Opioid overdose prevention education for medical students: Adopting harm reduction into mandatory clerkship curricula.

Background: Opioid overdose deaths constitute a public health crisis in the United States. Strategies for reducing opioid-related harm are underutilized due in part to clinicians' low knowledge about harm reduction theory and limited preparedness to prescribe naloxone. Educational interventions are needed to improve knowledge and attitudes about, and preparedness to address, opioid overdoses among medical students. Methods: Informed by the Department of Veterans Affairs' Overdose Education and Naloxone Distribution (OEND) program and narrative medicine, we developed and led a mandatory workshop on harm reduction for clerkship medical students. Using validated scales, we assessed students' knowledge and attitudes about, and preparedness to address, opioid overdoses before the workshop and 6 weeks after. Results: Of 75 participating students from February through December 2017, 55 (73%) completed pre-workshop and 38 (51%) completed both pre- and post-workshop surveys. At baseline, 40 (73%) encountered patients with perceived at-risk opioid use in the previous 6 weeks, but only 11 (20%) recalled their teams prescribing naloxone for overdose prevention. Among those completing both surveys, knowledge about and preparedness to prevent overdose showed large improvement (Cohen's d = 0.85, P < .001; Cohen's d = 1.24, P < .001, respectively) and attitudes showed moderate improvement (Cohen's d = 0.32, P = .04). Discussion: Educational interventions grounded in harm reduction theory can increase students' knowledge and attitudes about, and preparedness to address, opioid overdoses.

Naltrexone for the treatment of comorbid tobacco and pornography addiction.

BACKGROUND AND OBJECTIVES: Co-occurring addictive disorders are common, however treatment strategies for this population have not been extensively studied. This is especially the case for behavioral addictions. METHODS: We present a patient (N = 1) with tobacco use disorder and problematic pornography use treated with naltrexone. RESULTS: Naltrexone treatment resulted in a decrease in pornography viewing and cigarette smoking, however had the adverse effect of anhedonia. A lower dose modestly impacted pornography viewing but not smoking. DISCUSSIONS AND CONCLUSIONS: Relevant literature regarding co-occurring addictions as well as use of naltrexone is reviewed. SCIENTIFIC SIGNIFICANCE: This report represents the first case of tobacco and pornography co-addiction in the literature and supports the assertion that treatment of one addictive disorder can benefit another in the dually addicted patient. The efficacy of naltrexone for smoking is notable as previous studies of naltrexone in smoking have been disappointing. This case suggests future treatment strategies for comorbid addictions. (Am J Addict 2017;26:115-117).

The Use of a Small Private Online Course to Allow Educators to Share Teaching Resources Across Diverse Sites: The Future of Psychiatric Case Conferences?

OBJECTIVE: The authors sought to demonstrate the feasibility of integrating small private online course (SPOC) technology with flipped classroom techniques in order to improve neuroscience education across diverse training sites. METHODS: Post-graduate medical educators used SPOC web conferencing software and video technology to implement an integrated case conference and in-depth neuroscience discussion. RESULTS: Ten psychiatry training programs from across the USA and from two international sites took part in the conference. Feedback from participants was largely positive. CONCLUSION: This pilot demonstrated the feasibility of such a program and provided a diverse audience with the opportunity to engage in an interactive learning experience with expert faculty discussants. This may be a useful model for programs with limited local expertise to expand their teaching efforts in a wide range of topics.

Dyslipidemia associated with heavy alcohol use.

BACKGROUND AND OBJECTIVES: Alcohol has many effects on lipid metabolism and has been associated with elevated triglycerides. The purpose of this paper is to report a case of globally dysregulated lipids secondary to alcohol use and to describe the natural history of this phenomenon after drinking cessation. METHODS: We present a case of an otherwise healthy patient (N = 1) who was admitted to our facility for alcohol detoxification and found to have extreme lipid dysregulation. He was treated with benzodiazepines for alcohol withdrawal but no hypolipidemic agents were given. RESULTS: Lipid indices self-corrected and were found to be normal following just several weeks of sobriety in the absence of treatment with any hypolipidemic agents. DISCUSSION: The literature regarding the effects of alcohol on lipid metabolism is briefly reviewed followed by a discussion of how these findings might apply to this patient in particular as well as implications for broader clinical practice. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Alcohol has the ability to dysregulate several lipid indices in addition to elevating triglycerides. The rapid resolution of dyslipidemia suggests that additional treatment may not be necessary for patients who are able to abstain from alcohol but that hypolipidemic agents may be indicated for those patients who continue to drink. Additionally, clinicians should consider checking lipid panels in patients who present with alcohol intoxication and are found to have other laboratory abnormalites or those who have risk factors for hyperlipidemia.

Development of a pH-responsive particulate drug delivery vehicle for localized biologic therapy in inflammatory bowel disease.

The treatment of inflammatory bowel disease (IBD) recently has been revolutionized by the introduction of protein-based biologic therapies. However, biologic therapy is complicated by the requirement for administration with a needle, systemic side effects, and high cost. Particulate drug delivery systems have been shown to deliver drugs locally to the intestinal mucosa via oral administration. However, these systems have been largely unexplored for the delivery of biologics due to harsh particle fabrication conditions and the tendency of many particulate formulations to dissolve in the acidic upper GI tract. We have, therefore, fabricated an inexpensive and non-toxic novel microparticle capable of encapsulating proteins. We establish that the particle retains its contents at acidic pH and releases them at neutral pH. We also demonstrate particulate encapsulation of interleukin-10 (IL-10), a protein relevant to the treatment of IBD, at an encapsulation efficiency of 14.3 percent. Such a vehicle is promising for its oral route of administration and potential to decrease side effects and increase potency of biologics.

Development of a nanoparticulate formulation of retinoic acid that suppresses Th17 cells and upregulates regulatory T cells.

Retinoic acid (RA) is a small molecule capable of shunting developing T cells away from the Th17 lineage and towards the Treg phenotype, making it a potentially useful therapeutic for autoimmune and inflammatory diseases. However, therapy can be complicated by systemic toxicity and unpredictable bioavailability, making a targeted drug delivery vehicle for local therapy desirable. A promising approach is the use of nanoparticles, which have been demonstrated to increase potency and decrease toxicity of therapies in a variety of disease models including Th17 mediated diseases. Nanoparticles can also be targeted to specific cell types via surface modification, further increasing the potential specificity of this approach. We therefore constructed a nanoparticulate drug delivery platform from poly(lactic-co-glycolic acid) (PLGA) capable of encapsulating and releasing RA. Here we report the fabrication, characterization, and in vitro bioactivity of this platform. We demonstrate that RA containing PLGA nanoparticles suppress IL-17 production and ROR-γ(t) expression in T cells polarized towards the Th17 phenotype in vitro with similar potency to that of free drug. Furthermore, we show that these particles enhance TGF-ß dependent Foxp3 expression and IL-10 production of T cells in vitro with similar potency to free RA. Finally, we demonstrate that T cells polarized towards the Th17 phenotype in the presence of free and nanoparticulate RA have similarly suppressed ability to induce IL-6 production by fibroblasts. Our findings demonstrate the feasibility of RA delivery via biodegradable nanoparticles and represent an exciting technology for the treatment of autoimmune and inflammatory diseases.

Heterogeneous dynamics and dynamic heterogeneities at the glass transition probed with single molecule spectroscopy.

We studied the temperature dependence of the structural relaxation in poly(vinyl acetate) near the glass transition temperature with single molecule spectroscopy from Tg-1 K to Tg+12 K. The temperature dependence of the observed relaxation times matches results from bulk experiments; the observed relaxation times are, however, 80-fold slower than those from bulk experiments at the same temperature. We attribute this factor to the size of the probe molecule. The individual relaxation times of the single molecule environments are distributed normally on a logarithmic time scale, confirming that the dynamics in poly(vinyl acetate) is heterogeneous. The width of the distribution of individual relaxation times is essentially independent of temperature. The observed full width at half maximum (FWHM) on a logarithmic time axis is approximately 0.7, corresponding to a factor of about 5-fold, significantly narrower than the dielectric spectrum of the same material with a FWHM of about 2.0 on a logarithmic time axis, corresponding to a factor of about 100-fold. We explain this narrow width as the effect of temporal averaging of single molecule fluorescence signals over numerous environments due to a limited lifetime of the probed heterogeneities, indicating that heterogeneities are dynamic. We determine a loose upper limit for the ratio of the structural relaxation time to the lifetime of the heterogeneities (the rate memory parameter) of Q<80 for the range of investigated temperatures.