Barriers to, and Facilitators of, Checking Drugs for Adulterants in the Era of Fentanyl and Xylazine: Qualitative Study.

BACKGROUND: Overdose deaths continue to reach new records in New York City and nationwide, largely driven by adulterants such as fentanyl and xylazine in the illicit drug supply. Unknowingly consuming adulterated substances dramatically increases risks of overdose and other health problems, especially when individuals consume multiple adulterants and are exposed to a combination of drugs they did not intend to take. Although test strips and more sophisticated devices enable people to check drugs for adulterants including fentanyl and xylazine prior to consumption and are often available free of charge, many people who use drugs decline to use them. OBJECTIVE: We sought to better understand why people in the New York City area do or do not check drugs before use. We plan to use study findings to inform the development of technology-based interventions to encourage consistent drug checking. METHODS: In summer 2023, team members who have experience working with people who use drugs conducted 22 semistructured qualitative interviews with a convenience sample of people who reported illicit drug use within the past 90 days. An interview guide examined participants' knowledge of and experience with adulterants including fentanyl, xylazine, and benzodiazepines; using drug testing strips; and whether they had ever received harm reduction services. All interviews were audio recorded, transcribed, and analyzed for emerging themes. RESULTS: Most participants lacked knowledge of adulterants, and only a few reported regularly checking drugs. Reasons for not checking included lacking convenient access to test supplies, or a place to check samples out of the public's view, as well as time considerations. Some participants also reported a strong belief that they were not at risk from fentanyl, xylazine, or other adulterants because they exclusively used cocaine or crack, or that they were confident the people they bought drugs from would not sell them adulterated substances. Those who did report testing their drugs described positive interactions with harm reduction agency staff. CONCLUSIONS: New forms of outreach are needed not only to increase people's knowledge of adulterated substances and awareness of the increasing risks they pose but also to encourage people who use drugs to regularly check their substances prior to use. This includes new intervention messages that highlight the importance of drug checking in the context of a rapidly changing and volatile drug supply. This messaging can potentially help normalize drug checking as an easily enacted behavior that benefits public health. To increase effectiveness, messages can be developed with, and outreach can be conducted by, trusted community members including people who use drugs and, potentially, people who sell drugs. Pairing this messaging with access to no-cost drug-checking supplies and equipment may help address the ongoing spiral of increased overdose deaths nationwide.

Exploration of weekly variation in naloxone possession and carriage among people who use opioids in New York City before, during, and after the COVID-19 pandemic.

BACKGROUND: Naloxone is critical for reversing opioid-related overdoses. However, there is a dearth of research examining how naloxone possession and carriage are impacted by time-varying individual and social determinants, and if this differed during the height of the COVID-related mitigation measures (e.g., shutdowns). METHODS: We utilized weekly ecological momentary assessments (EMA) to measure factors associated with naloxone possession and carriage among 40 people who use illicit opioids in New York City, for 24 months. Descriptive statistics were used to explore the frequency of weeks with consistent naloxone possession and carriage. Mixed effects binary and multivariable logistic regression was used to test for the impact of time-varying EMA- and baseline-level factors on each outcome. RESULTS: Approximately 70% of weekly EMAs were associated with consistent naloxone possession or carriage. In multivariable models, compared to during the height of the COVID-related shutdowns (March 12, 2020-May 19, 2021), the time before was associated with lower odds of consistent possession (Odds Ratio (OR) = 0.05, 95% Confidence Interval (CI) = 0.01-0.15) and consistent carriage (OR = 0.06, CI = 0.01-0.25). Additionally, being female (OR = 11.15, CI = 2.85-43.42), being White versus being Black or Hispanic/Latinx (OR = 8.05, CI = 1.96-33.06), and lifetime overdose (OR = 1.96, CI = 1.16-19.80) were associated with higher odds of consistent possession. Recent opioid injection (OR = 3.66, CI = 1.34-9.94), being female (OR = 7.91, CI = 3.91-8.23), and being White (OR = 5.77, CI = 1.35-24.55) were associated with higher odds of consistent carriage. Not wanting to be perceived as a drug user was reported in nearly one third (29.0%; 190/656) of EMAs where inconsistent possession was reported. CONCLUSIONS: Our findings paint a relatively positive picture of possession and carriage during COVID-related shutdowns, particularly among white and female participants, and highlight the importance of capturing time-varying factors to understand naloxone-related behavior. To curb growing disparities, outreach to equip Black and Hispanic/Latinx people with naloxone is needed as well as interventions to reduce stigma as a barrier to naloxone engagement.

Overdose Risk and Brain Injury (Traumatic Brain Injury/Acquired Brain Injury), A Commentary.

OBJECTIVE: This commentary seeks to evaluate existing knowledge about the relationship between brain injury (BI) and overdose (OD), to unify distant bodies of literature, and to enhance prevention and treatment for opioid OD among individuals with BI. BACKGROUND: There is a hidden epidemic of undiagnosed BI in the United States. Due to lack of screening, the vast majority of BI sufferers do not know they have a BI. Not only are those with BI at elevated risk for opioid use, misuse, and opioid use disorder, but also they are at elevated risk for OD. Conversely, those with OUD and those who experienced an OD, are more likely to sustain BI. Key Findings/Conclusions: The existing literature suggests that primary strategies to reduce ABI (Acquired Brain Injury)/TBI (Traumatic Brain Injury) harms involve addressing: screening, stigma, racial disparities, and popular misconceptions about OD. The association between TBI and OD is an underexamined public health issue, exacerbated by the bidirectional nature of the relationship. Not only is TBI a risk factor for opioid OD; opioid OD was also found to be a major cause of ABI, which can have lifelong effects similar to Alzheimer's disease. Screening tools for BI were underutilized and inconsistently implemented across reviewed studies. Enhanced screening population wide is a promising intervention, complemented with expanded treatment and research. Black individuals face worse outcomes in BI and treatment outcomes. Anti-racist strategies must fight inequity while addressing social and structural drivers of overdose and BI within the opioid and opioid overdose crises.

The adaptive immune response to Trichuris in wild versus laboratory mice: An established model system in context.

Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to 'real world' immune function.

The diagnostic journey of pulmonary arterial hypertension patients: results from a multinational real-world survey.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening, progressive disease often diagnosed late in its course. OBJECTIVES: To present patient-reported data that were captured within a large, multinational, point-in-time survey of PAH-treating physicians and their patients to better understand the diagnostic journey. DESIGN: Cross-sectional survey conducted in five European countries (EU5), Japan and the USA. METHODS: PAH-treating pulmonologists, cardiologists, rheumatologists or internists (USA only) completed a patient record form (PRF) for the next four consecutive adult PAH patients they saw; these patients filled in a patient self-completion (PSC) form on an anonymous, voluntary basis. Our report focuses on patient data; data are from PSC forms unless stated otherwise. RESULTS: Physician-reported PRFs and self-completed PSC forms were obtained for 1152 and 572 patients, respectively. Patients' mean (SD) age was 59.1 (14.0) years, 55.6% were female, and 57.3% had idiopathic PAH. Patient-reported data showed an average delay of 17.0 months between symptom onset and PAH diagnosis. This is longer than physicians estimated (13.8 months): this disparity may be partly due to the time taken by patients to consult a physician about their symptoms [9.6 months overall, longest in the USA (15.3 months)]. Most patients (71.6%) initially consulted primary care physicians about their symptoms and 76.4% of patients were referred to a specialist. Misdiagnoses occurred in 40.9% of patients [most frequent in the USA (51.3%), least common in Japan (27.6%)] and they saw an average of 2.9 physicians overall (3.5 in EU5 versus 2.0 in Japan/USA) before being diagnosed. Diagnosis was most often made by cardiologists (50.4%) or pulmonologists (49.3%). CONCLUSION: Our data suggest that diagnostic delay in PAH results from patient- and physician-related factors, which differ across regions and include lack of awareness of PAH on both sides. Development of better screening strategies may help address this barrier to timely PAH diagnosis.

Evaluation of self-directed specimen collection for chlamydia and gonorrhea testing among people who use drugs.

Background: People who use drugs (PWUD) often have elevated sexually transmitted infection (STI) risk and unmet healthcare needs. Self-directed STI specimen collection (i.e., individuals collect the specimen and mail to the laboratory) may be valuable in addressing STI testing barriers among PWUD. Methods: Within a cohort study among PWUD in New York City, we conducted a cross-sectional substudy from November 2021-August 2022 assessing sexual health with a one-time online survey (n = 120); participants could opt-in to receive a self-collection kit. Participants who opted-in were mailed a kit containing collection materials (males: urine cup, females: vaginal swab), pre-paid return label, instructions, and educational information. Specimens were sent to the laboratory and tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). We measured the number of kits requested, delivered, mailed to the lab, and CT/GC positive; and examined differences in requesting a kit by sociodemographic and behavioral characteristics. Results: Sixty-three total kits were requested by 44 unique participants. Of the 63 requested, 41 were delivered; one kit was undeliverable at the provided address and the rest were not sent due to no address provided or being duplicate requests. Of the 41 kits delivered, three participants returned the kit to the lab; of those, one was positive for CT and GC. The greatest differences in those who did and did not request a kit were observed by age, sexual orientation, past-year sex trade and casual partnerships, and experiences of relationship violence. Conclusions: Self-directed specimen collection may be desirable for PWUD, but research is needed to understand barriers to this testing approach for this population.

"As safe as possible": a qualitative study of opioid withdrawal and risk behavior among people who use illegal opioids.

BACKGROUND: Opioid withdrawal is a regular occurrence among many people who use illicit opioids (PWUIO) that has also been shown to increase their willingness to engage in risk-involved behavior. The proliferation of fentanyl in the illicit opioid market may have amplified this relationship, potentially putting PWUIO at greater risk of negative health outcomes. Understanding the relationship between withdrawal and risk-involved behavior may also have important implications for the ways that problematic drug use is conceptualized, particularly in disease models of addiction, which position risk behavior as evidence of pathology that helps to justify ontological distinctions between addicts and non-addicts. Examining withdrawal, and its role in PWUIO's willingness to engage in risk, may aid in the development of alternative theories of risk involvement and create discursive spaces for de-medicalizing and de-othering people who use illegal drugs. METHODS: This article is based on 32 semi-structured interviews with PWUIO in the New York City area who also reported recent withdrawal experience. Interviews were conducted remotely between April and August 2022 and recorded for later transcription. Data were then coded and analyzed based on a combination of inductive and deductive coding strategies and informed by the literature. RESULTS: Participants described a strong relationship between withdrawal and their willingness to engage in risk-involved behavior that was exacerbated by the proliferation of fentanyl. Yet, their descriptions did not align with narratives of risk as a product of bad decisions made by individuals. Rather, data demonstrated the substantial role of social and structural context, particularly drug policies like prohibition and criminalization, in the kinds of risks that PWUIO faced and their ability to respond to them. CONCLUSIONS: Withdrawal should be taken more seriously both from an ethical perspective and as an important catalyst of risk behavior. However, theories that position activities taken to avoid withdrawal as irrational and as evidence of pathology are poorly aligned with the complexity of PWUIO's actual lives. We recommend the use of less deterministic and less medicalized theories of risk that better account for differences between how people view the world, and for the role of socio-structural forces in the production of risk.

Pathways to racial disparities in the effects of Good Samaritan Laws: A mixed methods pilot study.

BACKGROUND: Drug overdose deaths continue to rise, and considerable racial inequities have emerged. Overdose Good Samaritan laws (GSLs) are intended to encourage overdose witnesses to seek emergency assistance. However, evidence of their effectiveness is mixed, and little is known regarding racial disparities in their implementation. This study examined GSL impact by assessing racial differences in awareness of and trust in New York state's GSL. METHODS: Using a sequential mixed methods design, Black and white participants were recruited from an existing longitudinal cohort study of people who use illicit opioids in New York City to participate in a quantitative survey and qualitative interviews. Racially stratified survey responses were analyzed using chi-squared tests, Fisher exact tests, or t-tests. Qualitative interviews were analyzed using a hybrid inductive-deductive approach. RESULTS: Participants (n=128) were 56% male and predominantly aged 50 years or older. Most met criteria for severe opioid use disorder (81%). Fifty-seven percent reported that the New York GSL makes them more likely to call 911 even though 42% reported not trusting law enforcement to abide by the GSL; neither differed by race. Black people were less likely to have heard of the GSL (36.1% vs 60%) and were less likely to have accurate information regarding its protections (40.4% vs 49.6%). CONCLUSIONS: Though GSLs may reduce negative impacts of the criminalization of people who use drugs, their implementation may exacerbate existing racial disparities. Resources should be directed towards harm reduction strategies that do not rely on trust in law enforcement.

Racial/ethnic disparities in opioid overdose prevention: comparison of the naloxone care cascade in White, Latinx, and Black people who use opioids in New York City.

BACKGROUND: Drug overdose mortality is rising precipitously among Black people who use drugs. In NYC, the overdose mortality rate is now highest in Black (38.2 per 100,000) followed by the Latinx (33.6 per 100,000) and white (32.7 per 100,000) residents. Improved understanding of access to harm reduction including naloxone across racial/ethnic groups is warranted. METHODS: Using data from an ongoing study of people who use illicit opioids in NYC (N = 575), we quantified racial/ethnic differences in the naloxone care cascade. RESULTS: We observed gaps across the cascade overall in the cohort, including in naloxone training (66%), current possession (53%) daily access during using and non-using days (21%), 100% access during opioid use (20%), and complete protection (having naloxone and someone who could administer it present during 100% of opioid use events; 12%). Naloxone coverage was greater in white (training: 79%, possession: 62%, daily access: 33%, access during use: 27%, and complete protection: 13%, respectively) and Latinx (training: 67%, possession: 54%, daily access: 22%, access during use: 24%, and complete protection: 16%, respectively) versus Black (training: 59%, possession: 48%, daily access:13%, access during use: 12%, and complete protection: 8%, respectively) participants. Black participants, versus white participants, had disproportionately low odds of naloxone training (OR 0.40, 95% CI 0.22-0.72). Among participants aged 51 years or older, Black race (versus white, the referent) was strongly associated with lower levels of being trained in naloxone use (OR 0.20, 95% CI 0.07-0.63) and having 100% naloxone access during use (OR 0.34, 95% CI 0.13-0.91). Compared to white women, Black women had 0.27 times the odds of being trained in naloxone use (95% CI 0.10-0.72). CONCLUSIONS: There is insufficient protection by naloxone during opioid use, with disproportionately low access among Black people who use drugs, and a heightened disparity among older Black people and Black women.

How the rural risk environment underpins hepatitis C risk: Qualitative findings from rural southern Illinois, United States.

BACKGROUND: Hepatitis C virus (HCV) infection has increased among persons who inject drugs (PWID) in the United States with disproportionate burden in rural areas. We use the Risk Environment framework to explore potential economic, physical, social, and political determinants of hepatitis C in rural southern Illinois. METHODS: Nineteen in-depth semi-structured interviews were conducted with PWID from August 2019 through February 2020 (i.e., pre-COVID-19 pandemic) and four with key informants who professionally worked with PWID. Interviews were recorded, professionally transcribed, and coded using qualitative software. We followed a grounded theory approach for coding and analyses. RESULTS: We identify economic, physical, policy, and social factors that may influence HCV transmission risk and serve as barriers to HCV care. Economic instability and lack of economic opportunities, a lack of physically available HCV prevention and treatment services, structural stigma such as policies that criminalize drug use, and social stigma emerged in interviews as potential risks for transmission and barriers to care. CONCLUSION: The rural risk environment framework acknowledges the importance of community and structural factors that influence HCV infection and other disease transmission and care. We find that larger structural factors produce vulnerabilities and reduce access to resources, which negatively impact hepatitis C disease outcomes.

I Don't Believe a Person Has to Die When Trying to Get High: Overdose Prevention and Response Strategies in Rural Illinois.

BACKGROUND: Overdose is a leading cause of morbidity and mortality among people who inject drugs. Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths. METHODS: Semi-structured interviews were conducted with 23 participants (19 persons who inject drugs and 4 service providers) from rural southern Illinois. Data were analyzed using constant comparison and theoretical sampling methods. RESULTS: Participants were concerned about the growing presence of fentanyl in both opioids and stimulants, and many disclosed overdose experiences. Strategies participants reported using to lower overdose risk included purchasing drugs from trusted sellers and modifying drug use practices by partially injecting and/or changing the route of transmission. Approximately half of persons who inject drugs sampled had heard of fentanyl test strips, however fentanyl test strip use was low. To reverse overdoses, participants reported using cold water baths. Use of naloxone to reverse overdose was low. Barriers to naloxone access and use included fear of arrest and opioid withdrawal. CONCLUSIONS: People who inject drugs understood fentanyl to be a potential contaminant in their drug supply and actively engaged in harm reduction techniques to try to prevent overdose. Interventions to increase harm reduction education and information about and access to fentanyl test strips and naloxone would be beneficial.

MIMIC-IV on FHIR: converting a decade of in-patient data into an exchangeable, interoperable format.

OBJECTIVE: Convert the Medical Information Mart for Intensive Care (MIMIC)-IV database into Health Level 7 Fast Healthcare Interoperability Resources (FHIR). Additionally, generate and publish an openly available demo of the resources, and create a FHIR Implementation Guide to support and clarify the usage of MIMIC-IV on FHIR. MATERIALS AND METHODS: FHIR profiles and terminology system of MIMIC-IV were modeled from the base FHIR R4 resources. Data and terminology were reorganized from the relational structure into FHIR according to the profiles. Resources generated were validated for conformance with the FHIR profiles. Finally, FHIR resources were published as newline delimited JSON files and the profiles were packaged into an implementation guide. RESULTS: The modeling of MIMIC-IV in FHIR resulted in 25 profiles, 2 extensions, 35 ValueSets, and 34 CodeSystems. An implementation guide encompassing the FHIR modeling can be accessed at mimic.mit.edu/fhir/mimic. The generated demo dataset contained 100 patients and over 915 000 resources. The full dataset contained 315 000 patients covering approximately 5 840 000 resources. The final datasets in NDJSON format are accessible on PhysioNet. DISCUSSION: Our work highlights the challenges and benefits of generating a real-world FHIR store. The challenges arise from terminology mapping and profiling modeling decisions. The benefits come from the extensively validated openly accessible data created as a result of the modeling work. CONCLUSION: The newly created MIMIC-IV on FHIR provides one of the first accessible deidentified critical care FHIR datasets. The extensive real-world data found in MIMIC-IV on FHIR will be invaluable for research and the development of healthcare applications.

Provider Perspectives on Barriers to Routine HIV Testing of Adolescent and Young Adult Patients in Emergency Department Settings.

HIV testing rates among US youth aged 13-24 years are sub-optimal, with high rates of missed testing opportunities in emergency departments (EDs). We assessed barriers to routine HIV testing of youth in urban ED settings from the perspective of healthcare providers. Ten physicians and nurses were recruited from the pediatric and adult EDs at a high-volume hospital in New York City, USA to complete in-depth interviews to provide their perspectives on barriers to routine HIV testing of youth ages 13 to 24 in EDs. Interviews were conducted using a semi-structured interview guide with questions and probes. All interviews were conducted via Zoom due to the COVID-19 pandemic and were audio-recorded and transcribed verbatim. Transcripts were coded independently by two researchers using an inductive thematic analysis approach. Participants often offered HIV testing to youth in the ED based on their perceptions of patients' HIV risk, with pediatric providers sometimes discouraging adolescents they perceived to be at low HIV risk from testing. Participants cited other priorities, logistics of blood-based testing, and discomfort discussing HIV as other reasons for not offering HIV testing to all youth in the ED. Efforts are needed to encourage providers to offer HIV testing to all youth regardless of perceived risk, as the ED often serves as youths' only point of contact with the healthcare system. Emphasis on this and the importance of early detection, along with institutional change, clear guidance, and support for the testing process may help increase youth testing and avoid missed HIV diagnosis opportunities.

The wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype.

The murine bone marrow has a central role in immune function and health as the primary source of leukocytes in adult mice. Laboratory mice provide a human-homologous, genetically manipulable and reproducible model that has enabled an immeasurable volume of high-quality immunological research. However, recent research has questioned the translatability of laboratory mouse research into humans and proposed that the exposure of mice to their wild and natural environment may hold the key to further immunological breakthroughs. To date, there have been no studies providing an in-depth cellular analysis of the wild mouse bone marrow. This study utilized wild mice from an isolated island population (Isle of May, Scotland, UK) and performed flow cytometric and histological analysis to characterize the myeloid, lymphoid, hematopoietic progenitor, and adipocyte compartments within the wild mouse bone marrow. We find that, compared to laboratory mouse bone marrow, the wild mouse bone marrow differs in every cell type assessed. Some of the major distinctions include; a smaller B cell compartment with an enriched presence of plasma cells, increased proportions of KLRG1+ CD8+ T cells, diminished CD11b expression in the myeloid lineage and a five-fold enlargement of the eosinophil compartment. We conclude that the wild mouse bone marrow is dramatically distinct from its laboratory counterparts, with multiple phenotypes that to our knowledge have never been observed in laboratory models. Further research into these unique features may uncover novel immunological mechanisms and grant a greater understanding of the role of the immune system in a natural setting.

Using the participatory education and research into lived experience (PEARLE) methodology to localize content and target specific populations.

Technology-based behavioral health interventions offer potentially limitless opportunities to localize content and target specific populations. However, this ability to customize requires developers to make a wide range of decisions not only about who should appear on screen, but how each message should be refined to most effectively reach a particular group of intervention recipients. These issues become especially salient as interventions are scaled for delivery to multiple populations in different geographical locations or settings (e.g., a hospital emergency department versus the drop-in center of a community-based clinic), and in more than one language. To facilitate evidence-based development of customized, targeted intervention content, our team created a multi-step methodology over a series of NIH-funded research projects. The resulting Participatory Education and Research into Lived Experience (PEARLE) Methodology entails formative qualitative interviews to examine why members of a given population do not enact a specific health behavior such as HIV/HCV testing or vaccinating against COVID-19 (this step includes identifying potential gaps in related health literacy), followed by iterative evaluations of draft content designed to address these barriers, and extensive discussions with a Community Advisory Board. The final step is a clinical trial. PEARLE is designed to be highly flexible, adaptable to a variety of behavioral outcomes in clinical and community settings, and to create content in more than one language depending on the needs or preferences of a population. The current paper discusses how our team employed PEARLE to develop content in English and Spanish for our latest project, which is intended to increase COVID-19 vaccination uptake among people who inject drugs.

Targeting Apollo-NADP+ to Image NADPH Generation in Pancreatic Beta-Cell Organelles.

NADPH/NADP+ redox state supports numerous reactions related to cell growth and survival; yet the full impact is difficult to appreciate due to organelle compartmentalization of NADPH and NADP+. To study glucose-stimulated NADPH production in pancreatic beta-cell organelles, we targeted the Apollo-NADP+ sensor by first selecting the most pH-stable version of the single-color sensor. We subsequently targeted mTurquoise2-Apollo-NADP+ to various organelles and confirmed activity in the cytoplasm, mitochondrial matrix, nucleus, and peroxisome. Finally, we measured the glucose- and glutamine-stimulated NADPH responses by single- and dual-color imaging of the targeted sensors. Overall, we developed multiple organelle-targeted Apollo-NADP+ sensors to reveal the prominent role of beta-cell mitochondria in determining NADPH production in the cytoplasm, nucleus, and peroxisome.

U.S. Military veterans and the opioid overdose crisis: a review of risk factors and prevention efforts.

U.S. military veterans have been heavily impacted by the opioid overdose crisis, with drug overdose mortality rates increasing by 53% from 2010-2019. Risk for overdose among veterans is complex and influenced by ongoing interaction among physiological/biological, psychological, and socio-structural factors. A thorough understanding of opioid-related overdose among veterans, one that goes beyond simple pharmacological determinism, must examine the interplay of pain, pain treatment, and stress, as well as psychological and social experiences-before, during, and after military service. Comprehensive efforts to tackle the overdose crisis among veterans require interventions that address each of these dimensions. Promising interventions include widespread naloxone distribution and increased provision of low-threshold wrap-around services, including medications for opioid use disorder (MOUD) and holistic/complementary approaches. Interventions that are delivered by peers - individuals who share key experiential or sociodemographic characteristics with the population being served - may be ideally suited to address many of the barriers to opioid-related risk mitigation common among veterans. Community care models could be beneficial for the large proportion of veterans who are not connected to the Veterans Health Administration and for veterans who, for various reasons including mental health problems and the avoidance of stigma, are socially isolated or reluctant to use traditional substance use services. Interventions need to be tailored in such a way that they reach those more socially isolated veterans who may not have access to naloxone or the social support to help them in overdose situations. It is important to incorporate the perspectives and voices of veterans with lived experience of substance use into the design and implementation of new overdose prevention resources and strategies to meet the needs of this population. Key messagesU.S. military veterans have been heavily impacted by the opioid overdose crisis, with drug overdose mortality rates increasing by 53% from 2010-2019.The risks for overdose that veterans face need to be understood as resulting from an ongoing interaction among biological/physiological, psychological, and social/structural factors.Addressing drug overdose in the veteran population requires accessible and non-judgemental, low threshold, wraparound, and holistic solutions that recognise the complex aetiology of overdose risk for veterans.

"I Didn't Know What They're Gonna Do to Me: So That's Why I Said No": Why Youth Decline HIV Testing in Emergency Departments.

Youth between the ages of 13 and 24 account for over 20% of new HIV diagnoses in the United States but are the least likely age group to be HIV tested in healthcare settings including the emergency department. This is in part due to the fact that almost 50% of youth decline testing when offered. We elucidated youth patients' perspectives on barriers to and facilitators of routine HIV testing of youth in an urban emergency department setting. Thirty-seven patients aged 13-24 years were recruited from the pediatric and adult emergency departments at a high-volume hospital in New York City from August 2019 to March 2020. Semi-structured in-depth interviews were conducted with all participants. Interviews were audio-recorded and transcribed verbatim, and transcripts were coded using an inductive thematic analysis approach. Youths' main reasons for declining HIV testing when offered included low risk perception, privacy concerns, HIV-related stigma, and low levels of HIV-related knowledge. Participants' responses suggested that HIV educational materials provided when testing is offered may be insufficient. Participants recommended providing additional HIV education and better incorporating HIV testing into the emergency department routine to increase testing among youth. Efforts are needed to help youth recognize their own HIV risk and increase their HIV-related knowledge. This may be accomplished by providing youth with additional educational materials on HIV, possibly via tablet-based interventions or other methods that may enhance privacy, combined with discussions with healthcare providers. Such efforts may help increase HIV testing acceptance among youth seen in the emergency department.

Parenting and childcare responsibilities, harm reduction service engagement, and opioid overdose among women and men who use illicit opioids in New York City.

Background: Little is known regarding relationships among parenting, engagement in harm reduction services, and overdose risk among people who use illicit opioids (PWUIO), and whether associations differ by gender. Methods: Using baseline data from an ongoing study among PWUIO in New York City (n = 575), we measured childcare factors (i.e., residing with children, avoidance of drug treatment for fear of child welfare, difficulty accessing harm reduction due to childcare issues), and harm reduction services and overdose-related outcomes. Among those with children, we estimated prevalence ratios (PR) using modified Poisson regression with a product-interaction term for gender differences. Results: In the total sample (n = 575), approximately 70% reported having children. Compared to men, women were more likely to reside with children (25% vs 36%; p-value = 0.04), avoid treatment for fear of child welfare (16% vs 26%; p-value = 0.04), and less likely to be trained in naloxone administration (68% vs 61%; p-value = 0.09). Among participants with children (n = 403), residing with children was associated with naloxone training among men (aPR 1.28, 95% CI: 1.01, 1.62). Avoiding treatment for fear of child welfare was associated with carrying naloxone overall (aPR 0.68, 95% CI: 0.46, 0.99), with a stronger association among women (aPR 0.48, 95% CI: 0.26, 0.92). Difficulty accessing services due to childcare was associated with lifetime overdose (aPR 1.53, 95% CI: 1.05, 2.23). Conclusion: Childcare responsibilities may be a barrier for accessing substance use services and treatment for men and women. Further qualitative and mixed-methods research is needed to understand how to make treatment and services accessible for parents.