Buprenorphine/naloxone - one formulation that doesn't fit all: a case report.

BACKGROUND: Sublingual buprenorphine, approved for treatment of opioid use disorder since 2002, is most commonly available in co-formulation with naloxone. Naloxone is an opioid antagonist minimally absorbed when sublingual (SL) buprenorphine/naloxone is taken as prescribed; it is thought to reduce potential for misuse via intravenous administration. However, growing data and clinical experience demonstrate that previously accepted assumptions about the pharmacokinetics of these medications may not apply to all patients. CASE PRESENTATION: We present a patient whose adverse post-administration side effects on SL buprenorphine/naloxone resolved with transition to SL buprenorphine monoproduct. DISCUSSION: Naloxone can be detected in nearly all patients taking SL buprenorphine/naloxone, though with apparent variability in clinical effect. In a minority of patients, naloxone can contribute to adverse and potentially treatment-limiting side effects. Furthermore, the naloxone component is commonly misunderstood by patients and providers and can foster mistrust in the therapeutic relationship if providers are perceived to be withholding a more tolerable formulation. Prescribers should have a low threshold to offer buprenorphine alone when clinically appropriate.

Early Surgical Excision of Necrotic Tissue Following Unintentional Dermal Injection of Extended-Release Buprenorphine.

INTRODUCTION: Extended-release subcutaneous buprenorphine is an increasingly common treatment for opioid use disorder. Serious adverse events are rare and may be poorly understood. This report describes an early surgical intervention to address tissue necrosis resulting from misplaced subcutaneous buprenorphine injection. We review identifying characteristics that distinguish the necrotic reaction from other adverse effects of subcutaneous buprenorphine and offer guidance to continue treatment with subcutaneous buprenorphine. CASE REPORT: A 33-year-old patient returned to clinic within an hour of his buprenorphine injection, reporting pain and skin changes unlike his previous injections. Non blanching erythema consistent with early necrosis was evident, and the patient was referred for surgical removal of his buprenorphine depot. The patient had uncomplicated healing of the surgical site and was provided sublingual buprenorphine before returning to continue treatment with subcutaneous buprenorphine. DISCUSSION: Although skin necrosis is known to be a rare complication of subcutaneous buprenorphine injection, early surgical excision to limit injury has not been described. Signs and symptoms of skin necrosis must be better understood to facilitate early intervention and continued treatment. CONCLUSIONS: This case affirms that a patient may continue treatment with subcutaneous buprenorphine despite suffering skin necrosis and demonstrates the value of early surgical intervention after superficial placement of extended-release buprenorphine.

PrEP facilitators and barriers in substance use bridge clinics for women who engage in sex work and who use drugs.

BACKGROUND: Women who engage in sex work and use drugs (WSWUD) experience disproportionate HIV risks. Substance use treatment bridge clinics offer an opportunity to increase HIV pre-exposure prophylaxis (PrEP) delivery to WSWUD, but research on best practices is lacking. Therefore, we explored facilitators and barriers to PrEP across the PrEP care continuum in these settings. METHODS: Bridge clinic and affiliated harm reduction health service providers and WSWUD from Boston were recruited using passive and active outreach between December 2021 and August 2022. Participants were invited to take part in semi-structured phone or in-person interviews to explore HIV prevention and PrEP care experiences overall and within bridge clinic settings. Deductive codes were developed based on HIV risk environment frameworks and the Information-Motivation-Behavioral Skills model and inductive codes were added based on transcript review. Grounded content analysis was used to generate themes organized around the PrEP care continuum. RESULTS: The sample included 14 providers and 25 WSWUD. Most WSWUD were aware of PrEP and more than half had initiated PrEP at some point. However, most who initiated PrEP did not report success with daily oral adherence. Providers and WSWUD described facilitators and barriers to PrEP across the steps of the care continuum: Awareness, uptake, adherence, and retention. Facilitators for WSWUD included non-stigmatizing communication with providers, rapid wraparound substance use treatment and HIV services, having a PrEP routine, and service structures to support PrEP adherence. Barriers included low HIV risk perceptions and competing drug use and survival priorities. Provider facilitators included clinical note templates prompting HIV risk assessments and training. Barriers included discomfort discussing sex work risks, competing clinical priorities, and a lack of PrEP adherence infrastructure. CONCLUSION: WSWUD and bridge clinic providers favored integrated HIV prevention and substance use services in harm reduction and bridge clinic settings. Harm reduction and bridge clinic programs played a key role in HIV prevention and PrEP education for WSWUD. Effective behavioral and structural interventions are still needed to improve PrEP adherence for WSWUD.

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

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

Treating Benzodiazepine Withdrawal in a Bridge Clinic.

BACKGROUND: Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders. OBJECTIVE: Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic. METHODS: The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other secondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry. RESULTS: Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) and methamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8-43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%). CONCLUSIONS: Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes.

Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a rare paediatric lysosomal storage disorder, caused by the progressive accumulation of heparan sulphate, resulting in neurocognitive decline and behavioural abnormalities. Anecdotal reports from paediatricians indicate a more severe neurodegeneration in MPS IIIA patients, following infection, suggesting inflammation as a potential driver of neuropathology. To test this hypothesis, we performed acute studies in which WT and MPS IIIA mice were challenged with the TLR3-dependent viral mimetic poly(I:C). The challenge with an acute high poly(I:C) dose exacerbated systemic and brain cytokine expression, especially IL-1ß in the hippocampus. This was accompanied by an increase in caspase-1 activity within the brain of MPS IIIA mice with concomitant loss of hippocampal GFAP and NeuN expression. Similar levels of cell damage, together with exacerbation of gliosis, were also observed in MPS IIIA mice following low chronic poly(I:C) dosing. While further investigation is warranted to fully understand the extent of IL-1ß involvement in MPS IIIA exacerbated neurodegeneration, our data robustly reinforces our previous findings, indicating IL-1ß as a pivotal catalyst for neuropathological processes in MPS IIIA.

Post-Overdose Extended-Release Buprenorphine Initiation Facilitated by a Partnership Between Emergency Medical Services and an Outpatient Substance Use Disorder Observation Unit.

BACKGROUND: People who experience a nonfatal opioid overdose and receive naloxone are at high risk of subsequent overdose death but experience gaps in access to medications for opioid use disorder. The immediate post-naloxone period offers an opportunity for buprenorphine initiation. Limited data indicate that buprenorphine administration by emergency medical services (EMS) after naloxone overdose reversal is safe and feasible. We describe a case in which a partnership between a low-barrier substance use disorder (SUD) observation unit and EMS allowed for buprenorphine initiation with extended-release injectable buprenorphine after naloxone overdose reversal. CASE: A man in his 40's with severe opioid use disorder and numerous prior opioid overdoses experienced overdose in the community. EMS was activated and he was successfully resuscitated with intranasal naloxone, administered by bystanders and EMS. He declined emergency department (ED) transport and consented to transport to a 24/7 SUD observation unit. The patient elected to start buprenorphine due to barriers attending opioid treatment programs daily. His largest barrier was unsheltered homelessness. His severe opioid withdrawal symptoms were successfully treated with 16/4 mg sublingual buprenorphine/naloxone and 300 mg extended-release injectable buprenorphine (XR-buprenorphine), without precipitated withdrawal. Two weeks later, he reported no interval fentanyl use. DISCUSSION: We describe the case of a patient successfully initiated onto XR-buprenorphine in the immediate post-naloxone period via a partnership between an outpatient low-barrier addiction programs and EMS. Such partnerships offer promise in expanding buprenorphine access and medication choice, particularly for the high-risk population of patients who decline ED transport.

Validation and clinical discovery demonstration of breast cancer data from a real-world data extraction platform.

Objective: To validate and demonstrate the clinical discovery utility of a novel patient-mediated, medical record collection and data extraction platform developed to improve access and utilization of real-world clinical data. Materials and Methods: Clinical variables were extracted from the medical records of 1011 consented patients with breast cancer. To validate the extracted data, case report forms completed using the structured data output of the platform were compared to manual chart review for 50 randomly-selected patients with metastatic breast cancer. To demonstrate the platform's clinical discovery utility, we identified 194 patients with early-stage clinical data who went on to develop distant metastases and utilized the platform-extracted data to assess associations between time to distant metastasis (TDM) and early-stage tumor histology, molecular type, and germline BRCA status. Results: The platform-extracted data for the validation cohort had 97.6% precision (91.98%-100% by variable type) and 81.48% recall (58.15%-95.00% by variable type) compared to manual chart review. In our discovery cohort, the shortest TDM was significantly associated with metaplastic (739.0 days) and inflammatory histologies (1005.8 days), HR-/HER2- molecular types (1187.4 days), and positive BRCA status (1042.5 days) as compared to other histologies, molecular types, and negative BRCA status, respectively. Multivariable analyses did not produce statistically significant results. Discussion: The precision and recall of platform-extracted clinical data are reported, although specificity could not be assessed. The data can generate clinically-relevant insights. Conclusion: The structured real-world data produced by a novel patient-mediated, medical record-extraction platform are reliable and can power clinical discovery.

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

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

Obesity and Associated Outcomes for Blunt vs Penetrating Mechanism in Trauma Laparotomy Patients.

Obesity in trauma patients is an established risk factor contributing to postoperative complications, but the relationship between body mass index (BMI) and trauma patient outcomes is not well-defined, especially when stratified by mechanism of injury. We surveyed the trauma laparotomy registry at an academic level 1 trauma center over a 3-year period to identify mortality, injury severity score, and hospital length of stay (hLOS) outcome measures across BMI classes, with further stratification by mechanism of injury: blunt vs penetrating trauma. A total of 442 patients were included with mean age 44.6 (SD = 18.7) and mean BMI 28.55 (SD = 7.37). These were subdivided into blunt trauma (n = 313) and penetrating trauma (n = 129). Within the blunt trauma subgroup, the hLOS among patients who survived hospitalization significantly increased 9% for each successive BMI class (P = .022, 95% CI = 1.29-17.5). We conclude that successive increase in BMI class is associated with longer hospital stay for blunt trauma patient survivors requiring laparotomy, though additional analysis is needed to establish this relationship to other outcome measures and among penetrating trauma patients.

Addressing Unmet PrEP Needs in Women: Impact of a Laboratory-Driven Protocol at an Urban, Essential Hospital.

Background: HIV pre-exposure prophylaxis (PrEP) uptake in women remains low. We developed a laboratory result-driven protocol to link women with a positive bacterial sexually transmitted infection (STI) to HIV PrEP at an urban safety-net hospital. Methods: Electronic health records of women with positive chlamydia, gonorrhea, and/or syphilis tests were reviewed, and those eligible for PrEP were referred for direct or primary care provider-driven outreach. We assessed the proportion of women with STIs who received PrEP offers, acceptance, and prescriptions before (July 1, 2018-December 31, 2018) and after (January 1, 2019-June 30, 2020) implementation to evaluate changes in the delivery of key elements of the PrEP care cascade (ie, PrEP offers, acceptance, and prescribing) for women with STIs after protocol implementation. Results: The proportion of women who received PrEP offers increased from 7.6% to 17.6% (P < .001). After multivariable adjustment, only the postintervention period was associated with PrEP offers (odds ratio [OR], 2.49; 95% CI, 1.68-3.68). In subgroup analyses, PrEP offers increased significantly among non-Hispanic Black (OR, 2.75; 95% CI, 1.65-4.58) and Hispanic (OR, 5.34; 95% CI, 1.77-16.11) women but not among non-Hispanic White women (OR, 1.49; 95% CI, 0.54-4.05). Significant changes in PrEP acceptance and prescriptions were not observed in the sample overall. Conclusions: A laboratory result-driven protocol was associated with a significant increase in PrEP offers to Black and Hispanic women with STI. These results provide concrete suggestions for health systems seeking to increase PrEP access and equity among women.

Novel Uses of Methadone Under the "72-Hour Rule" to Facilitate Transitions of Care and Low-Dose Buprenorphine Induction in an Outpatient Bridge Clinic.

BACKGROUND: Federal regulations restrict methadone for opioid use disorder (OUD) treatment to licensed opioid treatment programs (OTPs). However, providers in other settings can administer methadone for opioid withdrawal under the "72-hour rule" while linking to further care. Prior work has demonstrated that methadone initiation in a low-barrier bridge clinic is associated with high OTP linkage and 1-month retention rates. We describe 2 other novel applications of the 72-hour rule in which methadone withdrawal management facilitated linkage to inpatient hospitalization and outpatient buprenorphine induction. CASE PRESENTATIONS: Patient 1 was a 46-year-old woman with OUD complicated by serious injection-related infections. Severe opioid withdrawal limited her ability to tolerate emergency department wait times and receive inpatient care. We administered methadone for opioid withdrawal in an outpatient bridge clinic immediately before emergency department referral; this enabled hospital admission for intravenous antibiotics and anticoagulation. Patient 2 was a 36-year-old man with OUD desiring buprenorphine treatment. He had been unable to complete traditional buprenorphine induction without experiencing precipitated withdrawal. Thus, we recommended a low-dose buprenorphine induction overlapping with a full opioid agonist. Given the patient's preference to stop using fentanyl immediately, he received 72 hours of methadone for withdrawal treatment during the induction phase and successfully transitioned to buprenorphine without significant concomitant fentanyl use. CONCLUSION: In addition to facilitating OTP linkage, on-demand 72-hour methadone administration for opioid withdrawal can reduce barriers to acute medical care and buprenorphine treatment.

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

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

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

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

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

Understanding the Strengths and Limitations of Current Methods for Surveying Partner Nation Medical Facilities.

INTRODUCTION: During exercises or operations, there may be times when U.S. medical capabilities are not available and the next best or only option may be to use partner nation (PN) or host nation capabilities. Joint Publication 4-02 Joint Health Services states that "medical planners should always consider the quality, suitability, and availability of multinational and host-nation support." It is normal practice for medical planners to survey PN medical capabilities as part of the pre-deployment planning process. Currently, medical capability surveys are not conducted in a consistent and systematic manner across the DoD global health engagement enterprise. The lack of a systematic approach undermines medical operations planners' ability to conduct efficient and adequate pre-deployment surveys. MATERIALS AND METHODS: The article presents the results of a descriptive analysis of 62 unclassified medical capability surveys of PN or host nation facilities from the U.S. Africa Command (USAFRICOM) area of responsibility that were conducted by U.S. DoD personnel. The team characterized the content and formats of surveys with respect to what medical capabilities were described, how the capabilities were described, and how the information was presented. These analyses focused on determining if a surveyor obtained information about a capability, not whether or not the facility had a capability. RESULTS: Approximately 75-80% of surveys included information describing the presence or absence of five key capabilities: Emergency department/trauma care, surgical services, intensive care unit, laboratory, and imaging. Conversely, 30-50% of surveys did not include any information describing the presence or absence of five other key capabilities: Pharmacy, blood bank, mass casualty plans, land evacuation, or air evacuation. Information on key capabilities and administrative information was not consistently reported across the sample of surveys. There was substantial variation in how capabilities were characterized, including number of staff, staff training, and available equipment. Additionally, the order in which information was presented in surveys varied within and across components. CONCLUSIONS: There are significant inconsistencies in the types of capabilities and services documented and how the quality of the capabilities and services is characterized. These inconsistencies can be attributed, in part, to the absence of information that explicitly confirmed whether or not the facility had a capability. Such variation results in obscured or incomplete depictions of facility capabilities, thereby undermining the ability of medical planners to coordinate effective medical readiness for engagements, exercises, or real-life operations. Guidance and survey templates could support better-informed decision-making by including information about survey methods and documenting the lack of confirmatory information. The DoD enterprise should consider how guidance and a standard survey template could improve the relevance, accuracy, and efficiency of data collection and reporting.

Intranasal Naloxone for Opioid Overdose.

This JAMA Insights describes indications for naloxone use in preventing opioid overdoses and benefits vs barriers to its availability following FDA approval of its availability without a prescription.

Mobile treatment for opioid use disorder: Implementation of community-based, same-day medication access interventions.

BACKGROUND: Medications for Opioid Use Disorder (MOUD) are lifesaving, but <20 % of individuals in the US who could benefit receive them. As part of the NIH-supported HEALing Communities Study (HCS), coalitions in several communities in Massachusetts and Ohio implemented mobile MOUD programs to overcome barriers to MOUD receipt. We defined mobile MOUD programs as units that provide same-day access to MOUD at remote sites. We aimed to (1) document the design and organizational structure of mobile programs providing same-day or next-day MOUD, and (2) explore the barriers and facilitators to implementation as well as the successes and challenges of ongoing operation. METHODS: Program staff from five programs in two states (n = 11) participated in semi-structured interviews. Two authors conducted thematic analysis of the transcripts based on the domains of the social-ecological model and the semi-structured interview guide. RESULTS: Mobile MOUD units sought to improve immediate access to MOUD ("Our answer is pretty much always, 'Yes, we'll get you started right here, right now,'"), advance equity ("making sure that we have staff who speak other languages, who are on the unit and have some resources that are in different languages,"), and decrease opioid overdose deaths. Salient program characteristics included diverse staff, including staff with lived experience of substance use ("She just had that personal knowledge of where we should be going"). Mobile units offered harm reduction services, broad medical services (in particular, wound care), and connection to transportation programs and incorporated consistency in service provision and telemedicine access. Implementation facilitators included trusting relationships with partner organizations (particularly pharmacies and correctional facilities), nuanced understanding of local politics, advertising, protocol flexibility, and on-unit prescriber hours. Barriers included unclear licensing requirements, staffing shortages and competing priorities for staff, funding challenges due to inconsistency in grant funding and low reimbursement ("It's not really possible that billing in and of itself is going to be able to sustain it"), and community stigma toward addiction services generally. CONCLUSIONS: Despite organizational, community, and policy barriers, participants described mobile MOUD units as an innovative way to expand access to life-saving medications, promote equity in MOUD treatment, and overcome stigma.

Sustained long-term disease correction in a murine model of MPSII following stem cell gene therapy.

Mucopolysaccharidosis type II (MPSII) is a pediatric lysosomal storage disease caused by deficiencies in the IDS (iduronate-2-sulfatase) gene resulting in accumulation of glycosaminoglycans, multisystem disease, and profound neurodegeneration in severe forms. Although enzyme replacement therapy is available for somatic forms of disease, the inability of native IDS to pass the blood-brain barrier renders it ineffective for the brain. We previously demonstrated the short-term efficacy of a brain-targeted hematopoietic stem cell gene therapy approach to treat MPSII mice using lentiviral IDS fused to the blood-brain-barrier-crossing peptide ApoEII (IDS.ApoEII) in comparison with a lentivirus expressing native IDS and an unmanipulated bone marrow transplant. Here we evaluated the longevity of disease correction for 12-16 months following treatment. We observed sustained IDS enzyme activity in organs of long-term IDS.ApoEII-treated MPSII mice, similar to those analyzed 6 months post-treatment, with continued clearance of storage material in the brain and peripheral organs, maintained correction of astrogliosis, microgliosis, and correction of altered cytokines and chemokines. IDS.ApoEII also significantly reduced retinal atrophy, characteristic of MPSII. Overall, IDS.ApoEII resulted in systemic prevention of the MPSII phenotype, with no observed toxicity following treatment. This provides evidence of the sustained efficacy and safety of this treatment ahead of a recently opened clinical trial.

Facilitating exit from encampments: combining low-barrier transitional housing with stabilizing treatment for substance related problems.

BACKGROUND: Tent encampments in the neighborhood surrounding Boston Medical Center (BMC) grew to include 336 individuals at points between 2019 and 21, prompting public health concerns. BMC, the City of Boston, and Commonwealth of Massachusetts partnered in 2/2022 to offer low-barrier transitional housing to encampment residents and provide co-located clinical stabilization services for community members with substance use disorders (SUDs) experiencing homelessness. METHODS: To meet the needs of some of the people who had been living in encampments, BMC established in a former hotel: 60 beds of transitional housing, not contingent upon sobriety; and a low-barrier SUD-focused clinic for both housing residents and community members, offering walk-in urgent care, SUD medications, and infection screening/prevention; and a 24/7 short-stay stabilization unit to manage over-intoxication, withdrawal, and complications of substance use (e.g., abscesses, HIV risk, psychosis). A secure medication-dispensing cabinet allows methadone administration for withdrawal management. Housing program key metrics include retention in housing, transition to permanent housing, and engagement in SUD treatment and case management. Clinical program key metrics include patient volume, and rates of initiation of medication for opioid use disorder. RESULTS: Housing: Between 2/1/22-1/31/2023, 100 people entered the low-barrier transitional housing (new residents admitted as people transitioned out); 50 former encampment residents and 50 unhoused people referred by Boston Public Health Commission. Twenty-five residents transferred to permanent housing, eight administratively discharged, four incarcerated, and four died (two overdoses, two other substance-related). The remaining 59 residents remain housed; none voluntarily returned to homelessness. One hundred residents (100%) engaged with case management, and 49 engaged with SUD treatment. CLINICAL: In the first 12 months, 1722 patients (drawn from both the housing program and community) had 7468 clinical visits. The most common SUDs were opioid (84%), cocaine (54%) and alcohol (47%) and 61% of patients had a co-occurring mental health diagnosis in the preceding 24-months. 566 (33%) patients were started on methadone and accepted at an Opioid Treatment Program (OTP). CONCLUSIONS: During the 1st year of operation, low-barrier transitional housing plus clinical stabilization care was a feasible and acceptable model for former encampment residents, 49% of whom engaged with SUD treatment, and 25% of whom transitioned to permanent housing.

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

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