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The article presents the author's comments on a paper by P. Thomas, P. Bracken, and S. Timimi on the limits of evidence-based medicine (EBM) in psychiatry. It presents a background of EBM and its applicable to psychiatry. It compares evidence-based psychiatry (EPB) with psychiatry and the theoretical requirements of EBM.

Purpose. Previous work from this laboratory has demonstrated that the vitamin D3 analogs EB 1089 and ILX 23-7553 enhance the response of breast tumor cells to ionizing radiation and promote radiation-induced apoptotic cell death. The current studies were designed to more closely simulate clinical radiotherapy in the treatment of breast cancer by examining the utility of ILX 23-7553 as an adjunct to fractionated ionizing radiation. The potential toxicity to normal tissue of the combination of ILX 23-7553 and fractionated radiation was assessed in a model of BJ human fibroblasts in culture. Methods. MCF-7 cells and human fibroblasts were treated with fractionated radiation alone (5×2 Gy over 3 days), ILX 23-7553 alone (50 nM) or ILX 23-7553 followed by 5×2 Gy. Viable cell numbers were determined by trypan blue exclusion and apoptosis by the TUNEL assay. A statistical model of additivity was utilized to assess the nature of the interaction between ILX 23-7553 and fractionated radiation. Results. Radiation and ILX 23-7553 each alone reduced viable cell numbers by 72±3.1% and 62±4.8%, respectively. Pretreatment with ILX 23-7553 followed by 5×2 Gy reduced viable cell numbers by 93.2±0.7%. The interaction between ILX 23-7553 and fractionated radiation appeared to be additive despite the fact that the combination of ILX 23-7553 and fractionated radiation also promoted a twofold increase in apoptotic cell death. ILX 23-7553 failed to enhance the response to radiation or to promote apoptosis in BJ human foreskin fibroblasts. Conclusions. ILX 23-7553 enhanced the antiproliferative and apoptotic effects of fractionated ionizing radiation in MCF-7 breast cancer cells. These effects appeared to be selective in that similar responses were not observed in a model of normal human fibroblasts. Vitamin D3 analogs such as ILX 23-7553 may prove to have utility in combination with conventional radiotherapy of breast cancer as well as other malignancies which are sensitive to vitamin D3. [ABSTRACT FROM AUTHOR]

The uptake and subcellular partitioning of benzo[a]pyrene (BaP) were examined in a rat-liver cell line (Clone 9) using confocal and multiphoton microscopy. Following a 16-h treatment, intracellular accumulation of BaP increased with increasing concentration, and cytoplasmic BaP fluorescence reached saturation at 10 μM. Analysis of the kinetics of BaP uptake at this concentration indicated that BaP is rapidly partitioned into all cytoplasmic membranes within several min, although saturation was not reached until 4 h. Based upon the rapid uptake of BaP into membranes, the chronology of changes in gap junction-mediated intercellular communication (GJIC), plasma membrane potential (PMP), and steady state levels of intracellular Ca2+ in relation to the time-course for induction of microsomal ethoxyresorufin-0-deethylase (EROD) activity were examined. EROD activity in Clone 9 cells treated for 16 h increased with increasing concentrations of BaP and reached the highest levels at 40 μM BaP. In addition, kinetic analysis of EROD activity in Clone 9 cells treated with 10 μM BaP indicated that significant induction of EROD activity was not detected before 3 h, and it reached maximal levels by 16 h of treatment at this concentration. Both GJIC and PMP were directly affected by the partitioning of BaP into cellular membranes. The most sensitive index of BaP-induced changes in membrane function was GJIC which revealed a 25% suppression in cells exposed to 0.4 μM BaP for 16 h. Kinetic analysis revealed that suppression of GJIC occurred within 15 min of exposure of cells to 10 μM BaP, whereas significant suppression of PMP was not detected prior to 30-min exposure at this concentration. Elevation of basal Ca2+ level was also detected simultaneously with PMP at this dose. These data suggest that early changes in cellular membrane functions occur prior to detectable induction of EROD activity, although basal metabolic activation of BaP may contribute to these changes. [ABSTRACT FROM PUBLISHER]

Many western industrialized countries are currently suffering from a crisis in health human resources, one that involves a debate over the recruitment and licensing of foreign-trained doctors and nurses. The intense public policy interest in foreign-trained medical personnel, however, is not new. During the 1960s, western countries revised their immigration policies to focus on highly-trained professionals. During the following decade, hundreds of thousands of health care practitioners migrated from poorer jurisdictions to western industrialized countries to solve what were then deemed to be national doctor and nursing 'shortages' in the developed world. Migration plummeted in the 1980s and 1990s only to re-emerge in the last decade as an important debate in global health care policy and ethics. This paper will examine the historical antecedents to this ethical debate. It will trace the early articulation of the idea of a 'brain drain', one that emerged from the loss of NHS doctors to other western jurisdictions in the 1950s and 1960s. Only over time did the discussion turn to the 'manpower' losses of 'third world countries', but the inability to track physician migration, amongst other variables, muted any concerted ethical debate. By contrast, the last decade's literature has witnessed a dramatically different ethical framework, informed by globalization, the rise of South Africa as a source donor country, and the ongoing catastrophe of the AIDS epidemic. Unlike the literature of the early 1970s, recent scholarship has focussed on a new framework of global ethics. [ABSTRACT FROM AUTHOR]

The article describes the cases of teenagers undergoing dialectical behavior treatment (DBT) program and the role of medical marijuana in them. One clinician mentions that cannabis will not be prescribed to a 19-year-old patient in light of his high-risk behaviours with history of overdoses on medications. Another clinician explains the factors he will consider in examining the effect of a DBT program on the patient. Also noted is the lack of effect of age on managing the case of a 15-year-old.

Medical assistance in dying (MAiD) was introduced into Canadian legislation in 2016. Mental illness as the sole underlying medical condition (MI-SUMC) is excluded from eligibility; this is expected to change in 2024. Incurability, intolerable suffering, capacity to make healthcare decisions, and suicidality have been publicly debated in connection with mental illness. Few studies have explored the views of persons with mental illness on the introduction and acceptability of MAiD MI-SUMC; this study aimed to fill this gap. Thirty adults, residing in Ontario, Canada, who self-identified as living with mental illness participated. A semi-structured interview including a persona-scenario exercise was designed to discuss participants' views on MAiD MI-SUMC and when it could be acceptable or not. Reflexive thematic analysis was used to inductively analyze data. Codes and themes were developed after extensive familiarization with the dataset. A lived-experience advisory group was engaged throughout the study. We identified six themes: The certainty of suffering ; Is there a suffering threshold to be met? The uncertainty of mental illness ; My own limits, values, and decisions ; MAiD MI- SUMC as acceptable when therapeutic means, and other supports, have been tried to alleviate long-term suffering ; and Between relief and rejection. These themes underline how the participants' lived experience comprised negative impacts caused by long-term mental illness, stigma, and in some cases, socioeconomic factors. The need for therapeutic and non-therapeutic supports was highlighted, along with unresolved tensions about the links between mental illness, capacity, and suicidality. Although not all participants viewed MAiD MI-SUMC as acceptable for mental illness, they autonomously embraced limits, values, and decisions of their own along their search for relief. Identifying individual and contextual elements in each person's experience of illness and suffering is necessary to understand diverse perspectives on MAiD MI-SUMC. • People with lived experience discuss medical assistance in dying in mental illness. • Suffering elicited by mental illness can only be understood by those living with it. • Contextual and social elements that can exacerbate suffering are identified. • Healthcare decisions are viewed as built on individual limits and values. • Medical assistance in dying can be acceptable under specific circumstances. [ABSTRACT FROM AUTHOR]

Medical assistance in dying for mental illness as a sole underlying medical condition (MAiD MI-SUMC) is a controversial and complex policy in terms of psychosocial and ethical medical practice implications. We discuss the status of MAiD MI-SUMC in Canada and argue for the use of the UK Medical Research Council's framework on complex interventions in programme evaluations of MAiD MI-SUMC. It is imperative to carefully and rigorously evaluate the implementation of MAiD MI-SUMC to ensure an understanding of the multiple facets of implementation in contexts permeated by unique social, economic, cultural and historical influences, with a correspondingly diverse array of outcomes. This requires a complexity-informed programme evaluation focused on context-dependent mechanisms and stakeholder experiences, including patients, service providers and other people affected by the policy. It is also important to consider the economic impact on health and social welfare systems. Such evaluations can provide the data needed to guide evidence-informed decision-making that can contribute to safer implementation and refinement of MAiD MI-SUMC.

Background: Palliative psychiatry has been proposed as a new clinical construct within mental health care and aims to improve quality of life (QoL) for individuals experiencing severe and persistent mental illness (SPMI). To date, explorations of palliative psychiatry have been largely theoretical, and more work is needed to develop its approaches into tangible clinical practice., Methods: In this paper, we synthesize existing literature with discussions held at a one-day knowledge user meeting titled "A Community of Practice for Palliative Psychiatry" to generate priorities for research, clinical practice, and education that will help advance the development of palliative psychiatry., Results: Palliative psychiatry will benefit from research that is co-produced by people with lived experience (PWLE) of mental illness, that clarifies contested concepts within mental health care and wider medicine, and that adapts existing interventions that have the potential to improve the QoL of individuals experiencing SPMI into the mental health care context. Specific methods and tools might be developed for use in clinical spaces taking a palliative psychiatry approach. More work must be done to understand the populations that might benefit from palliative psychiatry, and to mitigate mental health care providers' (MHCPs') anxieties about using these approaches in their work. As palliative psychiatry is developed, current MHCPs, trainees, individuals experiencing SPMI, and their loved ones will all require education about and orientation to this novel approach within mental health care., Conclusions: There are several priorities in research, clinical practice, and education that can help advance the development of palliative psychiatry. All future work must be considered through a human rights-based, anti-oppressive lens. Research projects, clinical models, and educational initiatives should all be developed in co-production with PWLE to mitigate the epistemic injustices common in mental health care.

Objective: This lived experience-engaged study aims to understand patient and family perspectives on the relationship between suicidality and medical assistance in dying when the sole underlying medical condition is mental illness (MAiD MI-SUMC)., Method: Thirty individuals with mental illness (age M  = 41.8 years, SD  = 14.2) and 25 family members (age M  = 47.5 years, SD  = 16.0) participated in qualitative interviews examining perspectives on MAiD MI-SUMC and its relationship with suicide. Audio recordings were transcribed and analysed using reflexive thematic analysis. People with lived experience were engaged in the research process as team members., Results: Four main themes were developed, which were consistent across individuals with mental illness and family members: (a) deciding to die is an individual choice to end the ongoing intolerable suffering of people with mental illness; (b) MAiD MI-SUMC is the same as suicide because the end result is death, although suicide can be more impulsive; (c) MAiD MI-SUMC is a humane, dignified, safe, nonstigmatized alternative to suicide; and (4) suicidality should be considered when MAiD MI-SUMC is requested, but suicidality's role is multifaceted given its diverse manifestations., Conclusion: For patient-oriented mental health policy and treatment, it is critical that the voices of people with lived experience be heard on the issue of MAiD MI-SUMC. Given the important intersections between MAiD MI-SUMC and suicidality and the context of suicide prevention, the role that suicidality should play in MAiD MI-SUMC is multifaceted. Future research and policy development are required to ensure that patient and family perspectives guide the development and implementation of MAiD MI-SUMC policy and practice., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Lisa D. Hawke, Hamer Bastidas-Bilbao, Vivien Cappe, Mary Rose van Kesteren, Alexander I. F. Simpson, Bartholemew H. Campbell, and Vicky Stergiopoulos declare that there is no conflict of interest. Donna Eileen Stewart declares that she has served in the Expert Panel on MAID and Mental Illness and the Canadian Psychiatric Association Working Group on MAID and as a reviewer of the Canadian Association of MAiD Assessors and Providers curriculum on MAID. Mona Gupta declares that she has received funding related to this subject from CIHR; she was the Chair of Health Canada's Task Group on MAID Practice Standards, the Chair of the Federal Expert Panel on MAID and Mental Illness, and the Chair of the AMPQ ad hoc committee on MAID. David Castle has received grant monies for research from NHMRC (Australia), Barbara Dicker Research Fund, Milken Institute, Canadian Institutes of Health Research, and Psyche Foundation; consulting fees from Seqirus; honoraria for talks from Seqirus, Servier, and Mindcafe Forum; honoraria as advisory board member from Seqirus and Lundbeck; he is a founder of the Optimal Health Program (OHP) and holds 50% of the IP for OHP, is part owner and board member of Clarity Healthcare, is unpaid board chair of the Psyche Institute, and does not knowingly have stocks or shares in any pharmaceutical company.

Background: Persons with mental illness as their sole underlying medical condition are eligible to access medical assistance in dying (MAiD) in a small number of countries, including Belgium, the Netherlands, Luxemburg and Switzerland. In Canada, it is anticipated that people experiencing mental illness as their sole underlying medical condition (MI-SUMC) will be eligible to request MAiD as of March 17th 2024. To date, few studies have addressed patient and family perspectives on MAiD MI-SUMC care processes. This study aimed to address this gap and qualitatively explore the perspectives of persons with lived experience of mental illness and family members on care considerations during MI-SUMC implementation., Methods: Thirty adults with lived experience of mental illness and 25 adult family members residing in Ontario participated in this study. To facilitate participant engagement, the semi-structured interview used a persona-scenario exercise to discuss perspectives on MAiD MI-SUMC acceptability and care considerations. Framework analysis was used to inductively analyze data using NVivo 12 Pro. Steps, processes, or other care considerations suggested by the participants were charted in a framework matrix after familiarization with the narratives. Key themes were further identified. A lived-experience advisory group participated in every aspect of this study., Results: Six themes were developed from the patient and family narratives: (1) Raising MAiD MI-SUMC awareness; (2) Sensitive Introduction of MAiD MI-SUMC in goals of care discussions; (3) Asking for MAiD MI-SUMC: a person-focused response; (4) A comprehensive circle of MAiD MI-SUMC care; (5) A holistic, person-centered assessment process; and (6) Need for support in the aftermath of the decision. These themes highlighted a congruence of views between patient and family members and described key desired process ingredients, including a person-centred non-judgmental stance by care providers, inter-professional holistic care, shared decision making, and the primacy of patient autonomy in healthcare decision making., Conclusions: Family and patient perspectives on the implementation of MAiD MI-SUMC offer important considerations for service planning that could complement existing and emerging professional practice standards. These stakeholders' perspectives will continue to be essential in MAiD MI-SUMC implementation efforts, to better address the needs of diverse communities and inform improvement efforts., (© 2024. The Author(s).)

Medical assistance in dying (MAiD) was introduced into Canadian federal legislation in 2016. Mental illness as the sole underlying medical condition (MI-SUMC) is currently excluded from eligibility; such exclusion is scheduled to expire on March 17, 2024. Irremediability, capacity, quality of life, autonomy, family involvement, and healthcare system constraints have been debated intensively. Recent studies have not explored the views of family members of persons with mental illness on MAiD MI-SUMC. This study aimed to fill this knowledge gap. Twenty-five Ontario residents who had a loved one with mental illness participated. A persona-scenario exercise was designed to explore participants' views on MAiD MI-SUMC in hypothetical situations. Reflexive thematic analysis was used to analyze the data. A lived experience-advisory panel was engaged throughout the study. Seven themes were developed: Witnessing suffering; A road with barriers and limitations; Societal barriers; The unknowns of mental illness; Individual choices: the life or death that a person wants; MAiD MI-SUMC as an acceptable choice when suffering cannot be relieved with available treatments and supports; and The emotional outcome. Participants constructed their views based on their experience of supporting a loved one with mental illness. MAiD MI-SUMC was perceived as a multifaceted issue, whose acceptability and potential introduction required a concurrent exploration and discussion of the challenges arising due to limitations of the healthcare system, the opportunities and limits to family involvement, and the value of patient autonomy., Competing Interests: Declaration of Conflicts InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Hamer Bastidas-Bilbao, Vicky Stergiopoulos, Vivien Cappe, Mary Rose van Kesteren, Alexander I. F. Simpson, Michael Dawthorne, and Lisa D. Hawke declare that there is no conflict of interest. Donna Eileen Stewart declares that she has served in the Expert Panel on MAiD and Mental Illness, the Canadian Psychiatric Association Working Group on MAiD, and as a reviewer of the Canadian Association of MAiD Assessors and Providers (CAMAP) curriculum on MAiD. Mona Gupta declares that she has received funding related to this subject from CIHR; she was Chair of Health Canada’s Task Group on MAiD Practice Standards, the Chair of the Federal Expert Panel on MAiD and Mental Illness, and the Chair of the AMPQ ad hoc committee on MAiD. Tarek K. Rajji has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute; he has also received for an investigator-initiated study in-kind equipment support from Newronika, and in-kind research online accounts from Scientific Brain Training Pro, and participated in 2021 and 2022 in an advisory activity for Biogen Canada Inc; he is also an inventor on the United States Provisional Patent No. 17/396,030 that describes cell-based assays and kits for assessing serum cholinergic receptor activity; he served on the MAiD Practice Standards Task Group as CAMH representative. David Castle has received grant monies for research from NHMRC (Australia), Barbara Dicker Research Fund, Milken Institute, Canadian Institutes of Health Research, and Psyche Foundation; consulting fees from Seqirus; honoraria for talks from Seqirus, Servier, and Mindcafe Forum; and honoraria as advisory board member from Seqirus and Lundbeck; he is a founder of the Optimal Health Program (OHP) and holds 50% of the IP for OHP; is part owner and board member of Clarity Healthcare; and is unpaid board chair of the Psyche Institute; he does not knowingly have stocks or shares in any pharmaceutical company.

Older adults with cancer present with complex multidimensional problems. Therefore, early integration of palliative care for the older adult with cancer is important, and a multidisciplinary team approach is critical for optimum care. The importance of incorporating geriatric and palliative concerns in assessment, as well as early involvement of the multidisciplinary team, is discussed as a manner of addressing the needs of older adults with cancer. Concerns related to metabolic changes that can occur with aging, as well as risk for polypharmacy and inappropriate prescribing for older adults, are also reviewed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: There is limited data about assessments that are associated with increased utilization of medical services among advanced oncology patients (AOPs). We aimed to identify factors related to healthcare utilization and death in AOP., Methods: AOPs at a comprehensive cancer center were enrolled in a Center for Medicare and Medicaid Innovation program. Participants completed the Edmonton Symptom Assessment Scale (ESAS) and the Functional Assessment of Cancer Therapy-General (FACT-G) scale. We examined factors associated with palliative care (PC), acute care (AC), emergency room (ER), hospital admissions (HA), and death., Results: In all, 817 AOPs were included in these analyses with a median age of 69. They were generally female (58.7%), white (61.4%), stage IV (51.6%), and represented common cancers (31.5% GI, 25.2% thoracic, 14.3% gynecologic). ESAS pain, anxiety, and total score were related to more PC visits (B=0.31, 95% CI [0.21, 0.40], p<0.001; B=0.24 [0.12, 0.36], p<0.001; and B=0.038 [0.02, 0.06], p=0.001, respectively). Total FACT-G score and physical subscale were related to total PC visits (B=-0.021 [-0.037, -0.006], p=0.008 and B=-0.181 [-0.246, -0.117], p<0.001, respectively). Lower FACT-G social subscale scores were related to more ER visits (B=-0.03 [-0.53, -0.004], p=0.024), while increased tiredness was associated with fewer AC visits (B=-0.039 [-0.073, -0.006], p=0.023). Higher total ESAS scores were related to death within 30 days (OR=0.87 [0.76, 0.98], p=0.027)., Conclusions: The ESAS and FACT-G assessments were linked to PC and AC visits and death. These assessments may be useful for identifying AOPs that would benefit from routine PC., (© 2023. The Author(s).)

Herein, we investigate the phytogenic synthesis of zinc oxide nanoparticles (ZnO-NPs) by using aqueous extract of seed coat of almond as a novel resource which can acts as a stabilizing and reducing agents. Successful biosynthesis of ZnO-NPs was observed by Ultraviolet-visible spectroscopy (UV-vis) showing peak at ~272 nm. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques confirm the circular shape with an average size of ~20 nm. Applications of ZnO-NPs were observed on carrot (Daucus carota) plant infected with pathogenic fungus Rhizoctonia solani. Spray with 50 ppm and 100 ppm ZnO-NPs caused significant increase in plant growth attributes and photosynthetic pigments of carrot plants. It has been reported that the synthesized ZnO-NPs demonstrated an inhibitory activity against plant pathogenic fungus R. solani and reduces disease in carrot plants. Scanning electron microscopy and confocal microscopy indicated adverse effect of ZnO-NPs on pathogens. Antifungal efficiency of ZnO-NPs was further explained with help of molecular docking analysis. Conformation with highest negative binding energy was used to predict binding site of receptor with NPs to know mechanistic approach. ZnO-NPs are likely to interact with the pathogens by mechanical enfolding which may be one of the major toxicity actions against R. solani by ZnO-NPs. RESEARCH HIGHLIGHTS: ZnO nanoparticles were synthesized using waste material from the coat of almond seeds. Images from SEM, TEM, and related techniques like EDS and SAED revealed the irregularity of the ZnO NPs as well as their atom composition. FTIR and XRD analyses confirmed the formation and the presence of crystalline ZnO NPs in nature. Biogenic ZnONPs were found to be effective against the plant pathogenic fungus R. solani. A spray of 50 ppm and 100 ppm ZnO-NPs significantly increased carrot plant growth characteristics and photosynthetic pigments., (© 2022 Wiley Periodicals LLC.)

Background: Medical assistance in dying (MAiD) was legalized in Canada in 2016, although it has been accessible as an end-of-life option in the province of Quebec since 2015. Before its implementation in clinical settings, few physicians had received formal training on requests assessments. New data indicate MAiD requesters have high rates of psychiatric comorbidities. Hence, assessment and management of psychiatric and psychosocial issues among MAiD requesters are important competencies to develop for assessors, although few training programs address them. The aim of our study was to explore physicians' self-perceived educational needs on psychiatric aspects related to MAiD in the province of Quebec., Methods: We conducted a cross-sectional online survey and used a non-probability sampling design in one academic tertiary care center. A descriptive analysis was performed, and responders were compared on different variables., Results: From twenty-five physician assessors, nineteen responded anonymously to an online survey (n=19). The findings of our pilot study revealed that participants felt highly competent in most psychiatric aspects at end-of-life and related to MAiD practice, except for psychotherapy and psychopharmacology as well as depression identification. Most indicated strong interest in further training. No statistical differences were found among responders regarding previous experience or training in palliative care., Conclusions: Based on our study, MAiD assessors reported high level of competency in managing psychiatric issues among requesters, but that they also expressed a strong desire for additional education.

Background: Palliative care (PC) is an essential part of oncologic care, but its optimal role within a cancer center remains unclear. This study examines oncology healthcare providers' perspectives about the role of PC at a comprehensive cancer center (CCC)., Methods: Physicians, nurses, and other oncology healthcare providers at a CCC were surveyed for their opinions about the role of inpatient and outpatient PC, preferences for PC services, and barriers to referral. Chi-squared tests and multiple regression analyses were performed to explore associations., Results: We received 137/221 completed questionnaires (61% response rate). Respondents were generally female (78%), had ≤ 10 years of service (69%), and included physicians (32%), nurses (32%), and advanced practice providers (17%). Most respondents (82%) agreed that more patients could benefit from PC. They also agreed that PC is beneficial for both outpatient and inpatient management of complex pain (96 and 88%), complex symptoms (84 and 74%), and advanced cancer patients (80 and 64%). Transition to hospice (64 vs. 42%, p = 0.007) and goals of care (62 vs. 49%, p = 0.011) provided by PC services were more valued by respondents for the inpatient than for the outpatient setting. Barriers to utilizing PC included lack of availability, unsure of when to refer, and poor communication. The majority of respondents (83%) preferred a cancer focused PC team to provide high-quality care., Conclusions: Overall, the majority of oncology health care providers believe that more patients could benefit from PC, but opinions vary regarding the roles of inpatient and outpatient PC. Barriers and areas for improvement include availability, referral process, and improved communication., (© 2022. The Author(s).)

Objectives: Emergency department (ED) visits for high blood pressure are increasing in frequency. We aimed to map those patients' trajectory, from referral sources to the type of care received at the ED to anticipated actions for future high blood pressure concerns, and to better understand their reasons for consulting the ED for high blood pressure values., Methods: Between 2018 and 2020, patients who presented to the Montreal Heart Institute's ED for elevated blood pressure were recruited in a prospective observational study including a post hoc structured telephone interview and medical chart review. Five possible referral sources were predetermined. We provided proportions and 95% confidence intervals., Results: A total of 100 patients were recruited (female: 59%, mean age: 69 ± 12). A majority (93%, 95% CI 88-98%) possessed a home blood pressure device, among which 46% (95% CI 36-56%) remembered receiving advice for its use. The main referral sources for high blood pressure to the ED were self-reference (53%, 95% CI 43-63%), advice of a lay person (19%, 95% CI 11-27%) or a nurse (13%, 95% CI 6-20%). Mainly, patients reported being concerned by concomitant symptoms or experiencing acute medical consequences (44%, 95% CI 34-54%), having followed the recommendation of a third party (33%, 95% CI 24-42%), or having concerns about their medication (6%, 95% CI 1-11%). Two weeks following their ED visits, consulting ED remained the main choice for future concerns about high blood pressure for 27% of participants. When specifically asked if they would return to the ED for elevated blood pressure, 73% (95% CI 64-83%) said yes., Conclusions: Most patients who consulted the ED for elevated blood pressure values were self-referred. More can be done to promote blood pressure education, effective use of personal blood pressure devices, and recommendations for patients and health professionals when confronted with high blood pressure results., (© 2022. The Author(s).)

Introduction: The World Health Organization introduced the workload indicators of staffing needs (WISN) in 1998 to improve country-level health workforce planning. This study presents the primary care health workforce planning experiences of India, South Africa and Peru., Methods: A case study approach was used to explore the lessons learnt in the implementation of WISN in India and South Africa. It also describes the methods developed and implemented to estimate health workforce in Peru. We identify the barriers and facilitators faced by countries during the implementation phase through the triangulation of literature, government reports and accounts of involved health planners in the three countries., Results: India implemented WISN in a referral pathway of three district health facilities, including a primary health centre, community health centre and district hospital. Implementation was impeded by limited technical support, poor stakeholder consultation and information systems challenges. South Africa implemented WISN for health workforce planning in primary care and found the skills mix and staff determinations to be unaffordable. The Peruvian Ministry of Health considered using WISN but decided to develop a context-specific tool to estimate the health workforce needed using its available resources such as the National Register of Health Personnel. The main challenge in using WISN was the insufficient information on its inputs., Conclusion: While India and South Africa had unique experiences with the integration of WISN in their health system, none of the countries has yet benefited from the implementation of WISN due to financial, infrastructure and technical challenges. Since the methodology developed by the Peruvian Ministry of Health is context-specific, its implementation has been promising for health workforce planning. The learnings from these countries' experiences will prove useful in bringing future changes for the health workforce.

Protein-folding can go wrong in vivo and in vitro , with significant consequences for the living organism and the pharmaceutical industry, respectively. Here we propose a design principle for small-peptide-based protein-specific folding modifiers. The principle is based on constructing a "xenonucleus", which is a prefolded peptide that mimics the folding nucleus of a protein. Using stopped-flow kinetics, NMR spectroscopy, Förster resonance energy transfer, single-molecule force measurements, and molecular dynamics simulations, we demonstrate that a xenonucleus can make the refolding of ubiquitin faster by 33 ± 5%, while variants of the same peptide have little or no effect. Our approach provides a novel method for constructing specific, genetically encodable folding catalysts for suitable proteins that have a well-defined contiguous folding nucleus.

Patients with acute kidney injury (AKI) in the intensive care unit (ICU) are often suitable for palliative care due to the high symptom burden. The role of palliative medicine in this patient population is not well defined and there is a lack of established guidelines to address this issue. Because of this, patients in the ICU with AKI deprived of the most comprehensive or appropriate care. The reasons for this are multifactorial including lack of palliative care training among nephrologists. However, palliative care in these patients can help alleviate symptoms, improve quality of life, and decrease suffering. Palliative care physicians can determine the appropriateness and model of palliative care. In addition to shared decision-making, advance directives should be established with patients early on, with specific instructions regarding dialysis, and those advance directives should be respected., Competing Interests: Conflict-of-interest statement: The authors have declared that no conflict of interest exists.

Pain management in end stage renal disease (ESRD) patients is a complex and challenging task to accomplish, and effective pain and symptom control improves quality of life. Pain is prevalent in more than 50% of hemodialysis patients and up to 75% of these patients are treated ineffectively due to its poor recognition by providers. A good history for PQRST factors and intensity assessment using visual analog scale are the initial steps in the management of pain followed by involvement of palliative care, patient and family counseling, discussion of treatment options, and correction of reversible causes. First line should be conservative management such as exercise, massage, heat/cold therapy, acupuncture, meditation, distraction, music therapy, and cognitive behavioral therapy. Analgesics are introduced according to WHO guidelines (by the mouth, by the clock, by the ladder, for the individual, and attention to detail) using three-step analgesic ladder model. Neuropathic pain can be controlled by gabapentin and pregabalin. Substitution/addition of opioid analgesics are indicated if pain control is not optimal. Commonly used opioids in ESRD patients are tramadol, oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine. Methadone, fentanyl, and buprenorphine are the ideal analgesics in ESRD. However, complex pain syndrome requires multidrug analgesic regimen comprising opioids, non-opioids, and adjuvant medication, which should be individualized to the patient to achieve adequate pain control., (© 2017 International Society for Hemodialysis.)

Objective: The authors describe the hidden ethics curriculum in two postgraduate psychiatry programs., Methods: Researchers investigated the formal, informal, and hidden ethics curricula at two demographically different postgraduate psychiatry programs in Canada. Using a case study design, they compared three sources: individual interviews with residents and with faculty and a semi-structured review of program documents. They identified the formal, informal, and hidden curricula at each program for six ethics topics and grouped the topics under two thematic areas. They tested the applicability of the themes against the specific examples under each topic. Results pertaining to one of the themes and its three topics are reported here., Results: Divergences occurred between the curricula for each topic. The nature of these divergences differed according to local program characteristics. Yet, in both programs, choices for action in ethically challenging situations were mediated by a minimum standard of ethics that led individuals to avoid trouble even if this meant their behavior fell short of the accepted ideal., Conclusions: Effective ethics education in postgraduate psychiatry training will require addressing the hidden curriculum. In addition to profession-wide efforts to articulate high-level values, program-specific action on locally relevant issues constitutes a necessary mechanism for handling the impact of the hidden curriculum.

Objective: All psychiatry residents in Canada are required to train in integrated care (also known as "shared care" or "collaborative care"). We sought to define the competencies required for integrated care practice, with an emphasis on those competencies necessary for all psychiatric postgraduate learners regardless of their intended future practice setting or population., Method: We conducted a mixed methods study including qualitative interviews with nine psychiatrists practicing integrated care across Canada and a quantitative survey of 35 experts using a modified Delphi method., Results: Our participants believed that integrated care aims to build capacity for improved quality of mental health care in unspecialized settings, and as such, its practice requires broad clinical expertise as well as competencies in interprofessional teamwork, collaborative leadership, knowledge exchange and program consultation. All psychiatrists require knowledge of evidence-based models of integrated care and the ability to work with organizations to implement these models., Conclusion: Psychiatrists are best prepared for integrated care practice through clinical exposure to primary care and/or community settings, as well as didactic teaching regarding the evidence for integrated care, quality improvement methods, leadership, health systems and population health., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution's practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic. Dexamethasone should be used for patients with central nervous system metastases or bowel obstruction. If your patient is near death, empiric metoclopramide, haloperidol or chlorpromazine is used without further investigation. For patients with a better prognosis, we exclude reversible causes and use the same first-line antiemetics, metoclopramide and haloperidol. For those who do not respond to first-line single antiemetics, olanzapine is second line and ondansetron is third. Rarely do we use combination therapy or cannabinoids. Olanzapine as a single agent has a distinct advantage over antiemetic combinations. It improves compliance, reduces drug interactions and has several routes of administration. Antiemetics, anticholinergics, octreotide and dexamethasone are used in combination to treat bowel obstruction. In opiod-na'ive patients, we prefer haloperidol, glycopyrrolate and an opioid as the first-line treatment and add or substitute octreotide and dexamethasone in those who do not respond. Non-pharmacologic interventions (mechanical stents and percutaneous endoscopic gastrostomy tubes) are used when nausea is refractory to medical management or for home-going management to relieve symptoms, reduce drug costs and rehospitalization.

Evidence-based medicine (EBM) is a concept that has come to dominate the medical literature over the last twenty years. Developed in the early 1990s at McMaster University in Canada, EBM captured a simple and compelling principle--that clinical decision-making should be based on the most up to date, rigorously generated research findings. The same principle has been applied in the development of evidence-based psychiatry. However, numerous scholars have pointed out epistemological problems in EBM's concept of evidence and have highlighted ways in which social factors can influence and distort the generation, interpretation and dissemination of EBM-preferred research data. These issues may be more problematic in psychiatry as compared to other medical specialties. Furthermore, as this paper argues, there are other kinds of data excluded by EBM that are essential to psychiatric practice. The validity of these data have been investigated empirically only rarely. In an era in which evidence- based psychiatric practice is becoming synonymous with "good" practice, developing a comprehensive understanding of what constitutes evidence in psychiatry -rather than the narrower version allowed by EBM- is an urgent priority. This paper represents an initial effort to develop a defensible, broader version of psychiatric evidence.

Many psychiatrists have endorsed the idea of evidence-based psychiatry, the application of the principles of evidence-based medicine (EBM) to psychiatric practice. Proponents of an evidence-based approach to psychiatry hope that if practice is driven by "hard" scientific data, there will be greater potential to help patients. In other words, advocates of evidence-based psychiatry aim to bolster psychiatry's ethical standing through scientific evidence. Can EBM provide this ethical substantiation to psychiatry? This article provides an overview of some of the main ethical issues within psychiatry and examines three interrelated questions: (1) to which ethical values is EBM committed? (2) which ethical theory is reflected in these values? and (3) can these values and theories resolve existing ethical issues in psychiatry? EBM strives for the "greatest good for the greatest number," where good is defined as improved health. This utilitarian orientation cannot, however, address critical areas of moral importance for psychiatry, such as how its practitioners differentiate normal from abnormal, how they determine which forms of suffering should be alleviated through psychiatric means, and when involuntary intervention is ethically justified. The ethical principles implicit in EBM are too limited to serve as an ethical basis for psychiatry.

Objective: Little has been written about teaching consultation-liaison inpatient psychotherapy to residents or other trainees., Method: Resident interviews at completion of consultation-liaison training identified learning needs. In response, the authors created a seminar series and modified it reiteratively eight times., Results: In this approach, the primary task of consultation-liaison psychotherapy assessment is to determine the success of a patient's adaptation to hospitalization, and to identify obstacles to adaptation. Selected determinants of adaptation are reviewed and organized as individual factors and intrahospital and extrahospital environmental factors. This provides a viable means of organizing and integrating disparate bodies of knowledge for the student., Conclusions: The teaching model awaits empirical validation as a tool that enhances teaching and patient care outcomes.

Purpose: The purpose of this study was to prepare crosslinked pullulan nanoparticles encapsulating bioactive molecules inside the aqueous core of Aerosol-OT/n-hexane reverse micellar droplets with narrow size distribution for drug and gene delivery applications., Methods: The nanoparticles have been characterised by various physico-chemical methods such as dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), loading capacity and in vitro release behaviour in aqueous buffer. The influence of these nanoparticles on human dermal fibroblasts in vitro has been assessed in terms of cell adhesion, cytotoxicity and light microscopy., Results: Size distribution studies using DLS and TEM show that the particles are spherical in shape with size of 42.0+/-2.5 nm diameter. Release of FITC-Dex from nanoparticles increased with time with 75% of dye released in 6 hours, while only 40% of the dye was released in the initial 2 hours. Results from cell adhesion/viability assay suggest that the pullulan nanoparticles are non-toxic to cells and do not cause any distinct harm to cells. Fibroblasts were healthy and maintained their morphology and adhesion capacity., Conclusions: These studies indicated that these nanoparticles have further merit as possible carriers for genes and nucleotide drugs for intracellular delivery.

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging contrast agents or in drug delivery applications. Tissue and cell-specific drug targeting by these nanoparticles can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. In this study, superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared and coupled to insulin for their targeting to cell expressed surface receptors and thereby preventing the endocytosis. The influence of these nanoparticles on human fibroblasts is studied using various techniques to observe cell-nanoparticle interaction that includes light, scanning, and transmission electron microscopy studies. The derivatization of the nanoparticle surface with insulin-induced alterations in cell behavior that were distinct from the underivatized nanoparticles suggests that cell response can be directed via specifically engineered particle surfaces. The results from cell culture studies showed that the uncoated particles were internalized by the fibroblasts due to endocytosis, which resulted in disruption of the cell membrane. In contradiction, insulin-coated nanoparticles attached to the cell membrane, most likely to the cell-expressed surface receptors, and were not endocytosed. The presence of insulin on the surface of the nanoparticles caused an apparent increase in cell proliferation and viability. One major problem with uncoated nanoparticles has been the endocytosis of particles leading to irreversible entry. These results provide a route to prevent this problem. The derivatized nanoparticles show high affinity for cell membrane and opens up new opportunities for magnetic cell separation and recovery that may be of crucial interest for the development of cellular therapies.

The development of drugs that are highly selective and yet produce minimal toxicity to host tissue remains one of the most difficult challenges in cancer therapeutics. Since the majority of malignancies are treated with drugs in combination rather than single agents, one practical approach to circumvent this problem is to develop new therapeutic agents that will potentiate the effectiveness of current clinical protocols. This strategy would accelerate the acceptance of new drugs as adjunct therapies since these agents could be used at concentrations well below their maximal tolerated doses. Tumor cells derived from a variety of different sources have been shown to express the Vitamin D(3)receptor and to be susceptible to growth arrest and/or cell death in response to Vitamin D(3)and its analogues. The hypercalcemia that generally accompanies the utilization of pharmacological concentrations of Vitamin D(3) has been ameliorated in part through the development of Vitamin D(3) analogues. Studies in cell culture and in animal model systems as well as clinical trials have established the potential utility of Vitamin D(3) and Vitamin D(3) analogues as agents which can enhance the antiproliferative and/or cytotoxic effects of conventional chemotherapeutic drugs as well as ionizing radiation. Consequently, Vitamin D(3) and Vitamin D(3) analogues, utilized at concentrations which produce limited hypercalcemia, are likely to prove effective as adjuncts to conventional chemotherapy and radiotherapy.