Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal.

Importance: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD). Objective: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal. Design, Setting, and Participants: This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023. Intervention: Injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care. Main Outcomes and Measures: Primary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score ≥13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment. Results: A total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication. Conclusions and Relevance: This nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine. Trial Registration: ClinicalTrials.gov Identifier: NCT04225598.

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti-spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti-type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

Natural history of SCLC patients treated in third-line and beyond: A retrospective real world study.

OBJECTIVES: To describe treatment patterns and estimate outcomes among real-world small cell lung cancer (SCLC) patients in the US who received three or more lines of therapy. MATERIALS AND METHODS: We conducted a retrospective analysis of adult patients with SCLC who received a front-line platinum-based regimen and two additional lines of therapy (ie., a cohort of at least three lines of therapy). De-identified patients were selected from a United States Flatiron Health oncology database of electronic health records. Treatment patterns were captured by line of therapy. Outcomes evaluated by line of therapy included real-world overall survival (rwOS), real-world progression free survival (rwPFS), real-world response rate (rwRR) and real-world duration of response (rwDOR). RESULTS: The analysis included 326 3L SCLC patients, of which 103 (32 %) received 4L treatment, and 38 % (39/103) of 4L treated received 5L of therapy. Among the 3L cohort, the average age was 67 years, 49 % were male, and nearly all had a history of smoking (96 %). In the 3L setting, the median rwOS was 5.3 months (95 % Confidence Interval (CI): 4.5, 6.0), median rwPFS was 2.5 months (95 % CI: 2.1, 2.7), rwRR was 19.3 % (95 % CI: 15.2, 24.0) and median DOR was 3.4 months (95 % CI: 2.8, 4.4). No differences were seen in outcomes between the overall cohort and a subgroup of patients treated with front-line platinum-based regimen with an anti-programmed cell death ligand 1 (PD-L1) agent (atezolizumab or durvalumab), in each respective line of therapy. CONCLUSION: Results from this large, real-world study of US patients with SCLC in the 3L setting and beyond highlight the poor treatment outcomes in advanced SCLC patients with existing therapies and underscore the dire need for new therapies for SCLC patients.

Integrating developmental neuroscience with community-engaged approaches to address mental health outcomes for housing-insecure youth: Implications for research, practice, and policy.

One in three children in the United States is exposed to insecure housing conditions, including unaffordable, inconsistent, and unsafe housing. These exposures have detrimental impacts on youth mental health. Delineating the neurobehavioral pathways linking exposure to housing insecurity with children's mental health has the potential to inform interventions and policy. However, in approaching this work, carefully considering the lived experiences of youth and families is essential to translating scientific discovery to improve health outcomes in an equitable and representative way. In the current paper, we provide an introduction to the range of stressful experiences that children may face when exposed to insecure housing conditions. Next, we highlight findings from the early-life stress literature regarding the potential neurobehavioral consequences of insecure housing, focusing on how unpredictability is associated with the neural circuitry supporting cognitive and emotional development. We then delineate how community-engaged research (CEnR) approaches have been leveraged to understand the effects of housing insecurity on mental health, and we propose future research directions that integrate developmental neuroscience research and CEnR approaches to maximize the impact of this work. We conclude by outlining practice and policy recommendations that aim to improve the mental health of children exposed to insecure housing.

Outcomes of an Emergency Department Program to Identify and Link Patients at Increased Risk for Acquiring HIV Infection to Outpatient HIV Prevention Services: The HIV PreventED Program.

BACKGROUND: Emergency departments (EDs) provide care to patients at increased risk for acquiring HIV, and for many of them, the ED serves as their sole point of entry into the healthcare system. We implemented the HIV PreventED Program to increase access to HIV prevention services for ED patients. SETTING: ED in Oakland, CA with an annual census of 57,000 visits. METHODS: This cross-sectional study evaluated the first 9 months of the HIV PreventED Program. In this program, a navigator surveyed adult ED patients who tested HIV negative to determine their risk for acquiring HIV infection, incorporating HIV prevention counseling into their assessments. Patients at higher risk for acquiring HIV were referred to outpatient prevention services, if interested. The primary outcome measure was the number and proportion of ED patients at higher risk for acquiring HIV who followed up for outpatient prevention services. RESULTS: In this study, 1233 patients who tested HIV negative were assessed by the navigator and received ED-based HIV prevention counseling. Of these, 193 (15.7%) were identified at higher risk and offered an outpatient referral for prevention services, of which 104 accepted (53.9%), 23 (11.9%) attended the referral, and 13 (6.7%) were prescribed preexposure prophylaxis (PrEP). The median time to linkage was 28 days (interquartile range 15-41 days). CONCLUSION: A navigator focused on providing ED-based HIV prevention counseling and linkage to outpatient services is feasible. Strategies to more efficiently identify ED patients at higher risk for HIV acquisition, such as automated identification of risk data from the electronic health record, and policies to improve follow-up and the receipt of PrEP, such as same-day PrEP initiation, should be prospectively evaluated.

Addition of constitutional symptoms to the SLEDAI-2K improves overall disease activity assessment: A pilot study.

OBJECTIVE: Constitutional symptoms (fatigue, lymphadenopathy, and weight loss) are not included in the SLE disease activity index-2000 (SLEDAI-2K). In this pilot study, we assessed the concurrent and construct validity of a revised SLEDAI-2K (SLED-R) that included these symptoms with the original SLEDAI-2K (SLED-O), using the physician global assessment of disease activity (PGA) as the reference. METHODS: Our revised SLED-R substituted the SLED-O's fever descriptor with a constitutional descriptor that included fever, fatigue, lymphadenopathy, and/or weight loss. SLED-O, SLED-R, PGA and patient global assessment (PtGA) scores were collected prospectively. Bland-Altman correlations for repeated measures were calculated and Meng's z-test was used to compare correlations between dependent and overlapping correlation coefficients. Associations between constitutional symptoms and disease activity measures were analyzed using Mann-Whitney U, Kruskal-Wallis, Chi-square tests and repeated measures correlations. RESULTS: 1123 SLED-O, SLED-R, PGA, and 1066 PtGA were collected in 239 subjects. The new descriptor was scored in 45 subjects (18.8%) and 92 instances (8.1%), while the original descriptor, fever, was scored in only 4 subjects (1.7%) and 5 instances (0.4%). Mean SLED-O, PGA and PtGA scores were higher when the constitutional descriptor was scored versus not (p < .001). The correlation between SLED-R and PGA was marginally higher than between SLED-O and PGA (p < .001). Fatigue contributed most to this increase (p = .001) and associated with both higher PGA and PtGA scores (p < .001). Mean SLED-O and PGA scores were higher when ≥1 constitutional symptom(s) were scored versus not (p < .002). Correlations between PGA and PtGA when the new descriptor was scored versus not were similar (p = .860). The frequency of concordance between PGA and PtGA was lower when the new descriptor was scored (55%) versus not (72.5%), with PGA > PtGA when the new descriptor was scored (p < .001). CONCLUSION: The addition of constitutional symptoms to SLEDAI-2K, particularly fatigue, resulted in a marginal increase in its correlation with PGA, and new constitutional symptoms associated with higher SLED-O and PGA scores. As fatigue is subjective and difficult to attribute to SLE, its validity and inter-rater reliability in scoring remains uncertain. The clinical utility of SLED-R remains unclear, and further studies of its validity and reliability are needed.

Outcomes of Patients with Acute Type B Aortic Dissection and High-Risk Features.

BACKGROUND: Recently the Society for Vascular Surgery (SVS) and Society for Thoracic Surgeons (STS) published contemporary guidelines clearly defining complicated versus uncomplicated acute type B aortic dissections (TBADs) with an additional high-risk grouping. Few studies have evaluated outcomes associated with "high-risk" TBADs. The objective of this study was to assess differences in demographics, clinical presentation, symptom onset, and outcomes in high-risk patients that underwent either thoracic endovascular aortic repair (TEVAR) or best medical management for acute TBAD compared to those with complicated and uncomplicated acute TBAD. METHODS: Patients admitted with acute TBADs from a single academic medical center from October 2011 to March 2020 were analyzed. Per the STS/SVS 2020 guidelines, high risk was defined as refractory pain/hypertension, bloody pleural effusion, aortic diameter >4 cm, false lumen diameter >22 mm, radiographic malperfusion, and early readmission, and complicated was defined as ruptured/malperfusion presentation. Uncomplicated patients were those without malperfusion/rupture and without high-risk features. The primary end-point was inpatient mortality. Secondary end-points included complications, reintervention, and survival. RESULTS: Of the 159 patients identified with acute TBAD, 63 (40%) met the high-risk criteria. In the high-risk cohort, 38 (60%) underwent TEVAR (HR-TEVAR), with refractory pain as the most common indication, while 25 (40%) were managed medically (HR-medical). Malperfusion or rupture was present in 63 (40%) patients (complicated TBAD (C-TBAD)), all of whom underwent TEVAR. An additional 33 patients had no high-risk features and were all managed medically (uncomplicated TBAD). There were no differences in age, body mass index, and race between groups. Among the 4 groups, there were variable distributions in sex, insurance status, and incidence of several baseline comorbidities including congestive heart failure, chronic obstructive pulmonary disease, and renal dysfunction (P < 0.05 for all). C-TBAD had increased length of stay (12, interquartile range [IQR] 9-22) compared to HR-TEVAR (11.5, IQR 7-15), HR-medical (6, IQR 5-8), and uncomplicated TBAD (7, IQR 5-10) (P < 0.01). C-TBAD had decreased days from admission to repair (0, IQR 0-2) compared to HR-TEVAR (3.5, IQR 1-8) (P < 0.01). C-TBAD patients had worse 3-year survival compared to other groups (log-rank P < 0.01), although when in-hospital mortality was excluded, survival was similar among groups (P = 0.37). Of patients initially managed medically, outpatient TEVAR was performed in 6 (24%) HR-medical and 4 (12%) uncomplicated patients, with no difference between rate of intervention between groups (P = 0.22). CONCLUSIONS: High-risk features, as defined in updated SVS/STS guidelines, are common in patients presenting with acute TBAD. High-risk patients had acceptable outcomes when managed either surgically or medically. High-risk patients that underwent TEVAR had improved perioperative outcomes and mortality compared to those undergoing TEVAR for C-TBAD, a finding which may help guide preoperative risk stratification and patient counseling.

Short-Term Dietary Restriction Potentiates an Anti-Inflammatory Circulating Mucosal-Associated Invariant T-Cell Response.

Short-term protein-calorie dietary restriction (StDR) is a promising preoperative strategy for modulating postoperative inflammation. We have previously shown marked gut microbial activity during StDR, but relationships between StDR, the gut microbiome, and systemic immunity remain poorly understood. Mucosal-associated invariant T-cells (MAITs) are enriched on mucosal surfaces and in circulation, bridge innate and adaptive immunity, are sensitive to gut microbial changes, and may mediate systemic responses to StDR. Herein, we characterized the MAIT transcriptomic response to StDR using single-cell RNA sequencing of human PBMCs and evaluated gut microbial species-level changes through sequencing of stool samples. Healthy volunteers underwent 4 days of DR during which blood and stool samples were collected before, during, and after DR. MAITs composed 2.4% of PBMCs. More MAIT genes were differentially downregulated during DR, particularly genes associated with MAIT activation (CD69), regulation of pro-inflammatory signaling (IL1, IL6, IL10, TNFα), and T-cell co-stimulation (CD40/CD40L, CD28), whereas genes associated with anti-inflammatory IL10 signaling were upregulated. Stool analysis showed a decreased abundance of multiple MAIT-stimulating Bacteroides species during DR. The analyses suggest that StDR potentiates an anti-inflammatory MAIT immunophenotype through modulation of TCR-dependent signaling, potentially secondary to gut microbial species-level changes.

Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease.

Hand dysfunction is a common observation after arteriovenous fistula (AVF) creation for hemodialysis access and has a variable clinical phenotype; however, the underlying mechanism responsible is unclear. Grip strength changes are a common metric used to assess AVF-associated hand disability but has previously been found to poorly correlate with the hemodynamic perturbations post-AVF placement implicating other tissue-level factors as drivers of hand outcomes. In this study, we sought to test if expression of a mitochondrial targeted catalase (mCAT) in skeletal muscle could reduce AVF-related limb dysfunction in mice with chronic kidney disease (CKD). Male and female C57BL/6J mice were fed an adenine-supplemented diet to induce CKD prior to placement of an AVF in the iliac vascular bundle. Adeno-associated virus was used to drive expression of either a green fluorescent protein (control) or mCAT using the muscle-specific human skeletal actin (HSA) gene promoter prior to AVF creation. As expected, the muscle-specific AAV-HSA-mCAT treatment did not impact blood urea nitrogen levels (P = 0.72), body weight (P = 0.84), or central hemodynamics including infrarenal aorta and inferior vena cava diameters (P > 0.18) or velocities (P > 0.38). Hindlimb perfusion recovery and muscle capillary densities were also unaffected by AAV-HSA-mCAT treatment. In contrast to muscle mass and myofiber size which were not different between groups, both absolute and specific muscle contractile forces measured via a nerve-mediated in-situ preparation were significantly greater in AAV-HSA-mCAT treated mice (P = 0.0012 and P = 0.0002). Morphological analysis of the post-synaptic neuromuscular junction uncovered greater acetylcholine receptor cluster areas (P = 0.0094) and lower fragmentation (P = 0.0010) in AAV-HSA-mCAT treated mice. Muscle mitochondrial oxidative phosphorylation was not different between groups, but AAV-HSA-mCAT treated mice had lower succinate-fueled mitochondrial hydrogen peroxide emission compared to AAV-HSA-GFP mice (P < 0.001). In summary, muscle-specific scavenging of mitochondrial hydrogen peroxide significantly improves neuromotor function in mice with CKD following AVF creation.

The Intersection of Substance Use Disorders and Infectious Diseases in the Emergency Department.

Substance use disorders (SUDs) intersect clinically with many infectious diseases, leading to significant morbidity and mortality if either condition is inadequately treated. In this article, we will describe commonly seen SUDs in the emergency department (ED) as well as their associated infectious diseases, discuss social drivers of patient outcomes, and introduce novel ED-based interventions for co-occurring conditions. Clinicians should come away from this article with prescriptions for both antimicrobial medications and pharmacotherapy for SUDs, as well as an appreciation for social barriers, to care for these patients.

Comparative outcomes of open mesenteric bypass after a failed endovascular or open mesenteric revascularization for chronic mesenteric ischemia.

INTRODUCTION: Clinical practice guidelines have recommended an endovascular-first approach (ENDO) for the management of patients with chronic mesenteric ischemia (CMI), whereas an open mesenteric bypass (OMB) is proposed for subjects deemed to be poor ENDO candidates. However, the impact of a previous failed endovascular or open mesenteric reconstruction on a subsequent OMB is unknown. Accordingly, this study was designed to examine the results of a remedial OMB (R-OMB) after a failed ENDO or a primary OMB (P-OMB) for patients with recurrent CMI. METHODS: All patients who underwent an OMB from 2002 to 2022 at the University of Florida were reviewed. Outcomes after an R-OMB (ie, history of a failed ENDO or P-OMB) and P-OMB were compared. The primary end point was 30-day mortality, whereas secondary outcomes included complications, reintervention, and survival. The Kaplan-Meier methodology was used to estimate freedom from reintervention and all-cause mortality, whereas multivariable Cox proportional hazards modeling identified predictors of death. RESULTS: A total of 145 OMB procedures (R-OMB, n = 48 [33%]; P-OMB, n = 97 [67%]) were analyzed. A majority of R-OMB operations were performed for a failed stent (prior ENDO, n = 39 [81%]; prior OMB, n = 9 [19%]). R-OMB patients were generally younger (66 ± 9 years vs P-OMB, 69 ± 11 years; P = .09) and had lower incidence of smoking exposure (29% vs P-OMB, 48%; P = .07); however, there were no other differences in demographics or comorbidities. R-OMB was associated with less intraoperative transfusion (0.6 units vs P-OMB, 1.4 units; P = .01), but there were no differences in conduit choice or bypass configuration.The overall 30-day mortality and complication rates were 7% (n = 10/145) and 53% (n = 77/145), respectively, with no difference between the groups. Notably, R-OMB had decreased cardiac (6% vs P-OMB, 21%; P < .01) and bleeding complication rates (2% vs P-OMB, 15%; P = .01). The freedom from reintervention (1 and 5 years: R-OMB: 95% ± 4%, 83% ± 9% vs P-OMB: 97% ± 2%, 93% ± 5%, respectively; log-rank P = .21) and survival (1 and 5 years: R-OMB: 82% ± 6%, 68% ± 9% vs P-OMB: 84% ± 4%, 66% ± 7%; P = .91) were similar. Independent predictors of all-cause mortality included new postoperative hemodialysis requirement (hazard ratio [HR], 7.4, 95% confidence interval [CI], 3.1-17.3; P < .001), pulmonary (HR, 2.7, 95% CI, 1.4-5.3; P = .004) and cardiac (HR, 2.4, 95% CI, 1.1-5.1; P = .04) complications, and female sex (HR, 2.1, 95% CI, 1.03-4.8; P = .04). Notably, R-OMB was not a predictor of death. CONCLUSIONS: The perioperative and longer-term outcomes for a remedial OMB after a failed intraluminal stent or previous open bypass appear to be comparable to a P-OMB. These findings support the recently updated clinical practice guideline recommendations for an endovascular-first approach to treating recurrent CMI due to the significant perioperative complication risk of OMB. However, among the subset of patients deemed ineligible for endoluminal reconstruction after failed mesenteric revascularization, R-OMB results appear to be acceptable and highlight the utility of this strategy in selected patients.

Economy of Effort or Sophisticated Programming? The Prevalence of Bidirectional Promoter Complexes in the Human Genome.

An abundance of antisense promoters in the vicinity of the transcriptional start site of coding genes suggests that they play an important role in gene regulation. The divergent transcription of housekeeping genes by a common central promoter region allows for coordinated regulation of genes in related pathways and is also linked to higher promoter activity. However, closely positioned transcription start sites can also result in competition between overlapping promoter elements and generate a binary switch element. Furthermore, the direct competition resulting from the presence of an antisense promoter immediately downstream of the transcription start site of the gene produces an element that can exist in only one of two stable transcriptional states: sense or antisense. In this review, we summarize analyses of the prevalence of antisense transcription in higher eukaryotes and viruses, with a focus on the antisense promoters competing with the promoters of coding genes. The structures of bidirectional promoters driving the simultaneous expression of housekeeping genes are compared with examples of human bidirectional elements that have been shown to act as switches. Since many bidirectional elements contain a noncoding RNA as the divergent transcript, we describe examples of functional noncoding antisense transcripts that affect the epigenetic landscape and alter the expression of their host gene. Finally, we discuss opportunities for additional research on competing sense/antisense promoters, uncovering their potential role in programming cell differentiation.

Emergency Department Access to Buprenorphine for Opioid Use Disorder.

Importance: Although substantial evidence supports buprenorphine for treatment of opioid use disorder (OUD) in controlled trials, prospective study of patient outcomes in clinical implementation of emergency department (ED) buprenorphine treatment is lacking. Objective: To examine the association between buprenorphine treatment in the ED and follow-up engagement in OUD treatment 1 month later. Design, Setting, and Participants: This multisite cohort study was conducted in 7 California EDs participating in a statewide implementation project to improve access to buprenorphine treatment. The study population included ED patients aged at least 18 years identified with OUD between April 1, 2021, and June 30, 2022. Data analysis was performed in October 2023. Exposure: All participants were offered buprenorphine treatment for OUD (either in ED administration, prescription, or both), the uptake of which was examined as the exposure of interest. Main Outcomes and Measures: The primary outcome was engagement in OUD treatment 30 days after the ED visit, determined by patient report or clinical documentation. The association of ED buprenorphine treatment with subsequent OUD treatment engagement was estimated using hierarchical generalized linear models. Results: This analysis included 464 ED patients with OUD. Their median age was 36.0 (IQR, 29.0-38.7) years, and most were men (343 [73.9%]). With regard to race and ethnicity, 64 patients (13.8%) self-identified as non-Hispanic Black, 183 (39.4%) as Hispanic, and 185 as non-Hispanic White (39.9%). Most patients (396 [85.3%]) had Medicaid insurance, and more than half (262 [57.8%]) had unstable housing. Self-reported fentanyl use (242 [52.2%]) and a comorbid mental health condition (328 [71.5%]) were common. Interest in buprenorphine treatment was high: 398 patients (85.8%) received buprenorphine treatment; 269 (58.0%) were administered buprenorphine in the ED and 339 (73.1%) were prescribed buprenorphine. With regard to OUD treatment engagement at 30 days after the ED visit, 198 participants (49.7%) who received ED buprenorphine treatment remained engaged compared with 15 participants (22.7%) who did not receive ED buprenorphine treatment. An association of ED buprenorphine treatment with subsequent OUD treatment engagement at 30 days was observed (adjusted risk ratio, 1.97 [95% CI, 1.27-3.07]). Conclusions and Relevance: The findings of this cohort study suggest that among patients with OUD presenting to EDs implementing low-threshold access to medications for OUD, buprenorphine treatment was associated with a substantially higher likelihood of follow-up treatment engagement 1 month later. Future research should investigate techniques to optimize both the uptake and effectiveness of buprenorphine initiation in low-threshold settings such as the ED.

Perioperative Cerebrospinal Fluid Drain Placement Does Not Increase Venous Thromboembolism Risk After Thoracic and Fenestrated Endovascular Aortic Repair.

BACKGROUND: Venous thromboembolism (VTE) incidence after thoracic and fenestrated endovascular aortic repair (TEVAR/FEVAR) is high (up to 6-7%) relative to other vascular procedures; however, the etiology for this discrepancy remains unknown. Notably, patients undergoing TEVAR/FEVAR commonly receive cerebrospinal fluid drains (CSFDs) for neuroprotection, requiring interruption of perioperative anticoagulation and prolonged immobility. We hypothesized that CSFDs are a risk factor for VTE after TEVAR/FEVAR. METHODS: Consecutive TEVAR/FEVAR patients at a single center were reviewed (2011-2020). Cerebrospinal fluid drains (CSFDs) were placed based on surgeon preference preoperatively or for spinal cord ischemia (SCI) rescue therapy postoperatively. The primary end-point was VTE occurrence, defined as any new deep venous thrombosis (DVT) or pulmonary embolism (PE) confirmed on imaging within 30 days postoperatively. Routine postoperative VTE screening was not performed. Patients with and without VTE, and subjects with and without CSFDs were compared. Logistic regression was used to explore associations between VTE incidence and CSFD exposure. RESULTS: Eight hundred ninety-seven patients underwent TEVAR/FEVAR and 43% (n = 387) received a CSFD at some point during their care (preoperative: 94% [n = 365/387]; postoperative SCI rescue therapy: 6% [n = 22/387]). CSFD patients were more likely to have previous aortic surgery (44% vs. 37%; P = 0.028) and received more postoperative blood products (780 vs. 405 mL; P = 0.005). The overall VTE incidence was 2.2% (n = 20). 70% (14) patients with VTE had DVT, 50% (10) had PE, and 20% (4) had DVT and PE. Among TEVAR/FEVAR patients with VTE, 65% (n = 13) were symptomatic. Most VTEs (90%, n = 18) were identified inhospital and the median time to diagnosis was 12.5 (interquartile range 7.5-18) days postoperatively. Patients with VTE were more likely to have nonelective surgery (95% vs. 41%; P < 0.001), had higher American Society of Anesthesiologists classification (4.1 vs. 3.7; P < 0.001), required longer intensive care unit admission (24 vs. 12 days; P < 0.001), and received more blood products (1,386 vs. 559 mL; P < 0.001). Venous thromboembolism (VTE) incidence was 1.8% in CSFD patients compared to 3.5% in non-CSFD patients (odds ratio 0.70 [95% confidence interval 0.28-1.78, P = 0.300). However, patients receiving CSFDs postoperatively for SCI rescue therapy had significantly greater VTE incidence (9.1% vs. 1.1%; P = 0.044). CONCLUSIONS: CSFD placement was not associated with an increased risk of VTE in patients undergoing TEVAR/FEVAR. Venous thromboembolism (VTE) risk was greater in patients undergoing nonelective surgery and those with complicated perioperative courses. Venous thromboembolism (VTE) risk was greater in patients receiving therapeutic CSFDs compared to prophylactic CSFDs, highlighting the importance of careful patient selection for prophylactic CSFD placement.

Safety and Pain Reduction in Emergency Practitioner Ultrasound-Guided Nerve Blocks: A One-Year Retrospective Study.

STUDY OBJECTIVE: Emergency practitioners use ultrasound-guided nerve blocks to alleviate pain. This study represents the largest registry of single-injection ultrasound-guided nerve blocks performed in an emergency department (ED) to date. We wished to assess the safety and pain score reductions associated with ED-performed ultrasound-guided nerve blocks. The main outcomes of interest were ultrasound-guided nerve block complication rates and change in patient-reported pain (0 to 10 on the VAS) pre and post ultrasound-guided nerve blocks. Other variables of interest were ultrasound-guided nerve block types and indications during the study period. METHODS: This is a retrospective analysis of 420 emergency practitioner-performed ultrasound-guided nerve blocks through chart review over 1 year in the Highland ED. Four emergency physician abstractors reviewed all templated ultrasound-guided nerve block notes and nursing records over the study period. Inter-rater reliability was assessed using 10 randomly selected charts with 100% agreement for 70 key variables (Kappa=1, P<.001). RESULTS: Seventy-five unique emergency practitioners performed 420 ultrasound-guided nerve blocks. Ultrasound-guided nerve blocks were most often performed by emergency residents (61.9%), advanced practice practitioners (21.2%), ultrasound fellowship-trained faculty (8.3%), interns (3.6%), nonultrasound fellowship-trained faculty (3.3%), and not recorded (1.7%). One complication occurred during the study (arterial puncture recognized through syringe aspiration without further sequelae). Among the 261 ultrasound-guided nerve blocks with preblock and postblock pain scores, there was an improvement in postblock pain scores. The mean pain scores decreased from 7.4 to 2.8 after an ultrasound-guided nerve block (difference 4.6, 95% confidence interval 3.9 to 5.2). CONCLUSIONS: This 1-year retrospective study supports that emergency practitioner-performed ultrasound-guided nerve blocks have a low complication rate and are associated with reduced pain.

Ultrasound-guided rhomboid intercostal block (RIB) for acute scapula fracture in the emergency department.

INTRODUCTION: Proper pain in acute scapular fractures can be challenging to achieve due to their anatomy and location. While the current mainstay of treatment relies on opioids, the Rhomboid Intercostal Block (RIB) has been utilized for anesthesia to effectively treat pain for scapular fractures. However, it has not yet been utilized in the emergency department (ED). CASE REPORT: In this case report, we present the first documented use of RIB to treat pain safely and effectively in a 69-year-old male with a scapula fracture following a ground-level fall in the ED. The RIB was performed under ultrasound guidance, providing precise localization and administration of the nerve block. CONCLUSION: The RIB demonstrated successful pain management in the ED. Although hopeful, further research is needed to understand limitations, potential side effects, length of pain control, and overall clinical outcomes of the RIB in the ED.

Bio-Experiential Technology to Support Persons With Dementia and Care Partners at Home (TEND): Protocol for an Intervention Development Study.

BACKGROUND: Alzheimer disease and related dementias are debilitating and incurable diseases. Persons with dementia and their informal caregivers (ie, dyads) experience high rates of emotional distress and negative health outcomes. Several barriers prevent dyads from engaging in psychosocial care including cost, transportation, and a lack of treatments that target later stages of dementia and target the dyad together. Technologically informed treatment and serious gaming have been shown to be feasible and effective among persons living with dementia and their care partners. To increase access, there is a need for technologically informed psychosocial interventions which target the dyad, together in the home. OBJECTIVE: This study aims to develop the toolkit for experiential well-being in dementia, a dyadic, "bio-experiential" intervention for persons with dementia and their caregivers. Per our conceptual model, the toolkit for experiential well-being in dementia platform aims to target sustained attention, positive emotions, and active engagement among dyads. In this paper, we outline the protocol and conceptual model for intervention development and partnership with design and development experts. METHODS: We followed the National Institutes of Health (NIH) stage model (stage 1A) and supplemented the model with principles of user-centered design. The first step includes understanding user needs, goals, and strengths. We met this step by engaging in methodology and definition synthesis and conducting focus groups with dementia care providers (N=10) and persons with dementia and caregivers (N=11). Step 2 includes developing and refining the prototype. We will meet this step by engaging dyads in up to 20 iterations of platform ß testing workshops. Step 3 includes observing user interactions with the prototype. We will meet this step by releasing the platform for feasibility testing. RESULTS: Key takeaways from the focus groups include balancing individualization and the dyadic relationship and avoiding confusing stimuli. As of September 2023, we have completed focus groups with providers, persons with dementia, and their caregivers. Additionally, we have conducted 4 iterations of ß testing workshops with dyads. Feedback from focus groups informed the ß testing workshops; data have not yet been formally analyzed and will be reported in future publications. CONCLUSIONS: Technological interventions, particularly "bio-experiential" technology, can be used in dementia care to support emotional health among persons with a diagnosis and caregivers. Here, we outline a collaborative intervention development process of bio-experiential technology through a research, design, and development partnership. Next, we are planning to test the platform's feasibility as well as its impact on clinical outcomes and mechanisms of action. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52799.

Abundant binary promoter switches in lineage-determining transcription factors indicate a digital component of cell fate determination.

Previous studies of the murine Ly49 and human KIR gene clusters implicated competing sense and antisense promoters in the control of variegated gene expression. In the current study, an examination of transcription factor genes defines an abundance of convergent and divergent sense/antisense promoter pairs, suggesting that competing promoters may control cell fate determination. Differentiation of CD34+ hematopoietic progenitors in vitro shows that cells with GATA1 antisense transcription have enhanced GATA2 transcription and a mast cell phenotype, whereas cells with GATA2 antisense transcription have increased GATA1 transcripts and an erythroblast phenotype. Detailed analyses of the AHR and RORC genes demonstrate the ability of competing promoters to act as binary switches and the association of antisense transcription with an immature/progenitor cell phenotype. These data indicate that alternative cell fates generated by promoter competition in lineage-determining transcription factors contribute to the programming of cell differentiation.