X-linked Alport syndrome presenting in mother and son with the same unique histopathological features.

Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4 and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman's capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman's capsule is more vulnerable to missense mutations in COL4A5 than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.

Screening for Psychological Distress in Healthcare Workers Using Machine Learning: A Proof of Concept.

The purpose of this study was to train and test preliminary models using two machine learning algorithms to identify healthcare workers at risk of developing anxiety, depression, and post-traumatic stress disorder. The study included data from a prospective cohort study of 816 healthcare workers collected using a mobile application during the first two waves of COVID-19. Each week, the participants responded to 11 questions and completed three screening questionnaires (one for anxiety, one for depression, and one for post-traumatic stress disorder). Then, the research team selected two questions (out of the 11), which were used with biological sex to identify whether scores on each screening questionnaire would be positive or negative. The analyses involved a fivefold cross-validation to test the accuracy of models based on logistic regression and support vector machines using cross-sectional and cumulative measures. The findings indicated that the models derived from the two questions and biological sex accurately identified screening scores for anxiety, depression, and post-traumatic stress disorders in 70% to 80% of cases. However, the positive predictive value never exceeded 50%, underlining the importance of collecting more data to train better models. Our proof of concept demonstrates the feasibility of using machine learning to develop novel models to screen for psychological distress in at-risk healthcare workers. Developing models with fewer questions may reduce burdens of active monitoring in practical settings by decreasing the weekly assessment duration.

The ever wider clinical spectrum of RMND1-related disorders and limitedness of phenotype-based classifications.

RMND1 has been identified as a mitochondriopathy-associated gene less than 12 years ago. The most common phenotype related to this gene is an early onset, severe form of encephalomyopathy that leads to death in a medium time of three years after birth. However, milder and later onset presentations have been reported in some individuals, including two in whom the mitochondriopathy was identified at ~ 40 years of age, and the early onset presentations have been the object of no reports in those who survived beyond age 10. It is thus unclear how lethal RMND1-related conditions really are. We herein describe the oldest case to have been identified hitherto with this condition, i.e., that of a white female who was 61 at the time of diagnosis but was still active in her everyday life. The gene defect identified was nonetheless associated with many manifestations including ovarian insufficiency and sensorineural hearing loss (two features of what is currently designated as Perrault syndrome) as well as chronic renal failure, asymptomatic myopathy, leukopenia, and a few others. In our opinion, this case is of great translational interest for at least three reasons. First, it hints towards the possibility of near-normal life expectancies in some if not many individuals with RMND1 insufficiency. Second, it underlines the wide clinical spectrum associated with this gene. Third, it brings us to question the use of eponyms and syndromic features to identify the true etiology of multisystemic phenotypes. KEY MESSAGES: RMND1-related conditions typically manifest at an early age with a progressive and lethal form of encephalomyopathy. More benign presentations have been described with some being categorized as Perrault syndrome but none have been diagnosed after the age of 45. The clinical spectrum and presenting age of RMND1-related mitochondriopathies are probably much more varied than implied in the current literature. The case reported in this manuscript illustrates the limitedness of phenotype-based classifications of genetic disorders to identify the defect at cause.

Longitudinal assessment and determinants of short-term and longer-term psychological distress in a sample of healthcare workers during the COVID-19 pandemic in Quebec, Canada.

Introduction: Previous research has demonstrated the negative impact of the COVID-19 pandemic emergency on the wellbeing of healthcare workers. However, few research contributions reported a longitudinal evaluation of psychological distress and examined determinants of its duration and course over time. The present study aims to explore the impact of the pandemic emergency on HCWs mental health by adopting a longitudinal design and assessing mental health as combination of overlapping clinical symptoms (post-traumatic stress disorder, depression and anxiety). Methods: Data were collected weekly through a mobile application during and after the first wave of COVID-19 in the province of Quebec, Canada, in 2020. Analysis was conducted on a final sample of 382 participants. Participants were grouped into "resilient" (RES) if they did not manifest clinical-level psychological distress during monitoring, "short-term distress" (STD) if distress exceeded the clinical threshold for 1-3 weeks, and longer-term distress (LTD) if it occurred for four or more weeks, even if not consecutively. Descriptive statistics for all variables were computed for each subgroup (RES, STD and LTD), and pairwise comparisons between each group for every descriptive variable were made using chi square statistics for categorical variables and t-test for continuous variables. Predictors of distress groups (STD and LTD vs RES) were assessed running multinomial hierarchical logistic regression models. Results: In our sample, almost two third (59.4%) HCWs did not manifest moderate or severe distress during the monitoring time. Short-term distress, mostly post-traumatic symptoms that lasted for less than 4 weeks, were the most common distress response, affecting almost one third of participants. Longer psychological distress occurred only in a smaller percentage (12.6%) of cases, as a combination of severe posttraumatic, depressive and anxiety symptoms. Perceived occupational stress was the most significant risk factor; moreover individual, peritraumatic work and family risk and protective factors, were likely to significantly affect the stress response. Discussion: Results tend to provide a more complex and resiliency-oriented representation of psychological distress compared to previous cross-sectional studies, but are in line with stress response studies. Findings allow us to better describe the profiles of distress response in STD and LTD groups. Participants that manifest short term distress experience acute stress reaction in which the interplay between personal, family and professional life events is associated with the stress response. Conversely, longer term distress response in HCWs presents a more complex mental health condition with an higher level of impairment and support needs compared to participants with short-term distress.

Efficacy of a Therapist-Assisted Self-Help Internet-Based Intervention Targeting PTSD, Depression, and Insomnia Symptoms After a Disaster: A Randomized Controlled Trial.

This study aimed at evaluating the efficacy of an online CBT intervention with limited therapist contact targeting a range of posttraumatic symptoms among evacuees from the 2016 Fort McMurray wildfires. One hundred and thirty-six residents of Fort McMurray who reported either moderate PTSD symptoms (PCL-5 ≥ 23) or mild PTSD symptoms (PCL-5 ≥ 10) with moderate depression (PHQ-9 ≥ 10) or subthreshold insomnia symptoms (ISI ≥ 8) were randomized either to a treatment (n = 69) or a waitlist condition (n = 67). Participants were on average 45 years old, and mostly identified as White (82%) and as women (76%). Primary outcomes were PTSD, depression, and insomnia symptoms. Secondary outcomes were anxiety symptoms and disability. Significant Assessment Time × Treatment Condition interactions were observed on all outcomes, indicating that access to the treatment led to a decrease in posttraumatic stress (F[1,117.04] = 12.128, p = .001; d = .519, 95% CI = .142-.895), depression (F[1,118.29] = 9.978, p = .002; d = .519, 95% CI = .141-.898) insomnia (F[1,117.60] = 4.574, p = .035; d = .512, 95% CI = .132-.892), and anxiety (F[1,119.64] = 5.465, p = .021; d = .421, 95% CI = .044-.797) symptom severity and disability (F[1,111.55] = 7.015, p = .009; d = .582, 95% CI = .200-.963). Larger effect sizes (d = 0.823-1.075) were observed in participants who completed at least half of the treatment. The RESILIENT online treatment platform was successful to provide access to specialized evidence-based mental health care after a disaster.

Environmental scan of mental health supports across Canadian burn centers: A healthcare providers' perspective.

BACKGROUND: Early mental health care and psychosocial support after burn injury provided by a variety of specialists and non-mental health professionals is instrumental in prevention of long-term mental health sequalae such as post-traumatic stress, depressive or substance use disorders. Diversity of mental health supports available to burn survivors vary across geography, resulting in variation of long-term mental health outcomes following burn injury. METHODS: A mixed-methods study utilizing a semi-structured questionnaire to explore resources available for burn survivors in Canada as an inpatient, outpatient, and more broadly in the aftercare community. Interviews were completed with 17 Canadian burn centers, with a variety of burn care professionals. RESULTS: In the continuum of burn care, a lack of available mental health professionals in certain regions and in the outpatient and community phases was observed. Emerging themes demonstrated the need for regular screening for mental health concerns among burn survivors and providing up to date discharge resources. In addition, increasing educational opportunities available to burn care staff with respect to burn survivor mental health was emphasized. Lastly, the importance of proactive and prolonged psychological support for burn survivors as they progress through an outpatient, rehabilitation and community setting was underlined. CONCLUSIONS: Identification of burn care practices and resources across Canada provides the opportunity to compare, unify and improve gaps in care that exist across the Canadian burn network.

Trainee Therapists' Perceptions of a Blended Intervention to Promote Resilience after a Natural Disaster: A Qualitative Case Study.

BACKGROUND: Natural disasters happen in an increased frequency, and telemental health interventions could offer easily accessible help to reduce mental health symptoms experienced by survivors. However, there are very few programs offered to natural disaster survivors, and no research exists on therapists' experiences with providing blended interventions for natural disaster survivors. AIMS: Our qualitative case study aims to describe psychologists' experiences with an online, therapist-assisted blended intervention for survivors of the Fort McMurray wildfires in Alberta, Canada. METHOD: The RESILIENT intervention was developed in the frames of a randomized controlled trial to promote resilience after the Fort McMurray wildfires by providing survivors free access to a 12-module, therapist-assisted intervention, aiming to improve post-traumatic stress, insomnia, and depression symptoms. A focus group design was used to collect data from the therapists, and emerging common themes were identified by thematic analysis. RESULTS: Therapists felt they could build strong alliances and communicate emotions and empathy effectively, although the lack of nonverbal cues posed some challenges. The intervention, according to participating therapists, was less suitable for participants in high-stress situations and in case of discrepancy between client expectations and the intervention content. Moreover, the therapists perceived specific interventions as easy-to-use or as more challenging based on their complexity and on the therapist support needed for executing them. Client engagement in the program emerged as an underlying theme that had fundamental impact on alliance, communication, and ultimately, treatment efficiency. Therapist training and supervision was perceived as crucial for the success of the program delivery. CONCLUSIONS: Our findings provided several implications for the optimalization of blended interventions for natural disaster survivors from our therapists' perspective.

Assessment of Psychological Distress in Health Care Workers During the First two Waves of COVID-19: A Follow-up of a Canadian Longitudinal Study.

Background: Health care workers (HCW) exposed to COVID-19 risk experiencing psychological distress. Little is known regarding longitudinal perspectives and evolutions of psychological distress within this population. The objective of this study is to extend the results of our previous study to the pandemic's second wave. Method: This prospective cohort study was conducted from May 8, 2020, to January 24, 2021, and includes 787 HCW. Symptoms of anxiety and depression were assessed using the Generalised Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Descriptive statistics illustrated the evolution of psychological distress indicators, whereas latent class analysis helped identify trajectories. Results: The results showed that a lower proportion of HCW exceeded the clinical threshold during the second wave (36,5% vs. 31,1%). As in the first wave, most of our sample fell onto the resilient trajectory (67.22%). We adapted the name of the remaining trajectories to better suit their evolution: rapid recovery (15.76%), slow recovery (9.66%), and delayed (7.37%). Conclusion: Approximately two-thirds of the HCW did not manifest significant distress. For those who did, the distress was transient. We observed a trend of positive adaptability among HCW, considering that the proportion of HCW experiencing psychological distress exceeding clinical threshold remained lower than during the first wave. Our data highlight the dynamic nature of psychological distress. To be able to detect psychological distress as it arises, HCW should use self-monitoring as an essential tool. This vigilance would allow institutions to offer timely support and resources for those experiencing psychological distress.

Assessment of Psychological Distress in Health-care Workers during and after the First Wave of COVID-19: A Canadian Longitudinal Study: Évaluation de la Détresse Psychologique Chez Les Travailleurs de la Santé Durant et Après la Première Vague de la COVID-19: une étude longitudinale canadienne.

OBJECTIVES: Health-care workers (HCW) exposed to COVID-19 are at risk of experiencing psychological distress. Although several cross-sectional studies have been carried out, a longitudinal perspective is needed to better understand the evolution of psychological distress indicators within this population. The objectives of this study were to assess the evolution of psychological distress and to identify psychological distress trajectories of Canadian HCW during and after the first wave of COVID-19. METHOD: This prospective cohort study was conducted from May 8 to September 4, 2020, and includes a volunteer sample of 373 HCW. Symptoms of post-traumatic disorder, anxiety, and depression were assessed using the Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders fifth edition (PCL-5), the Generalized Anxiety Disorder-7, and the Patient Health Questionnaire-9. Descriptive statistics were used to illustrate the evolution of psychological distress indicators, whereas latent class analysis was carried out to identify trajectories. RESULTS: During and after the first wave of COVID-19, the rates of clinical mental health symptoms among our sample varied between 6.2% and 22.2% for post-traumatic stress, 10.1% and 29.9% for depression, and 7.3% and 26.9% for anxiety. Finally, 4 trajectories were identified: recovered (18.77%), resilient (65.95%), subchronic (7.24%), and delayed (8.04%). CONCLUSION: The longitudinal nature of our study and the scarcity of our data are unique among existing studies on psychological distress of HCW in COVID-19 context and allow us to contextualize prior transversal data on the topic. Although our data illustrated an optimistic picture in showing that the majority of HCW follow a resilience trajectory, it is still important to focus our attention on those who present psychological distress. Implementing preventive mental health interventions in our health-care institutions that may prevent chronic distress is imperative. Further studies need to be done to identify predictors that may help to characterize these trajectories.

Psychological Symptoms Among Evacuees From the 2016 Fort McMurray Wildfires: A Population-Based Survey One Year Later.

Background: The 2016 wildfires in Fort McMurray (Alberta, Canada) led to a massive displacement of 88,000 people and destroyed 2,400 homes. Although no direct human fatality resulted, many individuals feared for their lives or those of their loved ones. Objectives: (1) To estimate the prevalence of post-traumatic stress, major depressive, insomnia, generalized anxiety, and substance use disorders in the adult population of Fort McMurray 1 year after the evacuation; (2) To identify pre-, peri-, and post-disaster correlates of mental health disorders. Methods: A phone survey using random digit sampling was used to survey evacuees. A total of 1,510 evacuees (response rate = 40.2%, 55.5% women, mean age = 44.11, SD = 12.69) were interviewed between May 9th and July 28th, 2017. Five validated scales were administered: the PTSD Symptoms Checklist (PCL-5), the Insomnia Severity Index (ISI), the depression and anxiety subscales of the Patient Health Questionnaire (PHQ-9, GAD-7), and the CAGE Substance Abuse Screening Tool. Results: One year after the wildfires, 38% had a probable diagnosis of either post-traumatic stress, major depressive, insomnia, generalized anxiety, or substance use disorder, or a combination of these. Insomnia disorder was the most common, with an estimated prevalence of 28.5%. Post-traumatic stress, major depressive and generalized anxiety disorders were almost equally prevalent, with ~15% each. The estimated prevalence of substance use disorder was 7.9%. For all five mental health disorders, having a mental health condition prior to the fires was a significant risk factor, as well as having experienced financial stress or strain due to the economic decline already present in Fort McMurray. Five post-disaster consequences were significant predictors of four of the five disorders: decrease in work, decrease in social life, poorer current health status, increase in drug and alcohol use, and higher level of stress experienced since the fires. Conclusion: One year after the fires, more than one third of the evacuees had clinically significant psychological symptoms, including those of insomnia, post-traumatic stress, depression, anxiety, and substance use. This study helped identify individuals more at risk for mental health issues after a natural disaster and could guide post-disaster psychosocial support strategies.

A Portrait of Mental Health Services Utilization and Perceived Barriers to Care in Men and Women Evacuated During the 2016 Fort McMurray Wildfires.

This study examines the influence of gender on mental health services utilization and on perceived barriers to treatment one year after the 2016 Fort McMurray wildfires. Data was collected through a phone survey from May to July 2017 (N = 1510). Participants were English-speaking evacuees aged 18 and older. Mental health services utilization and barriers to mental health care were assessed with the Perceived Need for Care questionnaire. Probable diagnoses of posttraumatic stress disorder, depression and insomnia were assessed with validated self-report questionnaires. Multiple logistic regressions confirmed that gender was a significant predictor of services utilization, after controlling for associated sociodemographic variables and presence of probable diagnoses. Women were respectively 1.50, 1.55 and 1.86 times more likely than men to receive information, medication and psychological help. Self-reliance was the most frequently reported reason for not receiving help, and motivational barriers, such as pessimism and stigma, were reported in a higher proportion than structural barriers, including nonresponse and finance. No significant gender differences were found in the types of perceived barriers to services. Among the Fort McMurray fire evacuees, mental health services utilization was similar to other studies on natural disaster victims, and higher in women than in men. Efforts to increase services utilization in natural disaster victims should focus on motivational barriers and offering treatments fostering people's autonomy, such as online treatments.

Concurrent Epicardial Cardiac Resynchronization at Time of Complicated Biventricular Device Extraction: A Potentially Life-Saving Option.

A 60-year-old man with cardiac resynchronization therapy defibrillator (CRT-D) lead endocarditis underwent transvenous lead extraction that was complicated by coronary sinus laceration and tamponade. Severe left ventricular dysfunction and unstable hemodynamic parameters persisted after emergent sternotomy, drainage, and repair. Reinstitution of cardiac resynchronization therapy with an epicardial device resulted in immediate hemodynamic improvement. Our case illustrates the potentially life-saving nature of single-stage extraction and reimplantation in resynchronization responders.

Don't take down the monkey bars: Rapid systematic review of playground-related injuries.

OBJECTIVE: To synthesize the available evidence on playground-related injuries and to determine the prevalence of these injuries in pediatric populations. DATA SOURCES: A rapid systematic review was conducted using PubMed, EMBASE, and the Cochrane Library, as well as the gray literature. STUDY SELECTION: The search was limited to studies published between 2012 and 2016 and identified a total of 858 articles, of which 22 met our inclusion criteria: original quantitative studies published in peer-reviewed journals in the past 5 years, concerning unintentional injuries in playgrounds in children aged 0 to 18 years. SYNTHESIS: Information was collected on study and injury characteristics, and the proportion of pediatric injuries related to playground activity was determined. Studies were performed in various countries and most were retrospective cohort studies. The prevalence of playground-related injury ranged from 2% to 34% (median 10%). Studies varied in the types of injuries investigated, including head injuries, genitourinary injuries, ocular and dental trauma, and various types of fractures. Most injuries were low severity. CONCLUSION: Although playgrounds are a common location where pediatric injuries occur, these injuries are relatively low in frequency and severity.

Subsyndromal delirium in the ICU: evidence for a disease spectrum.

OBJECTIVE: ICU delirium is common and adverse. The Intensive Care Delirium Screening Checklist (ICDSC) score ranges from 0 to 8, with a score of 4 or higher indicating clinical delirium. We investigated whether lower (subsyndromal) values affect outcome. PATIENTS: 600 patients were evaluated with the ICDSC every 8[Symbol: see text]h. MEASUREMENTS AND RESULTS: Of 558 assessed patients 537 noncomatose patients were divided into three groups: no delirium (score = 0; n = 169, 31.5%), subsyndromal delirium (score = 1-3; n = 179, 33.3%), and clinical delirium (score >or=4; n = 189, 35.2%). ICU mortality rates were 2.4%, 10.6%, and 15.9% in these three groups, respectively. Post-ICU mortality was significantly greater in the clinical delirium vs. no delirium groups (hazard ratio = 1.67) after adjusting for age, APACHE II score, and medication-induced coma. Relative ICU length of stay was: no delirium < subsyndromal delirium < clinical delirium and hospital LOS: no delirium < subsyndromal delirium approximately clinical delirium. Patients with no delirium were more likely to be discharged home and less likely to need convalescence or long-term care than those with subsyndromal delirium or clinical delirium. ICDSC score increments higher than 4/8 were not associated with a change in mortality or LOS. CONCLUSIONS: Clinical delirium is common, important and adverse in the critically ill. A graded diagnostic scale permits detection of a category of subsyndromal delirium which occurs in many ICU patients, and which is associated with adverse outcome.

Olanzapine vs haloperidol: treating delirium in a critical care setting.

OBJECTIVE: To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting. DESIGN: Prospective randomized trial. SETTING: Tertiary care university affiliated critical care unit. PATIENTS: All admissions to a medical and surgical intensive care unit with a diagnosis of delirium. INTERVENTIONS: Patients were randomized to receive either enteral olanzapine or haloperidol. MEASUREMENTS: Patient's delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium. MAIN RESULTS: Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects. CONCLUSIONS: Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

Delirium in critically ill patients.

Delirium in the intensive care unit is a serious problem that has recently attracted much attention. User-friendly and reliable tools, such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), offer the clinician the opportunity to identify delirium in patients better. Diagnosis of delirium in a critical care population is often a difficult task because classical psychiatric evaluation is impossible for a number of reasons. The CAM-ICU makes use of nonverbal assessments to evaluate the cardinal features of delirium (i.e. acute or fluctuating onset, inattention, disorganized thinking and altered level of consciousness). Its development for use in the critical care setting represents a significant advance that could lead to better care for such patients.