Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

Improving Health Professional Recognition and Response to Child Maltreatment and Intimate Partner Violence: Protocol for Two Mixed Methods Pilot Randomized Controlled Trials.

BACKGROUND: The optimal educational approach for preparing health professionals with the knowledge and skills to effectively recognize and respond to family violence, including child maltreatment and intimate partner violence, remains unclear. The Violence, Evidence, Guidance, and Action (VEGA) Family Violence Education Resources is a novel intervention that can be completed via self-directed learning or in a workshop format; both approaches focus on improving health professional preparedness to address family violence. OBJECTIVE: Our studies aim to determine the acceptability and feasibility of conducting a randomized controlled trial to evaluate the effectiveness of the self-directed (experimental intervention) and workshop (active control) modalities of VEGA, as an adjunct to standard education, to improve learner (Researching the Impact of Service provider Education [RISE] with Residents) and independent practice (RISE with Veterans) health professional preparedness, knowledge, and skills related to recognizing family violence in their health care encounters. METHODS: The RISE with Residents and RISE with Veterans research studies use embedded experimental mixed methods research designs. The quantitative strand for each study follows the principles of a pilot randomized controlled trial. For RISE with Residents, we aimed to recruit 80 postgraduate medical trainees; for RISE with Veterans, we intended to recruit 80 health professionals who work or have worked with Veterans (or their family members) of the Canadian military or the Royal Canadian Mounted Police in a direct service capacity. Participants complete quantitative assessments at baseline, after intervention, and at 3-month follow-up. A subset of participants from each arm also undergoes a qualitative semistructured interview with the aim of describing participants' perceptions of the value and impact of each VEGA modality, as well as research burden. Scores on potential outcome measures will be mapped to excerpts of qualitative data via a mixed methods joint display to aid in the interpretation of findings. RESULTS: We consented 71 individuals to participate in the RISE with Residents study. Data collection was completed on August 31, 2023, and data are currently being cleaned and prepared for analysis. As of January 15, 2024, we consented 34 individuals in the RISE with Veterans study; data collection will be completed in March 2024. For both studies, no data analysis had taken place at the time of manuscript submission. Results will be disseminated through peer-reviewed publications; academic conferences; and posting and sharing of study summaries and infographics on social media, the project website, and via professional network listserves. CONCLUSIONS: Reducing the impacts of family violence remains a pressing public health challenge. Both research studies will provide a valuable methodological contribution about the feasibility of trial methods in health professions education focused on family violence. They will also contribute to education science about the differences in the effectiveness of self-directed versus facilitator-led learning strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05490121, https://clinicaltrials.gov/study/NCT05490121; ClinicalTrials.gov NCT05490004, https://clinicaltrials.gov/study/NCT05490004. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50864.

Care considerations in medical assistance in dying for persons with mental illness as the sole underlying medical condition: a qualitative study of patient and family perspectives.

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.

Self-managing symptoms of Long COVID: an education and strategies research protocol.

Post-acute sequelae of SARS-COV-2 (PASC) is growing in prevalence, and involves symptoms originating from the central neurological, cardiovascular, respiratory, gastrointestinal, autonomic nervous, or immune systems. There are non-specific symptoms such as fatigue, headaches, and brain fog, which cannot be ascribed to a single system. PASC places a notable strain on our healthcare system, which is already laden with a large number of acute-COVID-19 patients. Furthermore, it impedes social, academic and vocational functioning, and impacts family life, relationships, and work/financial life. The treatment for PASC needs to target this non-specific etiology and wide-ranging sequelae. In conditions similar to PASC, such as "chemo brain," and prolonged symptoms of concussion, the non-specific symptoms have shown to be effectively managed through education and strategies for self-management and Mindfulness interventions. However, such interventions have yet to be empirically evaluated in PASC to our knowledge. In response to this gap, we have developed a virtual education intervention synthesized by psychiatrists and clinical psychologists for the current study. We will undertake a two-phase randomized controlled trial to determine the feasibility (Phase 1; N = 90) and efficacy (Phase 2; sample sized based on phase 1 results) of the novel 8 week Education and Self-Management Strategies group compared to a mindfulness skills program, both delivered virtually. Main outcomes include confidence/ability to self-manage symptoms, quality of life, and healthcare utilization. This study stands to mitigate the deleterious intrusiveness of symptoms on everyday life in patients with PASC, and may also help to reduce the impact of PASC on the healthcare system. Clinical trial registration:https://classic.clinicaltrials.gov/ct2/show/NCT05268523; identifier NCT05268523.

Medical Assistance in Dying for Mental Illness as a Sole Underlying Medical Condition and Its Relationship to Suicide: A Qualitative Lived Experience-Engaged Study: Aide Médicale à Mourir Pour Maladie Mentale Comme Seule Condition Médicale Sous-Jacente et Son Lien Avec le Suicide: Une Etude Qualitative Engagée Dans l'Expérience Vécue.

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.

Walking Alongside: Views of Family Members on Medical Assistance in Dying for Mental Illness as the Sole Underlying Medical Condition.

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.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Searching for relief from suffering: A patient-oriented qualitative study on medical assistance in dying for mental illness as the sole underlying medical condition.

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-SUMCas acceptable when therapeutic means, and othersupports, 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.

"Don't Just Study our Distress, Do Something": Implementing and Evaluating a Modified Stepped-Care Model for Health Care Worker Mental Health During the COVID-19 Pandemic.

OBJECTIVE: Throughout the COVID-19 pandemic, there have been concerns about the mental health of health care workers (HCW). Although numerous studies have investigated the level of distress among HCW, few studies have explored programs to improve their mental well-being. In this paper, we describe the implementation and evaluation of a program to support the mental health of HCW at University Health Network (UHN), Canada's largest healthcare network. METHODS: Using a quality improvement approach, we conducted a needs assessment and then created and evaluated a modified stepped-care model to address HCW mental health during the pandemic. This included: online resources focused on psychoeducation and self-management, access to online support and psychotherapeutic groups, and self-referral for individual care from a psychologist or psychiatrist. We used ongoing mixed-methods evaluation, combining quantitative and qualitative analysis, to improve program quality. RESULTS: The program is ongoing, running continuously throughout the pandemic. We present data up to November 30, 2021. There were over 12,000 hits to the UHN's COVID mental health intranet web page, which included self-management resources and information on group support. One hundred and sixty-six people self-referred for individual psychological or psychiatric care. The mean wait time from referral to initial appointment was 5.4 days, with an average of seven appointments for each service user. The majority had moderate to severe symptoms of depression and anxiety at referral, with over 20% expressing thoughts of self-harm or suicide. Post-care user feedback, collected through self-report surveys and semistructured interviews, indicated that the program is effective and valued. CONCLUSIONS: Development of a high-quality internal mental health support for HCW program is feasible, effective, and highly valued. By using early and frequent feedback from multiple perspectives and stakeholders to address demand and implement changes responsively, the program was adjusted to meet HCW mental health needs as the pandemic evolved.

Child Maltreatment and Intimate Partner Violence in Mental Health Settings.

Intimate partner violence (IPV) and child maltreatment (physical, emotional, sexual abuse, neglect, and children's exposure to IPV) are two of the most common types of family violence; they are associated with a broad range of health consequences. We summarize evidence addressing the need for safe and culturally-informed clinical responses to child maltreatment and IPV, focusing on mental health settings. This considers clinical features of child maltreatment and IPV; applications of rights-based and trauma- and violence-informed care; how to ask about potential experiences of violence; safe responses to disclosures; assessment and interventions that include referral networks and resources developed in partnership with multidisciplinary and community actors; and the need for policy and practice frameworks, appropriate training and continuing professional development provisions and resources for mental health providers. Principles for a common approach to recognizing and safely responding to child maltreatment and IPV are discussed, recognizing the needs in well-resourced and scarce resource settings, and for marginalized groups in any setting.

Future public health emergencies and disasters: sustainability and insights into support programs for healthcare providers.

BACKGROUND: The mental health of healthcare workers (HCWs) has been at the forefront throughout the COVID-19 pandemic. While workplace-based support programs have been developed in hospitals globally, few systematically collected data. While critical to their success, information on these programs and the experience of mental healthcare providers (MHP) who support colleagues is limited. The objective of this study was to explore the experiences of MHP caring for HCW colleagues within a novel workplace-based mental health support program during the COVID-19 pandemic, to provide insights on facilitators, areas for improvement and barriers to program sustainability. METHODS: This qualitative study used semi-structured interviews conducted by videoconference between September 2020 to October 2021. UHN CARES (University Health Network Coping and Resilience for Employees and Staff) Program was developed during the first wave of the COVID-19 pandemic in March 2020. It supports over 21,000 staff members within the UHN, Canada's largest academic health research institution, in Toronto, Canada. Purposive sampling was used to select 10 of the 22 MHP in the UHN CARES Program (n = 10). Using a critical realism framework, key components required to sustain a successful workplace-based mental health support program for HCWs and balance the needs of MHP were determined. RESULTS: Six psychiatrists and four psychologists (n = 10) with varying roles at UHN participated in 17 interviews, including seven repeat interviews exploring changes over time within the pandemic and program. Components which facilitated the success of the program included flexibility in scheduling, confidential health record storage, comprehensive administrative support, availability of resources and adaptive quality improvement approach. Recommendations for improvement included opportunities for peer supervision, triaging of cases, and managing HCW expectations. MHP found caring for HCWs to be meaningful and they utilized existing clinical skills during sessions. Challenges included working in a virtual setting, navigating boundaries when caring for colleagues, and managing the range of service users and their needs. CONCLUSIONS: These findings suggest how support programs can be structured for HCWs, how to provide support, and how to sustain this support, allowing health systems to balance the needs of HCWs and MHPs in preparation for future public health emergencies.

Researching the Impact of Service provider Education (RISE) Project - a multiphase mixed methods protocol to evaluate implementation acceptability and feasibility.

BACKGROUND: Health and social service providers receive limited education on recognizing and responding to family violence. With adequate education, providers could be prepared to identify individuals subjected to family violence and help reduce the risk of associated impairment. Informed by the Active Implementation Frameworks, our research will determine the scope of strategies needed for the uptake and sustainability of educational interventions focused on family violence for providers. It will also determine the acceptability, feasibility, and proof-of-concept for a new educational intervention, called VEGA (Violence, Evidence, Guidance, Action), for developing and improving primary care provider knowledge and skills in family violence. METHODS: This paper details the protocol for the Researching the Impact of Service provider Education (RISE) Project. The RISE Project follows a sequential multiphase mixed method research design; qualitative and quantitative data are being collected and integrated over three conceptually and methodologically linked research phases. Activities primarily occur in Ontario, Alberta, and Quebec. Phase 1 uses a sequential exploratory mixed method research design to characterize the scope and salience of learning and implementation needs and preferences for family violence education. Phase 2 will use an embedded mixed method research design to determine whether VEGA technology supports providers to achieve their family violence learning goals with effectiveness, efficiency, and satisfaction. Phase 3 will use a concurrent mixed method research design to determine acceptability, feasibility, and proof-of-concept for evaluating whether VEGA improves primary care providers' knowledge and skills in family violence. This final phase will provide information on implementation strategies for family violence education in the "real world." It will also generate data on provider recruitment, retention, and data completeness, as well as exploratory estimates of the effect for provider outcome measures proposed for a randomized controlled trial. DISCUSSION: The RISE Project comprehensively integrates an implementation approach to improve family violence education for the health and social service professions. It will provide important information about factors that could influence the uptake and effectiveness of a health profession's educational intervention into the real world, as well as provide foundational evidence concerning the tenability of using a randomized controlled trial to evaluate the impact of VEGA in primary care settings.

The development of a patient decision aid to reduce decisional conflict about antidepressant use in pregnancy.

BACKGROUND: People with moderate to severe depression in pregnancy must weigh potential risks of untreated or incompletely treated depression against the small, but uncertain risks of fetal antidepressant drug exposure. Clinical support alone appears insufficient for helping individuals with this complex decision. A patient decision aid (PDA) has the potential to be a useful tool for this population. The objective of our work was to use internationally recognized guidelines from the International Patient Decision Aids Standards Collaboration to develop an evidence-based PDA for antidepressant use in pregnancy. METHODS: A three-phased development process was used whereby, informed by patient and physician perspectives and evidence synthesis, a steering committee commissioned a web-based PDA for those deciding whether or not to start or continue antidepressant treatment for depression in pregnancy (Phase 1). A prototype was developed (Phase 2) and iteratively revised based on feedback during field testing based on a user-centred process (Phase 3). RESULTS: We developed a web-based PDA for people deciding whether to start or continue antidepressant use for depression in pregnancy. It has five interactive sections: (1) information on depression and treatment; (2) reasons to start/continue an antidepressant and to start/stop antidepressant medication; (3) user assessment of values regarding each issue; (4) opportunity to reflect on factors that contribute to decision making; and (5) a printable PDF that summarizes the user's journey through the PDA. CONCLUSIONS: This tool, which exclusively focuses on depression treatment with Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors, can be used by individuals making decisions about antidepressant use to treat depression during pregnancy. Limitations of the PDA are that it is not for other conditions, nor other medications that can be used for depression, and in its pilot form cannot be used by women who do not speak English or who have a visual impairment. Pending further study, it has the potential to enhance quality of care and patient experience.

A Qualitative Description of Resident Physicians' Understanding of Child Maltreatment: Impacts, Recognition, and Response.

Child maltreatment (CM) is a public health problem with devastating effects on individuals, families, and communities. Resident physicians have varied formal education in CM, and report feeling inadequately trained in identifying and responding to CM. The purpose of this study is to explore residents' understanding of the impacts of CM, and their perceptions of their role in recognizing and responding to CM to better understand their educational needs. This study analyzed qualitative data obtained from a larger project on family violence education. Twenty-nine resident physicians enrolled in pediatric, family medicine, emergency medicine, obstetrics and gynecology, and psychiatry training programs in Alberta, Ontario, and Québec participated in semi-structured interviews to elicit their ideas, experiences, and educational needs relating to CM. Conventional (inductive) content analysis guided the development of codes and categories. Residents had thorough knowledge about the impacts of CM and their duty to recognize CM, but there was less consistency in how residents understood their role in responding to CM. Residents identified the need for more education about recognizing and responding to CM, and the need for educational content to be responsive to training, patient and family factors, and systemic issues. Despite knowledge about the impacts of CM and laws pertaining to mandated reporting, residents reported challenges with responding to concerns of CM. Findings of this study emphasize the need for better training in response to CM. Future educational interventions should consider a multidisciplinary, experiential approach.

Neuropsychiatric Symptoms After Brain Tumor Resection in Children and Adolescents: A Scoping Review.

BACKGROUND: Brain tumors are one of the most common solid tumors in pediatric populations, with their treatments having significant neuropsychiatric impact. OBJECTIVE: The objective of this study was to review the literature on neuropsychiatric sequelae after surgical resection of brain tumors in children and adolescents. METHODS: Using a scoping method, we reviewed empirical articles describing pediatric patients with brain tumors who underwent partial or total resection and examined major neuropsychiatric domains postoperatively over time. RESULTS: The initial search yielded 15,543 articles. After duplicate removal, abstract screening, and review, 44 articles were included. Cognitive deficits were the most widely studied outcomes and found to be associated with tumor location, operative variables, perioperative complications, treatment types, and psychosocial factors. Cerebellar mutism, or posterior fossa syndrome, commonly co-occurred with emotional and behavioral dysregulation after posterior fossa resections. Depression, anxiety, and somatization were frequently grouped together as "distress," with higher rates among pediatric patients with brain tumor than among healthy peers. Problematic school behaviors, antisocial, and attention-deficit traits were increased; however, several other behaviors (e.g., risky sexual behaviors, substance use) were equal or lower when compared to peers. Posttraumatic stress disorder was highly prevalent and often interfered with social functioning. Delirium, eating disorders, and longer-term outcomes received inadequate attention. CONCLUSION: Identifying risk factors of neuropsychiatric sequelae and their impact after pediatric brain tumor resection is important for prognostication and the development of tailored management strategies for these children and adolescents.

Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease.

PURPOSE: Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes stroke and silent cerebral infarct (SCI). Our aim was to identify markers of brain injury in SCD. EXPERIMENTAL DESIGN: Plasma proteomes were analyzed using a sequential separation approach of hemoglobin (Hb) and top abundant plasma protein depletion, followed by reverse phase separation of intact proteins, trypsin digestion, and tandem mass spectrometry. We compared plasma proteomes of children with SCD with and without SCI in the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) to age-matched, healthy non-SCD controls. RESULTS: From the SCD group, 1172 proteins were identified. Twenty-five percent (289/1172) were solely in the SCI group. Twenty-five proteins with enriched expression in the human brain were identified in the SCD group. Neurogranin (NRGN) was the most abundant brain-enriched protein in plasma of children with SCD. Using a NRGN sandwich immunoassay and SIT Trial samples, median NRGN levels were higher at study entry in children with SCD (0.28 ng/mL, N = 100) compared to control participants (0.12 ng/mL, N = 25, p < 0.0004). CONCLUSIONS AND CLINICAL RELEVANCE: NRGN levels are elevated in children with SCD. NRGN and other brain-enriched plasma proteins identified in plasma of children with SCD may provide biochemical evidence of neurological injury.

The psychological burden of waiting for procedures and patient-centred strategies that could support the mental health of wait-listed patients and caregivers during the COVID-19 pandemic: A scoping review.

BACKGROUND: Waiting for procedures delayed by COVID-19 may cause anxiety and related adverse consequences. OBJECTIVE: To synthesize research on the mental health impact of waiting and patient-centred mitigation strategies that could be applied in the COVID-19 context. METHODS: Using a scoping review approach, we searched 9 databases for studies on waiting lists and mental health and reported study characteristics, impacts and intervention attributes and outcomes. RESULTS: We included 51 studies that focussed on organ transplant (60.8%), surgery (21.6%) or cancer management (13.7%). Most patients and caregivers reported anxiety, depression and poor quality of life, which deteriorated with increasing wait time. The impact of waiting on mental health was greater among women and new immigrants, and those of younger age, lower socio-economic status, or with less-positive coping ability. Six studies evaluated educational strategies to develop coping skills: 2 reduced depression (2 did not), 1 reduced anxiety (2 did not) and 2 improved quality of life (2 did not). In contrast, patients desired acknowledgement of concerns, peer support, and periodic communication about wait-list position, prioritization criteria and anticipated procedure date. CONCLUSIONS: Findings revealed patient-centred strategies to alleviate the mental health impact of waiting for procedures. Ongoing research should explore how to optimize the impact of those strategies for diverse patients and caregivers, particularly in the COVID-19 context. PATIENT OR PUBLIC CONTRIBUTION: Six patients and four caregivers waiting for COVID-19-delayed procedures helped to establish eligibility criteria, plan data extraction and review a draft and final report.