Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

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.

Randomized Controlled Trial of Automated Directly Observed Therapy for Measurement and Support of PrEP Adherence Among Young Men Who have Sex with Men.

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.

RESUMEN: La medición de la adherencia a la profilaxis oral previa a la exposición (PrEP) en tiempo real ha constituido un desafío. Hemos desarrollado DOT Diary, una aplicación para teléfonos inteligentes que combina la terapia automatizada observada de forma directa con un kit de herramientas para visualizar la adherencia a la PrEP, y testeamos su capacidad para medir la adherencia a la PrEP, así como para aumentar la adherencia entre una cohorte variada de hombres jóvenes que tienen sexo con hombres (HSH). Reclutamos a 100 HSH en San Francisco y Atlanta y los asignamos aleatoriamente 2:1 a DOT Diary con respecto a la asistencia estándar. La concordancia entre la medición del DOT Diary y los niveles de fármacos en gotas de sangre seca fue sustancial, con un 91,0% y un 85,3% de concordancia entre el uso del DOT Diary y el de emtricitabina-trifosfato y tenofovir-difosfato, respectivamente. No hubo diferencias significativas en la proporción de participantes con niveles detectables del fármaco de la PrEP a las 24 semanas entre los brazos del estudio. Estos resultados sugieren que DOT Diary es sustancialmente superior a las medidas de adherencia que se notifican de forma personal, aunque hacen falta intervenciones adicionales para mejorar la adherencia a la PrEP a largo plazo.

Well-being of Canadian Veterans during the COVID-19 pandemic: cross-sectional results from the COVID-19 Veteran well-being study.

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.

Antecedentes: Los impactos de la pandemia del COVID-19 han afectado de manera desproporcionada a diferentes grupos de la población. Los veteranos tienen más probabilidades de tener afecciones de salud mental preexistentes en comparación con la población canadiense en general, experimentar factores estresantes agravados como resultado de las interrupciones en los dominios familiares, sociales, y ocupacionales, y se enfrentan a cambios en la prestación de la atención médica (por ejemplo, telesalud). Los objetivos de este estudio son evaluar (a) el impacto en la salud mental del COVID-19 y los cambios de vida relacionados en el bienestar de los Veteranos y (b) las percepciones y la satisfacción con los cambios en los tratamientos y la entrega de la atención médica durante la pandemia.Métodos: Un total de 1136 veteranos canadienses participaron en una encuesta en línea. Los participantes completaron preguntas relacionadas con su salud mental y bienestar, cambios en el estilo de vida, e inquietudes relacionadas con la pandemia del COVID-19, así como experiencias y satisfacción con los tratamientos de atención médica durante la pandemia.Resultados: Los resultados mostraron que el 55,9% de los encuestados informaron un peor funcionamiento de la salud mental en comparación con antes de la pandemia. La frecuencia de probable trastorno de estrés postraumático, trastorno depresivo mayor, trastorno de ansiedad generalizada, trastorno por consumo de alcohol, e ideación suicida fue del 34,2%, 35,3%, 26,8%, 13,0% y 22,0%, respectivamente. Entre el 38,6% y el 53,1% de los encuestados atribuyeron sus síntomas como directamente relacionados con la pandemia o agravados por ella. Aproximadamente el 18% de los encuestados informó haber utilizado la telesalud para los servicios de salud mental durante la pandemia, y entre ellos, el 72,8% indicó que había optado por utilizar la telesalud incluso después de la pandemia.Conclusiones: Este estudio encontró que los Veteranos experimentaron un empeoramiento de la salud mental como resultado de la pandemia del COVID-19. El uso de los servicios de telesalud fue ampliamente respaldado por los Veteranos en busca de tratamiento de salud mental que hicieron la transición a la atención virtual durante la pandemia. Nuestros hallazgos tienen importantes implicaciones clínicas y para los administradores de programas, enfatizando la necesidad de ayudar a los veteranos, especialmente a aquellos con condiciones de salud mental preexistentes, y de mejorar y mantener la atención virtual incluso después de una pandemia.

Well-being of Canadian Armed Forces Veterans and Spouses of Veterans During the COVID-19 Pandemic: Protocol for a Prospective Longitudinal Survey.

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.

Impacts of morally distressing experiences on the mental health of Canadian health care workers during the COVID-19 pandemic.

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.

Antecedentes: Se necesita con urgencia investigaciones para comprender las experiencias de los dilemas éticos y morales que los trabajadores de la salud encontraron durante la pandemia de la COVID-19 y su asociación con las percepciones de la organización y el bienestar personal. Esta investigación es importante para prevenir la angustia moral y psicológica a largo plazo y para asegurar que los trabajadores de la salud puedan proveer de manera óptima los servicios de salud.Objetivo: Evaluar la asociación entre las experiencias en el lugar de trabajo durante la COVID-19, la angustia moral y el bienestar psicológico de los trabajadores de salud canadienses.Métodos: Se reclutó a un total de 1362 trabajadores de salud canadienses, que hablaban francés e inglés y que fueron contratados durante la pandemia de la COVID-19, para participar en un cuestionario en línea. Los participantes completaron mediciones que reflejaban la angustia moral, la percepción de la respuesta de la organización a la pandemia, el burnout y los síntomas de trastornos psicológicos, que incluían a la depresión, a la ansiedad y al trastorno de estrés postraumático (TEPT).Resultados: El modelo de ecuaciones estructurales mostró que cuando los predictores de la organización se consideraban en conjunto ­ los recursos adecuados, el impacto positivo en la vida laboral y un ambiente de trabajo ético ­, predijeron negativamente la gravedad de la angustia moral, mientras que la percepción del riesgo de contraer la COVID-19 predijo positivamente la gravedad de la angustia moral. La angustia moral también predijo de manera significativa y positiva los síntomas de la depresión, la ansiedad, el TEPT y el burnout.Conclusiones: Nuestros hallazgos resaltan la urgente necesidad de que las organizaciones de trabajadores de salud implementen estrategias diseñadas para prevenir la angustia moral y psicológica a largo plazo en el lugar de trabajo. El asegurar la disponibilidad de los recursos adecuados, el reducir el riesgo de que los trabajadores de salud contraigan la COVID-19, el proveer un soporte organizacional adecuado según las prioridades individuales y el respetar las consideraciones éticas son fundamentales para reducir la gravedad de la angustia moral en los trabajadores de salud.

Exploring the Well-being of Health Care Workers During the COVID-19 Pandemic: Protocol for a Prospective Longitudinal Study.

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.

Factor structure of deployment experiences and relations to mental health disorders among treatment-seeking Canadian armed forces personnel and veterans.

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).

Quantifying the magnitude and cost of collecting extraneous protocol data.

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.

Understanding the neuropsychiatric consequences associated with significant traumatic brain injury.

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.