Superior Sagittal Sinus Thrombectomy in Pediatric Head Injury.

INTRODUCTION: Injury and subsequent thrombosis of the cerebral venous sinuses may be caused by closed head injuries secondary to a variety of different mechanisms. Skull fractures can lacerate or otherwise disrupt adjacent dural sinuses. The sequelae of such injuries may include thrombosis and either partial or total occlusion of the sinus, ultimately resulting in significant venous congestion. Sagittal sinus injury is associated with a more serious outcome due to the obligatory flow into the sinus, especially posterior to the coronal suture. In such cases, venous infarction may be a severe and life-threatening complication of head injury. CASE PRESENTATION: A 2-year-old female presented with a depressed skull fracture near the midline and a thrombus in the sagittal sinus. Anticoagulation, the standard treatment cerebral venous sinus thrombosis (CVST), was contraindicated due to intracranial hemorrhage, so immediate thrombectomy was performed with successful neurologic recovery at 9-month follow-up. To our knowledge, this case is the youngest patient documented to receive mechanical thrombectomy for superior sagittal sinus (SSS) thrombosis due to trauma. CONCLUSION: Closed head injuries in pediatric patients may be associated with CVST, with resulting venous drainage compromise and profound neurologic sequelae. Unlike adult patients with spontaneous CVST in which anticoagulation are the standard of care, pediatric patients experiencing traumatic CVST may have contraindications to anticoagulants. If the patient has a contraindication to anticoagulation such as intracranial bleeding, endovascular mechanical thrombectomy may be an effective intervention when performed by an experienced neurointerventionalist.

National Institute on Drug Abuse Clinical Trials Network Meeting Report: Advancing Emergency Department Initiation of Buprenorphine for Opioid Use Disorder.

Opioid use disorder and opioid overdose deaths are a major public health crisis, yet highly effective evidence-based treatments are available that reduce morbidity and mortality. One such treatment, buprenorphine, can be initiated in the emergency department (ED). Despite evidence of efficacy and effectiveness for ED-initiated buprenorphine, universal uptake remains elusive. On November 15 and 16, 2021, the National Institute on Drug Abuse Clinical Trials Network convened a meeting of partners, experts, and federal officers to identify research priorities and knowledge gaps for ED-initiated buprenorphine. Meeting participants identified research and knowledge gaps in 8 categories, including ED staff and peer-based interventions; out-of-hospital buprenorphine initiation; buprenorphine dosing and formulations; linkage to care; strategies for scaling ED-initiated buprenorphine; the effect of ancillary technology-based interventions; quality measures; and economic considerations. Additional research and implementation strategies are needed to enhance adoption into standard emergency care and improve patient outcomes.

Implementing Programs to Initiate Buprenorphine for Opioid Use Disorder Treatment in High-Need, Low-Resource Emergency Departments: A Nonrandomized Controlled Trial.

STUDY OBJECTIVE: We hypothesized that implementation facilitation would enable us to rapidly and effectively implement emergency department (ED)-initiated buprenorphine programs in rural and urban settings with high-need, limited resources and dissimilar staffing structures. METHODS: This multicenter implementation study employed implementation facilitation using a participatory action research approach to develop, introduce, and refine site-specific clinical protocols for ED-initiated buprenorphine and referral in 3 EDs not previously initiating buprenorphine. We assessed feasibility, acceptability, and effectiveness by triangulating mixed-methods formative evaluation data (focus groups/interviews and pre/post surveys involving staff, patients, and stakeholders), patients' medical records, and 30-day outcomes from a purposive sample of 40 buprenorphine-receiving patient-participants who met research eligibility criteria (English-speaking, medically stable, locator information, nonprisoners). We estimated the primary implementation outcome (proportion receiving ED-initiated buprenorphine among candidates) and the main secondary outcome (30-day treatment engagement) using Bayesian methods. RESULTS: Within 3 months of initiating the implementation facilitation activities, each site implemented buprenorphine programs. During the 6-month programmatic evaluation, there were 134 ED-buprenorphine candidates among 2,522 encounters involving opioid use. A total of 52 (41.6%) practitioners initiated buprenorphine administration to 112 (85.1%; 95% confidence interval [CI] 79.7% to 90.4%) unique patients. Among 40 enrolled patient-participants, 49.0% (35.6% to 62.5%) were engaged in addiction treatment 30 days later (confirmed); 26 (68.4%) reported attending one or more treatment visits; there was a 4-fold decrease in self-reported overdose events (odds ratio [OR] 4.03; 95% CI 1.27 to 12.75). The ED clinician readiness increased by a median of 5.02 (95% CI: 3.56 to 6.47) from 1.92/10 to 6.95/10 (n(pre)=80, n(post)=83). CONCLUSIONS: The implementation facilitation enabled us to effectively implement ED-based buprenorphine programs across heterogeneous ED settings rapidly, which was associated with promising implementation and exploratory patient-level outcomes.

URINE TOXICOLOGY PROFILES OF EMERGENCY DEPARTMENT PATIENTS WITH UNTREATED OPIOID USE DISORDER: A MULTI-SITE VIEW.

BACKGROUND: Opioid overdose deaths in 2021 were the highest ever, driven by fentanyl and polysubstance use. OBJECTIVE: The aim of the study was to characterize drug use, assessed by urine drug screens (UDSs), in patients with untreated opioid use disorder (OUD) presenting to 28 emergency departments (EDs) nationally and by region. METHODS: We analyzed UDSs from patients enrolled in the CTN-0099 ED-INNOVATION (Emergency Department-Initiated Buprenorphine Validation) trial between July 12, 2020 and March 9, 2022. Participants were adult ED patients with OUD not engaged in addiction treatment with a UDS positive for an opioid, but negative for methadone. Sites were divided into "East" and "West" regions. RESULTS: A UDS was available for all 925 enrolled participants, 543 from East and 382 from West. Fentanyl was in 702 specimens (76%) (n = 485 [89%] East vs. n = 217 [57%] West; p < 0.01) and was the only opioid in 269 (29%). After fentanyl, the most common opioids were morphine (presumably heroin; n = 411 [44%]; n = 192 [35%] East vs. n = 219 [57%] West; p < 0.01) and buprenorphine (n = 329 [36%]; n = 186 [35%] East vs. n = 143 [37%] West; p = 0.32). The most common drugs found with opioids were stimulants (n = 545 [59%]), tetrahydrocannabinol (n = 417 [45%]), and benzodiazepines (n = 151 [16%]). Amphetamine-type stimulants were more common in West (n = 209 [55%] vs. East (n = 125 [23%]). Cocaine was more common in East (n = 223 [41%]) vs. West (n = 82 [21%]). The presence of multiple drugs was common (n = 759 [82%]). CONCLUSIONS: Most participants had UDS specimens containing multiple substances; a high proportion had fentanyl, stimulants, and buprenorphine. Regional differences were noted. Given the increased risk of death with fentanyl and polysubstance use, ED providers should be providing risk reduction counseling, treatment, and referral.

An Essential Role for Perforin-2 in Type I IFN Signaling.

Type I IFNs play a complex role in determining the fate of microbial pathogens and may also be deleterious to the host during bacterial and viral infections. Upon ligand binding, a receptor proximal complex consisting of IFN-α and -ß receptors 1 and 2 (IFNAR1, IFNAR2, respectively), tyrosine kinase 2 (Tyk2), Jak1, and STAT2 are assembled and promote the phosphorylation of STAT1 and STAT2. However, how the IFNARs proximal complex is assembled upon binding to IFN is poorly understood. In this study, we show that the membrane-associated pore-forming protein Perforin-2 (P2) is critical for LPS-induced endotoxic shock in wild-type mice. Type I IFN-mediated JAK-STAT signaling is severely impaired, and activation of MAPKs and PI3K signaling pathways are delayed in P2-deficient mouse bone marrow-derived macrophages, mouse embryonic fibroblasts (MEFs), and human HeLa cells upon IFN stimulation. The P2 N-glycosylated extracellular membrane attack complex/perforin domain and the P2 domain independently associate with the extracellular regions of IFNAR1 and IFNAR2, respectively, in resting MEFs. In addition, the P2 cytoplasmic tail domain mediated the constitutive interaction between STAT2 and IFNAR2 in resting MEFs, an interaction that is dependent on the association of the extracellular regions of P2 and IFNAR2. Finally, the constitutive association of P2 with both receptors and STAT2 is critical for the receptor proximal complex assembly and reciprocal transphosphorylation of Jak1 and Tyk2 as well as the phosphorylation and activation of STAT1 and STAT2 upon IFN-ß stimulation.

Association of substance use characteristics and future homelessness among emergency department patients with drug use or unhealthy alcohol use: Results from a linked data longitudinal cohort analysis.

Background: Homelessness and substance use are intricately related, and both are prevalent among emergency department (ED) patients. This study examined the longitudinal association of substance use characteristics with future homeless shelter entry among ED patients with any drug use or unhealthy alcohol use. Methods: We present results from a longitudinal cohort study of public hospital ED patients who screened positive for drug use or unhealthy alcohol use and who were not homeless at their baseline (index) ED visit. The primary outcome was homeless shelter entry within 12 months of baseline, ascertained in city homeless shelter administrative data. Primary independent variables of interest were alcohol use severity (AUDIT), drug use severity (DAST-10), and types of drugs used, as reported on baseline survey questionnaires. Results: Analyses included 1,210 ED patients. By 12 months following the baseline ED visit, 114 (9.4%) had entered a homeless shelter. Among patients with the most severe problems related to drug use (DAST-10 score 9-10), 40.9% entered a shelter within 12 months. Past shelter use was the strongest predictor of future shelter entry; once adjusting for historic shelter use the relationship of AUDIT and DAST-10 scores with future shelter entry was no longer statistically significant in multivariable models. Conclusions: ED patients with past year drug use or unhealthy alcohol use had relatively high likelihood of future shelter entry. Risk for homelessness should be addressed in future interventions with this population. Findings illustrate the complexity of relationships between substance use and homelessness.

Social relationships, homelessness, and substance use among emergency department patients.

Background: Emergency department (ED) patients commonly experience both substance use and homelessness, and social relationships impact each in varied ways not fully captured by existing quantitative research. This qualitative study examines how social relationships can precipitate or ameliorate homelessness and the connection (if any) between substance use and social relationships among ED patients experiencing homelessness. Methods: As part of a broader study to develop ED-based homelessness prevention interventions, we conducted in-depth interviews with 25 ED patients who used alcohol or drugs and had recently become homeless. We asked patients about the relationship between their substance use and homelessness. Interviews were recorded, transcribed, and coded line-by-line by investigators. Final codes formed the basis for thematic analysis through consensus discussions. Results: Social relationships emerged as focal points for understanding the four major themes related to the intersection of homelessness and substance use: (1) Substance use can create strain in relationships; (2) Help is there until it's not; (3) Social relationships can create challenges contributing to substance use; and (4) Reciprocal relationship of substance use and isolation. Sub-themes were also identified and described. Conclusions: The association between substance use and homelessness is multifaceted and social relationships are a complex factor linking the two. Social relationships are often critical for homelessness prevention, but they are impacted by and reciprocally affect substance use. ED-based substance use interventions should consider the high prevalence of homelessness and the impact of social relationships on the interaction between homelessness and substance use.

LPS modifications and AvrA activity of Salmonella enterica serovar Typhimurium are required to prevent Perforin-2 expression by infected fibroblasts and intestinal epithelial cells.

Cellular Perforin-2 (MPEG1) is a pore-forming MACPF family protein that plays a critical role in the defense against bacterial pathogens. Macrophages, neutrophils, and several other cell types that are part of the front line of innate defenses constitutively express high levels of Perforin-2; whereas, most other cell types must be induced to express Perforin-2 by interferons (α, ß and γ) and/or PAMPs such as LPS. In this study, we demonstrate that many bacterial pathogens can limit the expression of Perforin-2 in cells normally inducible for Perforin-2 expression, while ordinarily commensal or non-pathogenic bacteria triggered high levels of Perforin-2 expression in these same cell types. The mechanisms by which pathogens suppress Perforin-2 expression was explored further using Salmonella enterica serovar Typhimurium and cultured MEFs as well as intestinal epithelial cell lines. These studies identified multiple factors required to minimize the expression of Perforin-2 in cell types inducible for Perforin-2 expression. These included the PmrAB and PhoPQ two-component systems, select LPS modification enzymes and the Type III secretion effector protein AvrA.

Implementation of Oral and Extended-Release Naltrexone for the Treatment of Emergency Department Patients With Moderate to Severe Alcohol Use Disorder: Feasibility and Initial Outcomes.

STUDY OBJECTIVE: Despite evidence supporting naltrexone as an effective treatment for alcohol use disorder, its use in emergency department (ED) patients has not been described. We implemented a protocol that combined substance use navigation with either oral naltrexone or extended-release intramuscular naltrexone for patients with alcohol use disorder as a strategy to improve follow-up in addiction treatment after ED discharge. METHODS: In this descriptive study, we analyzed the results from adult patients discharged from the ED with moderate to severe alcohol use disorder who received either oral naltrexone or extended-release intramuscular naltrexone between May 1, 2020, and October 31, 2020, and assessed their engagement in formal addiction treatment within 30 days after discharge from the ED. RESULTS: Among 59 patients with moderate to severe alcohol use disorder who accepted naltrexone treatment, 41 received oral naltrexone and 18 received extended-release intramuscular naltrexone. The mean (SD) age of the patients was 45.2 (13.4) years; 22 patients (37.3%) were Latinx, 18 (30.5%) were Black, and 16 (27.1%) were White. Among all patients, 9 (15.3%) attended follow-up formal addiction treatment within 30 days after discharge; 5 patients (27.8%) who received extended-release intramuscular naltrexone and 4 patients (9.8%) who received oral naltrexone attended follow-up treatment within 30 days. CONCLUSION: We implemented a clinical protocol for ED patients with moderate to severe alcohol use disorder using oral naltrexone and extended-release intramuscular naltrexone together with substance use navigation. Identification of alcohol use disorder, a brief intervention, and initiation of naltrexone resulted in a 15% follow-up rate in formal addiction treatment. Future work should prospectively examine the effectiveness of naltrexone as well as the effect of substance use navigation for ED patients with alcohol use disorder.

Perforin-2 Breaches the Envelope of Phagocytosed Bacteria Allowing Antimicrobial Effectors Access to Intracellular Targets.

Perforin-2, the product of the MPEG1 gene, limits the spread and dissemination of bacterial pathogens in vivo. It is highly expressed in murine and human phagocytes, and macrophages lacking Perforin-2 are compromised in their ability to kill phagocytosed bacteria. In this study, we used Salmonella enterica serovar Typhimurium as a model intracellular pathogen to elucidate the mechanism of Perforin-2's bactericidal activity. In vitro Perforin-2 was found to facilitate the degradation of Ags contained within the envelope of phagocytosed bacteria. In contrast, degradation of a representative surface Ag was found to be independent of Perforin-2. Consistent with our in vitro results, a protease-sensitive, periplasmic superoxide dismutase (SodCII) contributed to the virulence of S. Typhimurium in Perforin-2 knockout but not wild-type mice. In aggregate, our studies indicate that Perforin-2 breaches the envelope of phagocytosed bacteria, facilitating the delivery of proteases and other antimicrobial effectors to sites within the bacterial cell.

Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen.

The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1, Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogen Listeria monocytogenes Within a few hours of systemic infection, the massive proliferation of L. monocytogenes in Perforin-2(-/-)mice leads to a rapid appearance of acute disease symptoms. We go on to show in cultured Perforin-2(-/-)cells that the vacuole-to-cytosol transitioning of L. monocytogenesis greatly accelerated. Unexpectedly, we found that in Perforin-2(-/-)macrophages,Listeria-containing vacuoles quickly (≤ 15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation of L. monocytogenes to its replicative niche in the cytosol. This hypothesis was supported by our finding that aL. monocytogenes strain expressing virulence factors at a constitutively high level replicated equally well in Perforin-2(+/+)and Perforin-2(-/-)macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification of Listeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity.

Emergency Department Visits for Homelessness or Inadequate Housing in New York City before and after Hurricane Sandy.

Hurricane Sandy struck New York City on October 29, 2012, causing not only a large amount of physical damage, but also straining people's health and disrupting health care services throughout the city. In prior research, we determined that emergency department (ED) visits from the most vulnerable hurricane evacuation flood zones in New York City increased after Hurricane Sandy for several medical diagnoses, but also for the diagnosis of homelessness. In the current study, we aimed to further explore this increase in ED visits for homelessness after Hurricane Sandy's landfall. We performed an observational before-and-after study using an all-payer claims database of ED visits in New York City to compare the demographic characteristics, insurance status, geographic distribution, and health conditions of ED patients with a primary or secondary ICD-9 diagnosis of homelessness or inadequate housing in the first week after Hurricane Sandy's landfall versus the baseline weekly average in 2012 prior to Hurricane Sandy. We found statistically significant increases in ED visits for diagnosis codes of homelessness or inadequate housing in the week after Hurricane Sandy's landfall. Those accessing the ED for homelessness or inadequate housing were more often elderly and insured by Medicare after versus before the hurricane. Secondary diagnoses among those with a primary ED diagnosis of homelessness or inadequate housing also differed after versus before Hurricane Sandy. These observed differences in the demographic, insurance, and co-existing diagnosis profiles of those with an ED diagnosis of homelessness or inadequate housing before and after Hurricane Sandy suggest that a new population cohort-potentially including those who had lost their homes as a result of storm damage-was accessing the ED for homelessness or other housing issues after the hurricane. Emergency departments may serve important public health and disaster response roles after a hurricane, particularly for people who are homeless or lack adequate housing. Further, tracking ED visits for homelessness may represent a novel surveillance mechanism to assess post-disaster infrastructure impact and to prepare for future disasters.

Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease.

RATIONALE: The clinical features of patients infected with pulmonary nontuberculous mycobacteria (PNTM) are well described, but the genetic components of infection susceptibility are not. OBJECTIVES: To examine genetic variants in patients with PNTM, their unaffected family members, and a control group. METHODS: Whole-exome sequencing was done on 69 white patients with PNTM and 18 of their white unaffected family members. We performed a candidate gene analysis using immune, cystic fibrosis transmembrance conductance regulator (CFTR), cilia, and connective tissue gene sets. The numbers of patients, family members, and control subjects with variants in each category were compared, as was the average number of variants per person. MEASUREMENTS AND MAIN RESULTS: A significantly higher number of patients with PNTM than the other subjects had low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue categories (35, 26, 90, and 90%, respectively). Patients with PNTM also had significantly more cilia and connective tissue variants per person than did control subjects (2.47 and 2.55 compared with 1.38 and 1.40, respectively; P = 1.4 × 10(-6) and P = 2.7 × 10(-8), respectively). Patients with PNTM had an average of 5.26 variants across all categories (1.98 in control subjects; P = 2.8 × 10(-17)), and they were more likely than control subjects to have variants in multiple categories. We observed similar results for family members without PNTM infection, with the exception of the immune category. CONCLUSIONS: Patients with PNTM have more low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue genes than their unaffected family members and control subjects. We propose that PNTM infection is a multigenic disease in which combinations of variants across gene categories, plus environmental exposures, increase susceptibility to the infection.

Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLD(S)-mediated axon protection independent of axonal mitochondria.

Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest a central role for axonal mitochondria in both degeneration and NMNAT/WLD(S) (Wallerian degeneration slow)-mediated protection. We used dorsal root ganglia (DRG) explants and Drosophila larval motor neurons (MNs) as models to address the role of mitochondria in Wallerian degeneration (WD). We find that expression of Drosophila NMNAT delays WD in human DRG neurons demonstrating evolutionary conservation of NMNAT function. Morphological comparison of mitochondria from WLD(S)-protected axons demonstrates that mitochondria shrink post-axotomy, though analysis of complex IV activity suggests that they retain their functional capacity despite this morphological change. To determine whether mitochondria are a critical site of regulation for WD, we genetically ablated mitochondria from Drosophila MN axons via the mitochondria trafficking protein milton. Milton loss-of-function did not induce axon degeneration in Drosophila larval MNs, and when axotomized WD proceeded stereotypically in milton distal axons although with a mild, but significant delay. Remarkably, the protective effects of NMNAT/WLD(S) were also maintained in axons devoid of mitochondria. These experiments unveil an axon self-destruction cascade governing WD that is not initiated by axonal mitochondria and for the first time illuminate a mitochondria-independent mechanism(s) regulating WD and NMNAT/WLD(S)-mediated axon protection.

Including frequent emergency department users with severe alcohol use disorders in research: assessing capacity.

STUDY OBJECTIVE: Frequent emergency department (ED) users with severe alcohol use disorders are often excluded from research, in part because assessing capacity to provide consent is challenging. We aim to assess the feasibility of using the University of California, San Diego Brief Assessment of Capacity to Consent, a 5-minute, easy-to-use, validated instrument, to screen for capacity to consent for research in frequent ED users with severe alcohol use disorders. METHODS: We prospectively enrolled a convenience sample of 20 adults to assess their capacity to provide consent for participation in 30-minute mixed-methods interviews using the 10-question University of California, San Diego Brief Assessment of Capacity to Consent. Participants were identified through an administrative database, had greater than 4 annual ED visits for 2 years, and had severe alcohol use disorders. The study was conducted with institutional review board approval from March to July 2013 in an urban, public, university ED receiving approximately 120,000 visits per year. Blood alcohol concentration and demographic data were extracted from the medical record. RESULTS: We completed assessments for 19 of 20 participants. One was removed because of agitation. Sixteen of 19 participants passed each question and were deemed capable of providing informed consent. Interventions to improve understanding (prompting and material review) were required for 15 of 19 participants. The mean duration to describe the study and perform the assessment was 10.4 minutes (SD 3 minutes). The mean blood alcohol concentration was 211.5 mg/dL (SD 137.4 mg/dL). The 3 patients unable to demonstrate capacity had blood alcohol concentrations of 226 and 348 mg/dL, with 1 not obtained. CONCLUSION: This pilot study supports the feasibility of using the University of California, San Diego Brief Assessment of Capacity to Consent to assess capacity of frequent ED users with severe alcohol use disorders to participate in research. Blood alcohol concentration was not correlated with capacity.

Voices of homeless alcoholics who frequent Bellevue Hospital: a qualitative study.

STUDY OBJECTIVE: We describe the evolution, environment, and psychosocial context of alcoholism from the perspective of chronically homeless, alcohol-dependent, frequent emergency department (ED) attendees. We use their words to explore how homelessness, health care, and other influences have contributed to the cause, progression, and management of their alcoholism. METHODS: We conducted detailed, semistructured, qualitative interviews, using a phenomenological approach with 20 chronically homeless, alcohol-dependent participants who had greater than 4 annual ED visits for 2 consecutive years at Bellevue Hospital in New York City. We used an administrative database and purposive sampling to obtain typical and atypical cases with diverse backgrounds. Interviews were audio recorded and transcribed verbatim. We triangulated interviews, field notes, and medical records. We used ATLAS.ti to code and determine themes, which we reviewed for agreement. We bracketed for researcher bias and maintained an audit trail. RESULTS: Interviews lasted an average of 50 minutes and yielded 800 pages of transcript. Fifty codes emerged, which were clustered into 4 broad themes: alcoholism, homelessness, health care, and the future. The participants' perspectives support a multifactorial process for the evolution of their alcoholism and its bidirectional reinforcing relationship with homelessness. Their self-efficacy and motivation for treatment is eroded by their progressive sense of hopelessness, which provides context for behaviors that reinforce stigma. CONCLUSION: Our study exposes concepts for further exploration in regard to the difficulty in engaging individuals who are incapable of envisioning a future. We hypothesize that a multidisciplinary harm reduction approach that integrates health and social services is achievable and would address their needs more effectively.

Imaging of frequent emergency department users with alcohol use disorders.

BACKGROUND: Patients with altered level of consciousness secondary to alcohol use disorders (AUDs) often undergo imaging in the emergency department (ED), although the frequency and yield of this practice over time are unknown. STUDY OBJECTIVES: We describe the use of imaging, the associated ionizing radiation exposure, cumulative costs, and identified acute and chronic injuries and abnormalities among frequent users of the ED with AUDs. METHODS: This is a retrospective case series of individuals identified through an administrative database having 10 or more annual ED visits in 2 consecutive years who were prospectively followed for a third year. International Classification of Diseases, 9(th) Revision, Clinical Modification and Current Procedural Terminology codes were used to select individuals with alcohol-related diagnoses, track imaging procedures, and calculate cost. Diagnoses, imaging results, and radiation exposure per computed tomography (CT) study were abstracted from the medical record. RESULTS: Fifty-one individuals met inclusion criteria and had a total of 1648 imaging studies over the 3-year period. Subjects had a median of 5 (interquartile range [IQR] 2-10) CT scans, 20 (IQR 10-33) radiographs, 28.3 mSv (IQR 8.97-61.71) ionizing radiation, 0.2% (IQR 0.07-0.4) attributable risk of cancer, and $2979 (IQR 1560-5440) in charges using a national rate. The incidence of acute fracture or intracranial head injury was 55%, and 39% of the cohort had a history of moderate or severe traumatic brain injury. CONCLUSION: The remarkable use of imaging and occurrence of injury among these highly vulnerable and frequently encountered individuals compels further study to refine clinical practices through the development of evidence-based, effective interventions.

Supracerebellar transtentorial approach to the parahippocampal gyrus.

The supracerebellar transtentorial technique (SCTT) is a versatile approach that grants access to medial and basal temporal (MBT) regions without transgressing normal lateral cortex, damaging the hippocampus, or requiring significant brain retraction. This video illustrates the SCTT in resecting a cavernous malformation within the parahippocampal gyrus to alleviate associated epilepsy and preserve cognition. The authors outline the anatomical considerations, alternative approaches, positioning, craniotomy, and dural opening. They demonstrate how to access the supracerebellar space, elevate the dura toward the tentorial incisura, and resect the malformation. This video serves as a practical reference for management of MBT lesions via minimally invasive procedures.

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.