Adolescent Residential Addiction Treatment In The US: Uneven Access, Waitlists, And High Costs.

Drug overdose deaths among adolescents are increasing in the United States. Residential treatment facilities are one treatment option for adolescents with substance use disorders, yet little is known about their accessibility or cost. Using the Substance Abuse and Mental Health Services Administration's treatment locator and search engine advertising data, we identified 160 residential addiction treatment facilities that treated adolescents with opioid use disorder as of December 2022. We called facilities while role-playing as the aunt or uncle of a sixteen-year-old child with a recent nonfatal overdose, to inquire about policies and costs. Eighty-seven facilities (54.4 percent) had a bed immediately available. Among sites with a waitlist, the mean wait time for a bed was 28.4 days. Of facilities providing cost information, the mean cost of treatment per day was $878. Daily costs among for-profit facilities were triple those of nonprofit facilities. Half of facilities required up-front payment by self-pay patients. The mean up-front cost was $28,731. We were unable to identify any facilities for adolescents in ten states or Washington, D.C. Access to adolescent residential addiction treatment centers in the United States is limited and costly.

Substance use disorder treatment and technology access among people who use drugs in rural areas of the United States: A cross-sectional survey.

PURPOSE: To evaluate how technology access affected substance use disorder (SUD) treatment prior to COVID-19 for people who use drugs in rural areas. METHODS: The Rural Opioid Initiative (January 2018-March 2020) was a cross-sectional study of people with prior 30-day injection drug or nonprescribed opioid use from rural areas of 10 states. Using multivariable mixed-effect regression models, we examined associations between participant technology access and SUD treatment. FINDINGS: Of 3,026 participants, 71% used heroin and 76% used methamphetamine. Thirty-five percent had no cell phone and 10% had no prior 30-day internet use. Having both a cell phone and the internet was associated with increased days of medication for opioid use disorder (MOUD) use (aIRR 1.29 [95% CI 1.11-1.52]) and a higher likelihood of SUD counseling in the prior 30 days (aOR 1.28 [95% CI 1.05-1.57]). Lack of cell phone was associated with decreased days of MOUD (aIRR 0.77 [95% CI 0.66-0.91]) and a lower likelihood of prior 30-day SUD counseling (aOR 0.77 [95% CI 0.62-0.94]). CONCLUSIONS: Expanding US rural SUD treatment engagement via telemedicine may require increased cell phone and mobile network access.

A novel rhesus macaque model of Huntington's disease recapitulates key neuropathological changes along with motor and cognitive decline.

We created a new nonhuman primate model of the genetic neurodegenerative disorder Huntington's disease (HD) by injecting a mixture of recombinant adeno-associated viral vectors, serotypes AAV2 and AAV2.retro, each expressing a fragment of human mutant HTT (mHTT) into the caudate and putamen of adult rhesus macaques. This modeling strategy results in expression of mutant huntingtin protein (mHTT) and aggregate formation in the injected brain regions, as well as dozens of other cortical and subcortical brain regions affected in human HD patients. We queried the disruption of cortico-basal ganglia circuitry for 30 months post-surgery using a variety of behavioral and imaging readouts. Compared to controls, mHTT-treated macaques developed working memory decline and progressive motor impairment. Multimodal imaging revealed circuit-wide white and gray matter degenerative processes in several key brain regions affected in HD. Taken together, we have developed a novel macaque model of HD that may be used to develop disease biomarkers and screen promising therapeutics.

Assessing Student Readiness to Work with People Who Use Drugs: Development of a Multi-disciplinary Addiction Educational Survey.

BACKGROUND: As health profession schools implement addiction curricula, they need survey instruments to evaluate the impact of the educational interventions. However, existing measures do not use current non-stigmatizing language and fail to capture core concepts. OBJECTIVE: To develop a brief measure of health profession student readiness to work with people who use drugs (PWUDs) and establish its content validity. METHODS: We conducted a literature review of existing instruments and desired clinical competencies related to providing care to PWUD and used results and expert feedback to create and revise a pool of 72 items. We conducted cognitive interviews with ten pre-clinical health profession students from various US schools of nursing, pharmacy, and medicine to ensure the items were easy to understand. Finally, we used a modified Delphi process with twenty-four health professions educators and addiction experts (eight each from nursing, pharmacy, and medicine) to select items for inclusion in the final scale. We analyzed expert ratings of individual items and interdisciplinary agreement on ratings to decide how to prioritize items. We ultimately selected 12 attitudes and 12 confidence items to include in the REadiness to Discuss Use, Common Effects, and HArm Reduction Measure (REDUCE-HARM). Experts rated their overall assessment of the final scale. RESULTS: Twenty-two of twenty-four experts agreed or strongly agreed that the attitudes scale measures student attitudes that impact readiness to work with PWUDs. Twenty-three of twenty-four experts agreed or strongly agreed that the confidence scale measures student self-efficacy in competencies that impact readiness to work with PWUDs. Seven of 72 initial items and none of the 24 selected items had statistically significant differences between disciplines. CONCLUSIONS: The REDUCE-HARM instrument has strong content validity and may serve as a useful tool in evaluating addiction education. Additional research is needed to establish its reliability, construct validity, and responsiveness to change.

Global Oral Anticoagulation Use Varies by Region in Patients With Recent Diagnosis of Atrial Fibrillation: The GLORIA-AF Phase III Registry.

Background Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent-onset AF enrolled in a large global registry. Methods and Results Eligible participants were recruited into GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation), a prospective observational cohort study from 2014 to 2016 in 4 international regions: North America, Europe, Asia, and Latin America. Cumulative incidence functions were generated for direct OACs (DOAC), vitamin K antagonists, and antiplatelet drugs considering competing risks, stratified by region and type of site. Time-to-treatment initiation after AF diagnosis was analyzed with Fine-Gray subdistribution hazard models. A total of 21 237 patients eligible for analysis were identified. By 30 days after AF diagnosis, 40%, 16%, and 8.6% of patients had DOAC, vitamin K antagonists, and antiplatelet drugs initiated, respectively. Earlier initiation of DOACs was observed in Europe, with Asia and Latin America having lower hazard rates of DOAC time-to-treatment initiation than Europe (hazard ratio [HR], 0.66; 95% CI, 0.62-0.70 and HR, 0.79; 95% CI, 0.73-0.85, respectively). DOAC initiation was highest in community hospitals, vitamin K antagonists in outpatient health care centers/anticoagulation clinics, and antiplatelet drugs in primary care clinics. Conclusions Important geographic variability exists with the use of OACs for patients with AF. Differences in the time-to-treatment initiation of OAC by type of site suggests suboptimal implementation of guideline recommendations and could result in less benefit and more harm. Optimizing OAC use for patients with AF may improve outcomes and reduce health care costs. Registration URL: http://www.clinicaltrials.gov; Unique identifiers: NCT01468701, NCT01671007.

Low-dose Buprenorphine Initiation in Hospitalized Adults With Opioid Use Disorder: A Retrospective Cohort Analysis.

OBJECTIVES: Patients with opioid use disorder (OUD) can initiate buprenorphine without requiring a withdrawal period through a low-dose (sometimes referred to as "micro-induction") approach. Although there is growing interest in low-dose buprenorphine initiation, current evidence is limited to case reports and small case series. METHODS: We performed a retrospective cohort study of patients with OUD seen by a hospital-based addiction medicine consult service who underwent low-dose buprenorphine initiation starting during hospital admission. We then integrated our practice-based experiences with results from the existing literature to create practice considerations. RESULTS: Sixty-eight individuals underwent 72 low-dose buprenorphine initiations between July 2019 and July 2020. Reasons for low-dose versus standard buprenorphine initiation included co-occurring pain (91.7%), patient anxiety around the possibility of withdrawal (69.4%), history of precipitated withdrawal (9.7%), opioid withdrawal intolerance (6.9%), and other reason/not specified (18.1%). Of the 72 low-dose buprenorphine initiations, 50 (69.4%) were completed in the hospital, 9 (12.5%) transitioned to complete as an outpatient, and 13 (18.1%) were terminated early. We apply our experiences and findings from literature to recommendations for varied clinical scenarios, including acute illness, co-occurring pain, opioid withdrawal intolerance, transition from high dose methadone to buprenorphine, history of precipitated withdrawal, and rapid hospital discharge. We share a standard low-dose initiation protocol with potential modifications based on above scenarios. CONCLUSIONS: Low-dose buprenorphine initiation offers a well-tolerated and versatile approach for hospitalized patients with OUD. We share lessons from our experiences and the literature, and provide practical considerations for providers.

Correlates of days of medication for opioid use disorder exposure among people living with HIV in Northern Vietnam.

BACKGROUND: In Vietnam, access to medications for opioid use disorder (MOUD) for people living with HIV has rapidly expanded, but MOUD use over time remains low. We sought to assess factors associated with days of MOUD treatment exposure. METHODS: From 2015 to 2019, patients with OUD in six Northern Vietnamese HIV clinics were randomized to receive HIV clinic-based buprenorphine (BUP/NX) or referral for methadone maintenance therapy (MMT) and followed for 12 months. All MOUD doses were directly observed and abstracted from dosing logs. The primary outcome was days of MOUD treatment exposure (buprenorphine or methadone) received over 12 months. Negative binomial regression modelled associations with days of MOUD exposure. RESULTS: Of 281 participants, 264 (94%) were eligible for analysis. Participants were primarily male (97%), unmarried (61%), employed (54%), and previously arrested (83%). Participants had a mean 187 (SD 150) days of MOUD exposure with 134 (51%) having at least 180 days, and 35 (13.2%) having at least 360 days of MOUD exposure. Age (IRR 1.26, 95% CI 1.02-1.55), income (IRR 0.96, 95% CI 0.93-1.001), and methadone (IRR 1.88, 95% CI 1.51-2.42) were associated with MOUD exposure in multivariate models. Multivariate models predicted 127 (95% CL 109-147) days of MOUD exposure for HIV clinic based-buprenorphine vs 243 (95% CL 205-288) for MMT. CONCLUSION: MOUD treatment exposure was suboptimal among patients with HIV and OUD in Northern Vietnam and was influenced by several factors. Interventions to support populations at risk of lower MOUD exposure as well programs administering MOUD should be considered in countries seeking to expand access to MOUD.

Assessing effective mask use by the public in two countries: an observational study.

OBJECTIVES: During the COVID-19 pandemic wearing a mask in public has been recommended in some settings and mandated in others. How often this advice is followed, how well, and whether it inadvertently leads to more disease transmission opportunities due to a combination of improper use and physical distancing lapses is unknown. DESIGN: Cross-sectional observational study performed in June-August 2020. SETTING: Eleven outdoor and indoor public settings (some with mandated mask use, some without) each in Toronto, Ontario, and in Portland, Oregon. PARTICIPANTS: All passers-by in the study settings. OUTCOME MEASURES: Mask use, incorrect mask use, and number of breaches (ie, coming within 2 m of someone else where both parties were not properly masked). RESULTS: We observed 36 808 persons, the majority of whom were estimated to be aged 31-65 years (49%). Two-thirds (66.7%) were wearing a mask and 13.6% of mask-wearers wore them incorrectly. Mandatory mask-use settings were overwhelmingly associated with mask use (adjusted OR 79.2; 95% CI 47.4 to 135.1). Younger age, male sex, Torontonians, and public transit or airport settings (vs in a store) were associated with lower adjusted odds of wearing a mask. Mandatory mask-use settings were associated with lower adjusted odds of mask error (OR 0.30; 95% CI 0.14 to 0.73), along with female sex and Portland subjects. Subjects aged 81+ years (vs 31-65 years) and those on public transit and at the airport (vs stores) had higher odds of mask errors. Mask-wearers had a large reduction in adjusted mean number of breaches (rate ratio (RR) 0.19; 95% CI 0.17 to 0.20). The 81+ age group had the largest association with breaches (RR 7.77; 95% CI 5.32 to 11.34). CONCLUSIONS: Mandatory mask use was associated with a large increase in mask-wearing. Despite 14% of them wearing their masks incorrectly, mask users had a large reduction in the mean number of breaches (disease transmission opportunities). The elderly and transit users may warrant public health interventions aimed at improving mask use.

Understanding the impact of the SARS-COV-2 pandemic on hospitalized patients with substance use disorder.

BACKGROUND: The SARS-COV-2 pandemic rapidly shifted dynamics around hospitalization for many communities. This study aimed to evaluate how the pandemic altered the experience of healthcare, acute illness, and care transitions among hospitalized patients with substance use disorder (SUD). METHODS: We performed a qualitative study at an academic medical center in Portland, Oregon, in Spring 2020. We conducted semi-structured interviews, and conducted a thematic analysis, using an inductive approach, at a semantic level. RESULTS: We enrolled 27 participants, and identified four main themes: 1) shuttered community resources threatened patients' basic survival adaptations; 2) changes in outpatient care increased reliance on hospitals as safety nets; 3) hospital policy changes made staying in the hospital harder than usual; and, 4) care transitions out of the hospital were highly uncertain. DISCUSSION: Hospitalized adults with SUD were further marginalized during the SARS-COV-2 pandemic. Systems must address the needs of marginalized patients in future disruptive events.

Practice Gap in Atrial Fibrillation Oral Anticoagulation Prescribing at Emergency Department Home Discharge.

INTRODUCTION: Current U.S. cardiology guidelines recommend oral anticoagulation (OAC) to reduce stroke risk in selected patients with atrial fibrillation (AF), but no formal AF OAC recommendations exist to guide emergency medicine clinicians in the acute care setting. We sought to characterize emergency department (ED) OAC prescribing practices after an ED AF diagnosis. METHODS: This retrospective study included index visits for OAC-naive patients ≥18 years old who were discharged home from the ED at an urban, academic, tertiary hospital with a primary diagnosis of AF from 2012-2014. Five hypothesis-blinded, chart reviewers abstracted data from patient problem lists and medical history in the electronic health record to assess stroke (CHA2DS2-VASc) and bleeding risk (HAS-BLED). The primary outcome was the provision of an OAC prescription at discharge in OAC-naive patients with high stroke risk. Descriptive statistics and multivariable logistic regression assessed associations between OAC prescription and patient characteristics. RESULTS: We included 138 patient visits in our analysis, of whom 39.9% (n = 55) were low stroke risk (CHA2DS2-VASc = 0 in males and 1 in females), 15.9% (n = 22) were intermediate risk (CHA2DS2-VASc = 1 in males), and 44.2% (n = 61) were high risk (CHA2DS2-VASc ≥ 2). Of patients with high stroke risk and low-to-intermediate bleeding risk (n = 57), 80.7% were not prescribed an OAC at discharge. Cardiology consultation and female gender, but not stroke risk (CHA2DS2-VASc score), were predictors of an ED provider prescribing an OAC to an OAC-naive AF patient at ED discharge. CONCLUSION: The majority of OAC-eligible patients were discharged home without an OAC prescription. In OAC-naive patients discharged home from the ED, cardiology consultation and female gender were associated with OAC prescription. Our findings suggest that access to expert opinion may improve provider comfort with OAC prescribing and highlight the need for improved guidelines specific to ED-management of AF.

Intra-striatal AAV2.retro administration leads to extensive retrograde transport in the rhesus macaque brain: implications for disease modeling and therapeutic development.

Recently, AAV2.retro, a new capsid variant capable of efficient retrograde transport in brain, was generated in mice using a directed evolution approach. However, it remains unclear to what degree transport will be recapitulated in the substantially larger and more complex nonhuman primate (NHP) brain. Here, we compared the biodistribution of AAV2.retro with its parent serotype, AAV2, in adult macaques following delivery into the caudate and putamen, brain regions which comprise the striatum. While AAV2 transduction was primarily limited to the injected brain regions, AAV2.retro transduced cells in the striatum and in dozens of cortical and subcortical regions with known striatal afferents. We then evaluated the capability of AAV2.retro to deliver disease-related gene cargo to biologically-relevant NHP brain circuits by packaging a fragment of human mutant HTT, the causative gene mutation in Huntington's disease. Following intra-striatal delivery, pathological mHTT-positive protein aggregates were distributed widely among cognitive, motor, and limbic cortico-basal ganglia circuits. Together, these studies demonstrate strong retrograde transport of AAV2.retro in NHP brain, highlight its utility in developing novel NHP models of brain disease and suggest its potential for querying circuit function and delivering therapeutic genes in the brain, particularly where treating dysfunctional circuits, versus single brain regions, is warranted.

AAV-PHP.B Administration Results in a Differential Pattern of CNS Biodistribution in Non-human Primates Compared with Mice.

The ability of recombinant adeno-associated virus (AAV) to deliver transgenes to the CNS has allowed for several advancements in the field of gene therapy to treat brain disorders. Although most AAVs do not readily cross the blood-brain barrier and transduce the CNS following peripheral administration, AAV-PHP.B has recently been shown to transduce brains of mice with higher efficiency compared with its parent serotype, AAV9, following injection into the retro-orbital sinus. Here, we extended this foundational work by comparing AAV-PHP.B transduction efficiency in wild-type C57BL/6J mice using four clinically applicable delivery strategies including two intravascular (intra-jugular vein and intra-carotid artery) and two intra-cerebral spinal fluid (CSF) routes (intra-cisterna magna and intra-lateral ventricle). We scaled up these comparisons in a larger-animal model and evaluated transduction efficiency of AAV-PHP.B in the rhesus macaque. We found widespread and largely equal CNS transduction in mice following all four injection strategies, whereas we observed a differential pattern of transduction in macaques with broad cortical and spinal cord transduction seen after intrathecal administration and only very low transduction following intravascular administration. Taken together, these results suggest that AAV-PHP.B may be a useful gene therapy vector for neurological disorders, particularly those stemming from broad cortical or spinal cord neuropathology.

Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma.

Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.