Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.

Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic. We demonstrate that monocytes differentiated by macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) resembled in vivo inflammatory macrophages, while moDCs resembled in vivo inflammatory DCs. Moreover, differentiated monocytes presented with profound transcriptomic, phenotypic, and functional differences. Monocytes integrated GM-CSF and IL-4 stimulation combinatorically and temporally, resulting in a mode- and time-dependent differentiation relying on NCOR2. Finally, moDCs are phenotypically heterogeneous and therefore necessitate the use of high-dimensional phenotyping to open new possibilities for better clinical tailoring of these cellular therapies.

Enolase represents a metabolic checkpoint controlling the differential exhaustion programmes of hepatitis virus-specific CD8+ T cells.

OBJECTIVE: Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction. DESIGN: Metabolic state, exhaustion and transcriptome of virus-specific CD8+ T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52) were determined ex vivo and during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were tested in vitro. Intrahepatic virus-specific CD8+ T cells were analysed by scRNA-Seq in a HBV-replicating murine in vivo model of acute and chronic infection. RESULTS: HBV-specific (core18-27, polymerase455-463) and HCV-specific (NS31073-1081, NS31406-1415, NS5B2594-2602) CD8+ T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase455-463 -specific CD8+ T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core18-27-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8+ T cells in a murine model of chronic infection. CONCLUSION: Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.

Implementation of the 'PicNic' handover huddle: A quality improvement project to improve the transition of infants between paediatric and neonatal intensive care units.

AIMS: Thorough handover and effective communication are crucial to the transfer of clinical information between different intensive care units. Following a sentinel patient safety event, an improvement project was initiated to reduce patient safety risks associated with the transfer of complex patients between the neonatal and paediatric intensive care. METHODS: A handover tool was implemented over a 4-month period, guiding handover through means of a handover huddle. The tool ensured a full ISBAR (Introduction, Situation, Background, Assessment, Response) handover, with a specified attendance register. It acknowledged specific safety points inclusive of outstanding investigations, procedural history and medication transcription. Post implementation, huddle checklist sheets were audited for compliance and a staff satisfaction survey was conducted. RESULTS: Thirty-nine handovers took place during this trial period, of which 69% were captured in the huddle process. Senior medical and nursing staff attendance was greater than 95% throughout the process, and 100% of huddles attended to a full ISBAR handover. Sixty staff satisfaction survey responses were received, 90% of which identified the process to improve the safety of patient handover. Responses also identified safety issues such as discontinuity of medication transcription between the units, and inappropriate patient transfers occurring outside of working hours. Qualitative feedback highlighted how the tool improved interdepartmental educational and collaboration opportunities. CONCLUSIONS: The 'PicNic' huddle effectively facilitated a standardised handover between paediatric and neonatal intensive care. It also recognised the importance of interdepartmental collaboration and education surrounding culturally different clinical practices. Further improvement cycles continue to progress the tool and initiate a digital format for ongoing use.

Family factors and health-related quality of life within 6 months of completion of childhood cancer treatment.

OBJECTIVE: The transition from active cancer treatment to survivorship represents a period of uncertainty for youth and their families, but factors associated with adaptation during this period are understudied. We evaluated associations among cancer and treatment-related variables, family factors (family functioning, caregiver health-related quality of life [HRQL], and caregiver distress), and patient HRQL after treatment completion. We assessed the indirect effects of neurocognitive difficulties on youth HRQL through family factors. METHODS: One hundred fifty-four caregivers (of patients' ages 0-18 years) and 52 youth (ages 7-18 years) completed questionnaires assessing family factors, neurocognitive difficulties, and HRQL for patients within 6 months following treatment completion. Electronic health records were reviewed for cancer and treatment-related information. Bootstrapping analyses assessed whether neurocognitive function had indirect effects on HRQL through family factors. RESULTS: Family factors were associated with self- and caregiver reports of children's HRQL. Controlling for demographic, cancer, and treatment covariates, caregiver reports of their child's neurocognitive difficulties had an indirect effect on their reports of child physical HRQL through family functioning. Caregiver reports of their child's neurocognitive difficulties indirectly related to caregiver reports of child psychosocial HRQL through family functioning and caregiver HRQL. Indirect effects for self-reported neurocognitive difficulties and HRQL were not supported. CONCLUSIONS: Findings highlight the need for routine psychosocial screening for youth and caregiver reports of family adjustment and HRQL during the transition off treatment. Providers are encouraged to offer interventions matched to specific needs for families at risk for poor family functioning to improve patient outcomes as they transition off treatment.

Feasibility and Safety of Outpatient Parenteral Antimicrobial Therapy in Conjunction With Addiction Treatment for People Who Inject Drugs.

BACKGROUND: Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections. METHODS: This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment. RESULTS: Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported. CONCLUSIONS: Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections.

Impact of Medications for Opioid Use Disorder on Discharge Against Medical Advice Among People Who Inject Drugs Hospitalized for Infective Endocarditis.

BACKGROUND AND OBJECTIVES: The impact of medications for opioid use disorder (MOUD) on against medical advice (AMA) discharges among people who inject drugs (PWID) hospitalized for endocarditis is unknown. METHODS: A retrospective review of all PWID hospitalized for endocarditis at our institution between 2016 and 2018 (n = 84). RESULTS: PWID engaged with MOUD at admission, compared with those who were not, were less likely to be discharged AMA but this did not reach statistical significance in adjusted analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.033-1.41; P = .11). Among out-of-treatment individuals, newly initiating MOUD did not lead to significantly fewer AMA discharges (OR, 0.98; 95% CI, 0.26-3.7; P = .98). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: PWID hospitalized for endocarditis are at high risk for discharge AMA but more research is needed to understand the impact of MOUD. (Am J Addict 2020;29:155-159).

Sexual Orientation, Religious Coping, and Drug Use in a Sample of HIV-Infected African-American Men Living in the Southern USA.

Religiosity and spirituality are associated with reduced drug use in the general population, but it is unclear whether this relationship generalizes to sexual minorities. This study investigated the relationship between religious coping, drug use, and sexual orientation in a sample of HIV-infected African-American men (40 heterosexuals; 64 sexual minorities). Most participants (76%) reported being "moderately" or "very" religious. We found no main effect of religious coping or sexual orientation on frequency of drug use. However, there was an interaction between positive religious coping and sexual orientation. Among heterosexuals, positive religious coping was inversely associated with frequency of drug use. However, this relationship was not significant among sexual minorities. Findings suggest HIV-infected African-American sexual minorities living in the South may need additional coping resources to decrease vulnerability to drug use.

A Comparison of Motivations for Marijuana Use in HIV-Positive and HIV-Negative Adults.

While medicinal marijuana use is common among persons with HIV, it is not known whether persons with HIV are more motivated to use marijuana medically compared to HIV-negative counterparts. This study examined motivations for marijuana use in a sample of 94 HIV+ and HIV- adults. Participants used marijuana 21.27 days in the last 30 days on average. HIV+ participants reported using marijuana for medical reasons more often than HIV- participants, but HIV+ and HIV- participants did not differ in other domains. Problematic marijuana use was associated with motives, regardless of HIV status. Motives were associated with mental and physical health functioning, but there were no interactions between motivations and HIV status. Overall this study found that motivations were similar for HIV+ and HIV- participants. Future research including qualitative work to further understand motivations would benefit the field, as would research examining the effectiveness of marijuana in treating physical symptoms.

ß2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system.

BACKGROUND: Most patients with MHC class I (MHC-I) deficiency carry genetic defects in transporter associated with antigen processing 1 (TAP1) or TAP2. The clinical presentation can vary, and about half of the patients have severe skin disease. Previously, one report described ß2-microglobulin (ß2m) deficiency as another monogenetic cause of MHC-I deficiency, but no further immunologic evaluation was performed. OBJECTIVE: We sought to describe the molecular and immunologic features of ß2m deficiency in 2 Turkish siblings with new diagnoses. METHODS: Based on clinical and serologic findings, the genetic defect was detected by means of candidate gene analysis. The immunologic characterization comprises flow cytometry, ELISA, functional assays, and immunohistochemistry. RESULTS: Here we provide the first extensive clinical and immunologic description of ß2m deficiency in 2 siblings. The sister had recurrent respiratory tract infections and severe skin disease, whereas the brother was fairly asymptomatic but had bronchiectasis. Not only polymorphic MHC-I but also the related CD1a, CD1b, CD1c, and neonatal Fc receptor molecules were absent from the surfaces of ß2m-deficient cells. Absent neonatal Fc receptor surface expression led to low serum IgG and albumin levels in both siblings, whereas the heterozygous parents had normal results for all tested parameters except ß2m mRNA (B2M) expression. Similar to TAP deficiency in the absence of a regular CD8 T-cell compartment, CD8(+) γδ T cells were strongly expanded. Natural killer cells were normal in number but not "licensed to kill." CONCLUSION: The clinical presentation of patients with ß2m deficiency resembles that of patients with other forms of MHC-I deficiency, but because of the missing stabilizing effect of ß2m on other members of the MHC-I family, the immunologic defect is more extensive than in patients with TAP deficiency.

Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation.

BACKGROUND & AIMS: The upregulation of several inhibitory signalling pathways by exhausted HBV-specific CD8+ T cells in chronic infection is thought to contribute to viral persistence. Blockade of inhibitory receptors to reinvigorate exhausted T cell function is a promising novel therapeutic approach. However, little information is available regarding the relative contribution of individual inhibitory pathways to HBV-specific CD8+ T cell failure and the impact of inhibitory receptor blockade on restoration of T cell function in chronic HBV. METHODS: 98 HLA-A2+ chronically infected patients were analysed ex vivo for HBV-specific CD8+ T cell responses, the expression of multiple inhibitory receptors and T cell differentiation markers. The effects of inhibitory receptor blockade targeting PD-1, 2B4, Tim-3, CTLA-4, and BTLA were assessed in vitro. RESULTS: In our cohort, ex vivo HBV-specific CD8+ T cell responses were identified preferentially in HBeAg patients with low ALT and low viral load (inactive carriers). We observed a clear hierarchy of inhibitory receptor expression dominated by PD-1. The response to inhibitory receptor blockade was heterogeneous. Compared to the blockade of other inhibitory receptors, blockade of the PD-1 pathway resulted in the strongest increase in function. Of note, a positive effect of PD-1 blockade was linked to intermediate T cell differentiation. CONCLUSIONS: Despite the expression of multiple inhibitory receptors by HBV-specific CD8+ T cells, expression and response to blockade was dominated by PD-1. However, PD-1 expression did not predict response to blockade. Rather, response to blockade was associated with intermediate T cell differentiation. These findings have important implications for our understanding of inhibitory receptor blockade as a novel therapeutic strategy.

Restoration of HCV-specific CD8+ T cell function by interferon-free therapy.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is characterised by a failure of virus-specific CD8+ T cells that is mainly caused by viral escape and T cell exhaustion. Constant antigen stimulation has been suggested to contribute to HCV-specific CD8+ T cell exhaustion. However, IFN-based therapies failed to recover HCV-specific CD8+ T cell function suggesting that the damage to CD8+ T cells may be permanent even after antigen removal. It was therefore the objective of this study to analyse the impact of inhibition of ongoing viral replication by IFN-free therapy with direct acting antivirals (DAA) on the phenotype and function of HCV-specific CD8+ T cells. METHODS: Virus-specific CD8+ T cells obtained from a patient cohort of 51 previously untreated chronically infected patients undergoing IFN-free therapy with a combination of faldaprevir (a protease inhibitor) and deleobuvir (a non-nucleoside polymerase inhibitor) with or without ribavirin were analysed ex vivo and after in vitro expansion at baseline, wk4, wk 12, and after treatment. RESULTS: Our results show the rapid restoration of proliferative HCV-specific CD8+ T cells in the majority of patients with SVR12 within 4 weeks of therapy suggesting that IFN-free therapy mediated antigen removal may restore CD8+ T cell function. CONCLUSIONS: This study indicates a specific restoration of proliferative HCV-specific CD8+ T cells under IFN-free therapy. This is in contrast to PegIFN-based therapies that have been shown not to restore T cell function during and after chronic infection.

Access challenges to opioid use disorder treatment among individuals experiencing homelessness: Voices from the streets.

BACKGROUND: Achieving equitable access to medications for opioid use disorder (MOUD) such as buprenorphine is a pressing issue. Evidence suggests disparities in MOUD access based on race and socioeconomic status, further exacerbated by the COVID-19 pandemic. However, the drivers behind this access gap remain poorly understood. This study explores barriers to treatment access among individuals with opioid use disorder (OUD) experiencing homelessness. METHODS: We interviewed 28 individuals in and around the Boston Public Health Commission (BPHC) Engagement Center, an area known for its high density of active substance use and homelessness. We asked about people's experiences, perceptions, and attitudes toward OUD treatment. We conducted a thematic analysis of our interview data. RESULTS: Fifty-four percent of participants sampled were not prescribed MOUD. None of the participants reported having an active prescription of sublingual buprenorphine or buprenorphine/naloxone. White participants were more likely to have been prescribed buprenorphine in the past compared to participants of other races even in this socioeconomically homogeneous sample. Themes that emerged in our data included challenges to accessing MOUD due to reduced services during the COVID-19 pandemic, lost or stolen medications, fewer inpatient withdrawal management beds for women, transportation challenges, fear of adverse effects of MOUD, the perception that taking MOUD replaces one addiction for another, and community disapproval of MOUD. Participants also reported stigma and discrimination based on race, gender, and socioeconomic status. CONCLUSION: Systems and individual-level factors contribute to the MOUD treatment gap across race and socioeconomic status. The COVID-19 pandemic posed additional access challenges. This study provides important, actionable insights about the barriers faced by a particularly vulnerable population of individuals with OUD experiencing homelessness.

Electrostimulable polymeric films with hyaluronic acid and lipid nanoparticles for simultaneous topical delivery of macromolecules and lipophilic drugs.

This study focused on developing electrically stimulable hyaluronic acid (HA) films incorporating lipid nanoparticles (NPs) designed for the topical administration of lipophilic drugs and macromolecules. Based on beeswax and medium-chain triglycerides, NPs were successfully integrated into silk fibroin/chitosan films containing HA (NP-HA films) at a density of approximately 1011 NP/cm2, ensuring a uniform distribution. This integration resulted in a 40% increase in film roughness, a twofold decrease in Young's modulus, and enhanced film flexibility and bioadhesion work. The NP-HA films, featuring Ag/AgCl electrodes, demonstrated the capability to conduct a constant electrical current of 0.2 mA/cm2 without inducing toxicity in keratinocytes and fibroblasts during a 15-min application. Moreover, the NPs facilitated the homogeneous distribution of lipophilic drugs within the film, effectively transporting them to the skin and uniformly distributing them in the stratum corneum upon film administration. The sustained release of HA from the films, following Higuchi kinetics, did not alter the macroscopic characteristics of the film. Although anodic iontophoresis did not noticeably affect the release of HA, it did enhance its penetration into the skin. This enhancement facilitated the permeation of HA with a molecular weight (MW) of up to 2 × 105 through intercellular and transcellular routes. Confocal Raman spectroscopy provided evidence of an approximate 100% increase in the presence of HA with a MW in the range of 1.5-1.8 × 106 in the viable epidermis of human skin after only 15 min of iontophoresis applied to the films. Combining iontophoresis with NP-HA films exhibits substantial potential for noninvasive treatments focused on skin rejuvenation and wound healing.

Butyrate and propionate are microbial danger signals that activate the NLRP3 inflammasome in human macrophages upon TLR stimulation.

Short-chain fatty acids (SCFAs) are immunomodulatory compounds produced by the microbiome through dietary fiber fermentation. Although generally considered beneficial for gut health, patients suffering from inflammatory bowel disease (IBD) display poor tolerance to fiber-rich diets, suggesting that SCFAs may have contrary effects under inflammatory conditions. To investigate this, we examined the effect of SCFAs on human macrophages in the presence of Toll-like receptor (TLR) agonists. In contrast to anti-inflammatory effects under steady-state conditions, we found that butyrate and propionate activated the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in the presence of TLR agonists. Mechanistically, these SCFAs prevented transcription of FLICE-like inhibitory protein (cFLIP) and interleukin-10 (IL-10) through histone deacetylase (HDAC) inhibition, triggering caspase-8-dependent NLRP3 inflammasome activation. SCFA-driven NLRP3 activation was potassium efflux independent and did not result in cell death but rather triggered hyperactivation and IL-1ß release. Our findings demonstrate that butyrate and propionate are bacterially derived danger signals that regulate NLRP3 inflammasome activation through epigenetic modulation of the inflammatory response.

Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1.2 to 2.3 µM. These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools such as molecular docking and quantitative structure-activity relationship (QSAR) models to analyze protein-ligand interactions, revealing that these naphthoquinones exhibit a protein binding pattern similar to brequinar, a potent HsDHODH inhibitor. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.

Attitudes Regarding Medications for Opioid Use Disorder Among Peer Recovery Coaches.

OBJECTIVES: A growing number of individuals are employed as peer recovery coaches to mentor, support, and educate those in recovery. Despite the robust evidence base for the benefits of medications for treating opioid use disorder (OUD), prior research has identified peers in recovery to hold both positive and negative attitudes toward medications for OUD (MOUDs). We aimed to survey peer recovery coaches in Massachusetts about their attitudes toward working with individuals utilizing MOUDs. METHODS: All 202 individuals certified as peer recovery coaches in Massachusetts were invited to participate in a brief, anonymous online survey between August and October 2020. The survey collected the respondents' age, sex, certification year, duration of employment as a coach, personal history of substance use disorders, and MOUD treatment. RESULTS: A total of 129 responses were received, representing a 63.9% response rate. Eighty-six (64.3%) reported a personal history of OUD, of whom 64 (74.4%) reported prior MOUD treatment. The majority held positive views about MOUDs, endorsing them as appropriate treatments to achieve sobriety. Coaches with personal history of MOUDs were more likely to report enjoying working with patients on methadone. Coaches without any personal history of OUD or MOUDs were older, more likely to have an alcohol use disorder, and more likely to encourage drug-free treatments before MOUDs and shorter duration of MOUD treatment. CONCLUSIONS: Results indicate that peer recovery coaches in Massachusetts hold generally positive attitudes toward MOUDs, but those without any personal history of OUD or MOUDs may be less likely to encourage MOUD treatment.

A Peer Recovery Coach Intervention for Hospitalized Patients with Opioid Use Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVES: Patients with opioid use disorder (OUD) are increasingly being hospitalized for acute medical illnesses. Despite initiation of medications for OUD (MOUDs), many discontinue treatment after discharge. To evaluate whether a psychosocial intervention can improve MOUD retention after hospitalization, we conducted a pilot randomized controlled trial of a peer recovery coach intervention. METHODS: An existing peer recovery coach intervention was adapted for this trial. Hospitalized adults with OUD receiving MOUD treatment were randomized to receive either a recovery coach intervention or treatment-as-usual. For those in the intervention arm, the coach guided the participant to complete a relapse prevention plan, maintained contact throughout the 6-month follow-up period, encouraged MOUD continuation, and helped to identify community resources. Those receiving treatment-as-usual were discharged with a referral to outpatient treatment. Primary outcome was retention in MOUD treatment at 6 months. Secondary outcomes were the proportion of participants readmitted to the hospital and the number of days until treatment discontinuation and to hospital readmission. RESULTS: Twenty-five individuals who provided consent and randomized to the recovery coach intervention (n = 13) or treatment-as-usual (n = 12) were included in the analysis. No significant differences were found in the proportion of participants retained in MOUD treatment at 6 months (38.5% vs 41.7%, P = 0.87), proportion of participants readmitted at 6 months (46.2% vs 41.2%, P = 0.82), or the time to treatment discontinuation (log-rank P = 0.92) or readmission (log-rank P = 0.85). CONCLUSIONS: This pilot trial failed to demonstrate that a recovery coach intervention improved MOUD treatment retention compared with treatment-as-usual among hospitalized individuals with OUD.

Smartphone Ownership, Smartphone Utilization, and Interest in Using Mental Health Apps to Address Substance Use Disorders: Literature Review and Cross-sectional Survey Study Across Two Sites.

BACKGROUND: In recent years, there has been increasing interest in implementing digital technologies to diagnose, monitor, and intervene in substance use disorders. Smartphones are now a vehicle for facilitating telepsychiatry visits, measuring health metrics, and communicating with health care professionals. In light of the COVID-19 pandemic and the movement toward web-based and hybrid clinic visits and meetings, it has become especially salient to assess phone ownership among individuals with substance use disorders and their comfort in navigating phone functionality and using phones for mental health purposes. OBJECTIVE: The aims of this study were to summarize the current literature around smartphone ownership, smartphone utilization, and the acceptability of using smartphones for mental health purposes and assess these variables across two disparate substance use treatment sites. METHODS: We performed a focused literature review via a search of two academic databases (PubMed and Google Scholar) for publications since 2007 on the topics of smartphone ownership, smartphone utilization, and the acceptability of using mobile apps for mental health purposes among the substance use population. Additionally, we conducted a cross-sectional survey study that included 51 participants across two sites in New England-an inpatient detoxification unit that predominantly treats patients with alcohol use disorder and an outpatient methadone maintenance treatment clinic. RESULTS: Prior studies indicated that mobile phone ownership among the substance use population between 2013 and 2019 ranged from 83% to 94%, while smartphone ownership ranged from 57% to 94%. The results from our study across the two sites indicated 96% (49/51) mobile phone ownership and 92% (47/51) smartphone ownership among the substance use population. Although most (43/49, 88%) patients across both sites reported currently using apps on their phone, a minority (19/48, 40%) reported previously using any apps for mental health purposes. More than half of the participants reported feeling at least neutrally comfortable with a mental health app gathering information regarding appointment reminders (32/48, 67%), medication reminders (33/48, 69%), and symptom surveys (26/45, 58%). Most patients were concerned about privacy (34/51, 67%) and felt uncomfortable with an app gathering location (29/47, 62%) and social (27/47, 57%) information for health care purposes. CONCLUSIONS: The majority of respondents reported owning a mobile phone (49/51, 96%) and smartphone (47/51, 92%), consistent with prior studies. Many respondents felt comfortable with mental health apps gathering most forms of personal information and with communicating with their clinician about their mental health. The differential results from the two sites, namely greater concerns about the cost of mental health apps among the methadone maintenance treatment cohort and less experience with downloading apps among the older inpatient detoxification cohort, may indicate that clinicians should tailor technological interventions based on local demographics and practice sites and that there is likely not a one-size-fits-all digital psychiatry solution.

Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study.

Background: Opioid use disorder (OUD) remains a major public health concern. Despite the use of medications for OUD such as buprenorphine, the current gold-standard treatment, relapse in the context of increased craving remains common. Cannabidiol (CBD) has been shown to reduce cue-induced craving in individuals with OUD, but among those who were not receiving any buprenorphine treatment. This small proof-of-concept open-label study sought to evaluate the effect of CBD on cue-induced craving among individuals with OUD who were being actively treated with buprenorphine. Methods: Participants (n = 5) received CBD (Epidiolex®) 600 mg once daily for 3 consecutive days in an open-label manner. Primary outcome was cue-induced craving measured on a visual analog scale of 0 to 10, calculated as the difference in craving in response to drug-related versus neutral cues. The cue-reactivity paradigm was performed at baseline before CBD administration, and was repeated after 3 days of CBD. Secondary outcomes included scores on depression, anxiety, pain, opioid withdrawal, and side effects. Results: All participants were actively taking buprenorphine for an average of 37.8 months (range 1-120 months). Cue-induced craving was significantly lower after CBD dosing compared with baseline (0.4 vs. 3.2, paired t-test, p = 0.0046). No significant changes in scores for depression, anxiety, pain, or opioid withdrawal were noted. CBD was well tolerated, although one participant experienced moderate sedation; otherwise, no other adverse effects were reported. Conclusions: Given the high risk for bias in a small uncontrolled open label study such as this, results must be interpreted with caution. A larger adequately powered trial with a suitable control group is needed to confirm the finding that CBD may help to reduce cue-induced craving among individuals with OUD currently on buprenorphine treatment. Research should further evaluate whether adjunctive use of CBD can improve clinical outcomes for individuals with OUD maintained on buprenorphine. ClinicalTrials.gov (NCT04192370).