Reliance on Community Emergency Departments by People Ever Detained in Jail: Retrospective Cross-Sectional Study.

Millions are confined in U.S. jails each year, often with unmet health and social needs. After release, many will visit the emergency department (ED). To illuminate their patterns of ED use, this study linked records from all individuals detained at a Southern urban jail over a 5-year period with health records from a large health care system with three EDs. Over half used the ED at least once, and of those who received care at the health system, 83% visited the ED. Jail-involved people made up 4.1% of the health care system's ED users but 21.3% of its chronic frequent ED users. Frequent ED use was associated with more frequent jail bookings and with co-occurring serious mental illness and substance use disorder. Health systems and jails have a common interest in addressing the needs of this population. Individuals with co-occurring disorders should be prioritized for intervention.

Relationships between substance use disorders, 'severe mental illness' and re-arrest in a county detention facility: A 4-year follow-up cohort study.

BACKGROUND: A growing body of literature demonstrates strong association between poor mental health and criminal recidivism, but research from county jails is limited. AIMS: Our aim was to examine the relationship between re-arrest and severe mental illnesses-schizophrenia, bipolar disorder and major depressive disorder-together and separately and with substance use disorders, separately and as comorbid conditions, in a mid-sized county jail cohort in the southeastern United States. METHODS: We examined the full cohort of 8097 individuals who were booked into the County Detention Facility between 31 January 2014 and 31 January 2015. Their incarceration data were merged with data from the local health system to investigate the presence of severe mental illness and substance use disorder diagnoses. Re-arrest data were tracked for 4 years after the index arrest. RESULTS: Approximately 60% of the cohort was re-arrested within 4 years. People with substance use disorders, with or without severe mental illness, had higher re-arrest rates than those with severe mental illness alone or neither diagnosis. Drug-associated arrests did not explain this finding. CONCLUSIONS: Using detailed mental illness diagnosis data with a complete cohort of detained arrestees, we have shown the wide range of need among such individuals. By demonstrating that drug-associated crimes per se do not drive repeated arrest, we underscore a need to examine other factors that promote the cycle of repeated arrest in this population. Each individual requires treatment tailored to their personal psychiatric and criminogenic needs.

Increasing Naloxone Prescribing in the Emergency Department Through Education and Electronic Medical Record Work-Aids.

BACKGROUND: Emergency department (ED) visits for opioid overdose continue to rise. Evidence-based harm reduction strategies for opioid use disorder (OUD), such as providing home naloxone, can save lives, but ED implementation remains challenging. METHODS: The researchers aimed to increase prescribing of naloxone to ED patients with OUD and opioid overdose by employing a model for improvement methodology, a multidisciplinary team, and high-reliability interventions. Monthly naloxone prescribing rates among discharged ED patients with opioid overdose and OUD-related diagnoses were tracked over time. Interventions included focused ED staff education on OUD and naloxone, and creation of electronic medical record (EMR)-based work-aids, including a naloxone Best Practice Advisory (BPA) and order set. Autoregressive interrupted time series was used to model the impact of these interventions on naloxone prescribing rates. The impact of education on ED staff confidence and perceived barriers to prescribing naloxone was measured using a published survey instrument. RESULTS: After adjusting for education events and temporal trends, ED naloxone BPA and order set implementation was associated with a significant immediate 21.1% increase in naloxone prescribing rates, which was sustained for one year. This corresponded to increased average monthly prescribing rates from 1.5% before any intervention to 28.7% afterward. ED staff education had no measurable impact on prescribing rates but was associated with increased nursing perceived importance and increased provider confidence in prescribing naloxone. CONCLUSIONS: A significant increase in naloxone prescribing rates was achieved after implementation of high-reliability EMR work-aids and staff education. Similar interventions may be key to wider ED staff engagement in harm reduction for patients with OUD.

The Emergency Department as an Opportunity for Naloxone Distribution.

INTRODUCTION: Substance use disorders, including opioid use disorders, are a major public health concern in the United States. Between 2005 and 2014, the rate of opioid-related emergency department (ED) visits nearly doubled, from 89.1 per 100,000 persons in 2005 to 177.7 per 100,000 persons in 2014. Thus, the ED presents a distinctive opportunity for harm-reduction strategies such as distribution of naloxone to patients who are at risk for an opioid overdose. METHODS: We conducted a systematic review of all existing literature related to naloxone distribution from the ED. We included only those articles published in peer-reviewed journals that described results relating to naloxone distribution from the ED. RESULTS: Of the 2,286 articles we identified from the search, five met the inclusion criteria and had direct relevance to naloxone distribution from the ED setting. Across the studies, we found variation in the methods of implementation and evaluation of take-home naloxone programs in the ED. In the three studies that attempted patient follow-up, success was low, limiting the evidence for the programs' effectiveness. Overall, in the included studies there is evidence that distributing take-home naloxone from the ED has the potential for harm reduction; however, the uptake of the practice remained low. Barriers to implementation included time allocated for training hospital staff and the burden on workflow. CONCLUSION: This systematic review of the best evidence available supports the ED as a potential setting for naloxone distribution for overdose reversal in the community. The variability of the implementation methods across the studies highlights the need for future research to determine the most effective practices.

Utilizing Bloom's taxonomy to design a substance use disorders course for health professions students.

BACKGROUND: Substance use disorders (SUDs) are a public health problem affecting millions of Americans. Despite their prevalence, there are few health care resources allocated for SUDs treatment. Relatively few health care professionals are exposed to SUDs education in their respective programs, which may be one reason for this resource insufficiency. In hopes of rectifying this gap, the authors developed a SUDs course for health professions students combining classroom learning with practical application to patient care. METHODS: The authors used Bloom's taxonomy of cognitive, affective, and psychomotor learning domains as an educational framework to create numerous opportunities for students to deepen their knowledge, assess their attitudes, and develop their motivational interviewing skills. The primary outcome of the study was a comparison of students' scores on the Substance Abuse Attitude Scale (SAAS) pre- and post-course completion. Secondary outcome was to compare students' self-assessment scores of their patient counseling with residents' assessments of them on the Liverpool Communication Skills Assessment Scale (LCSAS). RESULTS: One hundred twelve students participated in the authors' SUDs course over a 9-month period. Ninety-five students completed both the pre- and post-course SAAS surveys. The total SAAS survey score and individual domain scores for nonmoralizing, treatment optimism, and treatment intervention demonstrated significant improvement post-course. Eighty-nine students completed a motivational interview with a patient. Eighty students had a LCSAS self-assessment paired with a residents' assessment. Mean scores for individual items on the LCSAS for both groups' assessment were approximately 3.5, indicating that students' communication was assessed as "acceptable" to "good." CONCLUSIONS: This study demonstrates that Bloom's taxonomy was a useful educational framework to ensure a systematic development of the authors' SUDs course. Through participation in our course, students touched each of the 3 domains in Bloom's taxonomy. The authors believe their course design may serve as a framework for future SUDs courses.

Behavioral Inefficiency on a Risky Decision-Making Task in Adulthood after Adolescent Intermittent Ethanol Exposure in Rats.

Adolescence is a period of development in neural circuits that are critical for adult functioning. There is a relationship between alcohol exposure and risky decision-making, though the enduring effects of adolescent ethanol exposure on risky decision-making in adulthood have not been fully explored. Studies using positive reinforcement have shown that adolescent intermittent ethanol (AIE) exposure results in higher levels of risky decision-making in adulthood, but the effects of AIE on punishment-mediated decision-making have not been explored. Adolescent rats were exposed to AIE or saline vehicle across a 16-day period, and then allowed to mature into adulthood. They were then trained to lever press for food reward and were assessed for risky decision-making by pairing increased levels of food reward with the probability of footshock punishment. AIE did not alter punishment-mediated risky decision-making. However, it did result in a significant increase in the delay to lever pressing. This finding is consistent with previous reports, using other behavioral tasks, which show decreased behavioral efficiency in adulthood after AIE. These findings indicate that AIE increases behavioral inefficiency, but not punishment-mediated risk-taking, in adulthood. Thus they contribute to a more nuanced understanding of the long-term effects of AIE on adult behavior.

An Interprofessional Course on Substance Use Disorders for Health Professions Students.

PROBLEM: Substance use disorders (SUDs) affect millions of Americans. Nevertheless, there is insufficient health care resource allocation for these patients. One reason may be the lack of education and training about SUDs in health professions programs. APPROACH: The authors developed a required, interprofessional SUDs course for health professions students completing a one-month psychiatry clerkship within the Duke University Health System starting in November 2015. Students participated in six 1-hour class sessions led by an interdisciplinary faculty. Sessions focused on core areas in SUDs education and used either a lecture with discussion or a small-group team-based learning format. Students completed one motivational interview, attended a 12-step recovery meeting, and wrote a reflection paper. On the first and last day of the clerkship, students measured their attitudes toward individuals with SUDs using the Substance Abuse Attitude Scale (SAAS) and toward interprofessionalism using the Interprofessional Attitudes Scale (IPAS). OUTCOMES: Seventy-one students participated in the course from November 2015 to May 2016. Fifty-nine (83%) students had paired pre- and postcourse SAAS and IPAS data. On the SAAS, students showed significant improvement in their median total score and nonmoralizing, treatment optimism, and treatment intervention scores. On the IPAS, students showed significant improvement in their median score on the teamwork, roles, and responsibilities domain. NEXT STEPS: The authors will continue to assess the course. Starting in academic year 2016-2017, the course will include four additional elements, and beginning in July 2016, accelerated bachelor of science in nursing students will participate in the course.

Systems-level view of cocaine addiction: the interconnection of the immune and nervous systems.

The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction.

Phenotypic mapping of metabolic profiles using self-organizing maps of high-dimensional mass spectrometry data.

A metabolic system is composed of inherently interconnected metabolic precursors, intermediates, and products. The analysis of untargeted metabolomics data has conventionally been performed through the use of comparative statistics or multivariate statistical analysis-based approaches; however, each falls short in representing the related nature of metabolic perturbations. Herein, we describe a complementary method for the analysis of large metabolite inventories using a data-driven approach based upon a self-organizing map algorithm. This workflow allows for the unsupervised clustering, and subsequent prioritization of, correlated features through Gestalt comparisons of metabolic heat maps. We describe this methodology in detail, including a comparison to conventional metabolomics approaches, and demonstrate the application of this method to the analysis of the metabolic repercussions of prolonged cocaine exposure in rat sera profiles.

Race differences in the relation of vitamins A, C, E, and ß-carotene to metabolic and inflammatory biomarkers.

Using archival data, we conducted a secondary analysis to examine race differences in the relation of serum vitamins A, C, E and ß-carotene to insulin resistance (IR), fasting insulin and glucose, high sensitivity C-reactive protein (hs-CRP), and leukocyte count in 176 non-smoking, healthy, white, and African American (AA) adults aged 18 to 65 years (48% women, 33% AA). We hypothesized that micronutrient concentrations would be associated with early risk markers of cardiometabolic diseases in a race-dependent manner. Fasting blood samples were analyzed for micronutrients, insulin, glucose, hs-CRP, and leukocyte count. Insulin resistance was estimated using the homeostatic model assessment. After adjusting for age, body mass index, gender, educational level, use of vitamin supplements, alcohol intake, leisure time physical activity, menopausal status, and total cholesterol, we observed that ß-carotene was significantly associated with insulin resistance and fasting insulin in a race-dependent manner. Among AA, lower ß-carotene levels were associated with higher estimates of insulin resistance and fasting insulin; whereas, these same associations were not significant for whites. Race also significantly moderated the relation of vitamin C to leukocyte count, with lower vitamin C being associated with higher leukocyte count only in AA but not whites. For all subjects, lower ß-carotene was associated with higher hs-CRP. In AA, but not whites, lower levels of ß-carotene and vitamin C were significantly associated with early risk markers implicated in cardiometabolic conditions and cancer. Whether or not lower levels of micronutrients contribute uniquely to racial health disparities is a worthwhile aim for future research.

Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

RATIONALE: Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. OBJECTIVES: This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. METHODS: Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. RESULTS: CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. CONCLUSIONS: These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.

Use of the light/dark test for anxiety in adult and adolescent male rats.

The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-ß-carboline-3-carboxamide (FG-7142) and the α2 adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.

Depression inhibits the anti-inflammatory effects of leisure time physical activity and light to moderate alcohol consumption.

Light to moderate alcohol consumption and leisure time physical activity (LTPA) are independently associated with lower levels of high sensitivity C-reactive protein (CRP), a predictor of cardiometabolic risk. In contrast, depression, ranging from low mood disturbance to major depressive disorder, has been associated with elevated CRP. To test the hypothesis that depression attenuates the anti-inflammatory effects of LTPA and alcohol consumption, the current study tested the moderating effect of severity of depressive symptomatology on the relation of alcohol consumption and LTPA to CRP in 222 healthy adult men and women (18-65 years of age). Given the known effects of gender on inflammation, we also examined the effects of gender on the tested interactions. Depression was assessed using the Beck Depression Inventory. Frequency of alcohol consumption, hours of LTPA per week and other coronary risk/protective factors were assessed via self-report and structured interview. Fasting blood samples were used to measure CRP and lipids. As predicted, the interaction between LTPA and depressive symptomatology was significant (F=5.29, p<.03) such that lower CRP was associated with the combination of decreased depressive symptomatology and increased LTPA. Among those with increased depressive symptoms, increased LTPA was not associated with higher CRP. Similarly, depression interacted with alcohol consumption in predicting CRP in men but not women (F=5.03, p<.008) such that for men light to moderate alcohol consumption was associated with lower CRP but only among those with decreased depressive symptoms. Light to moderate alcohol consumption was not associated with lower CRP in those with increased depressive symptom severity. The pattern of the interactions between anti-inflammatory activities such as light to moderate alcohol consumption and LTPA and psychological distress as indexed by severity of depressive symptomatology suggests an important new avenue for future research.

Characterization of a semi-rapid method for assessing delay discounting in rodents.

Delay discounting is a key component of many psychiatric disorders, including drug addiction, compulsive gambling, ADHD, and obesity. However, its underlying mechanisms are not yet fully characterized. One impediment to full characterization of such mechanisms is the fact that rodent models of the task are often complicated and involve extended training of subjects, often requiring more than a month before a stable baseline is obtained. We have therefore characterized a version of the rodent delay discounting task which generates data more quickly than most other published versions. In this version of the task, learning of the operant response is established prior to introduction of the delay component, and delay is tested across subsequent daily sessions with a single delay length per day. We demonstrate here that this version generates a delay discounting curve similar to many published tasks, and is sensitive to changes in reward magnitude and to chronic treatment with cocaine. Furthermore, we present a detailed description of the within-session patterns of behavior in the task, which provides evidence of within-session learning and establishment of stable response patterns. This faster version of the delay discounting task will facilitate future studies involving pharmacological, electrophysiological, and other mechanistic studies of the underlying basis of this important disease process.

Individual differences in cocaine conditioned taste aversion are developmentally stable and independent of locomotor effects of cocaine.

Drugs of abuse induce complex motivational states in their users which have been shown to vary developmentally. In addition to developmental variation, interindividual variation in the rewarding and aversive effects of drugs of abuse is an important consideration. A rat model was used to assess whether the conditioned rewarding/aversive effects of cocaine were maintained as individuals matured from adolescence into adulthood. We tested rats in the cocaine conditioned taste aversion task as adolescents and again in adulthood. We observed a wide range of approach/avoidance behaviors in this task, and also observed that the relative interindividual differences in approach/avoidance are remarkably stable across the two developmental stages. Furthermore, we observed that these interindividual differences are not attributable to individual differences in cocaine-induced locomotor effects or individual differences in blood or brain cocaine levels. Taken together, these findings indicate that sensitivity to cocaine's motivational effects is stable across development and part of a unique neurological process.

Role of individual and developmental differences in voluntary cocaine intake in rats.

RATIONALE: Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addiction-like behavior and to examine factors that promote self-administration. METHODS: We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task. RESULTS: Adolescent animals initially sought more cocaine than adults. However, as the adolescents matured, their intake fell and they did not differ from adults in terms of unreinforced lever-pressing, extinction or reinstatement behavior. For both age groups, self-administration was positively correlated with the locomotor response to novelty, the locomotor response to cocaine, and with time in light in the light-dark task. The rats that were insensitive to cocaine's locomotor effects and that spent the least time in light in the light-dark task sought the least cocaine, appearing to be "protected" from the reinforcing effects of cocaine. There was no difference between the two age groups in appearance of this "protected" phenotype. CONCLUSIONS: These results suggest that early onset of drug taking may promote increased use, but does not promote progression to addiction-like behavior. Furthermore, protective factors, such as innate anxiety and insensitivity to cocaine's pharmacological effects, function across developmental stages.

Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.

BACKGROUND: Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects? METHODS: Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). RESULTS: We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. CONCLUSIONS: These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol.

Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models.

BACKGROUND AND RATIONALE: Epidemiological evidence suggests that people who begin experimenting with drugs of abuse during early adolescence are more likely to develop substance use disorders (SUDs), but this correlation does not guarantee causation. Animal models, in which age of onset can be tightly controlled, offer a platform for testing causality. Many animal models address drug effects that might promote or discourage drug intake and drug-induced neuroplasticity. METHODS: We have reviewed the preclinical literature to investigate whether adolescent rodents are differentially sensitive to rewarding, reinforcing, aversive, locomotor, and withdrawal-induced effects of drugs of abuse. RESULTS AND CONCLUSIONS: The rodent model literature consistently suggests that the balance of rewarding and aversive effects of drugs of abuse is tipped toward reward in adolescence. However, increased reward does not consistently lead to increased voluntary intake: age effects on voluntary intake are drug and method specific. On the other hand, adolescents are consistently less sensitive to withdrawal effects, which could protect against compulsive drug seeking. Studies examining neuronal function have revealed several age-related effects but have yet to link these effects to vulnerability to SUDs. Taken together, the findings suggest factors which may promote recreational drug use in adolescents, but evidence relating to pathological drug-seeking behavior is lacking. A call is made for future studies to address this gap using behavioral models of pathological drug seeking and for neurobiologic studies to more directly link age effects to SUD vulnerability.