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Background: Unhealthy alcohol use is an independent, modifiable risk factor for HIV, but limited research addresses alcohol use and HIV prevention synergistically. Groups that experience chronic stigma, discrimination, and/or other marginalization, such as sexual and gender minoritized groups, may have enhanced HIV risk related to unhealthy alcohol use. We described awareness of and experiences with pre-exposure prophylaxis (PrEP) among a community sample of Veterans reporting unhealthy alcohol use (relative to those without), overall and across self-reported sexual orientation and gender identity., Methods: Using data collected from a national online survey of Veterans recruited via Facebook ads, community organizations, and listservs, we assessed variation in four PrEP outcomes (knowledge, experience, willingness, and conversations with doctors) across patterns of unhealthy alcohol use among all respondents reporting any lifetime drinking (n = 1,041) and then within sexual orientation and gender identity groups using Chi-square or Fisher's exact tests., Results: Among 1,041 eligible Veterans, 440 (42%) screened positive for unhealthy alcohol use. Veterans with unhealthy alcohol use were not more likely to have heard of PrEP (58.2% vs. 55.4%, p = 0.37), but trended toward more likely to have taken PrEP (7.5% vs. 5.0%, p = 0.09), to be willing to take PrEP (30.5% vs. 27.6%, p = 0.06), and to have spoken with a doctor about PrEP (11.4% vs. 7.7%, p = 0.04). Those with heavy episodic drinking also trended toward higher prevalence of PrEP awareness (60.0% vs. 54.6%, p = 0.09), and were more likely to have taken PrEP (8.3% vs. 4.7%, p = 0.02), to be willing to use PrEP (34.6% vs. 25.5%, p < 0.01), and to have had conversations with doctors about PrEP (12.7% vs. 7.2%, p < 0.01). Similar patterns were observed for severe unhealthy alcohol use and past-year frequent heavy episodic drinking. Generally, sexual/gender minoritized Veterans with unhealthy alcohol use reported more PrEP-affirming responses than those without but associations with unhealthy alcohol use were similar., Conclusions: Unhealthy alcohol use was prevalent, particularly among Veterans with minoritized sexual orientation/gender identity, but not clearly linked to increased PrEP-literacy and use despite its known status as an HIV risk factor. Across groups, > 25% of individuals were willing to take PrEP. Interventions targeting both alcohol use and HIV prevention should capitalize on this., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent was obtained from all study participants. All study procedures were approved by the VA Puget Sound Healthcare System IRB. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Competing Interests: Competing interests E.C.H.W. and N.N.B. are employees of the US Food and Drug Administration and have no conflicts related to this manuscript. R.M.C. is an employee of the US Food and Drug Administration and has no conflicts related to this manuscript; prior to his appointment to the US Food and Drug Administration as Commissioner for Food and Drugs, he was an employee of and held equity in Verily Life Sciences and Google Health (Alphabet) and served on boards of directors for Cytokinetics, Centessa, Clinetic, Keystone Symposia, the Critical Path Institute (C-Path), the Clinical Research Forum and OneFifteen.

Background: Diagnosis of alcohol use disorder (AUD) in primary care is critical for increasing access to alcohol treatment. However, AUD is underdiagnosed and may be inequitably diagnosed due to societal structures that determine access to resources (e.g., structural racism that limits opportunities for some groups and influences interpersonal interactions in and beyond health care). This study described patterns of provider-documented AUD in primary care across intersections of race, ethnicity, sex, and community-level socioeconomic status (SES)., Methods: This cross-sectional study used EHR data from a regional healthcare system with 35 primary care clinics that included adult patients who completed alcohol screenings between 3/1/2015 and 9/30/2020. The prevalence of provider-documented AUD in primary care based on International Classification of Diseases-9 (ICD-9) and ICD-10 diagnoses was compared across intersections of race, ethnicity, sex, and community-level SES., Results: Among 439,375 patients, 6.6% were Latine, 11.0% Asian, 5.4% Black, 1.3% Native Hawaiian/Pacific Islander (NH/PI), 1.5% American Indian/Alaska Native (AI/AN), and 74.2% White, and 58.3% women. The overall prevalence of provider-documented AUD was 1.0% and varied across intersecting identities. Among women, the prevalence was highest for AI/AN women with middle SES, 1.5% (95% CI 1.0-2.3), and lowest for Asian women with middle SES, 0.1% (95% CI 0.1-0.2). Among men, the prevalence was highest for AI/AN men with high and middle SES, 2.0% (95% CI 1.1-3.4) and 2.0% (95% CI 1.2-3.2), respectively, and lowest for Asian men with high SES, 0.5% (95% CI 0.3-0.7). Black and Latine patients tended to have a lower prevalence of AUD than White patients, across all intersections of sex and SES except for Black women with high SES. There were no consistent patterns of the prevalence of AUD diagnosis that emerged across SES., Conclusion: The prevalence of provider-documented AUD in primary care was highest in AI/AN men and women and lowest in Asian men and women. Findings of lower prevalence of provider-documented AUD in Black and Hispanic than White patients across most intersections of sex and SES differed from prior studies. Findings may suggest that differences in access to resources, which vary in effects across these identity characteristics and lived experiences, influence the diagnosis of AUD in clinical care., (© 2024. The Author(s).)

Background: There is a growing interest in practice-based implementation research, yet too often research prioritizes and is most successful in academic settings. During a national implementation trial to evaluate the effectiveness of Collaborative Care for co-occurring opioid use and mental health disorders, we lost three of our 11 participating implementation sites, all representing community sites., Method: To better understand needed supports for implementation trial participation, we conducted exit interviews ( n  = 5) with key staff at these community sites. Interview transcripts were double-coded and analyzed using Rapid Assessment Process. Qualitative themes were iteratively reviewed by the study team., Results: Three themes emerged characterizing challenges for community sites, including that: (1) research threatens sites' most precious resource-staff; (2) staff lack comfort with and skills for research; and (3) research participation in its current form does not offer a clear return on investment., Conclusions: Learnings from this work illuminate some of the barriers community sites face when trying to participate in multisite implementation research. An undercurrent of participant perspectives was the belief that community sites like theirs are just not set up to successfully participate in clinical trial research, including population-based implementation trials. Future implementation trials should consider strategies that disrupt traditional approaches, increasing the equitable inclusion of diverse practice settings in implementation research., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work. The authors did not work with or were otherwise influenced by any external sponsors for this work. Andrew J. Saxon has received travel support from Alkermes, Inc., consulting fees from Indivior, Inc., and royalties from UpToDate, Inc. Anna D. Ratzliff, MD, PhD, receives royalties from Wiley for her book on integrated care., (© The Author(s) 2024.)

Introduction: Recent policy changes in Washington State presented a unique opportunity to pair evidence-based interventions with first responder services to combat increasing opioid overdoses. However, little is known about how these interventions should be implemented. In partnership with the Research with Expert Advisors on Drug Use team, a group of academically trained and community-trained researchers with lived and living experience of substance use, we examined facilitators and barriers to adopting leave-behind naloxone, field-based buprenorphine initiation, and HIV and hepatitis C virus (HCV) testing for first responder programs., Methods: Our team completed semi-structured, qualitative interviews with 32 first responders, mobile integrated health staff, and emergency medical services (EMS) leaders in King County, Washington, from February-May 2022. Semi-structured interviews were recorded, transcribed, and coded using an integrated deductive and inductive thematic analysis approach grounded in community-engaged research principles. We collected data until saturation was achieved. Data collection and analysis were informed by the Consolidated Framework for Implementation Research. Two investigators coded independently until 100% consensus was reached., Results: Our thematic analysis revealed several perceived facilitators (ie, tension for change, relative advantage, and compatibility) and barriers (ie, limited adaptability, lack of evidence strength and quality, and prohibitive cost) to the adoption of these evidence-based clinical interventions for first responder systems. There was widespread support for the distribution of leave-behind naloxone, although funding was identified as a barrier. Many believed field-based initiation of buprenorphine treatment could provide a more effective response to overdose management, but there were significant concerns that this intervention could run counter to the rapid care model. Lastly, participants worried that HIV and HCV testing was inappropriate for first responders to conduct but recommended that this service be provided by mobile integrated health staff., Conclusion: These results have informed local EMS strategic planning, which will inform roll out of process improvements in King County, Washington. Future work should evaluate the impact of these interventions on the health of overdose survivors., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This study was supported by a University of Washington Implementation Science Program Pilot Grant (PI van Draanen). There are no other conflicts of interest or sources of funding to declare.

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized 1-4 , but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver. This organ displays the remarkable ability to regenerate after acute injury, although liver regeneration in the context of recurring injury remains to be fully demonstrated. Here we performed single-nucleus RNA sequencing (snRNA-seq) on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression. We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture. Hepatocytes lose their zonation and considerable reorganization of the biliary tree takes place. More importantly, our study uncovers transdifferentiation events that occur between hepatocytes and cholangiocytes without the presence of adult stem cells or developmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K-AKT-mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this process could open new therapeutic avenues in the management of chronic diseases., (© 2024. The Author(s).)

Importance: Research has demonstrated an association between the COVID-19 pandemic and increased alcohol-related liver disease hospitalizations and deaths. However, trends in alcohol-related complications more broadly are unclear, especially among subgroups disproportionately affected by alcohol use., Objective: To assess trends in people with high-acuity alcohol-related complications admitted to the emergency department, observation unit, or hospital during the COVID-19 pandemic, focusing on demographic differences., Design, Setting, and Participants: This longitudinal interrupted time series cohort study analyzed US national insurance claims data using Optum's deidentified Clinformatics Data Mart database from March 2017 to September 2021, before and after the March 2020 COVID-19 pandemic onset. A rolling cohort of people 15 years and older who had at least 6 months of continuous commercial or Medicare Advantage coverage were included. Subgroups of interest included males and females stratified by age group. Data were analyzed from April 2023 to January 2024., Exposure: COVID-19 pandemic environment from March 2020 to September 2021., Main Outcomes and Measures: Differences between monthly rates vs predicted rates of high-acuity alcohol-related complication episodes, determined using claims-based algorithms and alcohol-specific diagnosis codes. The secondary outcome was the subset of complication episodes due to alcohol-related liver disease., Results: Rates of high-acuity alcohol-related complications were statistically higher than expected in 4 of 18 pandemic months after March 2020 (range of absolute and relative increases: 0.4-0.8 episodes per 100 000 people and 8.3%-19.4%, respectively). Women aged 40 to 64 years experienced statistically significant increases in 10 of 18 pandemic months (range of absolute and relative increases: 1.3-2.1 episodes per 100 000 people and 33.3%-56.0%, respectively). In this same population, rates of complication episodes due to alcohol-related liver disease increased above expected in 16 of 18 pandemic months (range of absolute and relative increases: 0.8-2.1 episodes per 100 000 people and 34.1%-94.7%, respectively)., Conclusions and Relevance: In this cohort study of a national, commercially insured population, high-acuity alcohol-related complication episodes increased beyond what was expected in 4 of 18 COVID-19 pandemic months. Women aged 40 to 64 years experienced 33.3% to 56.0% increases in complication episodes in 10 of 18 pandemic months, a pattern associated with large and sustained increases in high-acuity alcohol-related liver disease complications. Findings underscore the need for increased attention to alcohol use disorder risk factors, alcohol use patterns, alcohol-related health effects, and alcohol regulations and policies, especially among women aged 40 to 64 years.

Aims: Cardiac involvement is common in patients hospitalized with COVID-19 and correlates with an adverse disease trajectory. While cardiac injury has been attributed to direct viral cytotoxicity, serum-induced cardiotoxicity secondary to serological hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored., Methods and Results: To investigate serological drivers of cardiotoxicity in COVID-19 we have established a robust bioassay that assessed the effects of serum from COVID-19 confirmed patients on human embryonic stem cell (hESC)-derived cardiomyocytes. We demonstrate that serum from COVID-19 positive patients significantly reduced cardiomyocyte viability independent of viral transduction, an effect that was also seen in non-COVID-19 acute respiratory distress syndrome (ARDS). Serum from patients with greater disease severity led to worse cardiomyocyte viability and this significantly correlated with levels of key inflammatory cytokines, including IL-6, TNF-α, IL1-β, IL-10, CRP, and neutrophil to lymphocyte ratio with a specific reduction of CD4+ and CD8+ cells. Combinatorial blockade of IL-6 and TNF-α partly rescued the phenotype and preserved cardiomyocyte viability and function. Bulk RNA sequencing of serum-treated cardiomyocytes elucidated specific pathways involved in the COVID-19 response impacting cardiomyocyte viability, structure, and function. The observed effects of serum-induced cytotoxicity were cell-type selective as serum exposure did not adversely affect microvascular endothelial cell viability but resulted in endothelial activation and a procoagulant state., Conclusion: These results provide direct evidence that inflammatory cytokines are at least in part responsible for the cardiovascular damage seen in COVID-19 and characterise the downstream activated pathways in human cardiomyocytes. The serum signature of patients with severe disease indicates possible targets for therapeutic intervention., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objective: COVID-19 led to an unprecedented reliance on virtual modalities to maintain care continuity for patients living with chronic pain. We examined whether there were disparities in virtual specialty pain care for racial-ethnic minority groups during COVID-19., Design and Participants: This was a retrospective national cohort study with two comparison groups: primary care patients with chronic pain seen immediately prior to COVID-19 (3/1/19-2/29/20) (N = 1,649,053) and a cohort of patients seen in the year prior (3/1/18-2/28-19; n = 1,536,954)., Main Measures: We assessed use of telehealth (telephone or video) specialty pain care, in-person care specialty pain care, and any specialty pain care for both groups at 6 months following cohort inclusion. We used quasi-Poisson regressions to test associations between patient race and ethnicity and receipt of care., Key Results: Prior to COVID-19, there were Black-White (RR = 0.64, 95% CI [0.62, 0.67]) and Asian-White (RR = 0.63, 95% CI [0.54, 0.75]) disparities in telehealth use, and these lessened during COVID-19 (Black-White: RR = 0.75, 95% CI [0.73, 0.77], Asian-White: RR = 0.81, 95% CI [0.74, 0.89]) but did not disappear. Individuals identifying as American Indian/Alaska Native used telehealth less than White individuals during early COVID-19 (RR = 0.98, 95% CI [0.85, 1.13] to RR = 0.87, 95% CI [0.79, 0.96]). Hispanic/Latinx individuals were less likely than non-Hispanic/Latinx individuals to use telehealth prior to COVID-19 but more likely during early COVID-19 (RR = 0.70, 95% CI [0.66, 0.75] to RR = 1.06, 95% CI [1.02, 1.09]). Disparities in virtual pain care occurred over the backdrop of overall decreased specialty pain care during the early phase of the pandemic (raw decrease of n = 17,481 specialty care encounters overall from pre-COVID to COVID-era), including increased disparities in any VA specialty pain care for Black (RR = 0.81, 95% CI [0.80, 0.83] to RR = 0.79, 95% CI [0.77, 0.80]) and Asian (RR = 0.91, 95% CI [0.86, 0.97] to RR = 0.88, 95% CI [0.82, 0.94]) individuals., Conclusions: Disparities in virtual specialty pain care were smaller during the early phases of the COVID-19 pandemic than prior to the pandemic but did not disappear entirely, despite the rapid growth in telehealth. Targeted efforts to increase access to specialty pain care need to be concentrated among racial-ethnic minority groups., (© 2023. The Author(s).)

Background: Unhealthy alcohol use (UAU) is particularly dangerous for people with chronic liver disease. Liver clinics may be an important setting in which to provide effective alcohol-related care by integrating evidence-based strategies, such as brief intervention and medications for alcohol use disorder. We conducted qualitative interviews with clinical stakeholders and patients at liver clinics in four Veterans Health Administration (VA) medical centers to understand barriers and facilitators of integrating alcohol-related care and to support tailoring of a practice facilitation implementation intervention., Methods: Data collection and analysis were guided by the Consolidated Framework for Implementation Research (CFIR). Interviews were transcribed and qualitatively analyzed using a Rapid Assessment Process (RAP) guided by the CFIR., Results: We interviewed 46 clinical stakeholders and 41 patient participants and analyzed findings based on the CFIR. Clinical stakeholders described barriers and facilitators that ranged from operations/clinic resource-based (e.g., time and capacity, desire for additional provider types, referral processes) to individual perspective and preference-based (e.g., supportiveness of leadership, individual experiences/beliefs). Patient participants shared barriers and facilitators that ranged from relationship-based (e.g., trusting the provider and feeling judged) to resource and education-based (e.g., connection to a range of treatment options, education about impact of alcohol). Many barriers and facilitators to integrating alcohol-related care in liver clinics were similar to those identified in other clinical settings (e.g., time, resources, role clarity, stigmatizing beliefs). However, some barriers (e.g., fellow-led care and lack of integration of liver clinics with addictions specialists) and facilitators (e.g., presence of quality improvement staff in clinics and integrated pharmacists and behavioral health specialists) were more unique to liver clinics., Conclusions: These findings support the possibility of integrating alcohol-related care into liver clinics but highlight the importance of tailoring efforts to account for variation in provider beliefs and experiences and clinic resources. The barriers and facilitators identified in these interviews were used to tailor a practice facilitation implementation intervention in each clinic setting., (© 2024. The Author(s).)

Background: People who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction., Methods: We conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction., Results: Of the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved "sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding "agree or strongly agree" that they had a positive experience with the pharmacist., Conclusion: Nearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID., Clinicaltrialsgov Registration Number: NCT04698629., Competing Interests: The authors declare that all procedures were performed in compliance with relevant laws and institutional guidelines. Appropriate ethical safeguards, including privacy rights of human participants, and ethical approvals were obtained through the University of Washington's Institutional Review Board., (© 2024 The Authors. Published by Elsevier B.V.)

Background: Alcohol use disorder (AUD) commonly causes hospitalization, particularly for individuals disproportionately impacted by structural racism and other forms of marginalization. The optimal approach for engaging hospitalized patients with AUD in treatment post-hospital discharge is unknown. We describe the rationale, aims, and protocol for Project ENHANCE (ENhancing Hospital-initiated Alcohol TreatmeNt to InCrease Engagement), a clinical trial testing increasingly intensive approaches using a hybrid type 1 effectiveness-implementation approach., Methods: We are randomizing English and/or Spanish-speaking individuals with untreated AUD (n = 450) from a large, urban, academic hospital in New Haven, CT to: (1) Brief Negotiation Interview (with referral and telephone booster) alone (BNI), (2) BNI plus facilitated initiation of medications for alcohol use disorder (BNI + MAUD), or (3) BNI + MAUD + initiation of computer-based training for cognitive behavioral therapy (CBT4CBT, BNI + MAUD + CBT4CBT). Interventions are delivered by Health Promotion Advocates. The primary outcome is AUD treatment engagement 34 days post-hospital discharge. Secondary outcomes include AUD treatment engagement 90 days post-discharge and changes in self-reported alcohol use and phosphatidylethanol. Exploratory outcomes include health care utilization. We will explore whether the effectiveness of the interventions on AUD treatment engagement and alcohol use outcomes differ across and within racialized and ethnic groups, consistent with disproportionate impacts of AUD. Lastly, we will conduct an implementation-focused process evaluation, including individual-level collection and statistical comparisons between the three conditions of costs to providers and to patients, cost-effectiveness indices (effectiveness/cost ratios), and cost-benefit indices (benefit/cost ratios, net benefit [benefits minus costs). Graphs of individual- and group-level effectiveness x cost, and benefits x costs, will portray relationships between costs and effectiveness and between costs and benefits for the three conditions, in a manner that community representatives also should be able to understand and use., Conclusions: Project ENHANCE is expected to generate novel findings to inform future hospital-based efforts to promote AUD treatment engagement among diverse patient populations, including those most impacted by AUD., Clinical Trial Registration: Clinicaltrials.gov identifier: NCT05338151., (© 2023. Evans Medical Foundation, Inc. and BioMed Central Ltd.)

Introduction: Reproductive policies' impact on disparities in neonatal outcomes is understudied. Thus, we aimed to assess whether an index of reproductive autonomy is associated with black-white disparities in preterm birth (PTB) and low birthweight (LBW)., Methods: We used publicly available state-level PTB and LBW data for all live-births among persons aged 15-44 from January 1, 2016, to December 31, 2018. The independent measure was an index of state laws characterizing each state's reproductive autonomy, ranging from 5 (most restrictive) to 43 (most enabling), used continuously and as quartiles. Linear regression was performed to evaluate the association between both the index score (continuous, primary analysis; quartiles, secondary analysis) and state-level aggregated black-white disparity rates in PTB and LBW per 100 live births., Results: Among 10,297,437 black ( n =1,829,051 [17.8%]) and white ( n =8,468,386 [82.2%]) births, rates of PTB and LBW were 6.46 and 8.24 per 100, respectively. Regression models found that every 1-U increase in the index was associated with a -0.06 (confidence interval [CI]: -0.10 to -0.01) and -0.05 (CI: -0.08, to -0.01) per 100 lower black-white disparity in PTB and LBW rates ( p <0.05, p <0.01), respectively. The most enabling quartiles were associated with -1.21 (CI: -2.38 to -0.05) and -1.62 (CI: -2.89 to -0.35) per 100 lower rates of the black-white disparity in LBW, compared with the most restrictive quartile (both p <0.05)., Conclusion: Greater reproductive autonomy is associated with lower rates of state-level disparities in PTB and LBW. More research is needed to better understand the importance of state laws in shaping racialized disparities, reproductive autonomy, and birth outcomes., Competing Interests: No competing financial interests exist., (© Andrew S. Bossick et al., 2023; Published by Mary Ann Liebert, Inc.)

Importance: Medication for opioid use disorder (MOUD) (eg, buprenorphine and naltrexone) can be offered in primary care, but barriers to implementation exist., Objective: To evaluate an implementation intervention over 2 years to explore experiences and perspectives of multidisciplinary primary care (PC) teams initiating or expanding MOUD., Design, Setting, and Participants: This survey-based and ethnographic qualitative study was conducted at 12 geographically and structurally diverse primary care clinics that enrolled in a hybrid effectiveness-implementation study from July 2020 to July 2022 and included PC teams (prescribing clinicians, nonprescribing behavioral health care managers, and consulting psychiatrists). Survey data analysis was conducted from February to April 2022., Exposure: Implementation intervention (external practice facilitation) to integrate OUD treatment alongside existing collaborative care for mental health services., Measures: Data included (1) quantitative surveys of primary care teams that were analyzed descriptively and triangulated with qualitative results and (2) qualitative field notes from ethnographic observation of clinic implementation meetings analyzed using rapid assessment methods., Results: Sixty-two primary care team members completed the survey (41 female individuals [66%]; 1 [2%] American Indian or Alaskan Native, 4 [7%] Asian, 5 [8%] Black or African American, 5 [8%] Hispanic or Latino, 1 [2%] Native Hawaiian or Other Pacific Islander, and 46 [4%] White individuals), of whom 37 (60%) were between age 25 and 44 years. An analysis of implementation meetings (n = 362) and survey data identified 4 themes describing multilevel factors associated with PC team provision of MOUD during implementation, with variation in their experience across clinics. Themes characterized challenges with clinical administrative logistics that limited the capacity to provide rapid access to care and patient engagement as well as clinician confidence to discuss aspects of MOUD care with patients. These challenges were associated with conflicting attitudes among PC teams toward expanding MOUD care., Conclusions and Relevance: The results of this survey and qualitative study of PC team perspectives suggest that PC teams need flexibility in appointment scheduling and the capacity to effectively engage patients with OUD as well as ongoing training to maintain clinician confidence in the face of evolving opioid-related clinical issues. Future work should address structural challenges associated with workload burden and limited schedule flexibility that hinder MOUD expansion in PC settings.

Introduction: Coordinated alignment of the eyes during gaze fixation and eye movements are an important component of normal visual function. We have previously described the coordinated behavior of convergence eye movements and pupillary responses using a 0.1  Hz binocular disparity-driven sine profile and a step profile. The goal of this publication is to further characterize ocular vergence-pupil size coordination over a wider range of frequencies of ocular disparity stimulation in normal subjects., Methods: Binocular disparity stimulation is generated by presentation of independent targets to each eye on a virtual reality display, while eye movements and pupil size are measured by an embedded video-oculography system. This design allows us to study two complimentary analyses of this motion relationship. First, a macroscale analysis describes the vergence angle of the eyes in response to binocular disparity target movement and pupil area as a function of the observed vergence response. Second, a microscale analysis performs a piecewise linear decomposition of the vergence angle and pupil relationship to permit more nuanced findings., Results: These analyses identified three main features of controlled coupling of pupil and convergence eye movements. First, a near response relationship operates with increasing prevalence during convergence (relative to the "baseline" angle); the coupling is higher with increased convergence in this range. Second, the prevalence of "near response"-type coupling decreases monotonically in the diverging direction; the decrease persists after the targets move (converge back) from maximum divergence toward the baseline positions, with a minimum prevalence of near response segments near the baseline target position. Third, an opposite polarity pupil response is infrequent, but tends to be more prevalent when the vergence angles are at maximum convergence or divergence for a sinusoidal binocular disparity task., Discussion: We suggest that the latter response is an exploratory "range-validation" when binocular disparity is relatively constant. In a broader sense, these findings describe operating characteristics of the near response in normal subjects and form a basis for quantitative assessments of function in conditions such as convergence insufficiency and mild traumatic brain injury., Competing Interests: AK was employee by Neurolign USA, Inc. The role of AK was limited to device design and technical aspects of manuscript preparation. Hence, his employment by Neurolign USA, Inc. has no influence on the analysis, discussions, or conclusions of this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Balaban, Nayak, Williams, Kiderman and Hoffer.)

Sexual and reproductive healthcare standards for adolescents and young adults with sickle cell disease (SCD) are not established. A total of 50 young adults entering adult SCD care completed a Family Planning Survey assessing sexual and reproductive health needs from March 2019 to July 2020. Clinical data were abstracted from respondents' electronic medical records. Linear and logistic regression was applied to explore associations between clinical characteristics and survey results. Few respondents (8%) wished to be pregnant in the coming year, and 46% answered yes to at least one of four needs assessment questions. Those who were not employed full time were more likely to endorse needing help with getting sickle cell trait testing for a partner (OR adj  = 9.59, p -value = 0.05). Contraceptive use was associated with having an obstetrician-gynecologist (OR = 6.8, p -value = 0.01). Young adults with SCD entering adult care have diverse reproductive health needs, highlighting opportunities to provide multidisciplinary, SCD-specific reproductive healthcare., Competing Interests: The authors report no conflict of interests in the design, conduct, analysis, or presentation of this research. We disclose the following funding sources: EAL is supported by Grant Number T32 AG000247 from the National Institute on Aging, National Institutes of Health (NIH), ECW was supported by an American Society of Hematology (ASH) 2020 Hematology Opportunities for the Next‐Generation of Research Scientists (HONORS) Award; MLE is supported by an ASH Medical Student Physician‐Scientist Career Development Award; EP has no disclosures; RWS receives support from HRSA‐22‐124, and 2 U1EMC27864‐08‐00 and CHRC Pathways to Health Equity; SL receives research funding from Imara, Novartis, Global Blood Therapeutics, Takeda, CSL‐Behring, HRSA, PCORI, and MD CHRC; consultancy for Bluebird bio, Novo Nordisk, Pfizer, and Magenta; owns stock in Pfizer and Teva; LHP is funded through NIH/NHLBI K23HL146841 and NIH/NHLBI U01 HL156620‐01, the American Society of Hematology, Doris Duke Charitable Foundation Grant #2020147, and the Mellon Foundation and Alexion and is a consultant for Global Blood Therapeutics and Novo Nordisk., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Most people with opioid use disorder (OUD) have co-occurring substance use, which is associated with lower receipt of OUD medications (MOUD). Expanding MOUD provision and care linkage outside of substance use disorder (SUD) specialty settings is a key strategy to increase access. Therefore, it is important to understand how MOUD providers in these settings approach care for patients with co-occurring substance use. This qualitative study of Veterans Health Administration (VA) clinicians providing buprenorphine care in primary care, mental health, and pain settings aimed to understand (1) their approach to addressing OUD in patients with co-occurring substance use, (2) perspectives on barriers/facilitators to MOUD receipt for this population, and (3) support needed to increase MOUD receipt for this population., Methods: We interviewed a purposive sample of 27 clinicians (12 primary care, 7 mental health, 4 pain, 4 pharmacists) in the VA northwest network. The interview guide assessed domains of the Tailored Implementation for Chronic Diseases Checklist. Interviews were transcribed and qualitatively analyzed using inductive content analysis., Results: Participants reported varied approaches to identifying co-occurring substance use and addressing OUD in this patient population. Although they reported that this topic was not clearly addressed in clinical guidelines or training, participants generally felt that patients with co-occurring substance use should receive MOUD. Some viewed their primary role as providing this care, others as facilitating linkage to OUD care in SUD specialty settings. Participants reported multiple barriers and facilitators to providing buprenorphine care to patients with co-occurring substance use and linking them to SUD specialty care, including provider, patient, organizational, and external factors., Conclusions: Efforts are needed to support clinicians outside of SUD specialty settings in providing buprenorphine care to patients with co-occurring substance use. These could include clearer guidelines and policies, more specific training, and increased care integration or cross-disciplinary collaboration. Simultaneously, efforts are needed to improve linkage to specialty SUD care for patients who would benefit from and are willing to receive this care, which could include increased service availability and improved referral/hand-off processes. These efforts may increase MOUD receipt and improve OUD care quality for patients with co-occurring substance use., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Importance: Substance use disorders (SUDs) are underrecognized in primary care, where structured clinical interviews are often infeasible. A brief, standardized substance use symptom checklist could help clinicians assess SUD., Objective: To evaluate the psychometric properties of the Substance Use Symptom Checklist (hereafter symptom checklist) used in primary care among patients reporting daily cannabis use and/or other drug use as part of population-based screening and assessment., Design, Setting, and Participants: This cross-sectional study was conducted among adult primary care patients who completed the symptom checklist during routine care between March 1, 2015, and March 1, 2020, at an integrated health care system. Data analysis was conducted from June 1, 2021, to May 1, 2022., Main Outcomes and Measures: The symptom checklist included 11 items corresponding to SUD criteria in the Diagnostic and Statistical Manual for Mental Disorders (Fifth Edition) (DSM-5). Item response theory (IRT) analyses tested whether the symptom checklist was unidimensional and reflected a continuum of SUD severity and evaluated item characteristics (discrimination and severity). Differential item functioning analyses examined whether the symptom checklist performed similarly across age, sex, race, and ethnicity. Analyses were stratified by cannabis and/or other drug use., Results: A total of 23 304 screens were included (mean [SD] age, 38.2 [5.6] years; 12 554 [53.9%] male patients; 17 439 [78.8%] White patients; 20 393 [87.5%] non-Hispanic patients). Overall, 16 140 patients reported daily cannabis use only, 4791 patients reported other drug use only, and 2373 patients reported both daily cannabis and other drug use. Among patients with daily cannabis use only, other drug use only, or both daily cannabis and other drug use, 4242 (26.3%), 1446 (30.2%), and 1229 (51.8%), respectively, endorsed 2 or more items on the symptom checklist, consistent with DSM-5 SUD. For all cannabis and drug subsamples, IRT models supported the unidimensionality of the symptom checklist, and all items discriminated between higher and lower levels of SUD severity. Differential item functioning was observed for some items across sociodemographic subgroups but did not result in meaningful change (<1 point difference) in the overall score (0-11)., Conclusions and Relevance: In this cross-sectional study, a symptom checklist, administered to primary care patients who reported daily cannabis and/or other drug use during routine screening, discriminated SUD severity as expected and performed well across subgroups. Findings support the clinical utility of the symptom checklist for standardized and more complete SUD symptom assessment to help clinicians make diagnostic and treatment decisions in primary care.

Background: Nicotine replacement therapy, bupropion, and varenicline are smoking cessation medications (SCMs) shown to be similarly effective in people with and without human immunodeficiency virus (PWH and PWoH, respectively), although rates of receipt of these medications are unknown., Methods: We identified patients in the Veterans Aging Cohort Study with electronic health record-documented current smoking using clinical reminder data for tobacco use (2003-2018). We measured receipt of SCMs using Veterans Affairs pharmacy data for outpatient prescriptions filled 0-365 days after current smoking documentation. We used log-linear, Poisson-modified regression models to evaluate the relative risk (RR) for receiving SCM by human immunodeficiency virus (HIV) status, the annual rate of receipt, and rate difference among PWH relative to PWoH., Results: The sample included 92 632 patients (29 086 PWH), reflecting 381 637 documentations of current smoking. From 2003 to 2018, the proportion receiving SCMs increased from 15% to 34% for PWH and from 17% to 32% among PWoH. There was no statistical difference in likelihood of receiving SCM by HIV status (RR, 1.010; 95% confidence interval [CI], .994-1.026). Annual rates of receiving SCM increased for PWH by 4.3% per year (RR, 1.043; 95% CI, 1.040-1.047) and for PWoH by 3.7% per year (RR, 1.037; 95% CI, 1.036-1.038; rate difference +0.6% [RR, 1.006; 95% CI, 1.004-1.009])., Conclusions: In a national sample of current smokers, receipt of SCM doubled over the 16-year period, and differences by HIV status were modest. However, fewer than 35% of current smokers receive SCM annually. Efforts to improve SCM receipt should continue for both groups given the known dangers of smoking., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood., Methods: Ten-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced by COVID+ participants during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses to recombinant spike protein in a longitudinal cohort study., Results: In previously infected individuals (n=33), AB were more durable and robust following primary vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1 st and 2 nd dose (n=49 and 48, respectively) of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination, suggesting that vaccination in COVID+ individuals is associated with a more robust immune response., Discussion: Experiencing systemic and local symptoms post-vaccine was suggestive of higher AB, which may confer greater protection., Competing Interests: The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays U.S. Provisional Application Numbers: 62/994,252, 63/018,457, 63/020,503 and 63/024,436 and NDV-based SARS-CoV-2 vaccines U.S. Provisional Application Number: 63/251,020 which list Florian Krammer as co-inventor. Patent applications were submitted by the Icahn School of Medicine at Mount Sinai. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. FK has consulted for Merck and Pfizer before 2020, and is currently consulting for Pfizer, Third Rock Ventures, Seqirus and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Williams, Kizhner, Stark, Nawab, Muniz, Echeverri Tribin, Carreño, Bielak, Singh, Hoffer, Krammer, Pallikkuth and Pahwa.)

Background: The U.S. Preventive Services Task Force recommends routine population-based screening for drug use, yet screening for opioid use disorder (OUD) in primary care occurs rarely, and little is known about barriers primary care teams face., Objective: As part of a multisite randomized trial to provide OUD and behavioral health treatment using the Collaborative Care Model, we supported 10 primary care clinics in implementing routine OUD screening and conducted formative evaluation to characterize early implementation experiences., Design: Qualitative formative evaluation., Approach: Formative evaluation included taking detailed observation notes at implementation meetings with individual clinics and debriefings with external facilitators. Observation notes were analyzed weekly using a Rapid Assessment Process guided by the Consolidated Framework for Implementation Research, with iterative feedback from the study team. After clinics launched OUD screening, we conducted structured fidelity assessments via group interviews with each site to evaluate clinic experiences with routine OUD screening. Data from observation and structured fidelity assessments were combined into a matrix to compare across clinics and identify cross-cutting barriers and promising implementation strategies., Key Results: While all clinics had the goal of implementing population-based OUD screening, barriers were experienced across intervention, individual, and clinic setting domains, with compounding effects for telehealth visits. Seven themes emerged characterizing barriers, including (1) challenges identifying who to screen, (2) complexity of the screening tool, (3) staff discomfort and/or hesitancies, (4) workflow barriers that decreased screening follow-up, (5) staffing shortages and turnover, (6) discouragement from low screening yield, and (7) stigma. Promising implementation strategies included utilizing a more universal screening approach, health information technology (HIT), audit and feedback, and repeated staff trainings., Conclusions: Integrating population-based OUD screening in primary care is challenging but may be made feasible via implementation strategies and tailored practice facilitation that standardize workflows via HIT, decrease stigma, and increase staff confidence regarding OUD., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Occupational noise exposure and hearing loss are prominent in the fire service. Firefighters are routinely exposed to hazardous levels of noise arising from the tools and equipment they use, from sirens and alarm tones to the emergency response vehicles they drive. The present study utilized the Apple Watch to continuously measure environmental noise levels for on-duty firefighters. Participants included 15 firefighters from the metropolitan South Florida area, and 25 adult non-firefighter control subjects. Firefighters were recruited from a variety of roles across two stations to ensure noise exposure profiles were appropriately representative of exposures in the fire service. All participants wore an Apple Watch for up to three separate 24 h shifts and completed a post-shift survey self-reporting on perceived exposures over the 24 h study period. Cumulative exposures were calculated for each shift and noise dose was calculated relative to the NIOSH recommended exposure limit of 85 dBA as an 8 h time-weighted average. The maximum dBA recorded on the Apple Watches was statistically significant between groups, with firefighters experiencing a median of 87.79 dBA and controls a median of 77.27 dBA. Estimated Exposure Time at 85 dBA (EET-85) values were significantly higher for firefighters when compared to controls: 3.97 h (range: 1.20-14.7 h) versus 0.42 h (range: 0.05-8.21 h). Only 2 of 16 firefighters reported the use of hearing protection devices during their shifts. Overall, our results highlight the utility of a commonly used personal device to quantify noise exposure in an occupationally at-risk group.

Bulk sequencing experiments (single- and multi-omics) are essential for exploring wide-ranging biological questions. To facilitate interactive, exploratory tasks, coupled with the sharing of easily accessible information, we present bulkAnalyseR, a package integrating state-of-the-art approaches using an expression matrix as the starting point (pre-processing functions are available as part of the package). Static summary images are replaced with interactive panels illustrating quality-checking, differential expression analysis (with noise detection) and biological interpretation (enrichment analyses, identification of expression patterns, followed by inference and comparison of regulatory interactions). bulkAnalyseR can handle different modalities, facilitating robust integration and comparison of cis-, trans- and customised regulatory networks., (© The Author(s) 2022. Published by Oxford University Press.)

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment - 1) Assessing Laboratory Work and Scientific Thinking; 2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; 3) Appraising Forms of Scientific Communication; and 4) Metacognition of Learning - along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students' ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education.

The advances in high-throughput sequencing (HTS) have enabled the characterisation of biological processes at an unprecedented level of detail; most hypotheses in molecular biology rely on analyses of HTS data. However, achieving increased robustness and reproducibility of results remains a main challenge. Although variability in results may be introduced at various stages, e.g., alignment, summarisation or detection of differential expression, one source of variability was systematically omitted: the sequencing design, which propagates through analyses and may introduce an additional layer of technical variation. We illustrate qualitative and quantitative differences arising from splitting samples across lanes on bulk and single-cell sequencing. For bulk mRNAseq data, we focus on differential expression and enrichment analyses; for bulk ChIPseq data, we investigate the effect on peak calling and the peaks' properties. At the single-cell level, we concentrate on identifying cell subpopulations. We rely on markers used for assigning cell identities; both smartSeq and 10× data are presented. The observed reduction in the number of unique sequenced fragments limits the level of detail on which the different prediction approaches depend. Furthermore, the sequencing stochasticity adds in a weighting bias corroborated with variable sequencing depths and (yet unexplained) sequencing bias. Subsequently, we observe an overall reduction in sequencing complexity and a distortion in the biological signal across technologies, experimental contexts, organisms and tissues.

Importance: Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection is associated with lower mortality and is effective in individuals with alcohol use disorder (AUD). However, despite recommendations, patients with AUD may be less likely to receive DAAs., Objective: To assess the association between alcohol use and receipt of DAA treatment among patients with HCV within the Veterans Health Administration (VHA)., Design, Setting, and Participants: This cohort study included 133 753 patients with HCV born from 1945 to 1965 who had completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and had at least 1 outpatient visit in the VHA from January 1, 2014, through May 31, 2017, with maximal follow-up of 3 years until May 31, 2020; DAA receipt; or death, whichever occurred first., Exposures: Alcohol use categories generated using responses to the AUDIT-C questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses: current AUD, abstinent with AUD history, at-risk drinking, lower-risk drinking, and abstinent without AUD history. Demographic, other clinical, and pharmacy data were also collected., Main Outcomes and Measures: Associations between alcohol use categories and DAA receipt within 1 and 3 years estimated using Cox proportional hazards regression stratified by calendar year., Results: Of 133 753 patients (130 103 men [97%]; mean [SD] age, 60.6 [4.5] years; and 73 493 White patients [55%]), 38% had current AUD, 12% were abstinent with a history of AUD, 6% reported at-risk drinking, 14% reported lower-risk drinking, and 30% were abstinent without a history of AUD. Receipt of DAA treatment within 1 year was 7%, 33%, 53%, and 56% for patients entering the cohort in 2014, 2015, 2016, and 2017, respectively. For patients entering in 2014, those with current AUD (hazard ratio [HR], 0.72 [95%, CI, 0.66-0.77]) or who were abstinent with an AUD history (HR, 0.91 [95% CI, 0.84-1.00]) were less likely to receive DAA treatment within 1 year compared with patients with lower-risk drinking. For those entering in 2015-2017, patients with current AUD (HR, 0.75 [95% CI, 0.70-0.81]) and those who were abstinent with an AUD history (HR, 0.76 [95% CI, 0.68-0.86]) were less likely to receive DAA treatment within 1 year compared with patients with lower-risk drinking., Conclusions and Relevance: This cohort study suggests that individuals with AUD, regardless of abstinence, were less likely to receive DAA treatment. Improved access to DAA treatment for persons with AUD is needed.

Importance: Cannabis use is prevalent and increasing, and frequent use intensifies the risk of cannabis use disorder (CUD). CUD is underrecognized in medical settings, but a validated single-item cannabis screen could increase recognition., Objective: To evaluate the Single-Item Screen-Cannabis (SIS-C), administered and documented in routine primary care, compared with a confidential reference standard measure of CUD., Design, Setting, and Participants: This diagnostic study included a sample of adult patients who completed routine cannabis screening between January 28 and September 12, 2019, and were randomly selected for a confidential survey about cannabis use. Random sampling was stratified by frequency of past-year use and race and ethnicity. The study was conducted at an integrated health system in Washington state, where adult cannabis use is legal. Data were analyzed from May 2021 to March 2022., Exposures: The SIS-C asks about frequency of past-year cannabis use with responses (none, less than monthly, monthly, weekly, daily or almost daily) documented in patients' medical records., Main Outcomes and Measures: The Diagnostic and Statistical Manual, Fifth Edition (DSM-5) Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM) for past-year CUD was completed on a confidential survey and considered the reference standard. The SIS-C was compared with 2 or more criteria on the CIDI-SAM, consistent with CUD. All analyses were weighted, accounting for survey design and nonresponse, to obtain estimates representative of the health system primary care population., Results: Of 5000 sampled adult patients, 1688 responded to the cannabis survey (34% response rate). Patients were predominantly middle-aged (weighted mean [SD] age, 50.7 [18.1]), female or women (weighted proportion [SE], 55.9% [4.1]), non-Hispanic (weighted proportion [SE], 96.7% [1.0]), and White (weighted proportion [SE], 74.2% [3.7]). Approximately 6.6% of patients met criteria for past-year CUD. The SIS-C had an area under receiver operating characteristic curve of 0.89 (95% CI, 0.78-0.96) for identifying CUD. A threshold of less than monthly cannabis use balanced sensitivity (0.88) and specificity (0.83) for detecting CUD. In populations with a 6% prevalence of CUD, predictive values of a positive screen ranged from 17% to 34%, while predictive values of a negative screen ranged from 97% to 100%., Conclusions and Relevance: In this diagnostic study, the SIS-C had excellent performance characteristics in routine care as a screen for CUD. While high negative predictive values suggest that the SIS-C accurately identifies patients without CUD, low positive predictive values indicate a need for further diagnostic assessment following positive results when screening for CUD in primary care.

Background: The incidence of HIV among persons who inject drugs (PWID) in the USA has been increasing since 2014, signaling the need to identify effective ways to engage PWID in HIV prevention services, namely pre-exposure prophylaxis (PrEP). Yet, the uptake of PrEP in this population is minimal compared to other populations at risk of HIV acquisition. In this work, we sought to explore knowledge, attitudes, and perspectives of PrEP acceptability among PWID., Methods: In the context of a pilot study to explore the acceptability of pharmacy-based hepatitis C virus (HCV) treatment, we conducted semi-structured interviews (n = 24) and focus groups (n = 4, 16 participants) with people who were living with HCV and reported active injection drug use (≤ 90 days since last use). Participants were asked open-ended questions about their familiarity with and motivation to use PrEP. As part of a sub-analysis focused on PrEP, qualitative data were analyzed using a Rapid Assessment Process, where three coders used structured templates to summarize qualitative data and iteratively reviewed coded templates to identify themes. Participants also completed short quantitative questionnaires regarding drug use history and attitudes toward health concerns., Results: Forty-seven percent of participants expressed having little or no concern regarding HIV acquisition. Targeted analyses focused on HIV prevention identified three themes, which help characterize behavioral determinants of nonadoption. First, knowledge of PrEP was limited among PWID and influenced by infrequent open community discussions around HIV risk. Second, PWID perceived sexual behaviors-but not injection drug use-as a motivator for HIV risk prevention. Finally, PWID identified many individual and environmental barriers that hinder PrEP uptake., Conclusion: Among PWID, PrEP is rarely discussed and concerns about the feasibility of using daily PrEP are common. Taken with the prevalent perception that drug use is not a high risk for HIV acquisition, our findings point to opportunities for public health work to target PrEP education to PWID and to leverage other successful interventions for PWID as an opportunity to provide PrEP to this vulnerable population., (© 2022. The Author(s).)

We report a patient with hereditary erythrocytosis who underwent a therapeutic phlebotomy and had a post-phlebotomy hematocrit that was higher than the pre-phlebotomy hematocrit. We could not discern a reason for this hematocrit increase after phlebotomy. Instead of performing another phlebotomy, we performed an automated red cell depletion via an apheresis instrument. This procedure is essentially a red cell exchange, but 5% albumin is used as the replacement fluid instead of red blood cells. The patient's hematocrit decreased from 80% to 39% after three consecutive daily red cell depletion procedures. We share our experience to report the unusual finding of a patient's hematocrit that increased with phlebotomy and to raise awareness of the red cell depletion procedure., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Rushad Machhi et al.)

Background: US overdose deaths have reached a record high. Syringe services programs (SSPs) play a critical role in addressing this crisis by providing multiple services to people who use drugs (PWUD) that help prevent overdose death. This study examined the perspectives of leadership and staff from a geographically diverse sample of US SSPs on factors contributing to the overdose surge, their organization's response, and ongoing barriers to preventing overdose death., Methods: From 2/11/2021 to 4/23/2021, we conducted semi-structured interviews with leadership and staff from 27 SSPs sampled from the North American Syringe Exchange Network directory. Interviews were transcribed and qualitatively analyzed using a Rapid Assessment Process., Results: Respondents reported that increased intentional and unintentional fentanyl use (both alone and combined with other substances) was a major driver of the overdose surge. They also described how the COVID-19 pandemic increased solitary drug use and led to abrupt increases in use due to life disruptions and worsened mental health among PWUD. In response to this surge, SSPs have increased naloxone distribution, including providing more doses per person and expanding distribution to people using non-opioid drugs. They are also adapting overdose prevention education to increase awareness of fentanyl risks, including for people using non-opioid drugs. Some are distributing fentanyl test strips, though a few respondents expressed doubts about strips' effectiveness in reducing overdose harms. Some SSPs are expanding education and naloxone training/distribution in the broader community, beyond PWUD and their friends/family. Respondents described several ongoing barriers to preventing overdose death, including not reaching certain groups at risk of overdose (PWUD who do not inject, PWUD experiencing homelessness, and PWUD of color), an inconsistent naloxone supply and lack of access to intranasal naloxone in particular, inadequate funding, underestimates of overdoses, legal/policy barriers, and community stigma., Conclusions: SSPs remain essential in preventing overdose deaths amid record numbers likely driven by increased fentanyl use and COVID-19-related impacts. These findings can inform efforts to support SSPs in this work. In the face of ongoing barriers, support for SSPs-including increased resources, political support, and community partnership-is urgently needed to address the worsening overdose crisis., (© 2022. The Author(s).)

Transgender persons have high rates of alcohol and other drug use disorders (AUD and DUD, respectively) and commonly experience social and economic stressors that may compound risk for adverse substance-related outcomes. National VA electronic health record data were extracted for all outpatients in each facility with documented alcohol screening 10/1/09-7/31/17. We describe the prevalence of eight individual-level social and economic stressors (barriers to accessing care, economic hardship, housing instability, homelessness, social and family problems, legal problems, military sexual trauma, and other victimization) among transgender patients with and without AUD and DUD (alone and in combination), overall and compared to cisgender patients in a national sample of VA outpatients. Among 8,872,793 patients, 8619 (0.1%) were transgender; the prevalence of AUD, DUD, and both was 8.6%, 7.2%, and 3.1% among transgender patients and 6.1%, 3.9%, and 1.7% among cisgender patients, respectively. Among all patients, prevalence of stressors was higher among those with AUD, DUD, or both, relative to those with neither. Within each of these groups, prevalence was 2-3 times higher among transgender compared to cisgender patients. For instance, prevalence of housing instability for transgender vs. cisgender patients with AUD, DUD, and both was: 40.8% vs 24.1%, 45.8% vs. 36.6%, and 57.4% vs. 47.0%, respectively. (all p-values <0.001). Social and economic stressors were prevalent among patients with AUD, DUD, or both, and the experience of these disorders and social and economic stressors was more common among transgender than cisgender patients in all groups. Further research regarding experiences of transgender persons and influences of stressors on risk of AUD and DUD, substance-related outcomes, and treatment uptake are needed. Routine screening for social and economic stressors among patients with substance use disorders (SUDs) could improve equitable substance-related care and outcomes. Treatment of SUDs among all persons should consider social and economic risk factors., Competing Interests: None.

Importance: Substance use disorders (SUDs) are major contributors to morbidity and mortality globally, but they are often underrecognized and underdiagnosed, particularly in some sociodemographic subgroups. Understanding the extent to which clinical diagnoses underestimate these conditions within subgroups is imperative to achieving equitable treatment, regardless of race, ethnicity, gender, or age, and to informing and improving performance monitoring., Objective: To compare clinically documented diagnosis rates of alcohol use disorder (AUD), drug use disorder (DUD), and total SUD (AUD and/or DUD) with the prevalence of these disorders as reported in surveys-based on structured, validated diagnostic assessments-across demographic subgroups., Design, Setting, and Participants: A telephone-based survey was conducted from January 8, 2018, to April 30, 2019, among 5995 Veterans Health Administration (VHA) outpatients who were randomly sampled from 30 VHA facilities and were 18 years of age or older, could complete the survey in English, and had a valid address and telephone number. Survey data were linked to electronic health record (EHR) data for all participants. Statistical analysis was performed between January 29, 2020, and April 20, 2021., Exposures: Demographic subgroups based on self-report: gender (male or female), age (18-34, 35-49, 50-64, 65-74, and ≥75 years), and race and ethnicity (Black non-Hispanic, Hispanic, multiracial, other [Asian or Asian-American, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, and any other race endorsed by the participant], and White non-Hispanic)., Main Outcomes and Measures: Survey-based prevalence rates of AUD, DUD, and SUD were assessed using the Mini International Neuropsychiatric Interview, version 7.0, the only validated instrument available at study outset that measured Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for past 12-month diagnoses. Clinically documented diagnosis rates were measured using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses from VHA EHR data. Analyses compared survey-based prevalence rates of AUD, DUD, and SUD with diagnosis rates using sensitivity and specificity and difference-in-difference analysis. All analyses were weighted with survey weights to account for nonresponse., Results: Of 5995 participants, 4115 (68.6%) were White non-Hispanic, and 5429 (91.1%) were male; the mean (SD) age was 61.5 (15.3) years. The survey-based prevalence rates of AUD, DUD, and SUD were higher than the diagnosis rates among all patients (AUD, 608 [10.1%] vs 360 [6.0%]; DUD, 282 [4.7%] vs 275 [4.6%]; SUD, 768 [12.8%] vs 515 [8.6%]). Survey-based prevalence rates of AUD and SUD exceeded the diagnosis rates in every demographic subgroup. Gaps between diagnosis rates and survey-based prevalence rates for AUD and SUD were largest among patients aged 18 to 34 years (AUD diagnosis rate, 27 [6.9%; 95% CI, 4.8%-9.9%] vs AUD prevalence rate, 88 [22.4%; 95% CI, 17.3%-28.5%]; SUD diagnosis rate, 41 [10.5%; 95% CI, 8.1%-13.4%] vs SUD prevalence rate, 109 [27.7%; 95% CI, 22.6%-33.3%]) and Hispanic and Latinx patients (AUD diagnosis rate, 31 [7.6%; 95% CI, 5.3%-10.8%] vs AUD prevalence rate, 72 [17.7%; 95% CI, 14.0%-22.1%]; and SUD diagnosis rate, 48 [11.7%; 95% CI, 7.9%-16.9%] vs SUD prevalence rate, 88 [21.6%; 95% CI, 18.0%-25.8%]). For DUD, only patients aged 18 to 34 years had a true prevalence rate that significantly exceeded the diagnosis rate (diagnosis rate, 21 [5.4%; 95% CI, 3.7%-7.8%] vs prevalence rate, 40 [10.1%; 95% CI, 7.2%-14.0%])., Conclusions and Relevance: The results of this survey study suggest that existing diagnostic procedures and tools are insufficient to capture SUD prevalence rates, particularly among younger patients and Hispanic and Latinx patients. Clinics and health systems should implement standardized SUD assessments to ensure the provision of equitable care and the optimal identification of underlying conditions for performance monitoring.

Mindfulness is becoming increasingly popular in the workplace. This likely relates to a growing body of research linking mindfulness to a range of psychological outcomes such as reduced anxiety, depression and increased subjective wellbeing. However, while mindfulness has received a great deal of attention in clinical research, the evidence for workplace relevant benefits is less established. Additionally, outside of clinical research, mindfulness studies have rarely been replicated. Recent evidence suggests that the cognitive skills cultivated during meditation may be instrumental in reducing biased thinking and increasing prosocial behaviour, but these findings have not been previously tested in a workplace setting. Specifically, mindfulness has been linked to reductions in implicit age bias, sunk-cost decision-making bias and increases in organisational citizenship behaviours (OCB). In two experiments using a workplace and laboratory sample, the present investigation aimed to test the reliability and generalisability of previous findings that a brief mindfulness meditation can reduce age and sunk-cost decision-making biases. To more directly test the potential positive benefits of mindfulness in a workplace setting, this study also investigated the impact of a mindfulness intervention on intention to perform OCB. While meditation significantly increased OCB intent, predictions relating to bias were not supported. Considerations for the degree to which empirical evidence aligns with claims in popular culture, along with implications for the practical uses of mindfulness in the workplace are explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Williams and Polito.)

Background: Alcohol use is a significant risk factor for disability and death in U.S. adults, and approximately one out of every six Veterans seen in primary care (PC) report unhealthy alcohol use. Unhealthy alcohol use is associated with increased risk for poor medical outcomes, substantial societal costs, and death, including suicide. Based on substantial evidence from randomized controlled trials and the U.S. Preventive Services Task Force, VA/DoD clinical guidelines stipulate that all Veterans screening positive for unhealthy alcohol use should receive evidence-based alcohol care in PC, including brief counseling interventions (BI) and additional treatment (e.g., pharmacotherapy) for those with alcohol use disorders (AUD). The VA pioneered implementing alcohol screening and BI in PC, yet substantial implementation gaps remain. To improve alcohol-related care, this study will conduct a pilot study to assess whether a multi-faceted evidence-based implementation strategy-practice facilitation-has the potential to improve PC-based alcohol-related care at a single VA clinic., Methods: We will first recruit and conduct qualitative interviews with Veterans with unhealthy alcohol use (n = 20-25) and PC stakeholders (N = 10-15) to understand barriers and facilitators to high-quality alcohol care and use results to refine and hone the multifaceted practice facilitation intervention. Qualitative interviews, analysis, and refinement of the intervention will be guided by the Consolidated Framework for Implementation Research (CFIR). Focus groups with a small sample of PC providers and staff (n = 5-7) will be used to further refine the practice facilitation intervention and assess its acceptability and feasibility. The refined practice facilitation intervention will then be offered in the PC clinic to assess implementation (e.g., reach) and effectiveness (reduced drinking) outcomes based on the RE-AIM framework., Discussion: This research directly addresses one of the largest public health crises of our time, as alcohol kills more people than opioids and is associated with increased risk of suicide. If successful, this pilot may generate an intervention with far-reaching effects on adverse outcomes experienced by Veterans with unhealthy alcohol use, including increased access to care and suicide prevention. Trial registration Clinicaltrials.gov identifier: NCT04565899; Date of registration: 9/25/2020., (© 2022. The Author(s).)

Introduction: Opioid use disorder and high-risk opioid prescription increase the risks for overdose and death. In Veterans, military sexual trauma is associated with increased risk for assorted health conditions. This study evaluates the association of military sexual trauma with opioid use disorder and high-risk opioid prescription and potential moderation by gender., Methods: In a national sample of Veterans Health Administration outpatients receiving care from October 1, 2009 to August 1, 2017, logistic regression models were fit to evaluate the associations between military sexual trauma and opioid use disorder and high-risk opioid prescription, adjusting for demographic and clinical covariates. A second set of models included a gender X military sexual trauma interaction. Analyses were conducted in 2020-2021., Results: Patients with history of military sexual trauma (n=327,193) had 50% higher odds of opioid use disorder diagnosis (AOR=1.50, 95% CI=1.45, 1.54, p<0.001) and 5% higher odds of high-risk opioid prescription (AOR=1.05, 95% CI=1.04, 1.07, p<0.001) than those without history of military sexual trauma (n=7,738,665). The effect of military sexual trauma on opioid use disorder was stronger in men than in women . The predicted probability of opioid use disorder among men with history of military sexual trauma (1.5%) was nearly double that of women with history of military sexual trauma (0.8%)., Conclusions: Military sexual trauma was a significant risk factor for opioid use disorder and high-risk opioid prescription, with the former association particularly strong in men. Clinical care for Veterans with military sexual trauma should consider elevated risk of opioid use disorder and high-risk opioid prescription., (Copyright © 2021 American Journal of Preventive Medicine. All rights reserved.)

Background: Approximately 30% of US children aged 24 months have not received all recommended vaccines. This study aimed to develop a prediction model to identify newborns at high risk for missing early childhood vaccines., Methods: A retrospective cohort included 9080 infants born weighing ≥2000 g at an academic medical center between 2008 and 2013. Electronic medical record data were linked to vaccine data from the Washington State Immunization Information System. Risk models were constructed using derivation and validation samples. K-fold cross-validation identified risk factors for model inclusion based on alpha = 0.01. For each patient in the derivation set, the total number of weighted adverse risk factors was calculated and used to establish groups at low, medium, or high risk for undervaccination. Logistic regression evaluated the likelihood of not completing the 7-vaccine series by age 19 months. The final model was tested using the validation sample., Results: Overall, 53.6% failed to complete the 7-vaccine series by 19 months. Six risk factors were identified: race/ethnicity, maternal language, insurance status, birth hospitalization length of stay, medical service, and hepatitis B vaccine receipt. Likelihood of non-completion was greater in the high (77.1%; adjusted odds ratio [AOR] 5.6; 99% confidence interval [CI]: 4.2, 7.4) and medium (52.7%; AOR 1.9; 99% CI: 1.6, 2.2) vs low (38.7%) risk groups in the derivation sample. Similar results were observed in the validation sample., Conclusions: Our prediction model using information readily available in birth hospitalization records consistently identified newborns at high risk for undervaccination. Early identification of high-risk families could be useful for initiating timely, tailored vaccine interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Poppy seeds contain morphine and other opioid alkaloids and are commercially available in the United States. Users of poppy seed tea (PST) can consume several hundred morphine milligram equivalents per day, and opioid dependence from PST use can develop. We report a case of a patient with chronic pain and PST use leading to opioid use disorder (OUD). This case represents the first published report of OUD from PST successfully treated with buprenorphine (BUP) in a primary care setting. The provider in this case used a unique model of care with an opioid prescribing support team to deliver safe and effective care., Case Presentation: A 47-year-old man with chronic pain and prescription opioid use presented to primary care to discuss a flare of shoulder pain, and revealed in subsequent conversation a long-standing use of PST to supplement pain control. Attempts at cessation resulted in severe withdrawal symptoms, leading to return to PST use. The primary care provider consulted the VA Puget Sound SUpporting Primary care Providers in Opioid Risk reduction and Treatment (SUPPORT) team to evaluate the patient for OUD. The patient discontinued all opioids, and initiated BUP under the supervision of the primary care provider. He remained on a stable dosage, without relapse, 24 months later., Conclusions: PST, which can be made through purchase of readily available poppy pods, carries risk for development of OUD and overdose. Herein we highlight the utility of a primary care opioid prescribing support team in empowering a primary care provider to prescribe BUP to treat a patient with complex OUD., (© 2021. The Author(s).)

Background/objective: Evidence-based alcohol-related care-brief intervention for all patients with unhealthy alcohol use and specialty addictions treatment and/or pharmacotherapy for patients with alcohol use disorder (AUD)-should be routinely offered. Transgender persons may be particularly in need of alcohol-related care, given common experiences of social and economic hardship that may compound the adverse effects of unhealthy alcohol use. We examined receipt of alcohol-related care among transgender patients compared to non-transgender patients in a large national sample of Veterans Health Administration (VA) outpatients with unhealthy alcohol use., Methods: We extracted electronic health record data for patients from all VA facilities who had an outpatient visit 10/1/09-7/31/17 and a documented positive screen for unhealthy alcohol use (AUDIT-C ≥ 5). We identified transgender patients with a validated approach using transgender-related diagnostic codes. We fit modified Poisson models, adjusted for demographics and comorbidities, to estimate the average predicted prevalence of brief intervention (documented 0-14 days following most recent positive screening), specialty addictions treatment for AUD (documented 0-365 days following screening), and filled prescriptions for medications to treat AUD (documented 0-365 days following screening) for transgender patients, and compared to that of non-transgender patients., Results: Among transgender Veterans with unhealthy alcohol use (N = 1392), the adjusted prevalence of receiving brief intervention was 75.4% (95% CI 72.2-78.5), specialty addictions treatment for AUD was 15.7% (95% CI 13.7-17.7), and any AUD pharmacotherapy was 19.0% (95% CI 17.1-20.8). Receipt of brief intervention did not differ for transgender relative to non-transgender patients (Prevalence Ratio [PR] 1.01, 95% CI 0.98-1.04, p = 0.574). However, transgender patients were more likely to receive specialty addictions treatment (PR 1.24, 95% CI 1.12-1.37, p < 0.001) and pharmacotherapy (PR 1.16, 95% CI 1.06-1.28, p = 0.002)., Conclusions: Findings suggest the majority of transgender VHA patients with unhealthy alcohol use receive brief intervention, though a quarter still do not. Nonetheless, rates of specialty addictions treatment and pharmacotherapy are low overall, although transgender patients may be receiving this care at greater rates than non-transgender patients. Further research is needed to investigate these findings and to increase receipt of evidence-based care overall., (Copyright © 2021. Published by Elsevier Inc.)

Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver-related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol-associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow-up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD-cirrhosis and HCV-cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07-1.19 and aHR = 1.14, 95% CI = 1.08-1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07-1.30 and aHR = 1.08, 95% CI = 1.00-1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV-cirrhosis and ALD-cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Importance: With increasing rates of opioid use disorder (OUD) and overdose deaths in the US, increased access to medications for OUD (MOUD) is paramount. Rigorous effectiveness evaluations of large-scale implementation initiatives using quasi-experimental designs are needed to inform expansion efforts., Objective: To evaluate a US Department of Veterans Affairs (VA) initiative to increase MOUD use in nonaddiction clinics., Design, Setting, and Participants: This quality improvement initiative used interrupted time series design to compare trends in MOUD receipt. Primary care, pain, and mental health clinics in the VA health care system (n = 35) located at 18 intervention facilities and nonintervention comparison clinics (n = 35) were matched on preimplementation MOUD prescribing trends, clinic size, and facility complexity. The cohort of patients with OUD who received care in intervention or comparison clinics in the year after September 1, 2018, were evaluated. The preimplementation period extended from September 1, 2017, through August 31, 2018, and the postimplementation period from September 1, 2018, through August 31, 2019., Exposures: The multifaceted implementation intervention included education, external facilitation, and quarterly reports., Main Outcomes and Measures: The main outcomes were the proportion of patients receiving MOUD and the number of patients per clinician prescribing MOUD. Segmented logistic regression evaluated monthly proportions of MOUD receipt 1 year before and after initiative launch, adjusting for demographic and clinical covariates. Poisson regression models examined yearly changes in clinician prescribing over the same time frame., Results: Overall, 7488 patients were seen in intervention clinics (mean [SD] age, 53.3 [14.2] years; 6858 [91.6%] male; 1476 [19.7%] Black, 417 [5.6%] Hispanic; 5162 [68.9%] White; 239 [3.2%] other race [including American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, and multiple races]; and 194 [2.6%] unknown) and 7558 in comparison clinics (mean [SD] age, 53.4 [14.0] years; 6943 [91.9%] male; 1463 [19.4%] Black; 405 [5.4%] Hispanic; 5196 [68.9%] White; 244 [3.2%] other race; 250 [3.3%] unknown). During the preimplementation year, the proportion of patients receiving MOUD in intervention clinics increased monthly by 5.0% (adjusted odds ratio [AOR], 1.05; 95% CI, 1.03-1.07). Accounting for this preimplementation trend, the proportion of patients receiving MOUD increased monthly by an additional 2.3% (AOR, 1.02; 95% CI, 1.00-1.04) during the implementation year. Comparison clinics increased by 2.6% monthly before implementation (AOR, 1.03; 95% CI, 1.01-1.04), with no changes detected after implementation. Although preimplementation-year trends in monthly MOUD receipt were similar in intervention and comparison clinics, greater increases were seen in intervention clinics after implementation (AOR, 1.04; 95% CI, 1.01-1.08). Patients treated with MOUD per clinician in intervention clinics saw greater increases from before to after implementation compared with comparison clinics (incidence rate ratio, 1.50; 95% CI, 1.28-1.77)., Conclusions and Relevance: A multifaceted implementation initiative in nonaddiction clinics was associated with increased MOUD prescribing. Findings suggest that engagement of clinicians in general clinical settings may increase MOUD access.

Background: Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD., Methods: We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes., Results: Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples., Conclusions: Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population., (© 2021. The Author(s).)