.08–0.80).Conclusion: A high proportion of young heroin IDUs reported problematic prescription-type opioid use prior to initiating heroin use. Our study provides several avenues for future investigation to help further characterize this subset of IDUs and their risks and perceptions related to HIV and other blood-borne pathogens.Keywords: injection drug users, prescription-type opioids

Objective: To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes.Research Design and Methods: Muscle precursor cells were isolated from four age-matched subject groups: 1) nonobese, normal glucose tolerant; 2) obese, normal glucose tolerant; 3) obese, impaired glucose tolerant; and 4) obese, type 2 diabetes (T2D). The level of inflammation (nuclear factor-κB [NF-κB] signaling) and effect of pharmacological AMPK activation was assessed by Western blots, enzyme-linked immunosorbent assay, and radioactive assays (n = 5 for each subject group).Results: NF-κB-p65 DNA binding activity was significantly elevated in myocytes from obese T2D patients compared with nonobese control subjects. This correlated to a significant increase in tumor necrosis factor-α concentration in cell culture media. In addition, insulin-stimulated glucose uptake was completely suppressed in myocytes from obese impaired glucose tolerant and T2D subjects. It is interesting that activation of AMPK by A769662 attenuated NF-κB-p65 DNA binding activity in obese T2D cells to levels measured in nonobese myocytes; however, this had no effect on insulin sensitivity of the cells.Conclusions: This work provides solid evidence that differentiated human muscle precursor cells maintain in vivo phenotypes of inflammation and insulin resistance and that obesity alone may not be sufficient to establish inflammation in these cells. It is important that we demonstrate an anti-inflammatory role for AMPK in these human cells. Despite attenuation of NF-κB activity by AMPK, insulin resistance in obese T2D cells remained, suggesting factors in addition to inflammation may contribute to the insulin resistance phenotype in muscle cells. [ABSTRACT FROM AUTHOR]

Background: Long-term opioid therapy for chronic noncancer pain is becoming increasingly common in community practice. Concomitant with this change in practice, rates of fatal opioid overdose have increased. The extent to which overdose risks are elevated among patients receiving medically prescribed long-term opioid therapy is unknown.Objective: To estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy.Design: Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at the time of overdose.Setting: HMO.Patients: 9940 persons who received 3 or more opioid prescriptions within 90 days for chronic noncancer pain between 1997 and 2005.Measurements: Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes--nonfatal and fatal overdoses--were identified through diagnostic codes from inpatient and outpatient care and death certificates and were confirmed by medical record review.Results: 51 opioid-related overdoses were identified, including 6 deaths. Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate), patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate. Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate.Limitations: Increased overdose risk among patients receiving higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation.Conclusion: Patients receiving higher doses of prescribed opioids are at increased risk for overdose, which underscores the need for close supervision of these patients.Primary Funding Source: National Institute of Drug Abuse. [ABSTRACT FROM AUTHOR]

Background: The intersection of pain, addiction and mental health has not been adequately described. We describe the roles of these three conditions in a chronic pain patient population using opioid analgesics. Aims were to improve our understanding of this population as well as to explore ways of identifying different types of patients.Methods: We conducted a retrospective cohort study in a large integrated group medical practice in Washington State with persons using opioids chronically (n=704). Patient classes were derived with latent class analysis using factors representing DSM-IV opioid abuse and dependence, opioid misuse, pain, anxiety and depression. Regression analyses explored the utility of automated and interview data to distinguish the empirically derived patient groups.Results: Three classes were identified: a Typical group, the substantial majority that had persistent, moderate mental health and pain symptoms; an Addictive Behaviors group with elevated mental health symptoms and opioid problems, but pain similar to the Typical class; and a Pain Dysfunction class with significantly higher pain interference as well as elevated mental health and opioid problems. Prescribed average daily dose of opioids was three times higher for those in the two atypical groups and was strongly associated with class membership after adjusting for other variables.Conclusion: We describe three distinct types of patient classes as well as data elements that could help identify the two atypical types. Further research is needed to confirm these findings and determine the utility of this approach in other clinical settings. [ABSTRACT FROM AUTHOR]

Skin loss following severe burn requires prompt wound closure to avoid such complications as fluid and electrolyte imbalance, infection, immune suppression, and pain. In clinical situations in which insufficient donor skin is available, the development of cultured skin equivalents (dermal matrices seeded with keratinocytes and fibroblasts) may provide a useful alternative. The aim of this study was to assess the suitability of a porcine-derived dermal collagen matrix (PermacolTM) to function as a cultured skin equivalent in supporting the growth of keratinocytes in vitro and providing cover to full thickness wounds in the BALB C/nude mouse model. A histological comparison was against Glycerol treated-Ethylene Oxide Sterilised Porcine Dermis (Gly-EO Dermis) which has successfully been used as a cultured skin equivalent in previous studies. Both Gly-EO Dermis and to a lesser extent PermacolTM were able to support the growth of cultured keratinocytes following a 16-day period of cell culture, however, this study was only able to demonstrate the presence of an epidermal layer on Gly-EO dermis 2 weeks after grafting onto full-thickness wounds in the BALB C/nude mouse model. [ABSTRACT FROM AUTHOR]

Objective: Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR, defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans., Design: Cross-sectional study in men and women across a range of adiposity., Methods: Medication-free participants (n = 177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy. Fractional gluconeogenesis (frGNG) and hepatic DNL were measured using stable isotope tracer methodology following an overnight fast., Results: Although HI and HF groups had higher fasting plasma glucose and triglyceride concentrations when compared to NI and LF groups respectively, there was no difference in frGNG. However, HF participants tended to have lower frGNG than LF participants. HI participants had higher DNL compared to NI participants but there was no difference observed between liver fat groups., Conclusions: Taken together, we found no metabolic signature of selective hepatic IR in fasting humans. DNL may contribute to hypertriglyceridemia in individuals with HI but not those with HF. Glycogenolysis and systemic glucose clearance may have a larger contribution to fasting hyperglycemia than gluconeogenesis, especially in those with HF, and these pathways should be considered for therapeutic targeting., Competing Interests: Conflict of interest: None to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background: The 2022 mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBMSM). Mpox cases continue to be reported nationally. Vaccination is a tool to prevent the spread of and serious disease from mpox. To understand mpox vaccine uptake and hesitancy, a virtual focus group with unvaccinated GBMSM was conducted., Methods: In November 2022, a 60-minute, virtual focus group was conducted within an artificial intelligence (AI) platform that engages participants in chat-based conversation. The AI system uses machine learning and natural language processing to analyze and provide results immediately to the moderator. Descriptive frequencies, cross-tabulations and qualitative themes were analyzed., Results: Fifty-one GBMSM ages 18-55 participated, of whom 12 had attempted to get the mpox vaccine. The top barriers in accessing the vaccine included challenges in scheduling appointments (4/12), available vaccine locations (3/12), and transportation (2/12). Nine participants reported not wanting the vaccine and 22 were undecided; Of these, 15 (4/9 and 11/22, respectively) said they did not think they needed the vaccine due to low perceived risk or monogamy.. Among the undecided, after receiving health messaging about mpox, 12/22 said the messaging made them reconsider getting the vaccine., Conclusion: During an outbreak, many unvaccinated GBMSM who may be at increased risk for mpox either wanted the vaccine or, with appropriate health messaging, may be open to getting the vaccine. Messaging about mpox vaccine efficacy, potential side effects, and how to access the vaccine may improve vaccine uptake especially as cases continue to occur., Competing Interests: Conflict of Interest Statement: The authors have no conflicts to disclose., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Use of immunoassay test strips for the detection of fentanyl in drug samples has become commonplace in harm reduction, law enforcement, public health, customs, and forensic science settings for testing drug product. With the increase of xylazine in the drug supply in recent years, use of xylazine test strips has also increased. As use of test strips expands, a desire to implement them for other drugs may emerge. However, since these strips are designed for urine testing, it is important to understand their applicability to testing drug product. In this work, we investigate the utility of seven types of urine immunoassay test strips - amphetamine, benzodiazepine, cocaine, methamphetamine, nitazene, opiate, and xylazine - for drug checking applications. Reproducibility, sensitivity, cross-reactivity, and the effect of prolonged exposure to elevated temperatures were studied. Generally, the tests were found to be reproducible, able to detect trace (μg/mL) levels of the analyte of interest, and minimally affected by prolonged storage at elevated temperatures. Nearly all tests showed cross-reactivity with compounds other than the analyte of interest, highlighting the need to better understand these limitations prior to implementation in a drug checking scenario. The viability of expired cocaine, fentanyl, and methamphetamine test strips was also interrogated, and little to no change in sensitivity was found even though the tests were multiple years expired.

Background: A recent multicenter trial showed a reduction in tricuspid regurgitation (TR) progression when tricuspid annuloplasty was performed at the time of surgery for degenerative mitral regurgitation (MR), but with a 14% permanent pacemaker (PPM) rate. We present real-world outcomes at a high-volume center for degenerative MR surgery with/without tricuspid annuloplasty., Methods: Patients undergoing first-time degenerative mitral surgery between 2011 and 2021 were identified (n = 1738). After excluding patients undergoing aortic, aortic valve, or tricuspid replacement procedures, patients were stratified into mitral surgery alone (n = 1068) vs mitral surgery plus tricuspid annuloplasty (n = 417). Outcomes, including operative mortality, new PPM implantation, postoperative length of stay, and risk-adjusted overall mortality, were compared., Results: Among 1485 patients in this study, 98% underwent mitral repair. Compared with concomitant tricuspid annuloplasty patients, those undergoing mitral surgery alone were 6 years younger and had lower median The Society of Thoracic Surgeons predicted risk of mortality. Among concomitant tricuspid repair patients, 85% (355 of 417) had moderate or less preoperative TR, whereas 15% (61 of 417) had severe TR. Operative mortality was 1.4%. The incidence of new PPM implantation was 0.7% (7 of 1068) in the mitral only group and 5.5% (23 of 417) in the concomitant tricuspid group (P < .001). Although unadjusted cumulative survival was lower in the concomitant tricuspid group, after risk adjustment, concomitant tricuspid surgery was not associated with worse overall mortality (hazard ratio, 0.80; 95% CI, 0.53-1.19; P = .27)., Conclusions: Concomitant tricuspid annuloplasty is safe, with no difference in mortality and a <6% PPM rate at a high-volume mitral center. These data provide real-world context for concomitant tricuspid annuloplasty., Competing Interests: Disclosures Alexander A. Brescia is an Associate Editor for Digital Media and Digital Scholarship for The Annals of Thoracic Surgery. Matthew A. Romano reports a relationship with Edwards that includes: Consulting or advisory. Gorav Ailawadi reports a relationship with Edwards that includes: Consulting or advisory; with Abbott that includes: Consulting or advisory; with Medtronic that includes: Consulting or advisory; with Philips that includes: Consulting or advisory; with Arthrex that includes: Consulting or advisory. The other authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Opioid overdose mortality in the US has exceeded one million deaths over the last two decades. A regulated opioid supply may help prevent future overdose deaths by reducing exposure to the unregulated opioid supply. We examined the acceptability, delivery model preference, and anticipated effectiveness of different regulated opioid models among people in the Seattle area who inject opioids., Methods: We enrolled people who inject drugs in the 2022 Seattle-area National HIV Behavior Surveillance (NHBS) survey. Participants were recruited between July and December 2022 using respondent-driven sampling. Participants who reported injecting opioids (N = 453) were asked whether regulated opioids would be acceptable, their preferred model of receiving regulated opioids, and the anticipated change in individual overdose risk from accessing a regulated opioid supply., Results: In total, 369 (81 %) participants who injected opioids reported that a regulated opioid supply would be acceptable to them. Of the 369 who found a regulated opioid supply to be acceptable, the plurality preferred a take-home model where drugs are prescribed (35 %), followed closely by a dispensary model that required no prescription (28 %), and a prescribed model where drugs need to be consumed on site (13 %), a model where no prescription is required and drugs can be accessed in a community setting with a one-time upfront payment was the least preferred model (5 %). Most participants (69 %) indicated that receiving a regulated opioid supply would be "a lot less risky" than their current supply, 20 % said, "a little less risky", 10 % said no difference, and 1 % said a little or a lot more risky., Conclusion: A regulated opioid supply would be acceptable to most participants, and participants reported it would greatly reduce their risk of overdose. As overdose deaths continue to increase in Washington state pragmatic and effective solutions that reduce exposure to unregulated drugs are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We report the discovery of Gordonia phage Conley, a siphovirus isolated from Cullowhee Creek in the Fall of 2022. The 60,078bp genome contains 90 predicted protein-coding genes all transcribed in the same direction and has been assigned to genetic cluster DJ based on gene content similarity., Competing Interests: The authors declare no conflict of interest.

Animals with different life histories budget their intake energy differently when food availability is low. It has been shown previously that hornworm (larva of Manduca sexta ), a holometabolous insect species with a short development stage, prioritizes growth at the price of metabolism under food restriction, but it is unclear how hemimetabolous insect species with a relatively long development period budget their intake energy under food scarcity. Here, we use orange head cockroaches ( Eublaberus posticus ) to investigate this question. We found that for both species under food restriction, rates of metabolism and growth were suppressed, but the degree of reduction was more severe in growth than that of metabolism for cockroaches. Under both free-feeding and food restriction conditions, hornworms allocated a larger fraction of assimilated energy to growth than to metabolism, and cockroaches were the opposite. More importantly, when food availability was low, the fraction of assimilated energy allocated to growth was reduced by 120% in cockroaches, and the energy from growth was channeled to compensate for the reduction in metabolism; but, the fraction of assimilated energy allocated to growth was only reduced by 14% in hornworms. These results suggest that, compared to hornworms, cockroaches prioritize metabolism over growth.

Background: Methamphetamine overdose can cause severe psychological and physical health issues including psychosis, heart attack, and death. People who use methamphetamine (PWUM) who experience methamphetamine overdose symptoms (MOS) are advised to seek emergency healthcare; however, factors related to seeking care are not well characterized., Methods: This study used data from the 2021 Washington State Syringe Services Program (SSP) Health Survey, a cross-sectional survey administered to participants at 21 SSPs in Washington ( N  = 955). Participants answered questions related to substance use including emergency department/room (ER) utilization for methamphetamine use and whether they experienced psychological and physical MOS. Using Poisson regression, we assessed the association between ER utilization for methamphetamine use, non-fatal opioid overdose, and other key covariates among PWUM who experienced MOS., Results: Methamphetamine use in the last three months was reported by 86% of participants. Among PWUM, 31% reported psychological MOS, 19% reported physical MOS, and 37% reported ≥1 MOS in the prior three months. Non-fatal opioid overdose (adjusted prevalence ratio [APR] = 2.04, 95% CI = 1.38-3.03), main drug of goofball (heroin and methamphetamine combined) (APR = 1.98, 95% CI = 1.34-2.92) and recent blood infection/sepsis (APR = 2.07, 95% CI = 1.24-3.46) were associated with ER utilization for MOS., Conclusion: Among people who use SSPs in Washington State, methamphetamine use remains high, and MOS are common. Recent non-fatal opioid overdose was positively associated with ER utilization for methamphetamine use among PWUM who experienced MOS. Patients in the ER for MOS should be screened for opioid use disorder and linked with harm reduction supplies like naloxone and medications for opioid use disorder.

Background: Naloxone distribution has been implemented as an essential opioid overdose prevention measure for people who inject drugs (PWID), and many jurisdictions in the United States have implemented policy change to increase naloxone access. This project describes temporal trends in and correlates of naloxone possession and use among PWID in the Seattle area of Washington State., Methods: Using a repeat cross-sectional design, we utilized two sets of serial cross-sectional surveys of PWID, which included biennial surveys of Seattle area syringe service program (SSP) clients and community-based National HIV Behavioral Surveillance surveys of PWID (NHBS-PWID) conducted from 2012-2019. Survey participant characteristics were descriptively compared between participants reporting naloxone possession to those not reporting naloxone possession. Multivariable Poisson regression was used to calculate prevalence ratios for naloxone possession comparing later to earlier survey years, adjusting for age, gender, race/ethnicity, primary drug, and experiencing and witnessing an overdose in the past 12 months., Results: Naloxone possession and use increased in both survey populations. The prevalence of possessing naloxone was 2.8 times greater [2019 vs. 2013= 95% CI: 2.40-3.33] among SSP participants and 2.8 times greater [2018 vs. 2012=95% CI: 2.41-3.16] among NHBS-PWID participants for the most recent time period. The prevalence of naloxone use was 1.3 times greater [2019 vs. 2017= 95% CI: 1.13-1.58] and 2.1 times greater [2015 vs. 2012=95% CI:1.62-2.73] among SSP and NHBS-PWID participants, respectively, for the most recent time period., Conclusion: Naloxone possession and use increased in PWID in the Seattle area from 2012-2019, and is, at least in part, likely the result of numerous policy and programmatic efforts to facilitate easier naloxone accessibility in the wake of dramatic increases in overdose mortality. Further research on disparities in naloxone possession are needed to ensure equitable access., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Advancing age is the greatest risk factor for developing multiple age-related diseases. Therapeutic approaches targeting the underlying pathways of ageing, rather than individual diseases, may be an effective way to treat and prevent age-related morbidity while reducing the burden of polypharmacy. We harness the Open Targets Genetics Portal to perform a systematic analysis of nearly 1,400 genome-wide association studies (GWAS) mapped to 34 age-related diseases and traits, identifying genetic signals that are shared between two or more of these traits. Using locus-to-gene (L2G) mapping, we identify 995 targets with shared genetic links to age-related diseases and traits, which are enriched in mechanisms of ageing and include known ageing and longevity-related genes. Of these 995 genes, 128 are the target of an approved or investigational drug, 526 have experimental evidence of binding pockets or are predicted to be tractable, and 341 have no existing tractability evidence, representing underexplored genes which may reveal novel biological insights and therapeutic opportunities. We present these candidate targets for exploration and prioritisation in a web application., (© 2023. Springer Nature Limited.)

Background: Syringe service programs (SSPs) provide tools to people who inject drugs (PWID) to prevent overdose, reduce the risk of HIV and HCV infection, and reduce injection frequency. While effective, previous research suggests that SSPs may not adequately reach some marginalized or particularly vulnerable subpopulations of PWID., Methods: To identify disparities in SSP use, data from two cross-sectional surveys conducted in King County, Washington were compared: a survey of SSP clients and a community survey of PWID in King County. It was hypothesized that Black PWID, women, and gender minorities would be underrepresented in the SSP survey relative to the general population of PWID., Results: SSP clients identified as White at a significantly higher rate than the community sample of PWID (p = 0.030). Black (p < 0.001), American Indian/Alaska Native (p < 0.001), Latinx/Hispanic (p = 0.009), and Native Hawaiian/ Pacific Islander PWID (p = 0.034) were underrepresented in the SSP client survey. The gender of SSP clients was similar to the distribution seen in the community sample of PWID (p = 0.483)., Conclusions: Black PWID are underrepresented in Seattle-area SSPs, consistent with studies in other large US cities. Both nationally and in Seattle, overdose deaths have been increasing among Black PWID, and harm reduction strategies are vital to reversing this trend. SSPs should explore and test ways to be more accessible to minority populations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background : Adolescent opioid use and associated opioid poisoning rates have risen dramatically in the United States, yet this group has disproportionally poorer access to evidence-based medication treatment for opioid use disorder (MOUD). Methods : A transdisciplinary cohort (N = 77) who attended a learning series focused on MOUD for adolescents were surveyed with the purpose of understanding the landscape of current adolescent MOUD practices in Washington State; and needs and barriers to providing care. Results : Results indicated that a higher percentage of prescriber participants endorsed support for MOUD for adolescents than nonprescriber participants. Lack of adjunctive support services (i.e., social work; mental health) were cited as the highest barriers to providing this care. Conclusions : We discuss the importance of continued transdisciplinary training and collaboration, as well as funding ancillary services to address barriers to providing adolescent MOUD.

The viability of embryos cultured in vitro is poor compared to those that develop in vivo . The lack of maternally derived growth factors in vitro may contribute to this problem. Insulin-like growth factor binding protein 3 (IGFBP3) is one such growth factor that has been identified in the maternal reproductive system. This study examined the role of autocrine and exogenous IGFBP3 in mouse preimplantation embryos. Embryos expressed IGFBP3 across all stages of preimplantation development, and addition of exogenous IGFBP3 to embryo culture media increased the rate of development to the 2-, 4-, 5-, and 8-cell stages. Addition of inhibitors of the IGF1 and EGF receptors prevented this IGFBP3-mediated improvement in developmental rate, but the effect was not cumulative, indicating that both receptors are transactivated downstream of IGFBP3 as part of the same signalling pathway. Acute exposure to IGFBP3 increased phosphorylation of Akt and rps6 in 4-8 cell embryos, suggesting activation of the PI3-kinase/Akt pathway downstream of the IGF1 and EGFR receptors to promote cell proliferation and survival. In conclusion, addition of IGFBP3 to embryo culture media increases early cleavage rates independent of IGF1 signalling and therefore, IGFBP3 addition to IVF culture media should be considered.

Background: Opioid use disorder (OUD) is a serious health condition that is effectively treated with buprenorphine. However, only a minority of people with OUD are able to access buprenorphine. Many access points for buprenorphine have high barriers for initiation and retention. Health care and drug treatment systems have not been able to provide services to all-let alone the majority-who need it, and many with OUD report extreme challenges starting and staying on buprenorphine in those care settings. We describe the design and protocol for a study of a rapid access buprenorphine program model in six Washington State communities at existing sites serving people who are unhoused and/or using syringe services programs. This study aimed to test the effectiveness of a Community-Based Medication-First Program model., Methods: We are conducting a hybrid effectiveness-implementation study of a rapid access buprenorphine model of care staffed by prescribers, nurse care managers, and care navigators. The Community-Based Medication-First model of care was designed as a 6-month, induction-stabilization-transition model to be delivered between 2019 and 2022. Effectiveness outcomes will be tested by comparing the intervention group with a comparison group derived from state records of people who had OUD. Construction of the comparison group will align characteristics such as geography, demographics, historical rates of arrests, OUD medication, and health care utilization, using restriction and propensity score techniques. Outcomes will include arrests, emergency and inpatient health care utilization, and mortality rates. Descriptive statistics for buprenorphine utilization patterns during the intervention period will be documented with the prescription drug monitoring program., Discussion: Results of this study will help determine the effectiveness of the intervention. Given the serious population-level and individual-level impacts of OUD, it is essential that services be readily available to all people with OUD, including those who cannot readily access care due to their circumstances, capacity, preferences, and related systems barriers., (© 2022. The Author(s).)

Despite significant investigation of fly ash spills and mineralogical controls on the release of potentially toxic elements (PTEs) from fly ash, interactions with the surficial environment remain relatively poorly understood. We conducted 90-day batch leaching studies with paired analysis of supernatant and solid-phase mineralogy to assess the elemental release and transformation of fly ash upon reaction with aquatic media (18 MΩ cm -1 water and simulated rainwater). The fly ash in this study, collected from the University of Alaska Fairbanks stoker-boiler power plant, is high in unburned carbon (~20% LOI) and highly enriched in several PTEs relative to the upper continental crust. Supernatant concentrations of oxyanion-forming elements (e.g., As, Se, Mo, Sb) remained relatively low and constant, suggesting equilibrium with the solid phase, possibly ettringite [Ca 6 Al 2 (SO 4 ) 3 (OH) 12 •26H 2 O], which is known to incorporate and sorb oxyanion-forming PTEs and was identified by X-ray diffraction. Synthetic precipitation leaching procedure (SPLP) results failed to capture important temporal trends. Lead and Ba supernatant concentrations consistently exceeded drinking water standards, as well as others upon exposure to simulated physiological solutions. Seven-day experiments with dissolved organic matter-isolate solutions indicated that for certain elements, liberation was influenced by carbon concentration and/or the identity of the isolate. Overall, this paired approach can serve as a model for future studies, bridging existing gaps between batch leaching and single-element mineralogical, sorption, or speciation studies., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Opioid use disorder (OUD) and related comorbid conditions are highly prevalent among patients presenting to emergency department (ED) settings. Research has developed few comprehensive disease management strategies for at-risk patients presenting to the ED that both decrease illicit opioid use and improve initiation and retention in medication treatment for OUD (MOUD)., Methods: The research team conducted a pilot pragmatic clinical trial that randomized 40 patients presenting to a single ED to a collaborative care intervention (n = 20) versus usual care control (n = 20) conditions. Interviewers blinded to patient intervention and control group status followed-up with participants at 1, 3, and 6 months after presentation to the ED. The 3-month Emergency Department Longitudinal Integrated Care (ED-LINC) collaborative care intervention for patients at risk for OUD included: 1) a Brief Negotiated Interview at bedside, 2) overdose education and facilitation of MOUD, 3) longitudinal proactive care management, 4) utilization of the statewide health information exchange platform for 24/7 tracking of recurrent ED utilization, and 5) weekly caseload supervision that incorporated measurement-based care treatment assessment with stepped-up care for patients with recalcitrant symptoms., Results: Overall, the ED-LINC intervention was feasibly delivered and acceptable to patients. The pilot study achieved >80% follow-up rates at 1, 3, and 6 months. In adjusted longitudinal mixed model regression analyses, no statistically significant differences existed in days of opioid use over the past 30 days for ED-LINC intervention patients when compared to patients receiving usual care (incidence-rate ratio (IRR) 1.50, 95% CI 0.54-4.16). The unadjusted mean number of days of illicit opioid use decreased at the 1-month and 3-month follow-up time points for both groups. ED-LINC intervention patients had increased rates of MOUD initiation compared to control patients (50% versus 30%); intervention versus control comparisons did not achieve statistical significance, although power to detect significant differences in the pilot was limited., Conclusions: The ED-LINC intervention for patients with OUD can be feasibly implemented and warrants testing in larger scale, adequately powered randomized pragmatic clinical trial investigations., Clinicaltrials: gov NCT03699085., (Copyright © 2021 Elsevier Inc. All rights reserved.)