How Would You Manage HIV Pre-exposure Prophylaxis in This Patient With Medical Comorbidities? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Despite advances in treatment, HIV infection remains an important cause of morbidity and mortality, with more than 30 000 new cases diagnosed in the United States each year. There are several interventions traditionally used to prevent HIV transmission, but these vary in effectiveness and there are challenges to their implementation. In 2014, the Centers for Disease Control and Prevention published initial guidance on the use of antiretroviral pre-exposure prophylaxis (PrEP) to prevent transmission of HIV infection in persons at risk based on multiple studies that showed it to be highly efficacious in various populations. It was updated in 2021 to reflect new drug options. The U.S. Preventive Services Task Force also recently updated its recommendations for PrEP, which strongly support its use in persons at risk. Despite its well-established effectiveness, the implementation of PrEP in clinical practice has been variable, especially among populations underserved by the medical system and marginalized by society. Fewer than one third of persons in the United States who are eligible for PrEP currently receive it. Here, 2 physicians experienced in HIV PrEP debate how best to identify patients who might benefit from PrEP, how to decide what regimen to use, and how to monitor therapy.

Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease.

The conserved enzyme aminolevulinic acid synthase (ALAS) initiates heme biosynthesis in certain bacteria and eukaryotes by catalyzing the condensation of glycine and succinyl-CoA to yield aminolevulinic acid. In humans, the ALAS isoform responsible for heme production during red blood cell development is the erythroid-specific ALAS2 isoform. Owing to its essential role in erythropoiesis, changes in human ALAS2 (hALAS2) function can lead to two different blood disorders. X-linked sideroblastic anemia results from loss of ALAS2 function, while X-linked protoporphyria results from gain of ALAS2 function. Interestingly, mutations in the ALAS2 C-terminal extension can be implicated in both diseases. Here, we investigate the molecular basis for enzyme dysfunction mediated by two previously reported C-terminal loss-of-function variants, hALAS2 V562A and M567I. We show that the mutations do not result in gross structural perturbations, but the enzyme stability for V562A is decreased. Additionally, we show that enzyme stability moderately increases with the addition of the pyridoxal 5'-phosphate (PLP) cofactor for both variants. The variants display differential binding to PLP and the individual substrates compared to wild-type hALAS2. Although hALAS2 V562A is a more active enzyme in vitro, it is less efficient concerning succinyl-CoA binding. In contrast, the M567I mutation significantly alters the cooperativity of substrate binding. In combination with previously reported cell-based studies, our work reveals the molecular basis by which hALAS2 C-terminal mutations negatively affect ALA production necessary for proper heme biosynthesis.

Review of terrestrial temporarily conserved areas in Canada, the United States, and Mexico.

The establishment of protected areas is a cornerstone of conservation, but permanent protection could be inefficient or even impossible in some situations. We synthesized the literature on temporarily conserved areas (TCAs) across Canada, the United States, and Mexico. We used a comprehensive search string to retrieve peer-reviewed articles published from 2000 to 2021 from the Web of Science. We identified 27 relevant peer-reviewed articles that examined the potential benefits of TCAs in the study area, indicating TCA is a relatively understudied area of research in the peer-reviewed literature. The TCA studies were highly clustered; 77% of studies focused on protecting a single life stage of migratory species and 61% of studies related to temporary conservation of breeding or staging habitats for migratory birds. Ninety-three percent of studies focused on preventing human-driven threats, mainly on public lands of coastal areas, the Great Plains, and the Mississippi Valley in the central United States. Short-term and experimental studies were the dominant study types. TCAs have the potential to complement permanently protected areas and provide protection when permanent protection is difficult. Some included studies examined their conservation value, but the ecological, social, and economic outcomes of TCAs are unclear. More TCA research is needed to determine the role they could play in conservation worldwide. Embracing the concept of TCAs as conservation tool could lead to more comprehensive and consistent reporting of the outcomes of temporary area-based conservation measures. However, a global review and analysis of effectiveness of TCAs will be required if they are to play a formal role in meeting international targets for biodiversity conservation.

Revisión de áreas terrestres conservadas temporalmente en Canadá, Estados Unidos y México Resumen La creación de áreas protegidas es una piedra angular de la conservación, aunque en algunos casos la protección permanente podría ser ineficiente o incluso imposible. Condensamos la literatura sobre las áreas de conservación temporal (ACT) en Canadá, Estados Unidos y México. Usamos una cadena completa de búsqueda para obtener artículos revisados por pares publicados del 2000 al 2021 en Web of Science. Identificamos 27 artículos relevantes que analizaban el potencial de las ACT en el área de estudio, lo que indica que las ACT es un área poco estudiada en la literatura revisada por pares. Los estudios sobre ACT estaban muy agrupados: el 77% se enfocaban en la protección de un solo estadio de vida de las especies migratorias y el 61% se relacionaban con la conservación temporal de los hábitats de reproducción o de descanso de las aves migratorias. El 93% de los estudios se enfocó en la prevención de amenazas causadas por humanos, principalmente en los terrenos públicos de las áreas costeras, las Grandes Llanuras y el valle del Mississippi en el centro de los Estados Unidos. Los estudios experimentales y a corto plazo fueron el tipo de estudio dominante. Las áreas de conservación temporal tienen el potencial para complementar las áreas de protección permanente y proporcionar protección cuando es complicado proporcionarla permanentemente. Algunos de los estudios incluidos analizaron el valor para la conservación de las ACT, pero aún no están claros sus resultados ecológicos, sociales y económicos. Se necesita más investigación sobre las ACT para determinar el papel que podrían tener en la conservación mundial. Si se acepta el concepto de ACT como una herramienta de conservación, se podrían reportar los resultados de las medidas de conservación basadas en las ACT de forma más completa y consistente. Sin embargo, se requerirá una revisión y análisis global de la eficiencia de las ACT si se espera que tengan un papel formal en el cumplimiento de los objetivos internacionales de la conservación de la biodiversidad.

Feasibility of paying people who use drugs cash to distribute naloxone within their networks.

INTRODUCTION: Immediate access to naloxone is needed to prevent fatal opioid-related overdoses in the presence of fentanyl analogs saturating the opioid supply. Peer models engage impacted populations who are not accessing naloxone through standard venues, yet compensating peers who utilize syringe service programs with cash stipends to distribute naloxone within networks of people who use drugs is not well described. METHODS: As part of the HEALing Communities Study, syringe service program-based interventions were developed in Holyoke and Gloucester, MA, which paid people who use drugs ("peers") cash to distribute naloxone. Early program outcomes were evaluated for the time each program was funded within the HCS study period. RESULTS: During 22 study-months of observation, peers in two communities distributed 1104 naloxone kits. The total cost of peer compensation for program delivery was $10,510. The rate of peer-distributed naloxone per 100 K population reached 109 kits/mo and 222 kits/mo in the two communities. Participating peers addressed gaps in harm reduction outreach and distributed naloxone and other harm reduction equipment to individuals who were not syringe service program participants, expanding organizational reach. Being compensated with unrestricted cash stipends supported dignity and acknowledged peers' work in overdose prevention. CONCLUSION: The underutilization of compensated peer models is often attributed to funding and organizational barriers. These programs demonstrate that providing cash stipends to peers is feasible and expanded naloxone distribution at two existing syringe service programs. Providing cash stipends for peers who engage in secondary naloxone distribution offers promise in delivering naloxone to people not accessing syringe services.

Structural basis for dysregulation of aminolevulinic acid synthase in human disease.

Heme is a critical biomolecule that is synthesized in vivo by several organisms such as plants, animals, and bacteria. Reflecting the importance of this molecule, defects in heme biosynthesis underlie several blood disorders in humans. Aminolevulinic acid synthase (ALAS) initiates heme biosynthesis in α-proteobacteria and nonplant eukaryotes. Debilitating and painful diseases such as X-linked sideroblastic anemia and X-linked protoporphyria can result from one of more than 91 genetic mutations in the human erythroid-specific enzyme ALAS2. This review will focus on recent structure-based insights into human ALAS2 function in health and how it dysfunctions in disease. We will also discuss how certain genetic mutations potentially result in disease-causing structural perturbations. Furthermore, we use thermodynamic and structural information to hypothesize how the mutations affect the human ALAS2 structure and categorize some of the unique human ALAS2 mutations that do not respond to typical treatments, that have paradoxical in vitro activity, or that are highly intolerable to changes. Finally, we will examine where future structure-based insights into the family of ALA synthases are needed to develop additional enzyme therapeutics.

A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.

Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). SLS cases (n = 135) were recruited from Family Cancer Clinics across Australia and New Zealand. Targeted panel sequencing was performed on tumor (n = 137; 80×CRCs, 33×ECs and 24xSSTs) and matched blood-derived DNA to assess for microsatellite instability status, tumor mutation burden, COSMIC tumor mutational signatures and to identify germline and somatic MMR gene variants. MMR immunohistochemistry (IHC) and MLH1 promoter methylation were repeated. In total, 86.9% of the 137 SLS tumors could be resolved into established subtypes. For 22.6% of these resolved SLS cases, primary MLH1 epimutations (2.2%) as well as previously undetected germline MMR pathogenic variants (1.5%), tumor MLH1 methylation (13.1%) or false positive dMMR IHC (5.8%) results were identified. Double somatic MMR gene mutations were the major cause of dMMR identified across each tumor type (73.9% of resolved cases, 64.2% overall, 70% of CRC, 45.5% of ECs and 70.8% of SSTs). The unresolved SLS tumors (13.1%) comprised tumors with only a single somatic (7.3%) or no somatic (5.8%) MMR gene mutations. A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations.

Elevated tacrolimus levels among COVID-19 kidney transplant recipients are associated with worse disease severity and clinical outcomes.

BACKGROUND: The therapeutic effects of immunosuppressive drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections causing coronavirus disease 2019 (COVID-19) are being actively investigated. However, COVID-19's potential effects on serum calcineurin inhibitor levels have only been described recently. This study aimed to evaluate COVID-19's effect on tacrolimus levels in renal transplant recipients with moderate to severe symptoms and to assess their potential correlation with disease severity. MATERIALS AND METHODS: We retrospectively investigated 50 kidney transplant recipients with moderate to severe COVID-19. Their tacrolimus trough level on admission was compared to baseline levels, and their laboratory measurements and clinical course were reviewed on days 1 (admission), 7, 14, and 28. RESULTS: We found that 90% of patients had admission tacrolimus trough levels above baseline, with a mean increase of 176%. In addition, 71% had tacrolimus trough levels ≥ 50% above baseline, and 40% had supra-therapeutic trough levels of > 15 ng/mL. Supra-therapeutic trough levels were associated with greater hypoxemic respiratory failure, acute kidney injury, and increased 30-day mortality. CONCLUSION: Elevated tacrolimus levels occur in many renal transplant recipients with moderate to severe COVID-19 and are associated with worse clinical outcomes. Close drug monitoring is crucial to avoid toxicities and minimize over-immunosuppression complications.

Psychiatric genetic counseling: A survey of Australian genetic counselors' practice and attitudes.

Genetic counseling plays a critical role in supporting individuals and their families' adaption to psychiatric conditions, addressing the multifactorial nature of these conditions in a personally meaningful and empowering way. Yet data related to the practice and attitudes of Australian genetic counselors about psychiatric genetic counseling (PGC) is limited. This survey investigated the practice of Australian genetic counselors, and their attitudes toward PGC. Genetic counselors (N = 393) were invited to participate in an anonymous online survey between March and May 2022. Forty-four genetic counselors (response rate = 11%) from Australia and New Zealand responded. No respondents practice in psychiatric genetics as their speciality area; most respondents do not see any patients where the primary indication is a personal and/or family history of psychiatric disorders (91%). Greater than half of respondents (56%) believed there was sufficient evidence to support PGC, and 64% enquire about personal and/or family history of psychiatric disorders, but only 25% provide genetic counseling on this topic. Most respondents do not feel confident providing risk assessments for psychiatric disorders (72%), while the majority expressed interest in attending specialist training (95%), and in incorporating PGC into future practice (77%). Australian genetic counselors would benefit from psychiatric genetic education and training, and establishment of specialized PGC services would address this gap in patient care, while providing opportunities for genetic counselors to gain skills and experience in PGC.

Opioid Use Disorder.

Opioid use disorder (OUD) is a treatable chronic disorder with episodes of remission and recurrence characterized by loss of control of opioid use, compulsive use, and continued use despite harms. If untreated, OUD is associated with significant morbidity and mortality. Buprenorphine and methadone reduce fatal and nonfatal opioid overdose and infectious complications of OUD and are the first-line treatment options. Physicians have an important role to play in diagnosing OUD and its comorbidities, offering evidence-based treatment, and delivering overdose prevention and other harm reduction services to people who continue to use opioids. Interdisciplinary office-based addiction treatment programs support high-quality OUD care.

Carbonaceous adsorbents in the removal of aquaculture pollutants: A technical review of methods and mechanisms.

Carbonaceous adsorbents (CAs) are becoming increasingly popular owing to their low-cost, ease of preparation, and versatility. Meanwhile, aquaculture is becoming a fundamental food industry, globally, due to a wide range of advantages such as economic and nutritional benefits, whilst protecting the depletion of natural resources. However, as with any farming, the technique is known to introduce a plethora of chemicals into the surrounding environment, including antibiotics, nutrients, fertilisers and more. Therefore, the treatment of aquaculture effluent is gaining traction to ensure the sustainable growth of the industry. Although the existing mitigation techniques are somewhat effective, they suffer from degradation of the water quality or harm to local environments/organisms. This article aims to identify the sources and impacts of various aquaculture pollutants. After which the authors will provide an environmentally friendly and novel approach to the treatment of aquaculture effluent using carbonaceous adsorbents. The article will detail discussions about the product life span, including, synthesis, activation, modification, applications in aqueous media, regeneration and End-of-Life (EoL) approaches, with a particular focus on the impacts of competitive adsorption between pollutants and environmental matrices. Some research gaps were also highlighted, such as the lack of literature applying real-world samples, the effects of competitive adsorption and the EoL applications and management for CAs.

Pre-Paid Phone Distribution: A Tool for Improving Healthcare Engagement for People with Substance Use Disorder.

BACKGROUND: The COVID-19 pandemic drove significant disruptions in access to substance use disorder (SUD) treatment and harm reduction services. Healthcare delivery via telemedicine has increasingly become the norm, rendering access to a phone essential for engagement in care. METHODS: Adult patients with SUD who lacked phones (n = 181) received a free, pre-paid phone during encounters with inpatient and outpatient SUD programs. We evaluated changes in healthcare engagement including completed in-person and telemedicine outpatient visits and telephone encounters 30 days before and after phone receipt. We used descriptive statistics, where appropriate, and paired t-tests to assess the change in healthcare engagement measures. RESULTS: Patients were predominantly male (64%) and white (62%) with high rates of homelessness (81%) and opioid use disorder (89%). When comparing 30 days before to 30 days after phone receipt, there was a significant increased change in number of telemedicine visits by 0.3 (95% CL [0.1,0.4], p < 0.001) and telephone encounters by 0.2 (95% CL [0.1,0.3], p = 0.004). There was no statistically significant change in in-person outpatient visits observed. CONCLUSIONS: Pre-paid phone distribution to patients with SUD was associated with an increased healthcare engagement including telemedicine visits and encounters.

Communality in microbial stress response and differential metabolic interactions revealed by time-series analysis of sponge symbionts.

The diversity and function of sponge-associated symbionts is now increasingly understood; however, we lack an understanding of how they dynamically behave to ensure holobiont stability in the face of environmental variation. Here, we performed a metatransciptomic analysis on three microbial symbionts of the sponge Cymbastela concentrica in situ over 14 months and through differential gene expression and correlation analysis to environmental variables uncovered differences that speak to their metabolic activities and level of symbiotic and environmental interactions. The nitrite-oxidizing Ca. Porinitrospira cymbastela maintained a seemingly stable metabolism, with the few differentially expressed genes related only to stress responses. The heterotrophic Ca. Porivivens multivorans displayed differential use of holobiont-derived compounds and respiration modes, while the ammonium-oxidizing archaeon Ca. Nitrosopumilus cymbastelus differentially expressed genes related to phosphate metabolism and symbiosis effectors. One striking similarity between the symbionts was their similar variation in expression of stress-related genes. Our time-series study showed that the microbial community of C. concentrica undertakes dynamic gene expression adjustments in response to the surroundings, tuned to deal with general stress and metabolic interactions between holobiont members. The success of these dynamic adjustments likely underpins the stability of the sponge holobiont and may provide resilience against environmental change.

Real world outcomes and implementation pathways of exome sequencing in an adult genetic department.

PURPOSE: This study aimed to correlate the indications and diagnostic yield of exome sequencing (ES) in adult patients across various clinical settings. The secondary aim was to examine the clinical utility of ES in adult patients. METHODS: Data on demographics, clinical indications, results, management changes, and cascade testing were collected for 250 consecutive patients who underwent ES through an adult genetics department between 2016 and 2021. Data were analyzed using descriptive and inferential statistics. Testing in which traditional gene panels were in standard use, such as in heritable cancers, was excluded. RESULTS: The average age at testing was 43 years (range = 17-80 years). A molecular diagnosis was identified in 29% of patients. Older age at symptom onset did not pre-exclude a substantial diagnostic yield. Patients with syndromic intellectual disability and multiple system disorders had the highest yield. In >50% of patients with an exome diagnosis, the results changed management. Cascade testing occured in at least one family member for 30% of patients with a diagnosis. Diagnostic results had reproductive implications for 26% of patients and 31% of patients' relatives. CONCLUSION: ES has a robust diagnostic yield and clear clinical utility in adult patients across a range of ages and phenotypes.

Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma.

BACKGROUND: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog 2 (SIAH2)-mediated degradation of Zinc Finger Protein 521 (ZFP521). This study investigated the potential role of ZFP423, SIAH2 and ZFP521 in the adipogenic potential of WDLPS and DDLPS. METHODS: Human WDLPS and DDLPS fresh and paraffin-embedded tissues were used to assess the gene and protein expression of proadipogenic regulators. In parallel, normal adipose tissue stromal cells along with WDLPS and DDLPS cell lines were cultured, genetically modified, and induced to undergo adipogenesis in vitro. RESULTS: Impaired adipogenic potential in DDLPS was associated with reduced ZFP423 protein levels in parallel with reduced PPARG2 expression, potentially involving regulation of ZFP521. SIAH2 protein levels did not define a clear distinction related to adipogenesis in these liposarcomas. However, in primary tumor specimens, SIAH2 mRNA was consistently upregulated in DDLPS compared to WDLPS when assayed by fluorescence in situ hybridization or real-time PCR. CONCLUSIONS: These data provide novel insights into ZFP423 expression in adipogenic regulation between WDLPS and DDLPS adipocytic tumor development. The data also introduces SIAH2 mRNA levels as a possible molecular marker to distinguish between WDLPS and DDLPS.

A reciprocal inhibition model of alternations between under-/overemotional modulatory states in patients with PTSD.

Patients with posttraumatic stress disorder (PTSD) appear to manifest two opposing tendencies in their attentional biases and symptoms. However, whether common neural mechanisms account for their opposing attentional biases and symptoms remains unknown. We here propose a model in which reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) predicts synchronized alternations between emotional under- and overmodulatory states at the neural, behavioral, and symptom levels within the same patients. This reciprocal inhibition model predicts that when the amygdala is dominant, patients enter an emotional undermodulatory state where they show attentional bias toward threat and manifest re-experiencing symptoms. In contrast, when the vmPFC is dominant, patients are predicted to enter an emotional overmodulatory state where they show attentional bias away from threat and avoidance symptoms. To test the model, we performed a behavioral meta-analysis (total N = 491), analyses of own behavioral study (N = 20), and a neuroimaging meta-analysis (total N = 316). Supporting the model, we found the distributions of behavioral attentional measurements to be bimodal, suggesting alternations between the states within patients. Moreover, attentional bias toward threat was related to re-experiencing symptoms, whereas attentional bias away from threat was related with avoidance symptoms. We also found that the increase and decrease of activity in the left amygdala activity was related with re-experiencing and avoidance symptoms, respectively. Our model may help elucidate the neural mechanisms differentiating nondissociative and dissociative subtypes of PTSD, which usually show differential emotional modulatory levels. It may thus provide a new venue for therapies targeting each subtype.

Effect of police action on low-barrier substance use disorder service utilization.

BACKGROUND: Police action can increase risky substance use patterns by people who use drugs (PWUD), but it is not known how increased police presence affects utilization of low-barrier substance use disorder bridge clinics. Increased police presence may increase or decrease treatment-seeking behavior. We examined the association between Operation Clean Sweep (OCS), a 2-week police action in Boston, MA, and visit volume in BMC's low-barrier buprenorphine bridge clinic. METHODS: In this retrospective cohort, we used segmented regression to investigate whether the increased police presence during OCS was associated with changes in bridge clinic visits. We used General Internal Medicine (GIM) clinic visit volume as a negative control. We examined visits during the 6 weeks prior, 2 weeks during, and 4 weeks after OCS (June 18-September 11, 2019). RESULTS: Bridge clinic visits were 2.8 per provider session before, 2.0 during, and 3.0 after OCS. The mean number of GIM clinic visits per provider session before OCS was 7.0, 6.8 during, and 7.0 after OCS. In adjusted segmented regression models for bridge clinic visits per provider session, there was a nonsignificant level increase (0.643 P = 0.171) and significant decrease in slope (0.100, P = 0.045) during OCS. After OCS completed, there was a significant level increase (1.442, P = 0.003) and slope increase in visits per provider session (0.141, P = 0.007). There was no significant change in GIM clinic volume during the study period. CONCLUSIONS: The increased policing during OCS was associated with a significant decrease in bridge clinic visits. Following the completion of OCS, there was a significant increase in clinic visits, suggesting pent-up demand for medications for opioid use disorder, a life-saving treatment.

An updated review of cold shock and cold stress in fish.

Temperature is critical in regulating virtually all biological functions in fish. Low temperature stress (cold shock/stress) is an often-overlooked challenge that many fish face as a result of both natural events and anthropogenic activities. In this study, we present an updated review of the cold shock literature based on a comprehensive literature search, following an initial review on the subject by M.R. Donaldson and colleagues, published in a 2008 volume of this journal. We focus on how knowledge on cold shock and fish has evolved over the past decade, describing advances in the understanding of the generalized stress response in fish under cold stress, what metrics may be used to quantify cold stress and what knowledge gaps remain to be addressed in future research. We also describe the relevance of cold shock as it pertains to environmental managers, policymakers and industry professionals, including practical applications of cold shock. Although substantial progress has been made in addressing some of the knowledge gaps identified a decade ago, other topics (e.g., population-level effects and interactions between primary, secondary and tertiary stress responses) have received little or no attention despite their significance to fish biology and thermal stress. Approaches using combinations of primary, secondary and tertiary stress responses are crucial as a research priority to better understand the mechanisms underlying cold shock responses, from short-term physiological changes to individual- and population-level effects, thereby providing researchers with better means of quantifying cold shock in laboratory and field settings.

Integrating Harm Reduction into Outpatient Opioid Use Disorder Treatment Settings : Harm Reduction in Outpatient Addiction Treatment.

Opioid use disorder (OUD) is increasingly recognized as a chronic, relapsing brain disease whose treatment should be integrated into primary care settings alongside other chronic conditions. However, abstinence from all non-prescribed substance use continues to be prioritized as the only desired goal in many outpatient, primary care-based treatment programs. This presents a barrier to engagement for patients who continue to use substances and who may be at high risk for complications of ongoing substance use such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), superficial and deep tissue infections, and overdose. Harm reduction aims to reduce the negative consequences of substance use and offers an alternative to abstinence as a singular goal. Incorporating harm reduction principles into primary care treatment settings can support programs in engaging patients with ongoing substance use and facilitate the delivery of evidence-based screening and prevention services. The objective of this narrative review is to describe strategies for the integration of evidence-based harm reduction principles and interventions into outpatient, primary care-based OUD treatment settings. We will offer specific tools for providers and programs including strategies to support safer injection practices, assess the risks and benefits of continuing medications for opioid use disorder in the setting of ongoing substance use, promote a non-stigmatizing program culture, and address the needs of special populations with ongoing substance use including adolescents, parents, and families.

"Health Is on the Back Burner:" Multilevel Barriers and Facilitators to Primary Care Among People Who Inject Drugs.

BACKGROUND: The estimated 2.2 million people who inject drugs (PWID) in the USA experience significant gaps in preventive healthcare and a high burden of infectious, psychiatric, and other chronic diseases. Many PWID rely on emergency medical services, which are costly and not designed to deliver preventive services, manage chronic conditions, or address social needs. OBJECTIVE: The objective of this study was to explore barriers and facilitators to primary care utilization from the perspectives of PWID in New England, a region highly affected by the overdose crisis. DESIGN: Participants completed semi-structured qualitative interviews exploring substance use and healthcare utilization patterns. PARTICIPANTS: We recruited 78 PWID through community-based organizations (e.g., syringe service programs) in 16 urban and non-urban communities throughout Massachusetts and Rhode Island. APPROACH: Thematic analysis identified barriers and facilitators to primary care utilization at the individual, interpersonal, and systemic levels. KEY RESULTS: Among 78 PWID, 48 described recent primary care experiences; 33 had positive experiences and 15 described negative experiences involving discrimination or mistrust. Individual-level barriers to primary care utilization included perceived lack of need and competing priorities (e.g., avoiding opioid withdrawal, securing shelter beds). Interpersonal-level barriers included stigma and perceived low quality of care for PWID. Systemic-level barriers included difficulty navigating healthcare systems, inadequate transportation, long wait times, and frequent provider turnover. Participants with positive primary care experiences explained how appointment reminders, flexible hours, addiction medicine-trained providers, case management services, and transportation support facilitated primary care utilization and satisfaction. CONCLUSIONS: Findings regarding the multilevel barriers and facilitators to accessing primary care among PWID identify potential targets for programmatic interventions to improve primary care utilization in this population. Based on these findings, we make recommendations for improving the engagement of PWID in primary care as a means to advance individual and public health outcomes.

It's Time to Expand Chlamydia Treatment for Gay and Bisexual Men.

Expedited partner therapy involves prescribing sexually transmitted infection (STI) treatment for a patient's partner(s) without seeing the partner. It is approved for heterosexual partners of patients with chlamydia in most states. However, the Centers for Disease Control and Prevention recommends against expedited partner therapy in men-who-have-sex-with-men (MSM), citing limited data in this population and concerns that expedited partner therapy could discourage comprehensive STI testing, thereby driving increased HIV transmission. In this piece, we describe the case of a 33-year-old gay man on HIV pre-exposure prophylaxis (PrEP) whose cycle of chlamydia reinfection might have been prevented by expedited partner therapy. His case highlights how new HIV prevention strategies-including PrEP and Treatment as Prevention-challenge the assumption that all MSM with chlamydia are at risk for HIV. Until more data on expedited partner therapy in MSM are available, clinicians should incorporate characteristics of patients' sexual networks in weighing the risks and benefits of expedited partner therapy.