Faculty Bibliography

BACKGROUND:Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. METHODS:Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. DISCUSSION/CONCLUSIONS:This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Objective: The growth of psychedelic medicine creates new challenges in psychiatric education as physicians may soon be responsible for prescribing a number of psychedelic interventions. Despite this growing need for educated providers, very little is known about the training psychiatry residents receive in psychedelic medicine. We conducted a survey to determine the current educational opportunities as well as the priorities and concerns held by training directors about this emerging field. Methods: We emailed an online survey to US psychiatry residency training directors. Respondents answered questions about current offerings in psychedelic medicine, as well as their interest, priorities, and concerns about curricular materials and their delivery. Results: Sixty-one programs responded to our survey. The majority of respondents (64%) favored devoting additional time to psychedelic education, but many endorsed concerns about the dearth of educational materials (54%) and limited availability of faculty to deliver content (46%). The majority of programs (94%) expressed some interest in implementing a standardized curriculum in psychedelic medicine. Conclusion: Training directors recognized that their current curricular materials are limited, and they appeared interested in additional support to meet the upcoming demand in psychedelic education. Further research can inform curriculum development and implementation of psychedelic education in residency training.

IMPORTANCE/UNASSIGNED:No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder. OBJECTIVE/UNASSIGNED:To develop an individual-level prediction tool for risk of return to use in opioid use disorder. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities. INTERVENTION/UNASSIGNED:All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment. RESULTS/UNASSIGNED:The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84). CONCLUSIONS AND RELEVANCE/UNASSIGNED:The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Black individuals in the USA experience disparities in mental health that lead to unfavorable health outcomes and increased morbidity from mental illness due to centuries of racism. We emphasize the need to understand the roots of racial injustice to achieve racial equity. Historical factors such as European imperialism, enslavement, the myth of Black inferiority, and scientific racial classification have all perpetuated disparities, leading to the current underestimation, misdiagnosis, and inadequate treatment of mental illness in Black populations. Many of the issues discussed herein apply to Black people globally; however, our focus is on Black Americans and the inequities that result from the current US mental health system. We discuss the limitations of using the DSM-5 classification system and common epidemiological surveys, which do not capture or call for a comprehensive analysis of the systems producing mental health issues, to understand mental illness among Black Americans.

This study sought to evaluate the impact of telepsychiatry during the COVID-19 pandemic among patients discharged from psychiatric inpatient units in the New York City Health and Hospitals Corporation system. We compared patients discharged to telepsychiatry (April 2020, n = 739) and in-person follow-up (May 2019, n = 527); we collected number, timing and attendance for follow-up appointments and number and timing of emergency room (ER) visits and readmissions. We used logistic regression to evaluate the odds of having these encounters and Kaplan-Meier analyses to compare time to these encounters. Patients discharged in 2020 were more likely to have a follow-up (29.4 vs. 19.9%, p < 0.001) and an ER visit or readmission (40.5 vs. 28.7%, p < 0.001). Kaplan-Meier analyses showed shorter time to first follow-up (chi-square = 14.69, d.f.=1, p < 0.0001, follow-ups = 322) and ER visit or readmission (chi-square = 19.57, d.f.=1, p < 0.0001, ER visits or admissions = 450) in the 2020 cohort. In multivariable analyses, patients discharged in 2020 were more likely to have a follow-up visit (adjusted OR 1.85, 95% confidence interval 1.40, 2.45, p < 0.0001). We found an increase in psychiatric service utilization during the pandemic, with an increase in and shorter time until outpatient visits and ER visits or readmissions. Although increased use of psychiatric services during the height of the COVID-19 pandemic is encouraging, it also points to the depth of the crisis among vulnerable populations; this pattern warrants further exploration and intervention.

BACKGROUND/UNASSIGNED:Approximately 1800 opioid treatment programs (OTPs) in the US dispense methadone to upwards of 400,000 patients with opioid use disorder (OUD) annually, operating under longstanding highly restrictive guidelines. OTPs were granted novel flexibilities beginning March 15, 2020, allowing for reduced visit frequency and extended take-home doses to minimize COVID exposure with great variation across states and sites. We sought to use electronic health records to compare retention in treatment, opioid use, and adverse events among patients newly entering methadone maintenance in the post-reform period in comparison with year-ago, unexposed, controls. METHODS/UNASSIGNED:Retrospective observational cohort study across 9 OTPs, geographically dispersed, in the National Institute of Drug Abuse (NIDA) Clinical Trials Network. Newly enrolled patients between April 15 and October 14, 2020 (post-COVID, reform period) v. March 15-September 14, 2019 (pre-COVID, control period) were assessed. The primary outcome was 6-month retention. Secondary outcomes were opioid use and adverse events including emergency department visits, hospitalizations, and overdose. FINDINGS/UNASSIGNED: INTERPRETATION/UNASSIGNED:Policies allowing for extended take-home schedules were not associated with worse retention or adverse events despite slightly elevated rates of measured opioid use while in care. Relaxed guidelines were not associated with measurable increased harms and findings could inform future studies with prospective trials. FUNDING/UNASSIGNED:USDHHSNIDACTNUG1DA013035-15.

Clinical and basic science investigation indicates a link between insulin resistance and anhedonia. Previous results of this laboratory point to impaired nucleus accumbens (NAc) insulin signaling as an underpinning of diet-induced anhedonia, based on use of a glucose lick microstructure assay. The present study evaluated whether advanced glycation end products (AGEs) and their receptor (RAGE), known to mediate obesogenic diet-induced inflammation and pathological metabolic conditions, are involved in this behavioral change. Six weeks maintenance of male and female rats on a high fat-high sugar liquid diet (chocolate Ensure) increased body weight gain, and markedly increased circulating insulin and leptin, but induced anhedonia (decreased first minute lick rate and lick burst size) in males only. In these subjects, anhedonia correlated with plasma concentrations of insulin. Although the diet did not alter plasma or NAc AGEs, or the expression of RAGE in the NAc, marginally significant correlations were seen between anhedonia and plasma content of several AGEs and NAc RAGE. Importantly, a small molecule RAGE antagonist, RAGE229, administered twice daily by oral gavage, prevented diet-induced anhedonia. This beneficial effect was associated with improved adipose function, reflected in the adiponectin/leptin ratio, and increased pCREB/total CREB in the NAc, and a shift in the pCREB correlation with pThr34-DARPP-32 from near-zero to strongly positive, such that both phospho-proteins correlated with the rescued hedonic response. This set of findings suggests that the receptor/signaling pathway and cell type underlying the RAGE229-mediated increase in pCREB may mediate anhedonia and its prevention. The possible role of adipose tissue as a locus of diet-induced RAGE signaling, and source of circulating factors that target NAc to modify hedonic reactivity are discussed.