Emergency department staff compassion is associated with lower fear of enacted stigma among patients with opioid use disorder.

OBJECTIVES: Fear of enacted stigma (fear of discrimination or being treated unfairly) is associated with decreased health care-seeking behaviors among patients with opioid use disorder (OUD). We sought to describe the prevalence of fear of enacted stigma among patients presenting to the emergency department (ED) with OUD and to test whether experiencing greater compassion from ED staff is associated with lower fear of enacted stigma. METHODS: We conducted a cross-sectional study in the ED of an academic medical center between February and August 2023. We included adult patients with OUD presenting to the ED and assessed patient experience of compassion from ED staff using a previously validated 5-item compassion measure (score range 5-20). The primary outcome measure was fear of enacted stigma in the ED, measured using the validated 9-item subscale of the Substance Abuse Self-Stigma Scale (score range 9-45). RESULTS: Of the 116 subjects enrolled, 97% (95% confidence interval [CI] 91%-99%) reported some degree of stigma, with a median (interquartile range) score of 23 (16-31). In a multivariable model adjusting for potential confounders, patient experience of greater ED compassion was independently associated with lower fear of enacted stigma, ß = -0.66 (95% CI -1.03 to -0.29), suggesting that every 1-point increase in the 5-item compassion measure score is associated with a 0.66-point decrease in the fear of enacted stigma score. CONCLUSIONS: Among ED patients with OUD, fear of enacted stigma is common. Patient experience of compassion from ED staff is associated with lower fear of enacted stigma. Future research is warranted to test if interventions aimed at increasing compassion from ED staff reduce patient fear of enacted stigma among patients with OUD.

A Retrospective Cohort Study of Disparities in Urine Drug Testing During the Perinatal Period in an Urban, Academic Medical Center.

The purpose of this study was to evaluate disparities in urine drug testing (UDT) during perinatal care at a single academic medical center. This retrospective cohort study included patients who had a live birth and received prenatal care at our institution between 10/1/2015 and 9/30/2020. The primary outcomes were maternal UDT during pregnancy (UDTPN) and UDT only at delivery (UDTDEL). Secondary outcomes included the number of UDTs (UDTNUM) and the association between a positive UDT test result and race/ethnicity. Mixed model logistic regression and negative binomial regression with clustering based on prenatal care locations were used to control for confounders. Of 6,240 live births, 2,265 (36.3%) and 167 (2.7%) received UDTPN and UDTDEL, respectively. Black (OR 2.09, 95% CI 1.54-2.84) and individuals of Other races (OR 1.64, 95% CI 1.03-2.64) had greater odds of UDTPN compared to non-Hispanic White individuals. Black (beta = 1.12, p < 0.001) and Hispanic individuals (beta = 0.78, p < 0.001) also had a positive relationship with UDTNUM. Compared to individuals with non-Medicaid insurance, those insured by Medicaid had greater odds of UDTPN (OR 1.66, 95% CI 1.11-2.49) and had a positive relationship with UDTNUM (beta = 0.89, p < 0.001). No significant associations were found for UDTDEL and race/ethnicity. Despite receiving more UDT, Black individuals were not more likely to have a positive test result compared to non-Hispanic White individuals (OR 0.95, 95% CI 0.72-1.25). Our findings demonstrate persistent disparities in substance use testing during the perinatal period.

Lipid-coated mesoporous silica nanoparticles for anti-viral applications via delivery of CRISPR-Cas9 ribonucleoproteins.

Emerging and re-emerging viral pathogens present a unique challenge for anti-viral therapeutic development. Anti-viral approaches with high flexibility and rapid production times are essential for combating these high-pandemic risk viruses. CRISPR-Cas technologies have been extensively repurposed to treat a variety of diseases, with recent work expanding into potential applications against viral infections. However, delivery still presents a major challenge for these technologies. Lipid-coated mesoporous silica nanoparticles (LCMSNs) offer an attractive delivery vehicle for a variety of cargos due to their high biocompatibility, tractable synthesis, and amenability to chemical functionalization. Here, we report the use of LCMSNs to deliver CRISPR-Cas9 ribonucleoproteins (RNPs) that target the Niemann-Pick disease type C1 gene, an essential host factor required for entry of the high-pandemic risk pathogen Ebola virus, demonstrating an efficient reduction in viral infection. We further highlight successful in vivo delivery of the RNP-LCMSN platform to the mouse liver via systemic administration.

Camden Coalition Medical-Legal Partnership: Year One Analysis of Civil + Criminal MLP Model in Addiction Medicine Setting.

In 2022, the Camden Coalition Medical-Legal Partnership began providing civil and criminal legal services to substance use disorder patients at Cooper University Health Care's Center for Healing. This paper discusses early findings from the program's first year on the efficacy of the provision of criminal-legal representation, which is uncommon among MLPs and critical for this patient population. The paper concludes with takeaways for other programs providing legal services in an addiction medicine setting.

A Low-threshold Comprehensive Shared Medical Appointment Program for Perinatal Substance Use in an Underserved Population.

OBJECTIVES: We describe retention in care, medication for opioid use disorder (MOUD) prescribing, and urine toxicology outcomes of a comprehensive perinatal shared medical appointment model that combined medication, group-based counseling, and recovery supports. METHODS: We conducted a retrospective study of program retention between 11/1/16 and 3/31/20 in pregnant and postpartum women with substance dependence or use disorder. Disengagement reasons, MOUD prescribing, and urine toxicology were abstracted from medical records. A Cox proportional hazards model was used to evaluate risk factors for program disengagement. RESULTS: Approximately 87% of patients had OUD and 80% were pregnant at the initial visit (N = 140). Retention at 3 months, 6 months, 1 year, and 2 years was approximately 86%, 78%, 66%, and 48%, respectively. Over 97% of patients were prescribed MOUD and 88% of all urine toxicology results were negative for non-prescribed opioids. Patients enrolled after initiation of wraparound services (HR 0.52, 95% CI 0.28 - 0.96) and those attending more shared medical appointments (HR 0.90, 95% CI 0.87 - 0.93) had a lower hazard of disengagement after controlling for other covariates. Loss to follow-up was the most common disengagement reason. CONCLUSIONS: A low-threshold, comprehensive perinatal shared medical appointment program had high retention rates, increased access to evidence-based MOUD, and high rates of opioid-negative urine toxicology. Participants enrolled after wraparound services began had a lower hazard of disengagement. Future research in perinatal substance use should evaluate the most optimal and cost-effective components of comprehensive programs to inform standard of care.

Rat and human cytomegalovirus ORF116 encodes a virion envelope glycoprotein required for infectivity.

Herpesviruses encode multiple glycoproteins required for different stages of viral attachment, fusion, and envelopment. The protein encoded by the human cytomegalovirus (HCMV) open reading frame UL116 forms a stable complex with glycoprotein H that is incorporated into virions. However, the function of this complex remains unknown. Herein, we characterize R116, the rat CMV (RCMV) putative homolog of UL116. Two R116 transcripts were identified in fibroblasts with three proteins expressed with molecular weights of 42, 58, and 82 kDa. R116 is N-glycosylated, expressed with late viral gene kinetics, and is incorporated into the virion envelope. RCMV lacking R116 failed to result in productive infection of fibroblasts and siRNA knockdown of R116 substantially reduced RCMV infectivity. Complementation in trans of an R116-deficient virus restored ability of the virus to infect fibroblasts. Finally, UL116 knockdown also decreased HCMV infectivity indicating that R116 and UL116 both contribute to viral infectivity.

Antibody-Independent Quantification of Cytomegalovirus Virion Protein Incorporation Using HiBiT.

Human cytomegalovirus (HCMV) is a large double-stranded DNA virus and member of the ß-herpesvirus family. HCMV is ubiquitous in the human population and causes lifelong infections. HCMV infection is associated with high morbidity and mortality in immunocompromised individuals and the virus is a major cause of virus-mediated congenital disease. There have been a number of HCMV entry receptors identified that use one of two viral receptor binding complexes, including the gH/gL/gO complex and the pentamer made up of gH/gL/UL128/UL130/UL131a. Cytomegaloviruses (CMVs) are typically host-restricted requiring the use of species-specific modeling and culture conditions. We use rat CMV (RCMV) to study CMV-accelerated vascular disease and chronic allograft rejection. RCMV encodes homologous versions of the entry complex proteins but their incorporation and copy number per virion are still unknown. In this methods article, we describe a novel approach of HiBiT tagging viral proteins in order to detect and quantify protein incorporation into particles. This method is independent of protein-specific antibodies and can be standardized using a commercially available HiBiT protein standard. Using bacterial artificial chromosome (BAC) recombineering, we have constructed two individual viruses containing a HiBiT tag fused to the C'-terminus of either the UL128 homolog (R129) or the UL130 homolog (R131). Viruses containing these mutations were rescued, purified and analyzed. Our data demonstrate that R129 and R131 are both incorporated into RCMV virions at equimolar ratios relative to genome copy number, supporting this antibody-free approach for quantifying viral protein incorporation and its application toward the identification of domains required for incorporation.

The Genomics of Opioid Addiction Longitudinal Study (GOALS): study design for a prospective evaluation of genetic and non-genetic factors for development of and recovery from opioid use disorder.

BACKGROUND: The opioid use disorder and overdose crisis in the United States affects public health as well as social and economic welfare. While several genetic and non-genetic risk factors for opioid use disorder have been identified, many of the genetic associations have not been independently replicated, and it is not well understood how these factors interact. This study is designed to evaluate relationships among these factors prospectively to develop future interventions to help prevent or treat opioid use disorder. METHODS: The Genomics of Opioid Addiction Longitudinal Study (GOALS) is a prospective observational study assessing the interplay of genetic and non-genetic by collecting comprehensive genetic and non-genetic information on 400 participants receiving medication for opioid use disorder. Participants will be assessed at four time points over 1 year. A saliva sample will be collected for large-scale genetic data analyses. Non-genetic assessments include validated surveys measuring addiction severity, depression, anxiety, and adverse childhood experiences, as well as treatment outcomes such as urine toxicology results, visit frequency, and number of pre and post-treatment overdoses extracted from electronic medical records. DISCUSSION: We will use these complex data to investigate the relative contributions of genetic and non-genetic risk factors to opioid use disorder and related treatment outcomes.

Blocking the IL-1 receptor reduces cardiac transplant ischemia and reperfusion injury and mitigates CMV-accelerated chronic rejection.

Ischemia-reperfusion injury (IRI) is an important risk factor for accelerated cardiac allograft rejection and graft dysfunction . Utilizing a rat heart isogeneic transplant model, we identified inflammatory pathways involved in IRI in order to identify therapeutic targets involved in disease. Pathway analyses identified several relevant targets, including cytokine signaling by the IL-1 receptor (IL-1R) pathway and inflammasome activation. To investigate the role of IL-1R signaling pathways during IRI, we treated syngeneic cardiac transplant recipients at 1-hour posttransplant with Anakinra, a US Food and Drug Administration (FDA)-approved IL-1R antagonist; or parthenolide, a caspase-1 and nuclear factor kappa-light-chain-enhancer of activated B cells inhibitor that blocks IL-1ß maturation. Both Anakinra and parthenolide significantly reduced graft inflammation and cellular recruitment in the treated recipients relative to nontreated controls. Anakinra treatment administered at 1-hour posttransplant to recipients of cardiac allografts from CMV-infected donors significantly increased the time to rejection and reduced viral loads at rejection. Our results indicate that reducing IRI by blocking IL-1Rsignaling pathways with Anakinra or inflammasome activity with parthenolide provides a promising approach for extending survival of cardiac allografts from CMV-infected donors.

Buprenorphine Field Initiation of ReScue Treatment by Emergency Medical Services (Bupe FIRST EMS): A Case Series.

The opioid epidemic is currently a leading health crisis in the United States, and evidence supports Medication for Opioid Use Disorder (MOUD) as the most effective treatment (2). In our EMS system we are observing an ever increasing number of patients who, due to refusing transport after naloxone rescue, represent an access void at the point of overdose. We present a case series to illustrate a new treatment paradigm utilizing front line EMS paramedic units and high dose buprenorphine to treat withdrawal symptoms with next day bridge to long term care. The three patients described are exemplary cases, meant to represent overall characteristics of the intervention prior to complete data collection. Each patient was revived from opioid overdose with naloxone. Paramedics then treated each patient with 16 mg of buprenorphine to relieve and prevent withdrawal symptoms. Patients were provided with outpatient follow up irrespective of ED transport. To the best of our knowledge, this is the first EMS agency in the United States providing MOUD in the prehospital setting at the point of overdose. This innovative program provides EMS with education and tools to promote patient engagement. While still in its infancy, this approach utilizes existing EMS resources to bring MOUD to the prehospital setting, offering a new avenue to long term care. Keywords: Opioid, buprenorphine, emergency medical services, medication assisted therapy, naloxone, overdose.

Macrophage depletion of CMV latently infected donor hearts ameliorates recipient accelerated chronic rejection.

Cytomegalovirus (CMV) infection is linked to acceleration of solid organ transplant vascular sclerosis (TVS) and chronic rejection (CR). Donor latent CMV infection increases cardiac-resident macrophages and T cells leading to increased inflammation, promoting allograft rejection. To investigate the role of cardiac-resident passenger macrophages in CMV-mediated TVS/CR, macrophages were depleted from latently ratCMV (RCMV)-infected donor allografts prior to transplantation. Latently RCMV-infected donor F344 rats were treated with clodronate, PBS, or control liposomes 3 days prior to cardiac transplant into RCMV-naïve Lewis recipients. Clodronate treatment significantly increased graft survival from post-operative day (POD)61 to POD84 and decreased TVS at rejection. To determine the kinetics of the effect of clodronate treatment's effect, a time study revealed that clodronate treatment significantly decreased macrophage infiltration into allograft tissues as early as POD14; altered allograft cytokine/chemokine protein levels, fibrosis development, and inflammatory gene expression profiles. These findings support our hypothesis that increased graft survival as a result of allograft passenger macrophage depletion was in part a result of altered immune response kinetics. Depletion of donor macrophages prior to transplant is a strategy to modulate allograft rejection and reduce TVS in the setting of CMV + donors transplanted into CMV naïve recipients.

Rat Cytomegalovirus Virion-Associated Proteins R131 and R129 Are Necessary for Infection of Macrophages and Dendritic Cells.

Cytomegalovirus (CMV) establishes persistent, latent infection in hosts, causing diseases in immunocompromised patients, transplant recipients, and neonates. CMV infection modifies the host chemokine axis by modulating chemokine and chemokine receptor expression and by encoding putative chemokine and chemokine receptor homologues. The viral proteins have roles in cellular signaling, migration, and transformation, as well as viral dissemination, tropism, latency and reactivation. Herein, we review the contribution of CMV-encoded chemokines and chemokine receptors to these processes, and further elucidate the viral tropism role of rat CMV (RCMV) R129 and R131. These homologues of the human CMV (HCMV)-encoded chemokines UL128 and UL130 are of particular interest because of their dual role as chemokines and members of the pentameric entry complex, which is required for entry into cell types that are essential for viral transmission and dissemination. The contributions of UL128 and UL130 to acceleration of solid organ transplant chronic rejection are poorly understood, and are in need of an effective in vivo model system to elucidate the phenomenon. We demonstrated similar molecular entry requirements for R129 and R131 in the rat cells, as observed for HCMV, and provided evidence that R129 and R131 are part of the viral entry complex required for entry into macrophages, dendritic cells, and bone marrow cells.