Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: differences by gender, PTSD status, and chronic pain.

BACKGROUND: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. METHODS: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. RESULTS: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). CONCLUSION: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. TRIAL REGISTRATION: NCT04082637.

Addressing Biological Questions with Preclinical Cancer Imaging.

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.

Mental Health Distress Is Associated With Higher Pain Interference in Patients With Opioid Use Disorder Stabilized on Buprenorphine or Methadone.

BACKGROUND: The relationships between opioid use disorder (OUD), chronic pain, and mental health distress are complex and multidirectional. The objective of this exploratory study was to examine the relationship between mental health conditions and Chronic pain severity and interference among patients stabilized on either buprenorphine or methadone. METHODS: We report baseline data from a randomized trial of a mind-body intervention conducted at 5 outpatient clinics that provided either buprenorphine or methadone treatment. Validated scales were used to measure substance use, mental health distress, and pain severity and interference. Statistical analyses examined the relationship between mental health conditions and pain severity and interference. RESULTS: Of 303 participants, 57% (n = 172) reported Chronic pain. A total of 88% (n = 268) were prescribed buprenorphine. Mental health conditions were common, with one-quarter of the sample screening positive for all 3 mental health conditions (anxiety, depression, and posttraumatic stress disorder [PTSD]). Compared to participants without Chronic pain, participants with Chronic pain were more likely to screen positive for moderate-severe anxiety (47% vs 31%); moderate-severe depression (54% vs 41%); and the combination of anxiety, depression, and PTSD (31% vs 18%). Among participants with Chronic pain, mental health conditions were associated with higher pain interference. Pain severity was higher among participants with mental health conditions, but only reached statistical significance for depression. Pain interference scores increased with a higher number of co-occurring mental health conditions. CONCLUSIONS: Among individuals stabilized on either buprenorphine or methadone, highly symptomatic and comorbid mental health distress is common and is associated with increased pain interference. Adequate screening for, and treatment of, mental health conditions in patients with OUD and Chronic pain is needed.

CRISPR/Cas for PET Reporter Gene Engineering.

The relatively recent discovery of CRISPR/Cas has led to a revolution in our ability to efficiently manipulate the genome of eukaryotic cells. We describe here a protocol that employs CRISPR technology to precisely knock-in a PET imaging reporter transgene into a specific genetic locus of interest. Resulting transcription of the targeted reporter will more accurately mimic physiologic expression of the endogenous allele than conventional approaches, and so this method has the potential to become an efficient way to generate a new generation of "gold-standard" reporter transgenes. We break down the protocol into three experimental stages: how to identify the genomic location that the reporter transgene will be inserted, how to practically insert the reporter transgene into the genome, and how to screen resultant clones for the correct targeted event.

Nurse Care Management for Opioid Use Disorder Treatment: The PROUD Cluster Randomized Clinical Trial.

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. Design, Setting, and Participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. Intervention: The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. Main Outcomes and Measures: The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. Results: During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). Conclusions and Relevance: The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response.

Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [99mTc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.

Integrating Opioid Use Disorder Treatment Into Primary Care Settings.

Importance: Medication for opioid use disorder (MOUD) (eg, buprenorphine and naltrexone) can be offered in primary care, but barriers to implementation exist. Objective: To evaluate an implementation intervention over 2 years to explore experiences and perspectives of multidisciplinary primary care (PC) teams initiating or expanding MOUD. Design, Setting, and Participants: This survey-based and ethnographic qualitative study was conducted at 12 geographically and structurally diverse primary care clinics that enrolled in a hybrid effectiveness-implementation study from July 2020 to July 2022 and included PC teams (prescribing clinicians, nonprescribing behavioral health care managers, and consulting psychiatrists). Survey data analysis was conducted from February to April 2022. Exposure: Implementation intervention (external practice facilitation) to integrate OUD treatment alongside existing collaborative care for mental health services. Measures: Data included (1) quantitative surveys of primary care teams that were analyzed descriptively and triangulated with qualitative results and (2) qualitative field notes from ethnographic observation of clinic implementation meetings analyzed using rapid assessment methods. Results: Sixty-two primary care team members completed the survey (41 female individuals [66%]; 1 [2%] American Indian or Alaskan Native, 4 [7%] Asian, 5 [8%] Black or African American, 5 [8%] Hispanic or Latino, 1 [2%] Native Hawaiian or Other Pacific Islander, and 46 [4%] White individuals), of whom 37 (60%) were between age 25 and 44 years. An analysis of implementation meetings (n = 362) and survey data identified 4 themes describing multilevel factors associated with PC team provision of MOUD during implementation, with variation in their experience across clinics. Themes characterized challenges with clinical administrative logistics that limited the capacity to provide rapid access to care and patient engagement as well as clinician confidence to discuss aspects of MOUD care with patients. These challenges were associated with conflicting attitudes among PC teams toward expanding MOUD care. Conclusions and Relevance: The results of this survey and qualitative study of PC team perspectives suggest that PC teams need flexibility in appointment scheduling and the capacity to effectively engage patients with OUD as well as ongoing training to maintain clinician confidence in the face of evolving opioid-related clinical issues. Future work should address structural challenges associated with workload burden and limited schedule flexibility that hinder MOUD expansion in PC settings.

Extended-release Naltrexone Is Not Linked to Hepatotoxicity in Adults Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: The use of extended-release naltrexone (XR-NTX) as treatment for alcohol use disorder (AUD) has been limited by a prior black box warning for hepatotoxicity. We performed a secondary analysis of data from a randomized clinical trial to compare serum liver enzyme levels for those randomized to XR-NTX versus placebo. METHODS: The parent study aimed to test the efficacy of combined pharmacobehavioral harm-reduction treatment in improving alcohol and quality-of-life outcomes for adults experiencing homelessness and AUD. We compared the 2 arms that received intramuscular injections of either 380 mg XR-NTX (n = 74) or placebo (n = 77). Outcomes included ( a ) liver enzyme levels and ( b ) liver enzyme values categorized as normal (<1× upper limit of normal [ULN]), elevated (1-3× ULN), or high (>3× ULN). We performed multinomial logistic regression and negative binomial generalized estimating equations modeling to assess the effects of treatment group and the time × treatment group interaction on liver enzyme outcomes. RESULTS: The mean age was 47.9 ± 9.9 years, and the mean baseline alcohol consumption was 23.2 ± 14.0 drinks per day. There were no significant differences in the development of liver enzyme elevations 1 to 3× ULN or more than 3× ULN (all P s > 0.25) or in the change in liver enzyme values (all P s > 0.41) between the placebo and the XR-NTX groups over the treatment course. CONCLUSIONS: In our study of adults experiencing homelessness and AUD, receipt of XR-NTX was not associated with hepatotoxicity. These findings support the use of XR-NTX to treat AUD even in patients who are drinking heavily and physiologically dependent on alcohol.

Trauma Exposure Across the Lifespan among Individuals Engaged in Treatment with Medication for Opioid Use Disorder: Differences by Gender, PTSD Status, and Chronic Pain.

Background: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. Methods: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. Results: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). Conclusions: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. Trial Registration: NCT04082637.

Peer providers and linkage with buprenorphine care after hospitalization: A retrospective cohort study.

Background: People with opioid use disorder (OUD) are increasingly started on buprenorphine in the hospital, yet many patients do not attend outpatient buprenorphine care after discharge. Peer providers, people in recovery themselves, are a growing part of addiction care. We examine whether patients who received a low-intensity, peer-delivered intervention during hospitalization had a greater rate of linking with outpatient buprenorphine care relative to those not seen by a peer. Methods: This was a retrospective cohort study of adults with OUD who were started on buprenorphine during hospitalization. The primary outcome was receipt of a buprenorphine prescription within 30 days of discharge. Secondary outcomes included attendance at a follow-up visit with a buprenorphine provider within 30 days and hospital readmission within 90 days. Modified Poisson regression analyses tested for differences in the rate ratios (RR) of each binary outcome for patients who were versus were not seen by a peer provider. Peer notes in the electronic health record were reviewed to characterize peer activities. Results: 111 patients met the study inclusion criteria, 31.5% of whom saw a peer provider. 55.0% received a buprenorphine prescription within 30 days of hospital discharge. Patients with versus without peer provider encounters did not significantly differ in the rates of receiving a buprenorphine prescription (RR = 1.06, 95% CI: 0.74-1.51), hospital readmission (RR = 1.45, 95% CI: 0.80-2.64), or attendance at a buprenorphine follow-up visit (RR = 1.03, 95% CI: 0.68-1.57). Peers most often listened to or shared experiences with patients (68.6% of encounters) and helped facilitate medical care (60.0% of encounters). Conclusions: There were no differences in multiple measures of buprenorphine follow-up between patients who received this low-intensity peer intervention and those who did not. There is need to investigate what elements of peer provider programs contribute to patient outcomes and what outcomes should be assessed when evaluating peer programs.

PTP1B inhibitors protect against acute lung injury and regulate CXCR4 signaling in neutrophils.

Acute lung injury (ALI) can cause acute respiratory distress syndrome (ARDS), a lethal condition with limited treatment options and currently a common global cause of death due to COVID-19. ARDS secondary to transfusion-related ALI (TRALI) has been recapitulated preclinically by anti-MHC-I antibody administration to LPS-primed mice. In this model, we demonstrate that inhibitors of PTP1B, a protein tyrosine phosphatase that regulates signaling pathways of fundamental importance to homeostasis and inflammation, prevented lung injury and increased survival. Treatment with PTP1B inhibitors attenuated the aberrant neutrophil function that drives ALI and was associated with release of myeloperoxidase, suppression of neutrophil extracellular trap (NET) formation, and inhibition of neutrophil migration. Mechanistically, reduced signaling through the CXCR4 chemokine receptor, particularly to the activation of PI3Kγ/AKT/mTOR, was essential for these effects, linking PTP1B inhibition to promoting an aged-neutrophil phenotype. Considering that dysregulated activation of neutrophils has been implicated in sepsis and causes collateral tissue damage, we demonstrate that PTP1B inhibitors improved survival and ameliorated lung injury in an LPS-induced sepsis model and improved survival in the cecal ligation and puncture-induced (CLP-induced) sepsis model. Our data highlight the potential for PTP1B inhibition to prevent ALI and ARDS from multiple etiologies.

Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection.

Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram - an FDA-approved drug for alcohol use disorder - dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in a transfusion-related acute lung injury (TRALI) mouse model. We then tested whether disulfiram could confer protection in the context of SARS-CoV-2 infection, as NETs are elevated in patients with severe COVID-19. In SARS-CoV-2-infected golden hamsters, disulfiram reduced NETs and perivascular fibrosis in the lungs, and it downregulated innate immune and complement/coagulation pathways, suggesting that it could be beneficial for patients with COVID-19. In conclusion, an existing FDA-approved drug can block NET formation and improve disease course in 2 rodent models of lung injury for which treatment options are limited.

Low Dose Buprenorphine Induction With Full Agonist Overlap in Hospitalized Patients With Opioid Use Disorder: A Retrospective Cohort Study.

OBJECTIVE: To describe the outcomes of buprenorphine/naloxone low dose induction with overlap of full opioid agonists among hospitalized patients with opioid use disorder (OUD) as an alternative to standard induction strategies. METHODS: Retrospective cohort study of patients with OUD who were admitted to the hospital over a 1-year period and initiated ono buprenorphine using initial doses of 0.5 mg and gradually increased while the patient remained on full agonists. Descriptive variables included basic demographics, reason for switching to buprenorphine, baseline opioid and morphine equivalent dose. The primary outcome was a successful transition defined by the patient leaving the hospital with a buprenorphine prescription. Bivariate analysis identified factors associated with unsuccessful medication transitions. Secondary outcomes included reported withdrawal symptoms and 30 day follow up to an outpatient buprenorphine program. RESULTS: Sixty two patients underwent low dose with overlap induction during the study period. Fourteen patients were on methadone for OUD before hospital admission. Fifty one patients (82%) successfully left the hospital with a prescription for buprenorphine. Factors associated with lower likelihood of success included older age, transitioning due to discharge placement needs and presence of withdrawal symptoms during the transition. Overall, 66% (N = 23) of patients referred within the same health care system followed up within 30 days. CONCLUSIONS: Low dose inductions with overlap of full opioid agonists were largely successful in transitioning hospitalized patients from full agonist opioids to buprenorphine. However, there were several factors associated with lower likelihood of success. Future work could focus on treatment of withdrawal symptoms and system-level changes ensuring patient-centered medication decisions.

Video directly observed therapy for patients receiving office-based buprenorphine - A pilot randomized controlled trial.

BACKGROUND: We conducted a pilot study to assess feasibility of using video directly-observed therapy (DOT) for patients initiating buprenorphine to evaluate whether it is associated with better opioid use disorder (OUD) outcomes when compared to treatment-as-usual (TAU). METHODS: Pilot randomized controlled trial of adult patients with OUD initiating buprenorphine treatment (n = 78) at two sites (Seattle, WA and Boston, MA) from January 2019 to May 2020. Intervention was video DOT using a HIPAA-compliant smartphone application to record taking daily buprenorphine. Study smartphones, text reminders to upload a video, and calendar summaries of video DOT adherence were provided. Main outcomes were 1) percentage of 12 weekly urine drug tests (UDT) negative for illicit opioids and 2) engagement in treatment at week 12 (i.e., having an active prescription for buprenorphine within the last 7 days). RESULTS: Of 78 enrolled, 20 (26 %) were female; 29 (37 %) non-white; and 31 (40 %) homeless. The mean (standard deviation) percentage of doses confirmed by video was 31 % (34 %). In intention-to-treat analysis, the average percentage of weekly opioid negative UDT was 50 % (95 % CI: 40-63 %) in the intervention arm versus 64 % (95 % CI: 55-74 %) among controls; RR = 0.78 (95 % CI: 0.60-1.02, p = 0.07). Engagement at week 12 was 69 % (95 % CI: 56-86 %) v. 82 % (95 % CI: 71-95 %) in the intervention vs. TAU arms, respectively; RR = 0.84 (95 % CI: 0.65-1.10, p = 0.20). CONCLUSIONS: The video DOT intervention did not result in improvements in illicit opioid use and treatment engagement compared to TAU. The study was limited by low rates of intervention use. TRIAL REGISTRATION: ClinicalTrails.gov, NCT03779997, Registered on December 19, 2018.

Staff Attitudes toward Buprenorphine before and after Implementation of an Office-Based Opioid Treatment Program in an Urban Teaching Clinic.

PURPOSE: Improving access to buprenorphine treatment is necessary to address the national opioid use disorder (OUD) crisis. This study investigates attitudes about buprenorphine prescribing among staff at a primary care clinic and compares attitudes before and after implementation of an office-based opioid treatment (OBOT) program. METHODS: Providers and staff in an academic primary care clinic were surveyed prior to and one year following implementation of an OBOT program. Descriptive statistics, Pearson's Chi-2 tests and logistic regression models were used to compare staff and provider attitudes about use of buprenorphine for OUD and to compare attitudes before and after OBOT implementation. RESULTS: At baseline, 20% of staff indicated strong belief that buprenorphine is an effective treatment for OUD and 16% indicated strong belief that primary care providers should prescribe it. Staff appeared less likely than providers to believe strongly that buprenorphine is effective (OR 0.24, 95% CI= 0.08-.78, p = 0.02; aOR 0.28, 95% CI=.08-1.0, p = 0.05 adjusted for age, race and gender). Following implementation of an OBOT program, the percentage of staff who believed strongly in the effectiveness of buprenorphine for OUD increased from 20% to 40% (p = 0.31), and the percentage who believed that primary care providers (PCPs) should prescribe it increased from 16% to 30% (p = 0.52). CONCLUSIONS: Staff in a primary care clinic were less likely than providers to believe in the effectiveness of buprenorphine treatment or that PCPs should prescribe it for OUD. That their beliefs substantially changed after implementation of an OBOT program suggests that direct experience impacts attitudes.

Perspectives on electronic portal use among patients treated with medications for opioid use disorder in primary care.

OBJECTIVES: Office-based opioid treatment (OBOT) with buprenorphine is increasingly integrated in primary care to treat opioid use disorder (OUD). Online portals seek to engage patients in care of their chronic medical conditions, yet we know little about how patients with OUD experience these portals. Our study explores how patients with OUD perceive the impact of portal use on addiction treatment and clinical care. MATERIALS AND METHODS: We purposively sampled patients with an active portal account enrolled in an OBOT program embedded within primary care, stratifying by recent or distant portal use. The study conducted individual semistructured interviews to understand how patients perceived and interfaced with the portal until the study reached saturation of themes. The research team analyzed the data via thematic analysis and three investigators independently coded the data to identify themes, which all authors then refined. RESULTS: Among 17 participants, 9 were recent users and 8 were distant. Though we stratified analyses by level of portal use, the study observed no differences in resultant themes, thus the study combined themes, which we present here. Portal use was felt to (1) facilitate and reinforce OUD and other substance use treatment goals, (2) improve health care participation, (3) enable monitoring and addressing broader health concerns beyond SUD treatment, and (4) have mixed impacts on patient-provider trust. DISCUSSION: Our findings suggest that patients with OUD identify aspects of the patient portal contributing to their engagement and retention in substance use treatment. Lingering concerns remain about the potential of portal use to negatively impact the patient-provider relationship.

Buprenorphine utilization among all Washington State residents' based upon prescription monitoring program data - Characteristics associated with two measures of retention and patterns of care over time.

BACKGROUND: Opioid use disorder is a serious health condition for which buprenorphine is proven effective, yet providers substantially underutilize buprenorphine. We present two approaches to measuring treatment duration, factors associated with retention, and patterns of care. METHODS: The study determined incident buprenorphine prescribing for all Washingtonians utilizing prescription monitoring program data from 2012 to 2019. The study calculated episode of care and cumulative time in care. Generalized linear models estimated associations among the length of the first episode of care and cumulative time in care with sex, age, and rurality. Cox proportional hazards models estimated the time to discontinuing buprenorphine for the first four episodes of care and time to discontinuing the last episode of care. RESULTS: Mean and median duration of the first episode were 320 and 84 days, respectively, and for cumulative time in care 308 and 195 days. A minority of peoples' first episodes exceeded 180 days (37%). Being female and older were significantly associated with longer first episodes and cumulative time in care. Survival analyses indicated that the proportion of those still in care at 6, 12, and 24 months into their first episode of care declined for those with more than one episode of care; conversely the study found much smaller differences in retention for the last episode of care, indicating that many people were eventually able to be retained in care for longer periods of time. CONCLUSION: Episodes of care and cumulative time on buprenorphine were both short compared to minimum quality recommendations of 180 days. Median cumulative time in care was double that of the first episode, highlighting that many people engage in subsequent episodes of substantial length. Episode of care and cumulative care analyses should inform states, payers, health care systems and providers in measuring and setting treatment duration goals.

Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis.

The study aims to assess site assessment of the performance of 18F-PBR-111 as a neuroinflammation marker in the cuprizone mouse model of multiple sclerosis (MS). 18F-PBR-111 PET imaging has not been well evaluated in multiple sclerosis applications both in preclinical and clinical research. This study will help establish the potential utility of 18F-PBR-111 PET in preclinical MS research and future animal and future human applications. 18F-PBR-111 PET/CT was conducted at 3.5 weeks (n = 7) and 5.0 weeks (n = 7) after cuprizone treatment or sham control (n = 3) in the mouse model. A subgroup of mice underwent autoradiography with cryosectioned brain tissue. T2 weighted MRI was performed to obtain the brain structural data of each mouse. 18F-PBR-111 uptake was assessed in multiple brain regions with PET and autoradiography images. The correlation between autoradiography and immunofluorescence staining of neuroinflammation (F4/80 and CD11b) was measured. Compared to control mice, significant 18F-PBR-111 uptake in the corpus callosum (p < 0.001), striatum (caudate and internal capsule, p < 0.001), and hippocampus (p < 0.05) was identified with PET images at both 3.5 weeks and 5.0 weeks, and validated with autoradiography. No significant uptake differences were detected between 3.5 weeks and 5.0 weeks assessing these regions as a whole, although there was a trend of increased uptake at 5.0 weeks compared to 3.5 weeks in the CC. High 18F-PBR-111 uptake regions correlated with microglial/macrophage locations by immunofluorescence staining with F4/80 and CD11b antibodies. 18F-PBR-111 uptake in anatomic locations correlated with activated microglia at histology in the cuprizone mouse model of MS suggests that 18F-PBR-111 has potential for in vivo evaluation of therapy response and potential for use in MS patients and animal studies.