Implementing Heart Plus: Design and Early Results of a Novel Comanagement Clinic for Patients With Stimulant-associated Cardiomyopathy.

We describe the methodology, design, and early results of a novel multidisciplinary co management clinic model with Addiction Medicine and Cardiology providers using contingency management to engage patients with stimulant-associated cardiomyopathy (SA-CMP). Stimulant use, including methamphetamine and cocaine, is increasing in prevalence nationally and is associated with cardiovascular complications. People with SA-CMP have higher rates of mortality and acute care use (eg, emergency department visits, hospital admissions) and lower rates of outpatient care engagement than individuals with non-SA-CMP. This population also has disproportionately elevated rates of mental health and other medical comorbidities, challenges with social determinants of health, including housing and food insecurity, and representation from communities of color. This multidisciplinary comanagement care delivery model, called Heart Plus, was developed and funded as a quality improvement project. It led to a 5-fold increase in outpatient care engagement with a concomitant 53% decrease in acute care use. All participants reported a decrease in stimulant use. With increased clinical stability, patients were able to better engage with outpatient resources for social determinants of health, such as case management, social work, and housing and food service programs. Patients were also empowered to take control over their health while knowing that health care providers cared about their well-being.

A Mixed-methods Evaluation of an Addiction/Cardiology Pilot Clinic With Contingency Management for Patients With Stimulant-associated Cardiomyopathy.

OBJECTIVES: Contingency management (CM) is one of the most effective treatments for stimulant use disorder but has not been leveraged for people with stimulant-associated cardiomyopathy (SA-CMP), a chronic health condition with significant morbidity and mortality. We aimed to determine the feasibility and acceptability of a multidisciplinary addiction/cardiology clinic with CM for patients with SA-CMP and to explore barriers and facilitators to engagement and recovery. METHODS: We recruited patients with a hospitalization in the past 6 months, heart failure with reduced ejection fraction (<40%) and stimulant use disorder to participate in Heart Plus, a 12-week addiction/cardiology clinic with CM in an urban, safety-net, hospital-based cardiology clinic, which took place March 2021 through June 2021. Contingency management entailed gift card rewards for attendance and negative point-of-care urine drug screens. Our mixed-methods study used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. We obtained data from the medical record, staff surveys, and qualitative interviews with participants. RESULTS: Thirty-eight patients were referred, 17 scheduled an appointment, and 12 attended the intake appointment and enrolled in the study. Mean treatment duration was 8 of 12 weeks. Of the 9 participants who attended more than one visit, the median attendance was 82% of available visits for in-person visits and 83% for telephone visits, and all patients reported decreased stimulant use. CONCLUSIONS: Delivering CM through a multidisciplinary addiction/cardiology clinic for patients with SA-CMP was feasible and engaged patients in care. Further research is needed to assess whether this program is associated with improved heart failure outcomes.

Predictors of Linkage to an Opioid Treatment Program and Methadone Treatment Retention following Hospital Discharge in a Safety-Net Setting.

Background: Methadone is increasingly initiated during hospitalization for the treatment of opioid use disorder (OUD). However, little is known about which factors are associated with linkage to opioid treatment programs (OTP) and retention in methadone maintenance therapy (MMT) following hospital discharge. Materials & Methods: This is a retrospective study of adults with OUD hospitalized in an urban, safety-net hospital referred by inpatient clinicians to an onsite OTP for post-discharge MMT follow-up from October 2017 to July 2019. We used multivariable modified Poisson regression models to generate adjusted risk ratios (aRR) for associations of sociodemographic factors, mental health disorders, alcohol use, stimulant use, and prior care engagement with post-discharge OTP enrollment and MMT retention at 30 and 90-days. Results: Of the 125 patients referred, 40% enrolled in the OTP post-discharge. Among enrollees, 74% were retained at 30-days and 52% were retained at 90-days. Patients with co-occurring stimulant use were less likely to enroll in the OTP post-discharge compared to those without stimulant use (aRR 0.65, 95% CI 0.44-0.97). We found no associations with 30-day MMT retention, but patients who reported stable housing were more likely to be retained in MMT at 90-days compared to those without stable housing (aRR 1.66, 95% CI 1.03-2.66). Conclusion: Our findings suggest that hospitalized patients with co-occurring stimulant use may need additional support to optimize post-discharge OTP linkage. Stable housing may improve retention in MMT. Additional research is needed to identify trends in MMT engagement among those referred from the acute hospital setting.

Hepatitis C Elimination During a Global Pandemic: A Case Study of Resilience in Action.

Until the COVID-19 pandemic, San Francisco's hepatitis C virus (HCV) elimination initiative, End Hep C SF, was expanding and refining HCV testing and treatment strategies citywide, making progress toward local HCV elimination goals. Although a shelter-in-place health order issued in March 2020 categorized HCV testing as an "essential service," most HCV testing and treatment immediately stopped until COVID-19-safe protocols could be implemented. During the 14 months of pandemic-related organizational closures, End Hep C SF transitioned to a 100% virtual model, maintaining regularly scheduled meetings. Community-based HCV antibody testing decreased 80% from February to April 2020, and HCV treatment initiation also decreased, although both services started to rebound in mid-to-late 2020, partially as a result of End Hep C SF collaborations. End Hep C SF service providers, clinicians, and advocates reported that the continuous communication and common agenda of End Hep C SF-2 principles of the collective impact initiative-served as a familiar touchpoint and helpful source of information during this isolating and uncertain time. Ultimately, End Hep C SF allowed us to continue HCV elimination strategies through 6 lessons learned: maintaining HCV treatment access through telehealth and mobile services; leveraging research studies that provided HCV testing and treatment; offering HCV screening and linkage to care in tandem with COVID-19-related initiatives; being flexible and inventive, such as administering HCV treatment to residents of shelter-in-place hotels; establishing a data dashboard to track HCV testing and treatment; and relying on partnerships to solve problems and avoid burnout.

National trends in testing for hepatitis C virus in licensed opioid treatment programs: Differences by facility ownership and state medicaid expansion status.

BACKGROUND: The recent surge in hepatitis C virus (HCV) prevalence is primarily due to increased injection drug use. Opioid treatment programs (OTPs) are a major source of treatment for people at risk for HCV and are ideal settings for on-site HCV testing. The purpose of this national study was to identify state- and facility-level factors associated with HCV testing availability. METHODS: We used the National Survey of Substance Abuse Treatment Services (2019) to identify OTPs in the US (n = 1679). We used multilevel logistic regression to test for an association between HCV testing and state Medicaid expansion status, and assessed whether the association depended on private or non-profit OTP ownership, adjusted for state racial/ethnic minority populations, poverty, Medicaid access to HCV treatment, and HCV, opioid use disorder, and overdose rates. RESULTS: Two-thirds of OTPs offered HCV testing. Medicaid expansion (versus non-expansion) was associated with a higher odds of HCV testing within OTPs owned by non-profits (adjusted odds ratio=1.99, 95% CI=1.02-3.91, p = 0.04). Nearly all non-profit OTPs that were in expansion states had predicted probabilities that were higher than the national average. CONCLUSION: HCV testing was highest in non-profit OTPs in expansion states. This is concerning given the increasing dominance of private OTPs in the marketplace. Payment structures and reimbursement are likely factors driving the low rate of HCV testing in private facilities and could be addressed with health policies aimed at eliminating HCV. Expanding support for non-profit OTPs also has the potential to strengthen testing rates and improve health.

Time to ACT: launching an Addiction Care Team (ACT) in an urban safety-net health system.

Across the USA, morbidity and mortality from substance use are rising as reflected by increases in acute care hospitalisations for substance use complications and substance-related deaths. Patients with substance use disorders (SUD) have long and costly hospitalisations and higher readmission rates compared to those without SUD. Hospitalisation presents an opportunity to diagnose and treat individuals with SUD and connect them to ongoing care. However, SUD care often remains unaddressed by hospital providers due to lack of a systems approach and addiction medicine knowledge, and is compounded by stigma. We present a blueprint to launching an interprofessional inpatient addiction care team embedded in the hospital medicine division of an urban, safety-net integrated health system. We describe key factors for successful implementation including: (1) demonstrating the scope and impact of SUD in our health system via a needs assessment; (2) aligning improvement areas with health system leadership priorities; (3) involving executive leadership to create goal and initiative alignment; and (4) obtaining seed funding for a pilot programme from our Medicaid health plan partner. We also present challenges and lessons learnt.

Disagreement and Uncertainty Among Experts About how to Respond to Marijuana Use in Patients on Long-term Opioids for Chronic Pain: Results of a Delphi Study.

BACKGROUND: Marijuana use is common among patients on long-term opioid therapy (LTOT) for chronic pain, but there is a lack of evidence to guide clinicians' response. OBJECTIVE: To generate expert consensus about responding to marijuana use among patients on LTOT. DESIGN: Analysis from an online Delphi study. SETTING/SUBJECTS: Clinician experts in pain and opioid management across the United States. METHODS: Participants generated management strategies in response to marijuana use without distinction between medical and nonmedical use, then rated the importance of each management strategy from 1 (not at all important) to 9 (extremely important). A priori rules for consensus were established, and disagreement was explored using cases. Thematic analysis of free-text responses examined factors that influenced participants' decision-making. RESULTS: Of 42 participants, 64% were internal medicine physicians. There was consensus that it is not important to taper opioids as an initial response to marijuana use. There was disagreement about the importance of tapering opioids if there is a pattern of repeated marijuana use without clinical suspicion for a cannabis use disorder (CUD) and consensus that tapering is of uncertain importance if there is suspicion for CUD. Three themes influenced experts' perceptions of the importance of tapering: 1) benefits and harms of marijuana for the individual patient, 2) a spectrum of belief about the overall riskiness of marijuana use, and 3) variable state laws or practice policies. CONCLUSIONS: Experts disagree and are uncertain about the importance of opioid tapering for patients with marijuana use. Experts were influenced by patient factors, provider beliefs, and marijuana policy, highlighting the need for further research.

Common and Challenging Behaviors Among Individuals on Long-term Opioid Therapy.

OBJECTIVE: Long-term opioid therapy (LTOT) is commonly prescribed for chronic pain, despite risks such as opioid use disorder (OUD) and overdose. Caring for patients on LTOT can be difficult, given lack of evidence about assessment of challenging behaviors among patients on LTOT. To develop this evidence, a critical first step is to systematically identify the common and challenging behaviors that primary care providers encounter among patients on LTOT, and also to highlight to diverse range of behaviors encountered. METHOD: We conducted a Delphi study in 42 chronic pain experts to determine consensus on how to address the top common and challenging behaviors. This paper reports on the first round of the study, which elicited a range of behaviors. We conducted thematic analysis of the behaviors and also used the Diagnostic and Statistical Manual (DSM)-5 criteria for OUD as a priori codes. RESULTS: In all, 124 unique behaviors were identified by participants and coded into 4 thematic categories: concerning behaviors that map onto DSM-5 criteria for OUD, and those that do not which were: behaviors that suggest deception, signs of diversion, and nonadherence to treatment plan. Those behaviors that fell outside of OUD criteria we identified as "gray zone" behaviors. CONCLUSIONS: While some of these challenging behaviors fall under the criteria for an OUD, many fall outside of this framework, making diagnosis and treatment difficult, and consensus on how to deal with these "gray zone" behaviors is vital. Future research should explore how these "gray zone" behaviors can best be assessed and managed in a primary care setting.

Consensus-Based Treatment Approaches for Managing Concerning Behaviors in Patients on Long-term Opioid Therapy for Chronic Pain: Case-Based Applications.

Guidelines recommend careful monitoring of patients on long-term opioid therapy for chronic pain to assess for concerning medication-taking behaviors that may signal opioid misuse or the presence of a substance use disorder. However, specific management strategies to guide providers if concerning medication-taking behaviors emerge are lacking. Therefore, we recruited a Delphi panel-42 experts in chronic pain and opioid prescribing-to develop consensus-based treatment approaches to guide management of the 6 most common and concerning behaviors identified: missing prescriber appointments, taking opioids for symptoms other than pain, using more opioid medication than prescribed, asking for an increase in opioid dose, aggressive behavior, and alcohol and other substance use. The results of that process are published as a separate study. The purpose of the present study was to present clinical cases in which concerning medication-taking behaviors arise in the course of long-term opioid therapy and demonstrate for readers how the Delphi panel's consensus-based approaches could be applied.

Correction to: Managing Concerning Behaviors in Patients Prescribed Opioids for Chronic Pain: a Delphi Study.

In this paper, the author degrees were presented incorrectly. The correct listing is above.

Managing Concerning Behaviors in Patients Prescribed Opioids for Chronic Pain: A Delphi Study.

BACKGROUND: Current guideline-recommended monitoring of patients prescribed long-term opioid therapy (LTOT) for chronic pain will likely result in increased identification of behaviors of concern for misuse and addiction, but there is a dearth of empiric evidence about how these behaviors should be managed. OBJECTIVE: To establish expert consensus about treatment approaches for common and challenging concerning behaviors that arise among patients on LTOT. DESIGN: We used a Delphi approach, which allows for generation of consensus. PARTICIPANTS: Participants were clinical experts in chronic pain and opioid prescribing recruited from professional societies and other expert groups. MAIN MEASURES: The Delphi process was conducted online, and consisted of an initial brainstorming round to identify common and challenging behaviors, a second round to identify management strategies for each behavior, and two rounds to establish consensus and explore disagreement/uncertainty. KEY RESULTS: Forty-two participants completed round 1, 22 completed round 2, 30 completed round 3, and 28 completed round 4. Half of round 1 participants were female (52%), and the majority were white (83%). Most (71%) were physicians, and most participants practiced in academic primary (40%) or specialty care (19%).The most frequently cited common and challenging behaviors were missing appointments, taking opioids for symptoms other than pain, using more opioid medication than prescribed, asking for an increase in opioid dose, aggressive behavior, and alcohol and other substance use. Across behaviors, participants agreed that patient education and information gathering were important approaches. Participants also agreed that stopping opioids is not important initially, but if initial approaches do not work, tapering opioids and stopping opioids immediately may become important approaches. CONCLUSIONS: This study presents clinical expert consensus on how to manage concerning behaviors among patients on LTOT. Future research is needed to investigate how implementing these management strategies would impact patient outcomes, practice and policy.

Management of problematic behaviours among individuals on long-term opioid therapy: protocol for a Delphi study.

INTRODUCTION: Given the sharp rise in opioid prescribing and heightened recognition of opioid addiction and overdose, opioid safety has become a priority. Clinical guidelines on long-term opioid therapy (LTOT) for chronic pain consistently recommend routine monitoring and screening for problematic behaviours. Yet, there is no consensus definition regarding what constitutes a problematic behaviour, and recommendations for appropriate management to inform front-line providers, researchers and policymakers are lacking. This creates a barrier to effective guideline implementation. Thus, our objective is to present the protocol for a Delphi study designed to: (1) elicit expert opinion to identify the most important problematic behaviours seen in clinical practice and (2) develop consensus on how these behaviours should be managed in the context of routine clinical care. METHODS/ANALYSIS: We will include clinical experts, defined as individuals who provide direct patient care to adults with chronic pain who are on LTOT in an ambulatory setting, and for whom opioid prescribing for chronic non-malignant pain is an area of expertise. The Delphi study will be conducted online in 4 consecutive rounds. Participants will be asked to list problematic behaviours and identify which behaviours are most common and challenging. They will then describe how they would manage the most frequently occurring common and challenging behaviours, rating the importance of each management strategy. Qualitative analysis will be used to categorise behaviours and management strategies, and consensus will be based on a definition established a priori. ETHICS/DISSEMINATION: This study has been approved by the Institutional Review Board (IRB) of the University of Alabama at Birmingham (UAB). This study will generate Delphi-based expert consensus on the management of problematic behaviours that arise in individuals on LTOT, which we will publish and disseminate to appropriate professional societies. Ultimately, our findings will provide guidance to front-line providers, researchers and policymakers.

Heme oxygenase-2 modulates early pathogenesis after traumatic injury to the immature brain.

We determined if heme oxygenase-2 (HO-2), an enzyme that degrades the pro-oxidant heme, confers neuroprotection in the developing brain after traumatic brain injury (TBI). Male HO-2 wild-type (WT) and homozygous knockout (KO) mice at postnatal day 21 were subjected to TBI and euthanized 1, 7, and 14 days later. Relative cerebral blood flow, measured by laser Doppler, cortical and hippocampal pathogenesis, and motor recovery were evaluated at all time points. Cerebral blood flow was found to be similar between experimental groups. Blood flow significantly decreased immediately after injury, returned to baseline by 1 day, and was significantly elevated by 7 days, post-injury. Nonheme iron preferentially accumulated in the ipsilateral cortex, hippocampus, and external capsule in both WT and KO brain-injured genotypes. There were, however, a significantly greater number of TUNEL-positive cells in the hippocampal dentate gyrus and a significantly greater cortical lesion volume in KOs relative to WTs within the first week post-injury. By 14 days post-injury, however, cortical lesion volume and cell density in the hippocampal CA3 region and dorsal thalamus were similar between the two groups. Assays of fine motor function (grip strength) over the first 2 weeks post-injury revealed a general pattern of decreased strength in the contralateral forelimbs of KOs as compared to WTs. Together, these findings demonstrate that deficiency in HO-2 alters both the kinetics of secondary damage and fine motor recovery after TBI.

A role for conditioned ventral tegmental glutamate release in cocaine seeking.

Initiation of cocaine self-administration in rats was associated with release of glutamate in the ventral tegmental area (VTA). The glutamate release was transient, despite continued cocaine intake. Similar glutamate release was seen in rats earning, for the first time, unexpected saline rather than expected cocaine. VTA glutamate release was not seen in similarly trained rats earning saline instead of cocaine for the 13th time. VTA glutamate release was also seen in similarly trained rats that received yoked rather than earned cocaine injections on test day. VTA glutamate release was not seen in a group of rats that had never earned cocaine but had received yoked injections during the training period. Glutamate release was also not seen in a group of rats that received yoked injections but had no previous experience with cocaine. VTA GABA levels did not fluctuate during any aspect of cocaine seeking. Blockade of VTA glutamate receptors appeared to attenuate the rewarding effects of intravenous cocaine injections and blocked almost completely the conditioned responding normally seen during extinction trials. These findings indicate that VTA glutamate release is a conditioned response dependent on an associative process and is not a simple consequence of previous cocaine exposure. The findings implicate glutamate as at least one of the sources of VTA signals from reward-associated environmental stimuli.

Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking.

Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropin-releasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders.