"They were an advocate for me": A Qualitative Study Exploring Medical Student Longitudinal Relationships and Patient Well-Being.

BACKGROUND: Patient navigators, community health workers, and care management teams improve patient experience and health outcomes. Medical student involvement in these roles is limited. Evaluation of these programs focuses on the student experience with less attention to patient participants. OBJECTIVES: We sought (1) to understand the experience of being a participant in a medical education program; (2) to explore the patient-medical student relationship; and (3) to describe the impact of this relationship on patient health and well-being. DESIGN: This was a qualitative study that utilized in-depth semi-structured interviews. PARTICIPANTS: Participants were selected based on enrollment in a preceptorship program at an urban academic medical center between 2017 and 2020. Participants worked with a medical student during an 18-month period in which the medical student was embedded in a primary care medical home, serving as a health systems navigator for 1-2 medically and socially complex patients. APPROACH: Nine participants completed 1-h compensated phone interviews. This study was deemed IRB exempt. KEY RESULTS: Three themes and eight subthemes were identified, including Navigators Were Key to Accessing the System, Interpersonal Partnerships Improved Health, and Fulfillment in Teaching of Lived Experience. Navigators eased the burden of chronic illness by being a point of contact in the health system, which improved participants' overall experience. Participants also described the relationship as therapeutic, citing improvement and stability in both mental and physical health. Lastly, participants found meaning in chronic illness by teaching their students empathy. CONCLUSIONS: Longitudinal patient-medical student relationships may provide stability and health benefits. These partnerships have the possibility of adding value to patients' healthcare experiences. This study complements current literature highlighting the value of these relationships for pre-clinical medical students. As such, additional opportunities for and additional research regarding the value of longitudinal patient connection should be incorporated in undergraduate medical education.

Exploring how hospitalization can alter hepatitis c virus treatment prioritization and trajectories in people who use drugs: A qualitative analysis.

Background: People who use drugs (PWUD) have high rates of hepatitis C virus (HCV) infection. Hospitalization can be a time for PWUD to engage in addiction treatment, but little is known about how hospitalization shapes HCV treatment readiness. We aimed to describe how hospitalization and addiction medicine consult service (AMCS) can alter HCV prioritization of inpatient PWUD with HCV. Methods: We conducted a qualitative study consisting of semi-structured interviews (n = 27) of hospitalized adults with addiction and HCV infection seen by an AMCS at a single, urban, academic center. Interviews were audio-recorded, transcribed, and coded iteratively at the semantic level, and analyzed for themes. Results: Of the 27 participants, most identified as Caucasian (85%), male gender (67%), and they primarily used opioids (78%); approximately half (48%) reported HCV diagnosis over 5 years ago. We identified three main themes around hospitalization altering the prioritizations and HCV treatment preferences for PWUD: (1) HCV treatment non-engaged (2) HCV treatment urgency, and (3) HCV treatment in the future. Those wanting to treat HCV-whether urgently or in the future-shared the overlapping theme of hospitalization as a reachable moment for their addiction and HCV. These participants recognized the long-term benefits of addressing HCV and connected their hospitalization to substance use. Conclusion: In our study, PWUD with HCV expressed varying and competing priorities and life circumstances contributing to three main HCV treatment trajectories. Our results suggest ways hospitalization can serve as an HCV touchpoint for PWUD, especially in the context of addressing substance use, and could be used when designing and implementing targeted interventions to improve the HCV care continuum for PWUD.

"OPTIONS-DC", a feasible discharge planning conference to expand infection treatment options for people with substance use disorder.

BACKGROUND: Serious bacterial infections associated with substance use often result in long hospitalizations, premature discharges, and high costs. Out-of-hospital treatment options in people with substance use disorder (SUD) are often limited. METHODS: We describe a novel multidisciplinary and interprofessional care conference, "OPTIONS-DC," to identify treatment options agreeable to both patients and providers using the frameworks of harm reduction and patient-centered care. We retrospectively reviewed charts of patients who had an OPTIONS-DC between February 2018 and July 2019 and used content analysis to understand the conferences' effects on antibiotic treatment options. RESULTS: Fifty patients had an OPTIONS-DC during the study window. Forty-two (84%) had some intravenous (IV) substance use and 44 (88%) had an active substance use disorder. Participants' primary substances included opioids (65%) or methamphetamines (28%). On average, conferences lasted 28 min. OPTIONS-DC providers recommended out-of-hospital antibiotic treatment options for 34 (68%) of patients. OPTIONS-DC recommended first line therapy of IV antibiotics for 35 (70%) patients, long-acting injectable antibiotics for 14 (28%), and oral therapy for 1 (2%). 35 (70%) patients that had an OPTIONS-DC completed an antibiotic course and 6 (12%) left the hospital prematurely. OPTIONS-DC expanded treatment options by exposing and contextualizing SUD, psychosocial risk and protective factors; incorporating patient preferences; and allowing providers to tailor antibiotic and SUD recommendations. CONCLUSIONS: OPTIONS-DC is a feasible intervention that allows providers to integrate principles of harm reduction and offer patient-centered choices among patients needing prolonged antibiotic treatment.

Introductory Medical Spanish Elective: Creating and Evaluating a Case-Based Course Compatible with an 18-Month Pre-Clinical Medical Curriculum.

BACKGROUND: Limited English proficiency patients experience high rates of medical errors and receive lower quality of care. To better prepare the healthcare workforce, Latino Medical Student Association (LMSA) members at Oregon Health & Science University (OHSU) developed an Introductory Medical Spanish course to complement an 18-month pre-clinical curriculum. METHODS: This 10-week elective course consisted of 2 h of weekly instruction, two Cafecito cultural sessions, and one clinical standardized assessment (CSA). The authors used Bloom's taxonomy as a theoretical framework to design course components. Pre- and post-course surveys captured comfort scores with performing a history and physical (H&P) and building rapport in Spanish. Change in comfort was analyzed via paired T-test in STATA. The authors performed a content analysis of CSA feedback and a thematic analysis of Cafecito reflections. RESULTS: Fifteen preclinical medical students in cohort 1 and sixteen in cohort 2 completed the 10-week course. Comfort scores significantly (p < 0.05) increased by 2.87 and 1 point(s) for cohorts 1 and 2, respectively. There were differences between cohorts 1 and 2, including self-reported language fluency (93% vs 47% "beginner" level) and value of the cultural sessions (73% vs 50%), respectively. Qualitative content analysis of CSA feedback and thematic analysis of Cafecito reflections revealed students successfully applied learned material to a new case and developed a newfound appreciation for Latinx public health issues. CONCLUSIONS: This course effectively increased students' comfort using medical Spanish which successfully translated into simulated patient environments. It also provided a space to discuss nuances of health and Latinx cultures with peers. Ultimately, this course's feasible, effective structure can serve as a model to complement condensed pre-clinical undergraduate medical education (UME) curricula.

Utilising an access to care integrated framework to explore the perceptions of hepatitis C treatment of hospital-based interventions among people who use drugs.

BACKGROUND: Gaps remain in the hepatitis C virus (HCV) care cascade for people who use drugs (PWUD). Acute medical or surgical illnesses requiring hospitalisation are an opportunity to address addiction, but how inpatient strategies could affect HCV care accessibility for PWUD remains unknown. We explored patient perspectives of hospital-based interventions using an integrated framework of access to HCV care. METHODS: We conducted a qualitative study of hospitalised adults (n=27) with HCV and addiction admitted to an urban academic medical centre in the United States between June and November 2019. Individual interviews were audio-recorded, transcribed, and dual-coded. We analysed data with coding specific for hospital-based interventions including screening, conducting HCV-related laboratory work-up, starting treatment, connecting with peers, and coordinating outpatient care. We analysed coded data at the semantic level for emergent themes using a framework approach based off an integrated framework of access to HCV care. RESULTS: The majority of participants primarily used opioids (78%), were white (85%) and men (67%). Participants frequently reported HCV screening during previous hospitalisation with rare inpatient connection to HCV-related services. Participants expressed willingness to discuss HCV treatment candidacy during hospitalisation; however, lack of inpatient conversations led to perception that "nothing could be done" during admission. Participants expressed interest in completing inpatient HCV work-up to "get the ball rollin'" - consolidating care would enhance outpatient service permeability by reducing barriers. Others resisted HCV care coordination, preferring to focus on "immediate" issues including health conditions and addiction treatment. Participants also expressed openness to engaging with peers about HCV, noting shared drug use experience as critical to a peer relationship when discussing HCV. CONCLUSION: Hospitalised PWUD have varied priorities, necessitating adaptable interventions for addressing HCV. Hospitalisation can be an opportunity to address HCV access to care including identification of treatment eligibility, consolidation of care, and facilitation of HCV-related referrals.

Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial.

Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d', an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d' and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.

"Sobriety equals getting rid of hepatitis C": A qualitative study exploring the interplay of substance use disorder and hepatitis C among hospitalized adults.

BACKGROUND: People who use drugs (PWUD) commonly experience complex illness, psychosocial stressors, housing insecurity, and stigma, which may play key roles in their struggles with addiction. In a study of hospitalized PWUD with hepatitis C virus infection (HCV), participants described treating HCV as "part of recovery." These findings led us to explore how hospitalization and acute illness altered patients' perceptions of substance use disorder (SUD) and HCV. METHODS: Researchers audio recorded in-depth semi-structured individual interviews of 27 hospitalized adults with SUD and HCV seen by an addiction consult service (ACS) at an urban academic medical center between June and November 2019. Research staff transcribed interviews and dual coded them deductively and inductively at the semantic level. Researchers used a matrix visualization to discern relationships among codes and conducted a thematic analysis. RESULTS: Many participants believed addictions treatment should precede an HCV cure for varying reasons. Some wanted to avoid reinfection; others believed "getting clean" afforded the mental clarity to address health issues, including HCV. Patients newly engaged in SUD treatment described HCV treatment as a "step towards recovery" and could serve as motivation to continue SUD treatment. Participants believed HCV cure could facilitate sobriety by "mentally putting drugs in the past" and was a future-oriented action toward "better health." Many participants described the compounded stigma of having HCV infection and SUD by multiple groups, including friends/family who do not use drugs, other drug users, and health care workers. CONCLUSION: Hospitalized adults with SUD and HCV believed addictions engagement should precede HCV treatment and HCV cure could play an important role in their "recovery" journey. Discussing HCV treatment during hospitalization may be an opportunity to support engagement in SUD treatment and targets an untreated patient population critical for achieving HCV elimination.

Understanding the impact of the SARS-COV-2 pandemic on hospitalized patients with substance use disorder.

BACKGROUND: The SARS-COV-2 pandemic rapidly shifted dynamics around hospitalization for many communities. This study aimed to evaluate how the pandemic altered the experience of healthcare, acute illness, and care transitions among hospitalized patients with substance use disorder (SUD). METHODS: We performed a qualitative study at an academic medical center in Portland, Oregon, in Spring 2020. We conducted semi-structured interviews, and conducted a thematic analysis, using an inductive approach, at a semantic level. RESULTS: We enrolled 27 participants, and identified four main themes: 1) shuttered community resources threatened patients' basic survival adaptations; 2) changes in outpatient care increased reliance on hospitals as safety nets; 3) hospital policy changes made staying in the hospital harder than usual; and, 4) care transitions out of the hospital were highly uncertain. DISCUSSION: Hospitalized adults with SUD were further marginalized during the SARS-COV-2 pandemic. Systems must address the needs of marginalized patients in future disruptive events.

The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder.

RATIONALE: Individuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD. OBJECTIVES: To determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks. METHODS: We used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD. RESULTS: Tolcapone significantly reduced self-reported alcohol consumption (t (54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r (45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo. CONCLUSIONS: These data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02740582.

Dopamine and Risky Decision-Making in Gambling Disorder.

Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and cognitive control. These functions are thought to be regulated by dopamine within fronto-striatal circuits, but the role of altered dopamine neurotransmission in the etiology of gambling disorder remains controversial. Preliminary evidence suggests that increasing frontal dopamine tone might improve cognitive functioning in gambling disorder. We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n = 14) in a randomized double-blind placebo-controlled crossover study. Data were analyzed using hierarchical Bayesian parameter estimation and a combined risky choice drift diffusion model (DDM). Model comparison revealed a nonlinear mapping from value differences to trial-wise drift rates, confirming recent findings. An increase in risk-taking under tolcapone versus placebo was about five times more likely, given the data, than a decrease [Bayes factor (BF) = 0.2]. Examination of drug effects on diffusion model parameters revealed that an increase in the value dependency of the drift rate under tolcapone was about thirteen times more likely than a decrease (BF = 0.073). In contrast, a reduction in the maximum drift rate under tolcapone was about seven times more likely than an increase (BF = 7.51). Results add to previous work on COMT inhibitors in behavioral addictions and to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition.

Dopamine, time perception, and future time perspective.

RATIONALE: Impairment in time perception, a critical component of decision-making, represents a risk factor for psychiatric conditions including substance abuse. A therapeutic that ameliorates this impairment could be advantageous in the treatment of impulsivity and decision-making disorders. OBJECTIVES: Here we hypothesize that the catechol-O-methyltransferase (COMT) inhibitor tolcapone, which increases dopamine tone in frontal cortex (Ceravolo et al Synapse 43:201-207, 2002), improves time perception, with predictive behavioral, genetic, and neurobiological components. METHODS: Subjects (n = 66) completed a duration estimation task and other behavioral testing in each of two sessions after receiving a single oral dose of tolcapone (200 mg) or placebo in randomized, double-blind, counterbalanced, crossover fashion. Resting state fMRI data were obtained in a subset of subjects (n = 40). Subjects were also genotyped for the COMT (rs4680) polymorphism. RESULTS: Time perception was significantly improved across four proximal time points ranging from 5 to 60 s (T(524) = 2.04, p = 0.042). The degree of this improvement positively correlated with subjective measures of stress, depression, and alcohol consumption and was most robust in carriers of the COMT Val158 allele. Using seed regions defined by a previous meta-analysis (Wiener et al Neuroimage 49:1728-1740, 2010), we found not only that a connection from right inferior frontal gyrus (RIFG) to right putamen decreases in strength on tolcapone versus placebo (p < 0.05, corrected), but also that the strength of this decrease correlates inversely with the increase in duration estimation on tolcapone versus placebo (r = - 0.37, p = 0.02). CONCLUSIONS: Compressed time perception can be ameliorated by administration of tolcapone. Additional studies should be conducted to determine whether COMT inhibitors may be effective in treating decision-making disorders and addictive behaviors.

Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers.

Failures of self-regulation in problem and pathological gambling (PPG) are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patients with addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT), reduced delay discounting, a measure of impulsivity, in healthy subjects. To evaluate this potentially translational approach to augmenting prefrontal inhibitory control, here we hypothesized that increasing cortical dopamine tone would reduce delay discounting in PPG subjects in proportion to its ability to augment top-down control. To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. In this subject population, we found that greater BOLD activity during the placebo condition within the right inferior frontal cortex (RIFC), a region thought to be important for inhibitory control, correlated with greater declines in impulsivity on tolcapone versus placebo. Intriguingly, connectivity between RIFC and the right striatum, and not the level of activity within RIFC itself, increased on tolcapone versus placebo. Together, these findings support the hypothesis that tolcapone-mediated increases in top-down control may reduce impulsivity in PPG subjects, a finding with potential translational relevance for gambling disorders, and for behavioral addictions in general.

Prenatal deletion of the RNA-binding protein HuD disrupts postnatal cortical circuit maturation and behavior.

The proper functions of cortical circuits are dependent upon both appropriate neuronal subtype specification and their maturation to receive appropriate signaling. These events establish a balanced circuit that is important for learning, memory, emotion, and complex motor behaviors. Recent research points to mRNA metabolism as a key regulator of this development and maturation process. Hu antigen D (HuD), an RNA-binding protein, has been implicated in the establishment of neuronal identity and neurite outgrowth in vitro. Therefore, we investigated the role of HuD loss of function on neuron specification and dendritogenesis in vivo using a mouse model. We found that loss of HuD early in development results in a defective early dendritic overgrowth phase and pervasive deficits in neuron specification in the lower neocortical layers and defects in dendritogenesis in the CA3 region of the hippocampus. Subsequent behavioral analysis revealed a deficit in performance of a hippocampus-dependent task: the Morris water maze. Further, HuD knock-out (KO) mice exhibited lower levels of anxiety than their wild-type counterparts and were overall less active. Last, we found that HuD KO mice are more susceptible to auditory-induced seizures, often resulting in death. Our findings suggest that HuD is necessary for the establishment of neocortical and hippocampal circuitry and is critical for their function.