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Rationale: There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs., Objectives: This article provides recommendations that may be helpful to investigators seeking to work with psychedelics, with a focus on academic medical centers in the United States., Methods: The academic literature on relevant matters is reviewed, and the authors provide observations from their experiences either working for relevant regulatory agencies or conducting basic science studies, investigator-initiated trials, or industry sponsored trials with psychedelics., Results: Investigators planning to conduct psychedelic research should cultivate broad institutional support early. Challenges related to securing funding, obtaining approval for an Investigational New Drug application from the Food and Drug Administration, clinical grade drug sourcing, obtaining a Schedule I researcher registration from the Drug Enforcement Administration and an equivalent state license (if required), preparing spaces for treatment and study drug storage, managing controlled substance inventory, engaging the local community, and other issues should be anticipated., Conclusions: Investigators should anticipate several implementation challenges when planning to work with psychedelics. However, these are likely surmountable with planning, persistence, and assistance from colleagues and other experts., Competing Interests: Declarations. Competing interests: BSB holds stock options for CB Therapeutics. He has also served on advisory boards for CB Therapeutics, Compass Pathways, Janssen Pharmaceuticals, and Livanova. He receives monetary compensation for editorial work for DynaMed Plus (EBSCO Industries, Inc). He has received research funding from Compass Pathways, MindMed, and Reunion Neuroscience. Within the last two years he has consulted for Cerebral. MSD is an employee of Allucent. FK holds stock in Compass Pathways and Cybin. He also serves on the scientific advisory board for Apex Labs. He has consulted for Cybin in the last two years and has received monetary compensation from Vital for teaching. He has received research support from Tryp Therapeutics. EEM has received research support from Tryp Therapeutics. AC is a retired Assistant Special Agent in Charge of the Drug Enforcement Administration who, as an element of that position, had supervisory oversight of the local DEA Diversion Control Program which has Federal regulatory responsibility over Schedule I researchers. AC is a paid regulatory consultant for Mind Medicine, Inc, Multidisciplinary Association of Psychedelic Studies, and the Arizona Criminal Justice Commission. AC has also performed paid regulatory consultancies for Usona Institute, Pacific Neurological Institute Foundation, Fungi Perfecti, Freedom Biosciences, Journey Clinical, and a paid Subject Matter Expert for the US Health and Human Services, Substance Abuse and Mental Health Services Administration. Support for SMN through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. SMN was also co-investigator on a psilocybin clinical trial funded by Usona Institute. PSH is on the scientific advisory board of Bright Minds Biosciences Ltd., Eleusis Benefit Corporation, Journey Colab Corporation, and Reset Pharmaceuticals Inc. GRG is the President of the Heffter Research Institute. The other authors declare no conflicts of interest., (© 2024. The Author(s).)

Objectives: A resurgence of research investigating the administration of psychedelic compounds alongside psychotherapy suggests that this treatment is a promising intervention for anxiety, depression, and existential distress in people with cancer. However, psychedelic treatment that induces a mind-altering experience potentially poses barriers to vulnerable cancer patients, and health-care practitioners may have concerns about referring their patients to trials investigating this approach. The aim of the current study was to investigate the perceptions of cancer health-care practitioners based in New Zealand and the USA related to psychedelic-assisted therapy., Methods: This study utilized a cross-sectional survey of cancer health-care practitioners in New Zealand and the USA via convenience sampling to identify their perceptions about the concept of conducting psychedelic-assisted therapy with cancer patients., Results: Participants perceived that (1) psychedelic-assisted therapy has the potential to provide benefit for cancer patients, (2) research in this area across a variety of domains is important, (3) work should consider spiritual and indigenous perspectives of health, and (4) there was willingness to refer patients to trials in this area, especially patients with advanced disease who were no longer going through curative treatment. Participants in the USA had greater awareness of psychedelics than the New Zealand sample; however, New Zealand participants more strongly believed that spiritual/indigenous factors should be considered in psychedelic-assisted therapy., Significance of Results: Cancer health-care practitioners in our sample considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts.

Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A 42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in Psilocybe cubensis and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.

The Zero Suicide (ZS) model is a promising approach for preventing all suicides across health care settings. ZS provides guidelines for health care systems to implement best practices in suicide prevention. Patients with substance use disorders are at increased risk for suicide, but no known research has investigated how to integrate the ZS model into addiction treatment settings. This Open Forum encourages clinicians and researchers to integrate ZS into such settings and to study its feasibility and effectiveness. ZS integration into addiction treatment may improve both suicide and addiction outcomes, but additional research is needed., Competing Interests: Dr. Barnett reports being an advisory board member for and holding stock options in CB Therapeutics; receiving monetary compensation for editorial work from DynaMed Plus (EBSCO Industries, Inc.) and for consulting services from Cerebral, Compass Pathways, and Janssen Pharmaceuticals; and receiving research support from Compass Pathways and MindMed. The other authors report no financial relationships with commercial interests.

Objective: This study aimed to investigate the frequency of long COVID diagnosis among patients infected with severe acute respiratory syndrome coronavirus 2 with preexisting psychiatric conditions versus those without preexisting psychiatric conditions., Methods: The TriNetX Analytics platform, an aggregated electronic health record research network containing the deidentified electronic health record data of more than 90 million patients, was queried for patients who were diagnosed with COVID-19 infection based on International Classifications of Disease, Tenth Revision codes. Patients were stratified based on their preexisting psychiatric conditions, and new diagnoses of long COVID were recorded and reported as the primary outcome., Results: Among 1,180,948 patients previously diagnosed with COVID-19, 17,990 patients (1.52%) were diagnosed with long COVID based on the newly implemented International Classifications of Disease, Tenth Revision code "U09: post-COVID-19 condition." After propensity score matching, patients with any preexisting psychiatric diagnosis had a 1.52 (95% confidence interval [CI] = 1.47-1.58) times greater prevalence of diagnosed long COVID within 180 days of infection than patients without preexisting psychiatric diagnoses. Patients with diagnosed anxiety disorders (relative risk [RR] = 1.64; 95% CI = 1.57-1.71), mood disorders (RR = 1.65; 95% CI = 1.57-1.72), bipolar disorder (RR = 1.37; 95% CI = 1.21-1.54), major depressive disorder (RR = 1.69; 95% CI = 1.56-1.83), psychotic disorders (RR = 1.23; 95% CI = 1.06-1.44), and substance use disorders (RR = 1.28; 95% CI = 1.22-1.36) had higher risks for long COVID diagnoses when compared with patients without preexisting psychiatric illness at the time of diagnosis., Conclusions: Multiple preexisting psychiatric diagnoses are associated with an increased risk of being diagnosed with long COVID after COVID-19 infection., (Copyright © 2024 by the American Psychosomatic Society.)

For more than 2 decades, intravenous ketamine has been demonstrated to have rapid antidepressant effects. However, access to this generic drug is limited due to insurers claiming it is "experimental" because ketamine does not have a Food and Drug Administration indication for depression. In contrast, intranasal esketamine, an enantiomer of ketamine, is approved by the Food and Drug Administration for depression and is still under patent. The goal of this column is to provide a clearer understanding of formulary coverage of these similar medications by insurers. Formularies of all 2023 Ohio Health Insurance Marketplace and Medicaid plans were reviewed to determine the inclusion status of intravenous ketamine and intranasal esketamine for depression. This review found that intravenous ketamine was not covered by any Marketplace or Medicaid plan for depression, while intranasal esketamine was on 72.7% and 100% of formularies, respectively. Thus, members of the analyzed insurance plans can more easily access intranasal esketamine than intravenous ketamine for depression, despite the latter being more cost-effective and possibly more efficacious., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The clinical diagnosis and classification of Alexander disease (AxD) relies in part on qualitative neuroimaging biomarkers; however, these biomarkers fail to distinguish and discriminate different subtypes of AxD, especially in the presence of overlap in clinical symptoms. To address this gap in knowledge, we applied neurite orientation dispersion and density imaging (NODDI) to an innovative CRISPR-Cas9 rat genetic model of AxD to gain quantitative insights into the neural substrates and brain microstructural changes seen in AxD and to potentially identify novel quantitative NODDI biomarkers of AxD., Methods: Multi-shell DWI of age- and sex-matched AxD and wild-type Sprague Dawley rats (n = 6 per sex per genotype) was performed and DTI and NODDI measures calculated. A 3 × 2 × 2 analysis of variance model was used to determine the effect of genotype, biological sex, and laterality on quantitative measures of DTI and NODDI across regions of interest implicated in AxD., Results: There is a significant effect of genotype in the amygdala, hippocampus, neocortex, and thalamus in measures of both DTI and NODDI brain microstructure. A genotype by biological sex interaction was identified in DTI and NODDI measures in the corpus callosum, hippocampus, and neocortex., Conclusion: We present the first application of NODDI to the study of AxD using a rat genetic model of AxD. Our analysis identifies alterations in NODDI and DTI measures to large white matter tracts and subcortical gray nuclei. We further identified genotype by sex interactions, suggesting a possible role for biological sex in the neuropathogenesis of AxD., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity's relationship to length of stay (LOS) and risk of facility readmission., Methods: This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed., Results: Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission., Conclusions: This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk., Competing Interests: BSB is on the advisory board of CB Therapeutics and has stock options. He has also received monetary compensation for editorial work for DynaMed Plus (EBSCO Industries, Inc.) and consulting for Cerebral. The other authors report no potential conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Objective: This study aimed to characterize Z-drug prescribing with and without opioid coprescribing pre- and post-COVID-19 lockdown in the primary care clinics of a large health care system., Methods: A retrospective, cross-sectional study was conducted that measured the prevalence of Z-drug prescribing with and without opioids for adults aged ≥ 18 years that were seen in the primary care clinics of a large health care system in 2019 and 2020. The pre-COVID time period was defined as March 24, 2019-December 31, 2019, and the post-lockdown time period was defined as March 24, 2020-December 31, 2020., Results: Among 455,537 adult patients, 6,743 (1.48%) were prescribed a Z-drug during the study period. In addition, 1,064 (0.2%) were coprescribed a Z-drug and an opioid at least once, constituting 15.78% of patients receiving a Z-drug prescription. There was no change in the rate of Z-drug prescription post-lockdown (odds ratio [OR] = 0.978, 95% confidence interval [CI] = 0.942-1.010, P  = .233), though odds of coprescribing decreased (OR = 0.883, 95% CI = 0.789-0.988, P  = .031). Important correlates of receiving a Z-drug prescription during the study period were older age, White race, and diagnosis of opioid use disorder. Older age and a diagnosis of opioid use disorder were also associated with coprescribing. Receiving a de novo Z-drug prescription post-lockdown was associated with increased age, White race, and diagnosis of bipolar disorder, generalized anxiety disorder, and insomnia., Conclusions: Rates of Z-drug prescribing were unchanged post-lockdown, while rates of Z-drug with opioid coprescribing decreased. Some patient populations vulnerable to Z-drug adverse effects were at heightened risk of Z-drug prescription, while racial disparities in Z-drug prescribing were observed., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Background: Catatonia due to a general medical condition may result from a variety of causes, including substance intoxication and withdrawal. Stimulants are occasionally associated with catatonia, though there has been little investigation of methamphetamine's relationship to catatonia. Here we present 5 cases of catatonia associated with methamphetamine use and a systematic review of the associated literature from 1943 to 2020., Methods: We performed a systematic review of the literature and present 5 cases of catatonia evaluated using the Bush-Francis Catatonia Rating Scale and KANNER catatonia rating scale., Results: Methamphetamine use was associated with catatonia in a small number of cases in the literature. However, some of these reports included other possible etiologies. The patients in our case series met DSM-5 criteria for catatonia due to a general medical condition, with all reporting recent methamphetamine use and testing positive for amphetamines on urine drug screen., Conclusions: Given the ongoing rise in methamphetamine use in the United States, it is important that clinicians understand that methamphetamine use can be associated with catatonia. Patients with methamphetamine-associated catatonia may respond favorably to lorazepam and require shorter hospital stays than other catatonic patients. Lastly, methamphetamine-associated catatonia highlights how alteration in dopamine function and projections may be a critical neural mechanism underlying catatonia in general.

Background: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain., Methods: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period., Results: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation., Conclusions: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.)., (Copyright © 2023 Massachusetts Medical Society.)

Introduction: Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events., Methods: Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks., Results: There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group ( p  = 0.04)., Discussion: While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barnett, Wesselowski, Gordon, Saunders, Promislow, Schwartz, Chou, Evans, Kaeberlein and Creevy.)

Background: Patients with cerebral palsy, a group of movement disorders with motor, and possibly communication and behavioral features that mimic catatonic signs, may benefit from efforts to improve the detection and treatment of comorbid catatonia. Given that cerebral palsy frequently co-occurs with conditions associated with catatonia, such as autism spectrum disorder, epilepsy, intellectual disability, and mood and psychotic disorders, lifetime prevalence of catatonia in this population may be high., Objective: This study aimed to systematically review the literature on catatonia and the related condition of neuroleptic malignant syndrome (NMS) in patients with cerebral palsy while presenting 2 additional cases of catatonia., Methods: We used the terms "cerebral palsy" in combination with "catatoni∗," related terms for catatonia, and "neuroleptic malignant syndrome" to query Ovid MEDLINE (1948 to November 28, 2022), PsycINFO, Cumulative Index to Nursing, and Allied Health Literature, and Embase for applicable case reports. The Neuroleptic Malignant Syndrome Information Service database was also manually searched., Results: In addition to our 2 catatonia reports, we identified 10 reports of catatonia in patients with cerebral palsy, as well as 8 reports of NMS. Patients with both conditions responded well, and sometimes rapidly, to treatment. Notably, of the 5 patients with catatonia and cerebral palsy who received electroconvulsive therapy, 2 developed recurrent self-limited hyperthermia posttreatment. We also identified several cases of baclofen withdrawal, which can be life threatening because of seizure risk, presenting with NMS-like features in patients with cerebral palsy who had malfunctioning intrathecal baclofen pumps for spasticity management., Conclusions: Given frequent comorbidity of conditions associated with catatonia in patients with cerebral palsy, as well as routine treatment with medications that can induce NMS, such as metoclopramide and anticholinergics, catatonia and NMS may be underreported in the cerebral palsy patient population, despite being highly treatable. Possible underdiagnosis of catatonia in patients with cerebral palsy may be because of misattribution of overlapping features between the 2 conditions to cerebral palsy. Clinicians should be aware of possible recurrent self-limited fever when using electroconvulsive therapy to treat patients with catatonia and cerebral palsy while also being vigilant for intrathecal baclofen withdrawal when encountering NMS-like features in patients with cerebral palsy., (Copyright © 2022 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs., Sample: Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n=42) and/or completed the entire survey between January 20 and March 24, 2021 (n=646)., Procedures: The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post-hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs' death., Results: The EOLS was well-received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the three validation themes: cause of death (kappa = 0.73; 95% CI [0.5-0.95]), perimortem quality of life (kappa = 0.49; 95% CI [0.26-0.73]), and reason for euthanasia (kappa = 0.3; 95% CI [0.08-0.52]) and had no need for any substantial content alterations based on free-text analysis., Clinical Relevance: The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians' ability to care for the aging dog population by illuminating their understanding of companion dogs' end-of-life experiences.

Background: Since Kahlbaum's classic 19th-century description of catatonia, our conceptualization of this syndrome, as well treatment options for it, has advanced considerably. However, little is known about the current state of the catatonia literature since a comprehensive bibliometric analysis of it has not yet been undertaken., Objective: The purpose of this study was to conduct a bibliometric analysis, along with a content analysis of articles reporting new findings, to better understand the catatonia literature and how catatonia research is changing., Methods: Using the search term "Title(catatoni∗)" in Web of Science Core Collection for all available years (1965-2020), all available publications (articles, proceeding papers, reviews) pertaining directly to catatonia were identified, and metadata extracted. Semantic and coauthorship network analyses were conducted. A content analysis was also conducted on all available case reports, case series, and research articles written in English., Results: A total of 1015 articles were identified representing 2861 authors, 346 journals, and 15,639 references. The average number of publications per year over the last 20 years (31.3) more than doubled in comparison to that in the 20 years prior (12.8). The top 3 most common journals were Psychosomatics/Journal of the Academy of Consultation-Liaison Psychiatry, Journal of ECT, and Schizophrenia Research, which represented 12.6% of all publications. Content analysis revealed that catatonia articles are increasingly published in nonpsychiatric journals. There was a notable paucity of clinical trials throughout the study period. Since 2003, articles on catatonia secondary to a general medical condition, as well as articles including child/adolescent patients and patients with autism spectrum disorder or intellectual disability, have made up increasing shares of the literature, with a smaller proportion of articles reporting periodic or recurrent catatonia. We noted a decrease in the proportion of articles detailing animal/in vitro studies, genetic/heredity studies, and clinical trials, along with stagnation in the proportion of neuroimaging studies., Conclusions: The catatonia literature is growing through contributions from authors and institutions across multiple countries. However, recent growth has largely been driven by increased case reports, with significant downturns observed in both clinical and basic science research articles. A dearth of clinical trials evaluating potential treatments remain a critical gap in the catatonia literature., (Copyright © 2022 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: In 1967, concerns about the carcinogenic potential of psychedelics arose after a study reported chromosomal damage in human leukocytes following in vitro lysergic acid (LSD) exposure. Worries were further heightened by subsequent reports of leukemia and other cancers in LSD users. Additional investigations of psychedelics' effects on chromosomes were published over the next decade, with the majority suggesting these concerns were unfounded. However, the relationship between psychedelics and cancer has been explored only minimally from an epidemiological perspective., Aims: To determine whether associations exist between psychedelic use and either lifetime cancer or hematologic cancer diagnoses., Methods: We analyzed data from adult participants in the 2015-2019 administrations of the National Survey on Drug Use and Health for associations between lifetime use of psychedelics and lifetime diagnosis of either any cancer or hematologic cancer., Results: We identified no associations between lifetime psychedelic use and either lifetime cancer diagnosis or hematologic cancer diagnosis. Sub-analyses of lifetime lysergamide, phenethylamine, and tryptamine use also revealed no associations with lifetime cancer or hematologic cancer diagnosis., Conclusions: While laboratory studies and case reports from the 1960s and 1970s generated concerns about psychedelics' carcinogenic potential, this analysis of recent epidemiological data does not support an association between psychedelic use and development of cancer in general or hematologic cancer. Important study limitations to consider include a lack of information about psychedelic dosage, number of lifetime psychedelic exposures, and the temporal relationship between psychedelic use and cancer diagnosis.

Amid a reappraisal of the medicinal and societal worth of psychedelics in many countries, regulatory and financial barriers to conducting clinical research with these compounds appear to be receding. Still, there remains a strong need for a clearer understanding of naturalistic psychedelic use and its associated epidemiology, since this type of psychedelic use, which is growing in many places, will almost certainly always exceed clinical use. Furthermore, psychedelics behave differently depending on the settings in which they are used, meaning many research findings on their effects may significantly differ depending on the contexts in which they are observed. Therefore, improving the collection of data on real-world psychedelic use should be of higher priority for the public health community. Expanding data collection on psychedelic use in the United States National Survey on Drug Use and Health, an already vital tool for researchers examining naturalistic psychedelic use, could address this important public health need, helping ensure the general public, the scientific community, and regulators have access to high-quality information as peoples across the world reevaluate what psychedelics' place in medicine and society should be.

Here we describe the development and evaluation of a survey instrument to assess the research suitability of veterinary electronic medical records (EMRs) through the conduct of two studies as part of the Dog Aging Project (DAP). In study 1, four reviewers used the instrument to score a total of 218 records in an overlapping matrix of pairs to assess inter-rater agreement with respect to appropriate format (qualification), identification match (verification), and record quality. Based upon the moderate inter-rater agreement with respect to verification and the relatively large number of records that were incorrectly rejected the instrument was modified and more specific instructions were provided. In study 2, a modified instrument was again completed by four reviewers to score 100 different EMRs. The survey scores were compared to a gold standard of board-certified specialist review to determine receiver operating curve statistics. The refined survey had substantial inter-rater agreement across most qualification and verification questions. The cut-off value identified had a sensitivity of 95 and 96% (by reviewer 1 and reviewer 2, respectively) and a specificity of 82% and 91% (by reviewer 1 and reviewer 2, respectively) to predict gold standard acceptance or rejection of the record. Using just qualification and verification questions within the instrument (as opposed to full scoring) minimally impacted sensitivity and specificity and resulted in substantial time savings in the review process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Praczko, Tinkle, Arkenberg, McClelland, Creevy, Tolbert, Barnett, Chou, Evans, McNulty, Dog Aging Project Consortium and Levine.)

Despite resurgent interest in psychedelic-assisted therapy, our insights into psychiatrists' knowledge and opinions about medicinal psychedelic applications are surprisingly narrow. Therefore, we anonymously surveyed psychiatrists attending psychedelic didactic presentations at two national meetings about these issues using a 26-item questionnaire. Response rate was 40.20% (106/264). Respondents were 41.73 ± 13.31 years old (range: 24-80) and 64.42% were male. They largely believed psychedelics show treatment promise and strongly supported federal funding for medicinal psychedelic research. The most common concerns were the lack of trained psychedelic-assisted therapy providers, the logistics of psychedelic-assisted therapy delivery, the administration of psychedelics for patients with contraindications, and diversion. The most desired psychedelic-related educational topics were potential benefits of psychedelic-assisted therapy, how to conduct psychedelic-assisted therapy, psychedelic pharmacology, and psychedelic side effects. Factors associated with increased belief in psychedelics' treatment potential included working primarily in research, scoring higher on a psychedelic knowledge test, and reporting less concern about psychedelics' addictive potential. Working primarily in research and consult-liaison psychiatry fellowship training were positively associated with support for medicinal psychedelic legalization, while increased concerns about addictive potential and attending psychiatrist status were negatively associated. Support for legalization of non-medicinal psychedelic use was negatively associated with age and positively associated with support for legalization of medicinal psychedelic use.

The gut microbiome profoundly influences brain structure and function. The gut microbiome is hypothesized to play a key role in the etiopathogenesis of neuropsychiatric and neurodegenerative illness; however, the contribution of an intact gut microbiome to quantitative neuroimaging parameters of brain microstructure and function remains unknown. Herein, we report the broad and significant influence of a functional gut microbiome on commonly employed neuroimaging measures of diffusion tensor imaging (DTI), neurite orientation dispersion and density (NODDI) imaging, and SV2A 18 F-SynVesT-1 synaptic density PET imaging when compared to germ-free animals. In this pilot study, we demonstrate that mice, in the presence of a functional gut microbiome, possess higher neurite density and orientation dispersion and decreased synaptic density when compared to age- and sex-matched germ-free mice. Our results reveal the region-specific structural influences and synaptic changes in the brain arising from the presence of intestinal microbiota. Further, our study highlights important considerations for the development of quantitative neuroimaging biomarkers for precision imaging in neurologic and psychiatric illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yi, Pirasteh, Wang, Bradshaw, Jeffery, Barnett, Stowe, McMillan, Vivas, Rey and Yu.)

Purpose: Immunotherapy treats some cancers, but not ovarian cancer. Regulatory T cells (Tregs) impede anti-ovarian cancer immunity but effective human Treg-directed treatments are lacking. We tested Treg depletion with denileukin diftitox (DD) ± IFNα as ovarian cancer immunotherapy., Patients and Methods: Mice with syngeneic ID8 ovarian cancer challenge were treated with DD, IFNα, or both. The phase 0/I trial tested one dose-escalated DD infusion for functional Treg reduction, safety, and tolerability. The phase II trial added IFNα2a to DD if DD alone failed clinically., Results: DD depleted Tregs, and improved antitumor immunity and survival in mice. IFNα significantly improved antitumor immunity and survival with DD. IFNα did not alter Treg numbers or function but boosted tumor-specific immunity and reduced tumor Treg function with DD by inducing dendritic cell IL6. DD alone was well tolerated, depleted functional blood Tregs and improved immunity in patients with various malignancies in phase 0/I. A patient with ovarian cancer in phase 0/I experienced partial clinical response prompting a phase II ovarian cancer trial, but DD alone failed phase II. Another phase II trial added pegylated IFNα2a to failed DD, producing immunologic and clinical benefit in two of two patients before a DD shortage halt. DD alone was well tolerated. Adding IFNα increased toxicities but was tolerable, and reduced human Treg numbers in blood, and function through dendritic cell-induced IL6 in vitro ., Conclusions: Treg depletion is clinically useful but unlikely alone to cure ovarian cancer. Rational treatment agent combinations can salvage clinical failure of Treg depletion alone, even when neither single agent provides meaningful clinical benefit., (©2021 American Association for Cancer Research.)

Diffusion tensor imaging (DTI) has fundamentally transformed how we interrogate diseases and disorders of the brain in neuropsychiatric illness. DTI and recently developed multicompartment diffusion-weighted imaging (MC-DWI) techniques, such as NODDI (neurite orientation dispersion and density imaging), measure diffusion anisotropy presuming a static neuroglial environment; however, microglial morphology and density are highly dynamic in psychiatric illness, and how alterations in microglial density might influence intracellular measures of diffusion anisotropy in DTI and MC-DWI brain microstructure is unknown. To address this question, DTI and MC-DWI studies of murine brains depleted of microglia were performed, revealing significant alterations in axonal integrity and fiber tractography in DTI and in commonly used MC-DWI models. With accumulating evidence of the role of microglia in neuropsychiatric illness, our findings uncover the unexpected contribution of microglia to measures of axonal integrity and structural connectivity and provide unanticipated insights into the potential influence of microglia in diffusion imaging studies of neuropsychiatric disease., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

This study examined opinions of American psychiatrists regarding prior authorization (PA) requirements for third-party payer coverage of medications and quantified perceived impact of these requirements on clinical practice. One thousand selected psychiatrist members of the American Psychiatric Association were invited to participate in a survey. Response rate was 33.1%. Respondents predominantly believed the obligation to obtain PA reduces job satisfaction and negatively impacts patient care. A total of 59.9% of respondents reported employing either diagnosis modification or falsification of previous medication trials at least occasionally in order to obtain PA. A total of 66.6% refrained at least occasionally from prescribing preferred medications due to PA requirement or expectation of one. On multivariate analysis, risk factors for refraining at higher frequency included seeing 300 or more patients in the previous 3 months, engaging more frequently in diagnosis modification, and reporting increased perception that obtaining PA reduces time for patient care.

Synaptosomes are isolated nerve terminals that contain synaptic components, including neurotransmitters, metabolites, adhesion/fusion proteins, and nerve terminal receptors. The essential role of synaptosomes in neurotransmission has stimulated keen interest in understanding both their proteomic and metabolic composition. Mass spectrometric (MS) quantification of synaptosomes has illuminated their proteomic composition, but the determination of the metabolic composition by MS has been met with limited success. In this study, we report a proof-of-concept application of one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy for analyzing the metabolic composition of synaptosomes. We utilize this approach to compare the metabolic composition synaptosomes from a wild-type rat with that from a newly generated genetic rat model ( Disc1 svΔ2), which qualitatively recapitulates clinically observed early DISC1 truncations associated with schizophrenia. This study demonstrates the feasibility of using NMR spectroscopy to identify and quantify metabolites within synaptosomal fractions.

Purpose: Studies of factors affecting length of stay during psychiatric hospitalization in sub-Saharan Africa are sparse. A better understanding of such factors may lead to interventions resulting in quicker patient stabilization and discharge, freeing up needed psychiatric beds and reducing health care system expenditures. Therefore, we sought to identify factors associated with long length of stay in Malawi., Methods: We reviewed the charts of 417 patients hospitalized at Kamuzu Central Hospital's Bwaila Psychiatric Unit in Lilongwe, Malawi from January 1 to December 31, 2011. Multivariate logistic regression analysis was employed to test for associations between patient factors and long length of stay (defined as more than 28 days)., Results: Mean length of stay was 22.08 ± 27.70 days (range 0-243). 21.82% (91/417) of patients stayed longer than 28 days. Long length of stay was associated with living outside of Lilongwe district [aOR: 3.65 (1.66-8.01), p = 0.001] and treatment for antipsychotic extrapyramidal side effects (EPS) during hospitalization [aOR: 3.45 (1.32-9.03), p = 0.012]. Patients who had more interactions with medical providers for this episode of illness prior to presentation at the unit were less likely to have a long length of stay [aOR: 0.35 (0.16-0.76), p = 0.008]., Conclusions: Our findings demonstrate areas of possible intervention to reduce length of stay, including securing means for patient transport home, rapid identification and treatment of EPS, and reducing the risk of EPS by decreased use of high potency first-generation antipsychotics.

Objective: While psychological care, including supportive group therapy, is a mainstay of burn treatment in the developed world, few reports of support groups for burn survivors and their caregivers in the developing world exist. This study records the findings of a support group in Malawi and provides a qualitative analysis of thematic content discussed by burn survivors and caregivers., Materials and Methods: We established a support group for burn survivors and caregivers from February-May 2012 in the burn unit at Kamuzu Central Hospital in Lilongwe, Malawi. Sessions were held weekly for twelve weeks and led by a Malawian counselor. The group leader compiled transcripts of each session and these transcripts were qualitatively analyzed for thematic information., Results: Thematic analysis demonstrated a variety of psychological issues discussed by both survivors and caregivers. Caregivers discussed themes of guilt and self-blame for their children's injuries, worries about emotional distance now created between caregiver and survivor, fears that hospital admission meant likely patient death and concerns about their child's future and burn associated stigma. Burn survivors discussed frustration with long hospitalization courses, hope created through interactions with hospital staff, the association between mental and physical health, rumination about their injuries and how this would affect their future, decreased self-value, increased focus on their own mortality and family interpersonal difficulties., Conclusions: The establishment of a support group in our burn unit provided a venue for burn survivors and their families to discuss subjective experiences, as well as the dissemination of various coping techniques. Burn survivors and their caregivers in Malawi would benefit from the establishment of similar groups in the future to help address the psychological sequelae of burns., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Background: Xpert ® MTB/RIF is a molecular test for the detection of Mycobacterium tuberculosis and rifampicin resistance. It is considered to be a great advance over smear microscopy and culture. However, there is very little information regarding the performance characteristics of Xpert MTB/RIF in Malawi., Objective: We aimed to evaluate the performance of Xpert MTB/RIF in a Malawian setting., Methods: Stored sputum pellets were processed on Xpert MTB/RIF between June 2012 and May 2014. Results were compared to mycobacteria growth indicator tube and Löwenstein-Jensen cultures, LED fluorescent microscopy and GenoType ® MTBDR plus assay. Rifampicin resistance was confirmed by DNA sequencing., Results: Of the 348 specimens with valid Xpert MTB/RIF results, 129/348 (37%) were smear-positive and 198/348 (57%) were culture-positive. Xpert MTB/RIF demonstrated a sensitivity of 93.8% (95% CI 89.4% - 96.8%) and specificity of 97.4% (95% CI 93.5% - 99.3%), with a positive predictive value of 97.8% (95% CI 94.6% - 99.4%) and a negative predictive value of 92.6% (95% CI 87.4% - 96.1%). Xpert MTB/RIF correctly identified 185/186 (99.5%) rifampicin-sensitive and 2/2 (100%) rifampicin-resistant M. tuberculosis strains. Mutations were not detected by sequencing in one isolate which was rifampicin resistant on Xpert MTB/RIF but sensitive on MTBDR plus . Four non-tuberculous mycobacteria grew from four smear-negative specimens, namely, M. avium ( n = 1) and M. intracellulare ( n = 3). No cross-reactivity was observed with any of the non-tuberculous mycobacteria when using Xpert MTB/RIF., Conclusion: When fully implemented, Xpert MTB/RIF may have an impact on patient care in Malawi. The increased diagnostic yield of Xpert MTB/RIF over smear microscopy can increase laboratory-confirmed tuberculosis detection and ensure that treatment is given to appropriate individuals or groups., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article.

Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or both. Plant expression of Bacillus thuringiensis (Bt) crystal (Cry) insecticidal proteins have been the primary way to impart insect resistance in GM crops. Although deemed safe by regulatory agencies globally, previous studies have been the basis for discussions around the potential immuno-adjuvant effects of Cry proteins. These studies had limitations in study design. The studies used animal models with extremely high doses of Cry proteins, which when given using the ig route were co-administered with an adjuvant. Although the presumption exists that Cry proteins may have immunostimulatory activity and therefore an adjuvanticity risk, the evidence shows that Cry proteins are expressed at very low levels in GM crops and are unlikely to function as adjuvants. This conclusion is based on critical review of the published literature on the effects of immunomodulation by Cry proteins, the history of safe use of Cry proteins in foods, safety of the Bt donor organisms, and pre-market weight-of-evidence-based safety assessments for GM crops., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

Although rare, severe hypercalcemia can cause significant conduction system alterations, including complete atrioventricular block., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.

Cancers express tumor associated antigens that should elicit immune attack, but spontaneous immune rejection of established cancer is rare. Recent data demonstrate that specific and active tumor-mediated mechanisms hinder host anti-tumor immunity. CD4+CD25+ T regulatory cells (Tregs) are important mediators of active immune evasion in cancer. Disrupting tumor-mediated mechanisms hindering host immunity is a novel approach to tumor immunotherapy. Treg depletion improves endogenous anti-tumor immunity and the efficacy of active immunotherapy in animal models for cancer, suggesting that inhibiting Treg function could also improve the limited successes of human cancer immunotherapy. We have identified five strategies to block Treg activity: depletion, interference with trafficking, inhibition of differentiation, blockade of function or raising the effector T cell threshold for suppression. Discovery of additional regulatory cell populations expands the potential targets for these approaches. The fusion toxin denileukin diftitox (Ontak) reduces Treg numbers and function in the blood of some patients with cancer. We discuss specific strategies to block Treg activity and present some of our preliminary data in this area. Combining Treg depletion with active vaccination and other approaches poses additional challenges that are discussed.