Introduction: While polysubstance use has consistently been associated with higher rates of relapse, few studies have examined subgroups with specific combinations and time course of polysubstance use (i.e., polysubstance use patterns). This study aimed to classify and compare polysubstance use patterns, and their associations with relapse to regular opioid use in 2637 participants in three large opioid use disorder (OUD) treatment trials.Methods: We explored the daily patterns of self-reported substance use in the 28 days prior to treatment entry. Market basket analysis (MBA) and repeated measure latent class analysis (RMLCA) were used to examine the sub-groups of polysubstance use patterns, and multiple logistic regression was used to examine associations between identified classes and relapse.Results: MBA and RMLCA identified 34 "associations rules " and 6 classes, respectively. Specific combinations of polysubstance use and time course (high baseline use and rapid decrease of use prior to initiation) predicts a worse relapse outcome. MBA showed individuals who co-used cocaine, heroin, prescription opioids, and cannabis had a higher risk for relapse (OR = 2.82, 95%CI = 1.13, 7.03). In RMLCA, higher risk of relapse was observed in individuals who presented with high baseline prescription opioid (OR = 1.9, 95% CI = 1.3, 2.76) or heroin use (OR = 3.54, 95%CI = 1.86, 6.72), although use decreased in both cases prior to treatment initiation.Conclusions: Our analyses identified subgroups with distinct patterns of polysubstance use. Different patterns of polysubstance use differentially predict relapse outcomes. Interventions tailored to these individuals with specific polysubstance use patterns prior to treatment initiation may increase the effectiveness of relapse prevention.

Importance: National estimates regarding the frequency of presentations and patterns of care for eye pain are unknown. This information could guide research and clinical efforts to optimize outcomes.Objective: To estimate eye pain visits in the US in the outpatient and emergency department (ED) settings.Design, Setting, and Participants: This retrospective cross-sectional study of National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data (2008-2019) analyzed a population-based sample of visits to outpatient clinics and EDs. The sample consisted of patients presenting with eye pain. Data were analyzed from September 2023 to April 2024.Main Outcomes and Measures: Weighted sample data estimated outpatient and ED eye pain presentations including patient and clinician characteristics, diagnoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10]), and disposition.Results: From 2008 through 2019, 4.6 million (95% CI, 3.9 million to 5.3 million) outpatient and 1.0 million (95% CI, 0.8 million to 1.1 million) ED eye pain visits occurred annually. Patients were predominantly women (63.2% [95% CI, 59.4%-67.0%]) and older than 60 years (46.6% [95% CI, 42.4%-51.0%]) in the outpatient setting. Patients presenting to the ED were more often men (51.8% [95% CI, 48.7%-55.0%]) and aged younger than 45 years (aged <15 years: 16.4% [95% CI, 13.9%-18.8%]; 15-24 years: 19.2% [95% CI, 16.6%-21.7%]; and 25-44 years: 35.6% [95% CI, 32.7%-38.5%]). In nearly half of outpatient eye pain visits, the major problem was classified as nonacute (2.0 million [95% CI, 1.6 million to 2.3 million]). Eye pain was the primary reason for the visit (RFV) in 42.0% (95% CI, 37.8%-46.2%) of outpatient visits and 66.9% (95% CI, 62.9%-70.9%) of ED eye pain visits. It was the only RFV in 18.3% (95% CI, 15.0%-21.7%) of outpatient and 32.7% (95% CI, 29.0%-36.4%) of ED eye pain encounters. Ophthalmologists evaluated the largest number of outpatient visits (45.3% [95% CI, 38.8%-51.7%). The primary diagnosis was non–vision threatening for most outpatient (78.5% [95% CI, 56.8%-100%]) and ED (69.9% [95% CI, 62.1%-77.7%]) visits when eye pain was the primary RFV. Additional follow-up was scheduled in 89.4% (95% CI, 86.2%-92.6%) of visits.Conclusions and Relevance: More than 5 million eye pain visits occur annually; the largest percentage are outpatient with ophthalmologists. Most diagnoses were non–vision threatening in both the outpatient and ED setting and resulted in additional care. Expanding therapeutic approaches to treat the causes of eye pain may reduce the burden on the health care system and optimize outcomes.

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIV^neg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin⁻ BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIV^neg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIV^posEVs) and plasma depleted of EVs (HIV PL^depEVs). HIV^posEVs, but not HIV PL^depEVs or HIV^negEVs (EVs from HIV^neg individuals), increased atherosclerosis in apoE^−/− mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin⁻ BMCs. Small RNA-seq identified EV-miRs overrepresented in HIV^posEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIV^posEVs in vivo. Lin⁻ BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3′UTR and as such is resistant to miR-mediated regulation showed protection against HIV^posEVs-induced changes in lin⁻ BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.