What gets resident physicians stressed and how would they prefer to be supported? A best-worst scaling study.

INTRODUCTION: Physician burnout has severe consequences on clinician well-being. Residents face numerous work-stressors that can contribute to burnout; however, given specialty variation in work-stress, it is difficult to identify systemic stressors and implement effective burnout interventions on an institutional level. Assessing resident preferences by specialty for common wellness interventions could also contribute to improved efficacy. METHODS: This cross-sectional study used best-worst scaling (BWS), a type of discrete choice modelling, to explore how 267 residents across nine specialties (anaesthesiology, emergency medicine, internal medicine, neurology, obstetrics and gynaecology, pathology, psychiatry, radiology and surgery) prioritised 16 work-stressors and 4 wellness interventions at a large academic medical centre during the COVID-19 pandemic (December 2020). RESULTS: Top-ranked stressors were work-life integration and electronic health record documentation. Therapy (63%, selected as 'would realistically consider intervention') and coaching (58%) were the most preferred wellness supports in comparison to group-based peer support (20%) and individual peer support (22%). Pathology, psychiatry and OBGYN specialties were most willing to consider all intervention options, with emergency medicine and internal medicine specialties least willing to consider intervention options. CONCLUSION: BWS can identify relative differences in surveyed stressors, allowing for the generation of specialty-specific stressor rankings and preferences for specific wellness interventions that can be used to drive institution-wide changes to improve clinician wellness. BWS surveys are a potential methodology for clinician wellness programmes to gather specific information on preferences to determine best practices for resident wellness.

Should You Recommend Cannabinoids for This Patient With Painful Neuropathy? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Cannabis includes 140 active cannabinoid compounds, the most important of which are tetrahydrocannabinol and cannabidiol (CBD). Tetrahydrocannabinol is primarily responsible for the intoxicating effects of cannabis; CBD has potential therapeutic effects, including reduction in chronic pain. Recent legislative changes have resulted in the legal availability of cannabinoids in all 50 states, as well as a marked increase in patients' interest in their use. Despite an abundance of data, albeit of varied quality, clinicians may feel poorly prepared to counsel patients seeking advice on the suitability of CBD products for various indications, particularly chronic neuropathic pain. In 2018, on the basis of a systematic review of the literature, a Canadian Evidence Review Group published a guideline with recommendations for clinicians on prescribing cannabinoids in primary care practice. The overall quality of evidence was low to very low. In a meta-analysis of 15 randomized trials of medical cannabis for treating chronic pain, 39% of patients achieved at least a 30% reduction in pain. The corresponding value for placebo-treated patients was 30%; the number needed to treat was 11. More evidence exists for neuropathic pain than for other types of noncancer pain. Here, a general internist with a focus on addiction medicine and an addiction psychiatrist discuss how they would apply the literature to make recommendations for a patient with painful diabetic neuropathy, including counseling on both potential benefits and harms.

Buprenorphine in safety-sensitive positions.

The permissibility of buprenorphine in safety-sensitive positions is a controversial topic. As an opioid medication, concerns have arisen regarding the potential for impairment and any effects that this would have on an employee's ability to safely perform job duties. While there are no definitive guidelines on the use of buprenorphine for those employed in safety-sensitive lines of work, most employers do not permit its use under any circumstance due to the potential risk of harm to the public. In addition to overlooking the fact that buprenorphine is a well-established and life-saving treatment for opioid use disorder (OUD), there are many flaws in making this determination. For one, buprenorphine is a partial mu opioid agonist which makes it inherently unique in comparison to other opioids. Most studies on impairment have examined acute use of full agonist opioids instead of chronic dosing of buprenorphine. Furthermore, assessments of impairment are not tailored to the tasks required of specific positions. Importantly, policies banning buprenorphine may contribute to treatment discontinuation and stigma, which can lead to relapse and overdose. Considering the morbidity and mortality associated with OUD, along with the surge in overdose deaths during the COVID19 pandemic, buprenorphine policies should be considered carefully. Given the lack of evidence showing definitive and specific impairments as a result of chronic buprenorphine use, coupled with the consequences of universal bans on its use, determinations on the permissibility of buprenorphine treatment for safety-sensitive positions should be made on a case-by-case basis.

Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review.

Cannabidiol, a non-intoxicating phytocannabinoid, has potential therapeutic effects over a broad range of disorders. Recently, there has been increased interest in CBD, as several studies showed promising anticonvulsant efficacy with few side effects. In 2018, a CBD-based oral solution, Epidiolex®, was approved by the FDA to treat two severe forms of pediatric epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Although only these two syndromes are recognized indications for CBD, it has been consumed in an unregulated fashion for a variety of indications including chronic pain, muscle stiffness, inflammation, anxiety, smoking cessation, and even cancer. While CBD legislation in the USA is confusing due to the differences in state and federal laws, CBD has proliferated in the US market in several forms such as CBD oil or capsules, hemp oil/extract, and also as an ingredient in several dietary supplements, syrups, teas, and creams. With the ever-increasing use of CBD and its widespread availability to the general public, it is important to examine and report on possible drug-drug interactions between CBD and other therapeutic agents as well as addictive substances such as alcohol and tobacco. A detailed literature search for CBD's possible interactions was conducted using online databases. As expected, CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol. This review provides a comprehensive list of interacting drugs. The possible mechanisms for these drug-drug interactions are presented in table format. Given the growing popularity of CBD as a medication and the dearth of available information on CBD drug-drug interactions, it is critical to be aware of current drug-drug interactions and it will be important to investigate the impact of CBD upon concomitant medication use in future randomized, controlled trials.

Care of the Patient Using Cannabis.

The past 2 decades have seen a revolution in legal access to cannabis, driven largely by activists and business interests. As a result, the population of cannabis users nationwide-especially daily users-has grown significantly. An estimated 4.5-7 million persons in the United States now meet criteria for cannabis use disorder annually. This article focuses on the effects of cannabis use, intoxication, and withdrawal while also reviewing the developmental pathways of cannabis use disorder as well as evidence-based pharmacologic and psychosocial treatments.

Denoising scanner effects from multimodal MRI data using linked independent component analysis.

Pooling magnetic resonance imaging (MRI) data across research studies, or utilizing shared data from imaging repositories, presents exceptional opportunities to advance and enhance reproducibility of neuroscience research. However, scanner confounds hinder pooling data collected on different scanners or across software and hardware upgrades on the same scanner, even when all acquisition protocols are harmonized. These confounds reduce power and can lead to spurious findings. Unfortunately, methods to address this problem are scant. In this study, we propose a novel denoising approach that implements a data-driven linked independent component analysis (LICA) to identify scanner-related effects for removal from multimodal MRI to denoise scanner effects. We utilized multi-study data to test our proposed method that were collected on a single 3T scanner, pre- and post-software and major hardware upgrades and using different acquisition parameters. Our proposed denoising method shows a greater reduction of scanner-related variance compared with standard GLM confound regression or ICA-based single-modality denoising. Although we did not test it here, for combining data across different scanners, LICA should prove even better at identifying scanner effects as between-scanner variability is generally much larger than within-scanner variability. Our method has great promise for denoising scanner effects in multi-study and in large-scale multi-site studies that may be confounded by scanner differences.

The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?

BACKGROUND: Reexposure to methamphetamine with a single "priming dose" can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril "molecular container" calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. METHODS: Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. RESULTS: Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. CONCLUSIONS: These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.

How Emergency Physicians Approach Refusal of Observation after Naloxone Resuscitation.

BACKGROUND: Patients who are resuscitated with naloxone frequently refuse a period of observation, even though they may be suffering from a variety of medical and psychiatric comorbidities. Emergency physicians (EPs) are then confronted with the challenge of how best to serve patients' interests while respecting autonomy. OBJECTIVES: We sought to characterize how EPs think about this kind of dilemma and the strategies they use to resolve them. METHODS: We conducted qualitative semi-structured interviews with a convenience sample of 59 emergency physicians attending the American College of Emergency Physicians' Scientific Assembly in October 2018. Three case vignettes highlighting different clinical and ethical features served as prompts. Interviews were analyzed using a constant comparative method to identify patterns of responses and derive key themes. RESULTS: Across the vignettes, EPs demonstrated diverse approaches to observation, assessing decision-making capacity and encouraging compliance. Some EPs refused to comply with a patient's wishes even when they had determined a patient demonstrated capacity. Conversely, a few EPs were willing to allow patients to leave the emergency department (ED) without assessing capacity, or despite determining that the patient lacked capacity. Common reasons for complying with patients' demands were concerns about the patients' rights and concerns about the safety of staff. Most physicians interviewed reported no institutional guidelines or education on the topic, and many physicians expressed an interest in providing medication for addiction treatment in the ED. CONCLUSIONS: EPs approach this clinical and ethical dilemma in widely divergent ways. Consensus about strategies for navigating patients' wishes relative to clinical concerns are needed to help EPs manage these challenging cases.

Review: Non-Invasive Brain Stimulation in Behavioral Addictions: Insights from Direct Comparisons With Substance Use Disorders.

BACKGROUND AND OBJECTIVES: Treatment models developed for substance use disorders (SUDs) are often applied to behavioral addictions (BAs), even though the correspondence between these forms of addiction is unclear. This is also the case for noninvasive brain stimulation (NIBS) techniques being investigated as potential treatment interventions for SUDs and BAs. OBJECTIVES: to contribute to the development of more effective NIBS protocols for BAs. METHODS: Two literature searches using PubMed and Google Scholar were conducted identifying a total of 35 studies. The first search identified 25 studies examining the cognitive and neurophysiological overlap between BAs and SUDs. The second search yielded 10 studies examining the effects of NIBS in BAs. RESULTS: Impulsivity and cravings show behavioral and neurophysiologic overlaps between BAs and SUDs, however, other outcomes like working-memory abilities or striatal connectivity, differ between BAs and SUDs. The most-employed NIBS target in BAs was dorsolateral prefrontal cortex (DLPFC), which was associated with a decrease in cravings, and less frequently with a reduction of addiction severity. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Direct comparisons between BAs and SUDs revealed discrepancies between behavioral and neurophysiological outcomes, but overall, common and distinctive characteristics underlying each disorder. The lack of complete overlap between BAs and SUDs suggests that investigating the cognitive and neurophysiological features of BAs to create individual NIBS protocols that target risk-factors associated specifically with BAs, might be more effective than transferring protocols from SUDs to BAs. Individualizing NIBS protocols to target specific risk-factors associated with each BA might help to improve treatment interventions for BAs. (Am J Addict 2019;00:1-23).

Nabilone pharmacotherapy for cannabis dependence: A randomized, controlled pilot study.

BACKGROUND AND OBJECTIVES: We assessed the safety, tolerability, and preliminary efficacy of nabilone, a cannabinoid agonist, to treat cannabis dependence. METHODS: Eighteen adults with DSM-IV cannabis dependence were randomized to receive either 2 mg/day of nabilone (n = 10) or placebo (n = 8) for 10 weeks in addition to medication management. Twelve participants, six in each group, completed treatment. The safety and tolerability of nabilone was assessed at each visit. Any side effects from nabilone or the placebo were documented. Cannabis use outcomes were assessed via self-report of days of use and twice-weekly urine cannabinoid tests; secondary outcomes included cannabis craving and anxiety. RESULTS: We assessed safety and tolerability at each study visit. A total of eight adverse events, all mild or moderate, were reported in two participants in the nabilone group, and six events were reported in four participants in the placebo group during study treatment. A total of eight adverse events were reported in two participants in the nabilone group and six events were reported in four participants in the placebo group during study treatment. All reported adverse events were rated mild-to-moderate. There were no side effects deemed serious enough to be classified as an FDA-defined serious adverse event. In general, participants in both groups reported reduced cannabis use according to self-report over the course of the study, although these reductions were not statistically discernible. Moreover, there was no difference in cannabis use between the nabilone group and the placebo group as measured by self-report. DISCUSSION AND CONCLUSIONS: Nabilone pharmacotherapy was safe and well-tolerated in participants with cannabis dependence. Future studies might evaluate a higher dose of nabilone to determine its effects on cannabis use outcomes in participants with cannabis dependence. SCIENTIFIC SIGNIFICANCE: There remains a clear need for additional pharmacotherapy trials for cannabis dependence, and nabilone remains a candidate for such trials. (Am J Addict 2017;26:795-801).

Development of Adaptive Coping From Mid to Late Life: A 70-Year Longitudinal Study of Defense Maturity and Its Psychosocial Correlates.

The present study examines changes in defense maturity from mid to late life using data from an over 70-year longitudinal study. A sample of 72 men was followed beginning in late adolescence. Participants' childhoods were coded for emotional warmth. Defense mechanisms were coded by independent raters using the Q-Sort of Defenses (, Ego mechanisms of defense: A guide for clinicians and researchers 217-233) based on interview data gathered at approximately ages 52 and 75. We examined psychosocial correlates of defenses at midlife, late life, and changes in defense from mid to late life. Overall, defenses grew more adaptive from midlife to late life. However, results differed on the basis of the emotional warmth experienced in the participants' childhoods. In midlife, men who experienced warm childhoods used more adaptive (mature) defenses; yet by late life, this difference in defensive maturity had disappeared. Men who experienced less childhood warmth were more likely to show an increase in adaptive defenses during the period from mid to late life.

Health-related quality of life among prescription opioid-dependent patients: Results from a multi-site study.

BACKGROUND: Although prescription opioid use disorder has recently increased sharply in the United States, relatively little is known about the general well-being of this population. Assessment of quality of life in patients with substance use disorders has been recommended to improve clinical care. OBJECTIVES: Health-related quality of life was examined in prescription opioid-dependent patients at entry to a national multi-site clinical trial, to compare quality of life scores in the study sample to other populations; further, background variables associated with quality of life in the literature were examined. METHODS: Prescription opioid-dependent patients (N = 653) were compared to general populations on the Medical Outcome Study Short Form-36 (SF-36) quality of life measure; and the association between patient background variables and quality of life was examined. RESULTS: Compared to a general population, the current sample of prescription opioid-dependent patients had worse physical (-1.7 points, p < .001) and mental quality of life (-12.3 points, p < .001) as measured by the SF-36, similar to other opioid-use disorder populations. Within our sample, women showed more impairment than men in mental quality of life (-4.3 points, p < .001); older patients scored worse on physical (-5.2 points, p < .001), but not mental, quality of life. Chronic pain was associated with poorer physical quality of life (-9.0 points, p < .001). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The growing focus on wellness underscores the importance of measuring quality of life in addition to substance use outcomes. Routine assessment of health-related quality of life can add an important dimension to overall evaluation of patients' treatment response.

Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review.

IMPORTANCE: As of March 2015, 23 states and the District of Columbia had medical marijuana laws in place. Physicians should know both the scientific rationale and the practical implications for medical marijuana laws. OBJECTIVE: To review the pharmacology, indications, and laws related to medical marijuana use. EVIDENCE REVIEW: The medical literature on medical marijuana was reviewed from 1948 to March 2015 via MEDLINE with an emphasis on 28 randomized clinical trials of cannabinoids as pharmacotherapy for indications other than those for which there are 2 US Food and Drug Administration-approved cannabinoids (dronabinol and nabilone), which include nausea and vomiting associated with chemotherapy and appetite stimulation in wasting illnesses. FINDINGS: Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence. Six trials that included 325 patients examined chronic pain, 6 trials that included 396 patients investigated neuropathic pain, and 12 trials that included 1600 patients focused on multiple sclerosis. Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications. CONCLUSIONS AND RELEVANCE: Medical marijuana is used to treat a host of indications, a few of which have evidence to support treatment with marijuana and many that do not. Physicians should educate patients about medical marijuana to ensure that it is used appropriately and that patients will benefit from its use.

Opioid use disorder and role of yoga as an adjunct in management (OUDARYAM): Study protocol for a randomized controlled trial.

Background: The proposed research aims to test the effects and mechanisms of a six-month yoga-based intervention as an add-on to standard treatment in opioid use disorder (OUD) by conducting a randomized controlled study with the following primary outcome variables: 1) clinical: abstinence (opioid negative urine test), and reductions in pain and craving, and 2) mechanisms: reward circuit activation in response to opioid visual cue craving paradigm, activation in response to a cognitive control task, and resting state functional connectivity through fMRI, and plasma beta-endorphin levels. Secondary outcome variables are perceived stress, anxiety, sleep quality, cognitive performance, pain threshold, buprenorphine dosage and side effects, withdrawal symptoms, socio-occupational functioning, vedic personality traits, heart rate variability, serum cortisol, and brain GABA levels through magnetic resonance spectroscopy (MRS). Methods: In this single-blinded, randomized, controlled, parallel-group superiority trial with 1:1 allocation ratio, 164 patients with OUD availing the outpatient/ inpatient clinical services at a tertiary mental healthcare hospital in India will be enrolled after giving informed consent. Consecutive consenting patients will be randomly allotted to one of the two groups - yoga arm (standard treatment + yoga-based intervention), or waitlist group (standard treatment alone). Allocation concealment will be followed, the clinicians, outcome assessors and data analysts will remain blind to subject-group allocation. A validated and standardized yoga program for OUD will be used as an intervention. Participants in the yoga arm will receive 10 supervised in-person sessions of yoga in the initial two weeks followed by tele-yoga sessions thrice a week for the next 22 weeks. The wait-list control group will continue the standard treatment alone for 24 weeks. Assessments will be done at baseline, two weeks, 12 weeks, and 24 weeks. Data from all randomized subjects will be analysed using intent-to-treat analysis and mixed model multivariate analysis. Dissemination: Findings will be disseminated through peer-reviewed publication, conference presentations, and social media. Trial registration number: The trial has been registered under Clinical Trials Registry-India with registration number CTRI/2023/03/050737.