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IntroductionDeaths from drug overdoses are rising dramatically in the United States. Treatment for opioid use disorders may include behavioral treatments as well as medications for opioid use disorders (MOUD). Buprenorphine can be prescribed by physicians, nurse practitioners (NPs), other advanced practice registered nurses (APRNs), and physician assistants (PAs) and required a training and a federal waiver until recently. The number of NP MOUD prescribers grew steadily over the past decade, but research has identified state-level scope of practice regulations as a barrier to NP MOUD prescribing. This article explores the contributions of, and remaining barriers faced by NP and other APRN MOUD prescribers. We describe qualitative findings from a study of NPs and other key stakeholders involved in MOUD treatment in four states with two differing levels of regulatory structure.MethodsIn this qualitative study, we conducted site visits and semi-structured interviews with NPs and other APRNs, physicians, clinic managers, and regulators in four states including New Mexico and West Virginia (full practice authority for NPs), and Ohio and Michigan (which require physician supervision). Interview notes were entered into a qualitative software package and coded and reviewed by two members of the research team. Data were grouped into key themes.ResultsA total of 76 participants participated in individual or small group interviews in the four states. We found key themes and several subthemes that describe NP practice in MOUD. Participants described key contributions of NP engagement in MOUD, including increasing access, serving rural areas, the unique role of psychiatric NPs, and the value of the nursing model of care in working with people with substance use disorders (SUD). Participants also identified barriers including scope of practice regulations, other regulatory barriers, stigma, and lack of supportive services to address psychosocial needs.ConclusionsThe waiver requirements were eliminated at the end of 2022 in federal budget legislation. Other barriers for NP and other APRN prescribers remain and should be addressed in practice, and in state and federal regulations. Research needs to explore the impact of the waiver elimination on MOUD prescribing and access to services.

IntroductionDrug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes.DesignThe aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs).MethodsThe policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations.ResultsAlthough there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states.ConclusionIncremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed.Clinical relevanceOne of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid agonist, and gold standard medication treatment for OUD, but only 5% of the prescribing workforce possess the required Drug Enforcement Agency (DEA) X waiver. A growing body of evidence demonstrates that Advanced Practice Registered Nurses are accelerating the growth in waiver update and buprenorphine use, despite the considerable barriers and limitations described in this policy analysis.

BackgroundOpioid misuse is a major public health concern in the United States. Opioid agonist medications are evidence-based treatments for opioid use disorders (OUD) that can be prescribed by advance practice registered nurses (APRNs) with prescriptive authority and appropriate training.PurposeArticle examines factors influencing preparation to provide medications for opioid use disorder (MOUD) in APRN education.MethodsData from semi-structured interviews addressing the role of education in preparing APRNs to provide MOUD were grouped into key themes using thematic analysis. Data were collected in a mixed methods study in four states with high opioid overdose deaths whose main findings were previously published.FindingsTwo overarching themes emerged: "addressing attitudes" and "curriculum change." Sub-themes include affective barriers to providing OUD treatment; motivation to respond to the OUD crisis; and attitude change through experience with MOUD.Discussion and conclusionAPRNs can play a key role in reducing the harms caused by OUD. Attention to attitudinal issues, such as stigma, toward people using opioids is important in educating APRNs about providing MOUD.

BackgroundPatients experiencing homelessness have higher rates of substance use and related mortality, often driven by opioid overdose. Conversely, opioid use disorder (OUD) is a leading risk factor for homelessness. Our goal was to test the efficacy of an electronic health record (EHR) screen in identifying this vulnerable population during hospitalization and to assess the feasibility of a bundled intervention in improving opioid safety.MethodsWe assessed patients' housing status, substance use, previous MOUD treatment, barriers to MOUD treatment and readiness to take MOUD in and out of the hospital. For each post discharge follow up call, patients were asked about their MOUD status, barriers accessing treatment, current substance use, and housing status. We also assessed team members perceptions and experiences of the study.ResultsWe enrolled 32 patients with housing insecurity and OUD. The mean age was 44, the majority self-identified as male (78%), and mostly as White (56%) or Black (38%). At each follow up within the 6-months post-discharge, reach rates were low: 40% of enrollees answered at least 1 call and the highest reach rate (31% of patients) occurred at week 4. At the third and sixth-month follow ups, >50% of subjects still taking MOUD were also using opioids.ConclusionOur clinician augmented EHR screen accurately identified inpatients experiencing OUD and PEH. This intervention showed high rates of attrition among enrolled patients, even after providing cellphones. The majority of patients who were reached remained adherent to MOUD though they reported significant barriers.

During the COVID-19 pandemic, there was slower growth in the number of new waivers authorizing clinicians to provide buprenorphine treatment for opioid use disorder. However, treatment capacity grew at a stable rate as a result of already authorized clinicians obtaining waivers for larger patient panels. Advanced practice nurses accounted for the largest portion of capacity growth during the pandemic.

This study identifies how to screen for harmful alcohol use among gender minority (e.g., transgender and gender-expansive) people using brief screening methods and identifies which screening methods perform best among gender-expansive, transfeminine, and transmasculine subgroups, as screening recommendations are not currently available. Using 2018 Annual Questionnaire data from The PRIDE Study, area under the curve (AUC) values were compared to identify which screening methods (4 or more or 5 or more drinks on one occasion in the past year, or one or more items from the Alcohol Use Disorders Identification Test [AUDIT]) best predicted (i) harmful alcohol use and (ii) one or more past year alcohol dependence symptoms or consequences. Among 1892 participants, 5 or more drinks on one occasion (AUC ranges: 0.82-0.86) performed better than 4 or more drinks (AUC ranges: 0.78-0.81) in predicting harmful drinking. The screening methods 4 or more drinks, 5 or more drinks, and the consumption items of the AUDIT (AUDIT-C) using a cutoff score of 3 all maximized sensitivity and specificity to predict alcohol dependence symptoms or consequences in gender minority people overall (AUC: 0.77-0.78). Screening for 5 or more drinks on one occasion within the past year performed as well as or better than other screening methods to detect both harmful drinking and alcohol dependence-related symptoms or consequences. This single-item screening method can identify if more extensive alcohol use assessment is warranted with gender minority people.

Muscle stem cells (MuSCs) exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here, we show that fetal MuSCs resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. After transplantation, fetal MuSCs expand more efficiently and contribute to muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSCs, including tenascin-C, fibronectin, and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSCs change the way in which they remodel their microenvironment to direct stem cell behavior and support the unique demands of muscle development or repair.

Chronic inflammation is a hallmark of several muscle-wasting diseases and impairs the normal regenerative response. IL-6 is among the inflammatory cytokines present during the initial stages of muscle repair and [...], The progressive loss of muscle regenerative capacity with age or disease results in part from a decline in the number and function of satellite cells, the direct cellular contributors to muscle repair (1-11). However, little is known about the molecular effectors underlying satellite cell impairment and depletion. Elevated levels of inflammatory cytokines, including interleukin-6 (IL-6), are associated with both age-related and muscle-wasting conditions (12-15). The levels of STAT3, a downstream effector of IL-6, are also elevated with muscle wasting (16, 17), and STAT3 has been implicated in the regulation of self-renewal and stem cell fate in several tissues (18-21). Here we show that IL-6-activated Stat3 signaling regulates satellite cell behavior, promoting myogenic lineage progression through myogenic differentiation 1 (Myodl) regulation. Conditional ablation of Stat3 in Pax7-expressing satellite cells resulted in their increased expansion during regeneration, but compromised myogenic differentiation prevented the contribution of these cells to regenerating myofibers. In contrast, transient Stat3 inhibition promoted satellite cell expansion and enhanced tissue repair in both aged and dystrophic muscle. The effects of STAT3 inhibition on cell fate and proliferation were conserved in human myoblasts. The results of this study indicate that pharmacological manipulation of STAT3 activity can be used to counteract the functional exhaustion of satellite cells in pathological conditions, thereby maintaining the endogenous regenerative response and ameliorating muscle-wasting diseases.

Physician supervision of nurse practitioners (NPs) was temporarily waived in Massachusetts in response to a state of emergency due to the COVID-19 pandemic. The authors examined the impact of the scope-of-practice changes and pandemic-related demands on psychiatric mental health NPs (PMHNPs) during the state's first COVID-19 surge. A mixed-methods Web-based survey was conducted in May and June of 2020. Fisher's exact test was used to compare associations across certification types, and inductive content analysis was applied to open-ended responses. The survey response rate was 41% (N=389 of 958), consisting of 26 PMHNPs and 363 other NPs. Compared with other NPs, PMHNPs were significantly more likely to work in a telehealth setting (42% vs. 11%, p<0.001), to spend more time working during the initial surge (50% vs. 26%, p<0.05), and to believe that the waiver improved clinical work (52% vs. 25%, p<0.01). Content analysis of PMHNPs' open-ended responses identified four themes: the supervision waiver reduced burden on PMHNPs, collaboration and mentorship models persisted, the pandemic exacerbated the already high demand for psychiatric care, and telehealth helped meet the high demand for such care. PMHNPs may be more sensitive to the scope-of-practice changes and telehealth expansion than other NPs because of the constraints of the psychiatrist shortage and high relative uptake of telehealth in psychiatric care. The interactions of workforce supply, telehealth expansion, and scope-of-practice laws are important to consider in the development of policies to improve access to mental health care. [ABSTRACT FROM AUTHOR]

Two recent studies have shown that alterations in muscle stem cell-niche interactions during aging underlie the functional decline in regenerative potential. The reconstitution of this communication restores stem cell function [...]

Development of human embryonic stem cell (hESC)-based therapy requires derivation of in vitro expandable cell populations that can readily differentiate to specified cell types and engraft upon transplantation. Here, we report that hESCs can differentiate into skeletal muscle cells without genetic manipulation. This is achieved through the isolation of cells expressing a mesodermal marker, platelet-derived growth factor receptor-α (PDGFRA), following embryoid body (EB) formation. The ESC-derived cells differentiated into myoblasts in vitro as evident by upregulation of various myogenic genes, irrespective of the presence of serum in the medium. This result is further corroborated by the presence of sarcomeric myosin and desmin, markers for terminally differentiated cells. When transplanted in vivo, these pre-myogenically committed cells were viable in tibialis anterior muscles 14 days post-implantation. These hESC-derived cells, which readily undergo myogenic differentiation in culture medium containing serum, could be a viable cell source for skeletal muscle repair and tissue engineering to ameliorate various muscle wasting diseases. [ABSTRACT FROM AUTHOR]

Generation of in vitro induced pluripotent cells (hiPSCs)-derived skeletal muscle progenitor cells (SMPCs) holds great promise for regenerative medicine for skeletal muscle wasting diseases, as for example Duchenne Muscular Dystrophy (DMD). Multiple approaches, involving ectopic expression of key regulatory myogenic genes or small molecules cocktails, have been described by different groups to obtain SMPC towards cell-transplantation in vivo as a therapeutic approach to skeletal muscle diseases. However, hiPSCs-derived SMPC generated using transgene-free protocols are usually obtained in a low amount and resemble a more embryonal/fetal stage of differentiation. Here we demonstrate that modulation of the JAK2/STAT3 signaling pathway during an in vitro skeletal muscle differentiation protocol, increases the yield of PAX7+ and CD54+ SMPCs and drive them to a postnatal maturation stage, in both human ES and patient-derived iPSCs. Importantly, upon removal of the inhibition from the cultures, the obtained SMPCs are able to differentiate into multinucleated myotubes in vitro. These findings reveal that modulation of the JAK2/STAT3 signaling pathway is a potential therapeutic avenue to generate SMPCs in vitro with increase potential for cell-therapy approaches., Competing Interests: Conflict of Interest Statement The authors declare that they have no conflict of interest.

Macrophages and dendritic cells have long been appreciated for their ability to migrate to and engulf dying cells and debris, including some of the billions of cells that are naturally eliminated from our body daily. However, a substantial number of these dying cells are cleared by 'non-professional phagocytes', local epithelial cells that are critical to organismal fitness. How non-professional phagocytes sense and digest nearby apoptotic corpses while still performing their normal tissue functions is unclear. Here, we explore the molecular mechanisms underlying their multifunctionality. Exploiting the cyclical bouts of tissue regeneration and degeneration during the hair cycle, we show that stem cells can transiently become non-professional phagocytes when confronted with dying cells. Adoption of this phagocytic state requires both local lipids produced by apoptotic corpses to activate RXRα, and tissue-specific retinoids for RARγ activation. This dual factor dependency enables tight regulation of the genes requisite to activate phagocytic apoptotic clearance. The tunable phagocytic program we describe here offers an effective mechanism to offset phagocytic duties against the primary stem cell function of replenishing differentiated cells to preserve tissue integrity during homeostasis. Our findings have broad implications for other non-motile stem or progenitor cells which experience cell death in an immune-privileged niche., Competing Interests: Competing Interest E.F. has served on the scientific advisory boards of L’Oreal and Arsenal Biosciences. C.V.R is a senior editor for eLife. S.G. has received grant support from Mirati Therapeutics. The other authors declare no competing interests.

Competing Interests: Conflict-of-Interest Disclosures: Mr. Tierney discloses that he receives personal fees from the American Society of Addiction Medicine, the Medical Education and Research Foundation, and The Association for Multidisciplinary Education and Research in Substance use and Addiction.

Competing Interests: Conflict-of-Interest Disclosures: Dr. Bottner acknowledges receiving grants from SAMHSA and the AAMC. Dr. Jordan acknowledges receiving grants from NIH and FORE. Dr. Weimer reports serving as a paid medical advisor to Path Inc., CCM; CVS Health; and the American Society of Addiction Medicine.