Integrating Opioid Use Disorder Treatment Into Primary Care Settings.

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.

Integrating Routine Screening for Opioid Use Disorder into Primary Care Settings: Experiences from a National Cohort of Clinics.

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.

Ist2 recruits the lipid transporters Osh6/7 to ER-PM contacts to maintain phospholipid metabolism.

ER-plasma membrane (PM) contacts are proposed to be held together by distinct families of tethering proteins, which in yeast include the VAP homologues Scs2/22, the extended-synaptotagmin homologues Tcb1/2/3, and the TMEM16 homologue Ist2. It is unclear whether these tethers act redundantly or whether individual tethers have specific functions at contacts. Here, we show that Ist2 directly recruits the phosphatidylserine (PS) transport proteins and ORP family members Osh6 and Osh7 to ER-PM contacts through a binding site located in Ist2's disordered C-terminal tethering region. This interaction is required for phosphatidylethanolamine (PE) production by the PS decarboxylase Psd2, whereby PS transported from the ER to the PM by Osh6/7 is endocytosed to the site of Psd2 in endosomes/Golgi/vacuoles. This role for Ist2 and Osh6/7 in nonvesicular PS transport is specific, as other tethers/transport proteins do not compensate. Thus, we identify a molecular link between the ORP and TMEM16 families and a role for endocytosis of PS in PE synthesis.

The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity.

Human innate immunity to Trypanosoma brucei involves the trypanosome C-terminal kinesin TbKIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show that TbKIFC1 preferentially associates with cholesterol-containing membranes and is indispensable for mammalian infectivity. Knockdown of TbKIFC1 did not affect trypanosome growth in vitro but rendered the parasites unable to infect mice unless antibody synthesis was compromised. Surface clearance of Variant Surface Glycoprotein (VSG)-antibody complexes was far slower in these cells, which were more susceptible to capture by macrophages. This phenotype was not due to defects in VSG expression or trafficking but to decreased VSG mobility in a less fluid, stiffer surface membrane. This change can be attributed to increased cholesterol level in the surface membrane in TbKIFC1 knockdown cells. Clearance of surface-bound antibodies by T. brucei is therefore essential for infectivity and depends on high membrane fluidity maintained by the cholesterol-trafficking activity of TbKIFC1.

Trypanosoma brucei Secreted Aromatic Ketoacids Activate the Nrf2/HO-1 Pathway and Suppress Pro-inflammatory Responses in Primary Murine Glia and Macrophages.

African trypanosomes, such as Trypanosoma brucei (T. brucei), are protozoan parasites of the mammalian vasculature and central nervous system that are best known for causing fatal human sleeping sickness. As exclusively extracellular parasites, trypanosomes are subject to constant challenge from host immune defenses but they have developed very effective strategies to evade and modulate these responses to maintain an infection while simultaneously prolonging host survival. Here we investigate host parasite interactions, especially within the CNS context, which are not well-understood. We demonstrate that T. brucei strongly upregulates the stress response protein, Heme Oxygenase 1 (HO-1), in primary murine glia and macrophages in vitro. Furthermore, using a novel AHADHinT. brucei cell line, we demonstrate that specific aromatic ketoacids secreted by bloodstream forms of T. brucei are potent drivers of HO-1 expression and are capable of inhibiting pro-IL1ß induction in both glia and macrophages. Additionally, we found that these ketoacids significantly reduced IL-6 and TNFα production by glia, but not macrophages. Finally, we present data to support Nrf2 activation as the mechanism of action by which these ketoacids upregulate HO-1 expression and mediate their anti-inflammatory activity. This study therefore reports a novel immune evasion mechanism, whereby T. brucei secretes amino-acid derived metabolites for the purpose of suppressing both the host CNS and peripheral immune response, potentially via induction of the Nrf2/HO-1 pathway.

Trypanosoma brucei metabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion.

The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form of T. brucei excretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1ß. These data demonstrate an important role for indolepyruvate in immune evasion by T. brucei.

A Descriptive Study of Body Pain and Work-Related Musculoskeletal Disorders Among Latino Farmworkers Working on Sweet Potato Farms in Eastern North Carolina.

Agricultural work is a physically demanding occupation. The purpose of this project was to describe the prevalence of work-related musculoskeletal disorders (WMSDs) and self-reported pain among Latino farmworkers who work extensively hand harvesting sweet potatoes. Data were obtained from a cross-sectional survey of farmworkers (N = 120) in eastern North Carolina. Univariate and bivariate analyses were used to describe personal, work characteristics, and self-reported pain associated with musculoskeletal injuries. Overall, 79% of farmworkers reported any type of pain or discomfort. The highest reported areas of pain were in the back (66%) and shoulder areas (31%). Younger participants experienced more shoulder pain (P = .04) than older workers, and working more than 5 years as a farmworker was significantly associated with back pain (P = .01). Interventions aimed at administrative and engineering controls for reducing risk factors that contribute to WMSDs are warranted.

Didymosphenia geminata in the Upper Esopus Creek: Current Status, Variability, and Controlling Factors.

In May of 2009, the bloom-forming diatom Didymosphenia geminata was first identified in the Upper Esopus Creek, a key tributary to the New York City water-supply and a popular recreational stream. The Upper Esopus receives supplemental flows from the Shandaken Portal, an underground aqueduct delivering waters from a nearby basin. The presence of D. geminata is a concern for the local economy, water supply, and aquatic ecosystem because nuisance blooms have been linked to degraded stream condition in other regions. Here we ascertain the extent and severity of the D. geminata invasion, determine the impact of supplemental flows from the Portal on D. geminata, and identify potential factors that may limit D. geminata in the watershed. Stream temperature, discharge, and water quality were characterized at select sites and periphyton samples were collected five times at 6 to 20 study sites between 2009 and 2010 to assess standing crop, diatom community structure, and density of D. geminata and all diatoms. Density of D. geminata ranged from 0-12 cells cm(-2) at tributary sites, 0-781 cells cm(-2) at sites upstream of the Portal, and 0-2,574 cells cm(-2) at sites downstream of the Portal. Survey period and Portal (upstream or downstream) each significantly affected D. geminata cell density. In general, D. geminata was most abundant during the November 2009 and June 2010 surveys and at sites immediately downstream of the Portal. We found that D. geminata did not reach nuisance levels or strongly affect the periphyton community. Similarly, companion studies showed that local macroinvertebrate and fish communities were generally unaffected. A number of abiotic factors including variable flows and moderate levels of phosphorous and suspended sediment may limit blooms of D. geminata in this watershed.

On the connection coefficients of the Chebyshev-Boubaker polynomials.

The Chebyshev-Boubaker polynomials are the orthogonal polynomials whose coefficient arrays are defined by ordinary Riordan arrays. Examples include the Chebyshev polynomials of the second kind and the Boubaker polynomials. We study the connection coefficients of this class of orthogonal polynomials, indicating how Riordan array techniques can lead to closed-form expressions for these connection coefficients as well as recurrence relations that define them.

Embracing street culture: fitting health care into the lives of street youth.

The purpose of this article is to describe a unique model for the provision of comprehensive primary health care for homeless youth in Seattle, Washington. Through the description of our program, we argue for the use of youth-centric instead of youth-friendly programs. This means a change from using the friendly health program as the central focus to having the young people be the starting point and adapting the health service to meet their needs. We describe how our model of care optimizes chances for homeless youth to establish positive connections with caring adults. We also show how homeless youth have their own street culture, which is of primary importance to them and which has a powerful impact on how they use and view health care.