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Background: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period., Methods: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466)., Findings: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline., Conclusions: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity., Funding: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific., Competing Interests: Declaration of interests J.D.R. has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services, Inc. (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Center for Mental Health, Joseph M. West Family Memorial Fund, and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion, Braxia Health, Braxia Scientific Corp., and COMPASS. R.S.M. has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC), and the Milken Institute and speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. R.S.M. is a CEO of Braxia Scientific Corp. C.S.-Q. has received education scholarship support from Academic Scholars Award, Department of Psychiatry, University of Toronto, and Young Leaders Program and Cancer Experience Program, Princess Margaret Cancer Center, University Health Network. He is on the board of directors for the Canadian Academy for Consultation and Liaison Psychiatry. M.G.B. currently works as an independent contractor serving clients for psychedelic-assisted psychotherapy with Braxia Scientific Corp.; in a consulting role, he owns stake in a psychedelic technology company called Entheosense and has received speaking fees as an honorarium for providing a training lecture on psychedelic spiritual care for psychotherapists in this Braxia clinical trial. R.B.M. has received research grant support from the CIHR, the PSI Foundation, and the Baszucki Brain Research Fund and an Academic Scholars Award, Department of Psychiatry, University of Toronto. F.A.G. has received research grant support from the Brain & Behavior Research Foundation (BBRF), Southeastern Ontario Academic Medical Organization (SEAMO), and Queen’s Health Sciences and speaker/consultation fees from Lundbeck, Otsuka, and Abbvie. Z.D., RN, is a clinical project lead with Braxia Scientific Corp. J.B. was a paid co-chair of a psilocybin therapist training event with Braxia Scientific Corp., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Measurement of adherence to oral pre-exposure prophylaxis (PrEP) in real-time has been challenging. We developed DOT Diary, a smartphone application that combines automated directly observed therapy with a PrEP adherence visualization toolkit, and tested its ability to measure PrEP adherence and to increase adherence among a diverse cohort of young men who have sex with men (MSM). We enrolled 100 MSM in San Francisco and Atlanta and randomly assigned them 2:1 to DOT Diary versus standard of care. Concordance between DOT Diary measurement and drug levels in dried blood spots was substantial, with 91.0% and 85.3% concordance between DOT Diary and emtricitabine-triphosphate and tenofovir-diphosphate, respectively. There was no significant difference in the proportion of participants with detectable PrEP drug levels at 24 weeks between study arms. These results suggest DOT Diary is substantially better than self-reported measures of adherence, but additional interventions are needed to improve PrEP adherence over time., (© 2022. The Author(s).)

Background: The impacts of the COVID-19 pandemic have disproportionally affected different population groups. Veterans are more likely to have pre-existing mental health conditions compared to the general Canadian population, experience compounded stressors resulting from disruptions to familial, social, and occupational domains, and were faced with changes in health-care delivery (e.g. telehealth). The objectives of this study are to assess (a) the mental health impact of COVID-19 and related life changes on the well-being of Veterans and (b) perceptions of and satisfaction with changes in health-care treatments and delivery during the pandemic., Methods: A total of 1136 Canadian Veterans participated in an online survey. Participants completed questions pertaining to their mental health and well-being, lifestyle changes, and concerns relating to the COVID-19 pandemic, as well as experiences and satisfaction with health-care treatments during the pandemic., Results: Results showed that 55.9% of respondents reported worse mental health functioning compared to before the pandemic. The frequency of probable posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, alcohol use disorder, and suicidal ideation were 34.2%, 35.3%, 26.8%, 13.0%, and 22.0%, respectively. Between 38.6% and 53.1% of respondents attributed their symptoms as either directly related to or exacerbated by the pandemic. Approximately 18% of respondents reported using telehealth for mental health services during the pandemic, and among those, 72.8% indicated a choice to use telehealth even after the pandemic., Conclusions: This study found that Veterans experienced worsening mental health as a result of the COVID-19 pandemic. The use of telehealth services was widely endorsed by mental health treatment-seeking Veterans who transitioned to virtual care during the pandemic. Our findings have important clinical and programmeadministrator implications, emphasizing the need to reach out to support veterans, especially those with pre-existing mental health conditions and to enhance and maintain virtual care even post-pandemic., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The COVID-19 pandemic has resulted in significant changes to everyday life, including social distancing mandates, changes to health care, and a heightened risk of infection. Previous research has shown that Canadian Armed Forces (CAF) veterans are at higher risk of developing mental and physical health conditions. Veterans and their families may face unique social challenges that can compound with pandemic-related disruptions to negatively impact well-being., Objective: This study aims to longitudinally characterize the mental health of CAF veterans and spouses of CAF veterans throughout the pandemic and to understand the dynamic influences of pandemic-related stressors on psychological health over time., Methods: We employed a prospective longitudinal panel design using an online data collection platform. Study participation was open to all CAF veterans and spouses of CAF veterans residing in Canada. Participants were asked to complete a comprehensive battery of assessments representing psychological well-being, chronic pain, health care access patterns, physical environment, employment, social integration, and adjustment to pandemic-related lifestyle changes. Follow-up assessments were conducted every 3 months over an 18-month period. This study was approved by the Western University Health Sciences and Lawson Health Research Institute Research Ethics Boards., Results: Baseline data were collected between July 2020 and February 2021. There were 3 population segments that participated in the study: 1047 veterans, 366 spouses of veterans, and 125 veterans who are also spouses of veterans completed baseline data collection. As of November 2021, data collection is ongoing, with participants completing the 9- or 12-month follow-up surveys depending on their date of self-enrollment. Data collection across all time points will be complete in September 2022., Conclusions: This longitudinal survey is unique in its comprehensive assessment of domains relevant to veterans and spouses of veterans during the COVID-19 pandemic, ranging from occupational, demographic, social, mental, and physical domains, to perceptions and experiences with health care treatments and access. The results of this study will be used to inform policy for veteran and veteran family support, and to best prepare for similar emergencies should they occur in the future., International Registered Report Identifier (irrid): DERR1-10.2196/34984., (©Callista A Forchuk, Anthony Nazarov, Rachel A Plouffe, Jenny J W Liu, Erisa Deda, Tri Le, Dominic Gargala, Vanessa Soares, Jesse Bourret-Gheysen, Kate St Cyr, Maede S Nouri, Fardous Hosseiny, Patrick Smith, Gabrielle Dupuis, Maya Roth, Michelle Marlborough, Rakesh Jetly, Alexandra Heber, Ruth Lanius, J Don Richardson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.01.2022.)

Background: Research is urgently needed to understand health care workers' (HCWs') experiences of moral-ethical dilemmas encountered throughout the COVID-19 pandemic, and their associations with organizational perceptions and personal well-being. This research is important to prevent long-term moral and psychological distress and to ensure that workers can optimally provide health services., Objective: Evaluate associations between workplace experiences during COVID-19, moral distress, and the psychological well-being of Canadian HCWs., Method: A total of 1362 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in an online survey. Participants completed measures reflecting moral distress, perceptions of organizational response to the pandemic, burnout, and symptoms of psychological disorders, including depression, anxiety, and posttraumatic stress disorder (PTSD)., Results: Structural equation modelling showed that when organizational predictors were considered together, resource adequacy, positive work life impact, and ethical work environment negatively predicted severity of moral distress, whereas COVID-19 risk perception positively predicted severity of moral distress. Moral distress also significantly and positively predicted symptoms of depression, anxiety, PTSD, and burnout., Conclusions: Our findings highlight an urgent need for HCW organizations to implement strategies designed to prevent long-term moral and psychological distress within the workplace. Ensuring availability of adequate resources, reducing HCW risk of contracting COVID-19, providing organizational support regarding individual priorities, and upholding ethical considerations are crucial to reducing severity of moral distress in HCWs., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Health care workers (HCWs) have experienced several stressors associated with the COVID-19 pandemic. Structural stressors, including extended work hours, redeployment, and changes in organizational mandates, often intersect with interpersonal and personal stressors, such as caring for those with COVID-19 infections; worrying about infection of self, family, and loved ones; working despite shortages of personal protective equipment; and encountering various difficult moral-ethical dilemmas., Objective: The paper describes the protocol for a longitudinal study seeking to capture the unique experiences, challenges, and changes faced by HCWs during the COVID-19 pandemic. The study seeks to explore the impact of COVID-19 on the mental well-being of HCWs with a particular focus on moral distress, perceptions of and satisfaction with delivery of care, and how changes in work structure are tolerated among HCWs providing clinical services., Methods: A prospective longitudinal design is employed to assess HCWs' experiences across domains of mental health (depression, anxiety, posttraumatic stress, and well-being), moral distress and moral reasoning, work-related changes and telehealth, organizational responses to COVID-19 concerns, and experiences with COVID-19 infections to self and to others. We recruited HCWs from across Canada through convenience snowball sampling to participate in either a short-form or long-form web-based survey at baseline. Respondents to the baseline survey are invited to complete a follow-up survey every 3 months, for a total of 18 months., Results: A total of 1926 participants completed baseline surveys between June 26 and December 31, 2020, and 1859 participants provided their emails to contact them to participate in follow-up surveys. As of July 2021, data collection is ongoing, with participants nearing the 6- or 9-month follow-up periods depending on their initial time of self-enrollment., Conclusions: This protocol describes a study that will provide unique insights into the immediate and longitudinal impact of the COVID-19 pandemic on the dimensions of mental health, moral distress, health care delivery, and workplace environment of HCWs. The feasibility and acceptability of implementing a short-form and long-form survey on participant engagement and data retention will also be discussed., International Registered Report Identifier (irrid): DERR1-10.2196/32663., (©Jenny J W Liu, Anthony Nazarov, Rachel A Plouffe, Callista A Forchuk, Erisa Deda, Dominic Gargala, Tri Le, Jesse Bourret-Gheysen, Vanessa Soares, Maede S Nouri, Fardous Hosseiny, Patrick Smith, Maya Roth, Arlene G MacDougall, Michelle Marlborough, Rakesh Jetly, Alexandra Heber, Joy Albuquerque, Ruth Lanius, Ken Balderson, Gabrielle Dupuis, Viraj Mehta, J Don Richardson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 27.09.2021.)

Objective: Among a sample of 341 treatment-seeking veterans and currently serving Canadian Forces members, our objectives were to identify factors of deployment experiences and determine whether they were related to the severity of posttraumatic stress disorder (PTSD) symptom clusters and depressive, anxiety, and alcohol use symptom severity., Method: Participants completed questionnaires during intake to an outpatient mental health clinic. Factor analysis was used to determine factors of deployment experiences and which mental health conditions were associated with the factors., Results: Exploratory factor analysis grouped experiences into 3 factors: (a) combat, (b) exposure to injury or death, and (c) potential moral injury and atrocity. Potential moral injury and atrocity was significantly associated with all outcomes except for alcohol use disorder, and combat was significantly associated with the arousal PTSD symptom cluster and depressive symptom severity., Conclusions: Our study demonstrates the association between combat experiences and PTSD symptom, depression, and anxiety severity. Clinically, it stresses the importance of evaluating specific traumatic events to improve treatment outcomes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Although most research professionals believe that protocol designs contain a growing number of unnecessary and redundant procedures generating unused data, incurring high cost, and jeopardizing study success, there are no published studies systematically examining this issue. Between November 2011 and May 2012, Tufts Center for the Study of Drug Development conducted a study among a working group of 15 pharmaceutical companies in which a total of 25,103 individual protocol procedures were evaluated and classified using clinical study reports and analysis plans. The results show that the typical later-stage protocol had an average of 7 objectives and 13 end points of which 53.8% are supplementary. One (24.7%) of every 4 procedures performed per phase-III protocol and 17.7% of all phase-II procedures per protocol were classified as "Noncore" in that they supported supplemental secondary, tertiary, and exploratory end points. For phase-III protocols, 23.6% of all procedures supported regulatory compliance requirements and 15.9% supported those for phase-II protocols. The study also found that on average, $1.7 million (18.5% of the total) is spent in direct costs to administer Noncore procedures per phase-III protocol and $0.3 million (13.1% of the total) in direct costs are spent on Noncore procedures for each phase-II protocol. Based on the results of this study, the total direct cost to perform Noncore procedures for all active annual phase-II and phase-III protocols is conservatively estimated at $3.7 billion annually, not including the indirect costs associated with collecting and managing Noncore procedure data and the ethical costs of exposing study volunteers to unnecessary risks associated with conducting extraneous procedures.

Background: Traumatic brain injury (TBI) can give rise to a variety of neuropsychiatric syndromes. The objective of this review is to describe the neurobiological mechanisms that have been proposed to underlie many of these post-TBI syndromes, explore the utility of various investigative modalities and review the mechanisms of treatment available for them., Methods: Six authors reviewed PubMed and Ovid literature that addressed TBI in the context of the neuropsychiatric sequelae, evaluation and management., Results: Depressed mood, anxiety, impulsive/aggressive behaviour, impaired memory and sleep disturbances are among the most prevalent sequelae of severe TBI. Delirium, while less common, can also result from TBI, predisposing individuals to other psychiatric conditions, while psychosis, usually presenting with atypical features, is relatively rare. The evaluation of the brain following TBI has often relied on traditional structural imaging which, according to recent studies, is less sensitive than chemical and functional neuroimaging. A variety of pharmacologic and non-pharmacologic treatments have been investigated with varying degrees of success in managing the spectrum of post-TBI psychiatric illnesses., Conclusions: Neuropsychiatric sequelae are common following TBI. Several of these syndromes are amenable to treatment. Further investigations are required, however, to better understand the mechanistic aetiology of these conditions and the effectiveness of various therapeutic modalities.