Blood pressure response to extended-release naltrexone in heroin and prescription opioid users and its implications for cardiovascular morbidity.

BACKGROUND: Consuming opioid agonists is a risk factor for cardiovascular disease particularly in intravenous heroin users. The monthly injectable extended-release opioid antagonist, naltrexone (XR-NTX) is an effective treatment for opioid use disorder. The impact of opioid receptor blockade through XR-NTX on blood pressure, a critical risk factor for cardiovascular morbidity, has not yet been characterized. METHODS: The study evaluated the change in blood pressure during XR-NTX treatment among 14 patients who predominately used intravenous heroin and 24 patients who used prescription oral opioids, all with opioid use disorder. Blood pressure was measured in each patient immediately before the first XR-NTX injection and ∼two weeks after the first injection. The change in diastolic and systolic pressure was compared between the heroin users and the prescription opioids users using analysis of variance. RESULTS: XR-NTX treatment was associated with significant decreases in diastolic blood pressure in the heroin group, but not in the prescription opioids group. Systolic blood pressure values in the heroin users showed a decline at trend level only. CONCLUSIONS: Further research is warranted to replicate our findings and to determine whether XR-NTX effect is relatively specific to blood pressure or generalizes to other components of metabolic syndrome. Distinguishing between heroin and prescription opioid users could shed light on the unique clinical and pharmacological profiles of opioid drugs, particularly regarding their cardiovascular safety. This information can be useful in developing personalized therapeutic strategies based on the route of opioid administration.

Unfilled prescriptions: Surveying patients' experiences with buprenorphine treatment in Massachusetts before and during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: We explored potential challenges to accessing office-based opioid treatment (OBOT) with buprenorphine during the COVID-19 pandemic. METHODS: Using Facebook advertisements, we recruited a sample of N = 72 participants and conducted four repeated-measures analysis of variance comparing ratings of participants' abilities to access aspects of OBOT treatment. RESULTS: Participants reported increased difficulty filling buprenorphine prescriptions during the pandemic than before, p = .011, partial η2 = 0.092, and this was correlated with past month opioid use, r = .236, p = .042. DISCUSSION, CONCLUSIONS, AND SCIENTIFIC SIGNIFICANCE: This is the first investigation to report unfilled prescriptions during the pandemic and an association with opioid use. Unfilled prescriptions may contribute to relapse and partially explain increased overdose deaths during COVID-19.

Author Correction: Metabolic and Addiction Indices in Patients on Opioid Agonist Medication-Assisted Treatment: A Comparison of Buprenorphine and Methadone.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Metabolic and Addiction Indices in Patients on Opioid Agonist Medication-Assisted Treatment: A Comparison of Buprenorphine and Methadone.

Metabolic hormones stabilize brain reward and motivational circuits, whereas excessive opioid consumption counteracts this effect and may impair metabolic function. Here we addressed the role of metabolic processes in the course of the agonist medication-assisted treatment for opioid use disorder (OUD) with buprenorphine or methadone. Plasma lipids, hemoglobin A1C, body composition, the oral glucose tolerance test (oGTT) and the Sweet Taste Test (STT) were measured in buprenorphine- (n = 26) or methadone (n = 32)- treated subjects with OUD. On the whole, the subjects in both groups were overweight or obese and insulin resistant; they displayed similar oGTT and STT performance. As compared to methadone-treated subjects, those on buprenorphine had significantly lower rates of metabolic syndrome (MetS) along with better values of the high-density lipoproteins (HDL). Subjects with- vs. without MetS tended to have greater addiction severity. Correlative analyses revealed that more buprenorphine exposure duration was associated with better HDL and opioid craving values. In contrast, more methadone exposure duration was associated with worse triglycerides-, HDL-, blood pressure-, fasting glucose- and hemoglobin A1C values. Buprenorphine appears to produce beneficial HDL- and craving effects and, contrary to methadone, its role in the metabolic derangements is not obvious. Our data call for further research aimed at understanding the distinctive features of buprenorphine metabolic effects vis-à-vis those of methadone and their potential role in these drugs' unique therapeutic profiles.

Mechanisms Underlying Unconscious Processing and Their Alterations in Post-traumatic Stress Disorder: Neuroimaging of Zero Monetary Outcomes Contextually Framed as "No Losses" vs. "No Gains".

Although unconscious processing is a key element of mental operation, its neural correlates have not been established. Also, clinical observations suggest that unconscious processing may be involved in the pathophysiology of post-traumatic stress disorder (PTSD), but the neurobiological mechanisms underlying such impairments remain unknown. The purpose of the present study was to examine putative mechanisms underlying unconscious processing by healthy participants and to determine whether these mechanisms may be altered in PTSD patients. Twenty patients with PTSD and 27 healthy individuals were administered a validated wheel of fortune-type gambling task during functional magnetic resonance imaging (fMRI). Unconscious processing was elicited using unconscious contextual framing of the zero monetary outcomes as "no loss," "no gain" or as "neutral." Brief passive visual processing of the "no loss" vs. "no gain" contrast by healthy participants yielded bilateral frontal-, temporal- and insular cortices and striatal activations. Between-group comparison revealed smaller activity in the left anterior prefrontal-, left dorsolateral prefrontal-, right temporal- and right insular cortices and in bilateral striatum in PTSD patients with the left dorsolateral prefrontal cortex activity been more pronounced in those with greater PTSD severity. These observations implicate frontal-, temporal-, and insular cortices along with the striatum in the putative mechanisms underlying unconscious processing of the monetary outcomes. Additionally, our results support the hypothesis that PTSD is associated with primary cortical and subcortical alterations involved in the above processes and that these alterations may be related to some aspects of PTSD symptomatology.

Implementing group visits for opioid use disorder: A case series.

Background: Group-based models of Office-Based Opioid Treatment with buprenorphine-naloxone (B/N) are increasingly being implemented in clinical practice to increase access to care and provide additional therapeutic benefits. While previous studies reported these Group-Based Opioid Treatment (GBOT) models are feasible for providers and acceptable to patients, there has been no literature to help providers with the more practical aspects of how to create and maintain GBOT in different outpatient settings. Case series: We present 4 cases of GBOT implementation across a large academic health care system, highlighting various potential approaches for providers who seek to implement GBOT and demonstrate "success" based on feasibility and sustainability of these models. For each case, we describe the pros and cons and detail the personnel and resources involved, patient mix and group format, workflow logistics, monitoring and management, and sustainability components. Discussion: The implementation details illustrate that there is no one-size-fits-all approach, although feasibility is commonly supported by a team-based, patient-centered medical home. This approach includes the capacity for referral to higher levels of mental health and addiction support services and is bolstered by ongoing provider communication and shared resources across the health system. Future research identifying the core and malleable components to implementation, their evidence base, and how they might be influenced by site-specific resources, culture, and other contextual factors can help providers better understand how to implement a GBOT model in their unique clinical environment.

Building a Group-Based Opioid Treatment (GBOT) blueprint: a qualitative study delineating GBOT implementation.

BACKGROUND: Group-Based Opioid Treatment (GBOT) has recently emerged as a mechanism for treating patients with opioid use disorder (OUD) in the outpatient setting. However, the more practical "how to" components of successfully delivering GBOT has received little attention in the medical literature, potentially limiting its widespread implementation and utilization. Building on a previous case series, this paper delineates the key components to implementing GBOT by asking: (a) What are the core components to GBOT implementation, and how are they defined? (b) What are the malleable components to GBOT implementation, and what conceptual framework should providers use in determining how to apply these components for effective delivery in their unique clinical environment? METHODS: To create a blueprint delineating GBOT implementation, we integrated findings from a previously conducted and separately published systematic review of existing GBOT studies, conducted additional literature review, reviewed best practice recommendations and policies related to GBOT and organizational frameworks for implementing health systems change. We triangulated this data with a qualitative thematic analysis from 5 individual interviews and 2 focus groups representing leaders from 5 different GBOT programs across our institution to identify the key components to GBOT implementation, distinguish "core" and "malleable" components, and provide a conceptual framework for considering various options for implementing the malleable components. RESULTS: We identified 6 core components to GBOT implementation that optimize clinical outcomes, comply with mandatory policies and regulations, ensure patient and staff safety, and promote sustainability in delivery. These included consistent group expectations, team-based approach to care, safe and confidential space, billing compliance, regular monitoring, and regular patient participation. We identified 14 malleable components and developed a novel conceptual framework that providers can apply when deciding how to employ each malleable component that considers empirical, theoretical and practical dimensions. CONCLUSION: While further research on the effectiveness of GBOT and its individual implementation components is needed, the blueprint outlined here provides an initial framework to help office-based opioid treatment sites implement a successful GBOT approach and hence potentially serve as future study sites to establish efficacy of the model. This blueprint can also be used to continuously monitor how components of GBOT influence treatment outcomes, providing an empirical framework for the ongoing process of refining implementation strategies.

Reward and aversion processing in patients with post-traumatic stress disorder: functional neuroimaging with visual and thermal stimuli.

In patients with post-traumatic stress disorder (PTSD), a decrease in the brain reward function was reported in behavioral- and in neuroimaging studies. While pathophysiological mechanisms underlying this response are unclear, there are several lines of evidence suggesting over-recruitment of the brain reward regions by aversive stimuli rendering them unavailable to respond to reward-related content. The purpose of this study was to juxtapose brain responses to functional neuroimaging probes that reliably produce rewarding and aversive experiences in PTSD subjects and in healthy controls. The stimuli used were pleasant, aversive and neutral images selected from the International Affective Picture System (IAPS) along with pain-inducing heat applied to the dorsum of the left hand; all were administered during 3 T functional magnetic resonance imaging. Analyses of IAPS responses for the pleasant images revealed significantly decreased subjective ratings and brain activations in PTSD subjects that included striatum and medial prefrontal-, parietal- and temporal cortices. For the aversive images, decreased activations were observed in the amygdala and in the thalamus. PTSD and healthy subjects provided similar subjective ratings of thermal sensory thresholds and each of the temperatures. When 46 °C (hot) and 42 °C (neutral) temperatures were contrasted, voxelwise between-group comparison revealed greater activations in the striatum, amygdala, hippocampus and medial prefrontal cortex in the PTSD subjects. These latter findings were for the most part mirrored by the 44 vs. 42 °C contrast. Our data suggest different brain alterations patterns in PTSD, namely relatively diminished corticolimbic response to pleasant and aversive psychosocial stimuli in the face of exaggerated response to heat-related pain. The present findings support the hypothesis that brain sensitization to pain in PTSD may interfere with the processing of psychosocial stimuli whether they are of rewarding or aversive valence.

Co-occurring Disordered Gambling Among Treatment-Seekers at a Community Outpatient Addiction Clinic.

BACKGROUND: Parallel to the ongoing expansion of legalized gambling activities is a growing concern about rising occurrence of uncontrollable gambling. People with preexisting gambling and/or chemical addictions may be particularly vulnerable, but the extent of such co-occurring conditions and their demographic and clinical characteristics have not been sufficiently elucidated. To that end, the present study attempted to both, quantify the presence and to characterize co-occurring pathological or problem gambling (ie, respectively, at least 1- or at least 5 pathological gambling criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) among treatment-seeking patients at a community outpatient addiction program. METHODS: The patients were assessed with the South Oaks Gambling Screen and their charts were reviewed for the extraction of demographic and clinical information according to a predetermined template. Data from 183 subjects withstood quality control procedures and were included. RESULTS: The prevalence rates of co-occurring problem- (18.6%) and pathological (10.9%) gambling were strikingly higher than those found in the general population (2% and 0.5%, respectively). No increase in the clinical severity indices was observed across the gambling groups. CONCLUSIONS: Our data replicate those of prior studies reporting heightened prevalence of problematic gambling in patients with substance use disorders and extend the prior findings by including a subject population of treatment-seekers. In the era of the gambling industry growth, these results call for creation and/or adjustment of clinical addiction services to meet emerging preventive and therapeutic needs.

Using educational prescriptions to teach medical students evidence-based medicine.

PURPOSE: To evaluate feasibility and impact of evidence-based medicine (EBM) educational prescriptions (EPs) in medical student clerkships. METHODS: Students answered clinical questions during clerkships using EPs, which guide learners through the "four As" of EBM. Epidemiology fellows graded EPs using a rubric. Feasibility was assessed using descriptive statistics and student and fellow end-of-study questionnaires, which also measured impact. In addition, for each EP, students reported patient impact. Impact on EBM skills was assessed by change in EP scores over time and scores on an EBM objective structured clinical exam (OSCE) that were compared to controls from the prior year. RESULTS: 117 students completed 402 EPs evaluated by 24 fellows. Average score was 7.34/9.00 (SD 1.58). 69 students (59%) and 21 fellows (88%) completed questionnaires. Most students thought EPs improved "Acquiring" and "Appraising". Almost half thought EPs improved "Asking" and "Applying". Fellows did not value grading EPs. For 18% of EPs, students reported a "change" or "potential change" in treatment. 56% "confirmed" treatment. EP scores increased by 1.27 (95% CI: 0.81-1.72). There were no differences in OSCE scores between cohorts. CONCLUSIONS: Integrating EPs into clerkships is feasible and has impact, yet OSCEs were unchanged, and research fellows had limitations as evaluators.

Progress testing: critical analysis and suggested practices.

Educators have long lamented the tendency of students to engage in rote memorization in preparation for tests rather than engaging in deep learning where they attempt to gain meaning from their studies. Rote memorization driven by objective exams has been termed a steering effect. Progress testing (PT), in which a comprehensive examination sampling all of medicine is administered repeatedly throughout the entire curriculum, was developed with the stated aim of breaking the steering effect of examinations and of promoting deep learning. PT is an approach historically linked to problem-based learning (PBL) although there is a growing recognition of its applicability more broadly. The purpose of this article is to summarize the salient features of PT drawn from the literature, provide a critical review of these features based upon the same literature and psychometric considerations drawn from the Standards for Educational and Psychological Testing and provide considerations of what should be part of best practices in applying PT from an evidence-based and a psychometric perspective.

Emerging adult age status predicts poor buprenorphine treatment retention.

Emerging adults (18-25 years old) are often poorly retained in substance use disorder treatment. Office-based buprenorphine often enhances treatment retention among people with opioid dependence. In this study, we examined the records of a collaborative care buprenorphine treatment program to compare the treatment retention rates of emerging adults versus older adults. Subjects were 294 adults, 71 (24%) aged 18-25, followed in treatment with buprenorphine, nurse care management, and an intensive outpatient program followed by weekly psychosocial treatment. Compared to older adults, emerging adults remained in treatment at a significantly lower rate at 3 months (56% versus 78%) and 12 months (17% versus 45%), and were significantly more likely to test positive for illicit opioids, relapse, or drop out of treatment. Further research into factors associated with buprenorphine treatment retention among emerging adults is needed to improve treatment and long-term outcomes in this group.

Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes.

BACKGROUND: Prescribing benzodiazepines during buprenorphine treatment is a topic of active discussion. Clinical benefit is unclear. Overdose, accidental injury, and benzodiazepine misuse remain concerns. We examine the relationship between benzodiazepine misuse history, benzodiazepine prescription, and both clinical and safety outcomes during buprenorphine treatment. METHODS: We retrospectively examined outpatient buprenorphine treatment records, classifying patients by past-year benzodiazepine misuse history and approved benzodiazepine prescription at intake. Primary clinical outcomes included 12-month treatment retention and urine toxicology for illicit opioids. Primary safety outcomes included total emergency department (ED) visits and odds of an ED visit related to overdose or accidental injury during treatment. RESULTS: The 12-month treatment retention rate for the sample (N=328) was 40%. Neither benzodiazepine misuse history nor benzodiazepine prescription was associated with treatment retention or illicit opioid use. Poisson regressions of ED visits during buprenorphine treatment revealed more ED visits among those with a benzodiazepine prescription versus those without (p<0.001); benzodiazepine misuse history had no effect. The odds of an accidental injury-related ED visit during treatment were greater among those with a benzodiazepine prescription (OR: 3.7, p<0.01), with an enhanced effect among females (OR: 4.7, p<0.01). Overdose was not associated with benzodiazepine misuse history or prescription. CONCLUSIONS: We found no effect of benzodiazepine prescriptions on opioid treatment outcomes; however, benzodiazepine prescription was associated with more frequent ED visits and accidental injuries, especially among females. When prescribing benzodiazepines during buprenorphine treatment, patients need more education about accidental injury risk. Alternative treatments for anxiety should be considered when possible, especially among females.

Single and Multiple Ability Estimation in the SEM Framework: A Non-Informative Bayesian Estimation Approach.

Latent variable models with many categorical items and multiple latent constructs result in many dimensions of numerical integration, and the traditional frequentist estimation approach, such as maximum likelihood (ML), tends to fail due to model complexity. In such cases, Bayesian estimation with diffuse priors can be used as a viable alternative to ML estimation. The present study compares the performance of Bayesian estimation to ML estimation in estimating single or multiple ability factors across two types of measurement models in the structural equation modeling framework: a multidimensional item response theory (MIRT) model and a multiple-indicator multiple-cause (MIMIC) model. A Monte Carlo simulation study demonstrates that Bayesian estimation with diffuse priors, under various conditions, produces quite comparable results to ML estimation in the single- and multi-level MIRT and MIMIC models. Additionally, an empirical example utilizing the Multistate Bar Examination is provided to compare the practical utility of the MIRT and MIMIC models. Structural relationships among the ability factors, covariates, and a binary outcome variable are investigated through the single- and multi-level measurement models. The paper concludes with a summary of the relative advantages of Bayesian estimation over ML estimation in MIRT and MIMIC models and suggests strategies for implementing these methods.

Psychiatry in the Harvard Medical School-Cambridge Integrated Clerkship: an innovative, year-long program.

OBJECTIVE: The authors present what is to their knowledge the first description of a model for longitudinal third-year medical student psychiatry education. METHOD: A longitudinal, integrated psychiatric curriculum was developed, implemented, and sustained within the Harvard Medical School-Cambridge Integrated Clerkship. Curriculum elements include longitudinal mentoring by attending physicians in an outpatient psychiatry clinic, exposure to the major psychotherapies, psychopharmacology training, acute psychiatry "immersion" experiences, and a variety of clinical and didactic teaching sessions. RESULTS: The longitudinal psychiatry curriculum has been sustained for 8 years to-date, providing effective learning as demonstrated by OSCE scores, NBME shelf exam scores, written work, and observed clinical work. The percentage of students in this clerkship choosing psychiatry as a residency specialty is significantly greater than those in traditional clerkships at Harvard Medical School and greater than the U.S. average. CONCLUSION: Longitudinal integrated clerkship experiences are effective and sustainable; they offer particular strengths and opportunities for psychiatry education, and may influence student choice of specialty.

Commentary: measurement and interpretation challenges in comparing student performance outcomes from different medical schools.

This commentary points to several measurement issues that arise in assessing medical student performance outcomes and then discusses the challenge of interpreting between-school differences. A problem often encountered in assessing student learning is creating an instrument that is at the right "pay grade." If it is too easy, ceiling effects compress scores. If it is too difficult, examinee performance can compress about chance values, and morale problems can occur. These issues are discussed in the context of a report by Williams and colleagues that measures medical student performance across five institutions on instruments assessing diagnostic pattern recognition and clinical data interpretation. The author of this commentary observes that, when interpreting between-school differences in assessing student learning, what can seem like small differences can have important consequences.