Tala El Tal, MD

Hospital for Sick Children
Title of Project: Examining Cognitive Dysfunction and its Relationship to Disease and Patient-Reported Outcomes in Childhood-onset Lupus: A Prospective Longitudinal Study
Mentor: Andrea Knight, MD, MSCE

About the Researcher

My interest in pediatric rheumatology first sparked during my pediatric and adolescent medicine residency at the American University of Beirut, in Lebanon when I saw many patients devastated by their chronic disabling diseases, in the absence of a pediatric rheumatologist in the country. Stigma towards childhood-onset systemic erythematosus lupus (cSLE), particularly neuropsychiatric lupus, and mental health was common, due to the lack of awareness and cultural sensitivity.

I had the great privilege of completing my pediatric rheumatology fellowship training (July 2019-June 2021) at The Hospital for Sick Children (SickKids), with exceptional pediatric rheumatologists who have shown me the wonderful blend of clinical skill of physical examination and clinical research. During this time, I led the Canadian Paediatric Surveillance Program study in Multisystem Inflammatory Syndrome in Children (MIS-C) at a national and hospital level, publishing a first-author (El Tal et al, CRAJ 2021) and co-author paper (Tam et al, CMAJ, 2021). This highlighted early on to me the importance of collaboration, and the use of knowledge translation of scholarly work as an excellent advocacy tool. Similarly to cSLE, the multi-system nature of MIS-C called for a multi- disciplinary team, called “MIS-C working group”, which I played a key role in, leading weekly meetings, ensuring comprehensive and coordinated care. This prepared me for the multidisciplinary approach adapted in SLE clinic, whereby the divisions of rheumatology, nephrology, neuropsychology, adolescent medicine and psychiatry come together to serve each patient and family. This collaborative care model has been shown to improve patient-reported outcomes and is increasingly being recognized in treating behavioral health disorders including depression and anxiety. I also gained experience in quality improvement (QI) and patient safety through the Pediatric Rheumatology Care and Outcome Improvement Network (PR-COIN) fellow program and Co-Learning QI course. Through PR-COIN fellow program, working with incredibly passionate pediatric rheumatologists, I worked to develop a consensus approach for a treat- to-target strategy in juvenile idiopathic arthritis, publishing a first-author manuscript (El Tal et al J Rheumatol 2022). In working on the treat-to-target approach to better incorporate the patient perspective for shared decision-making, I developed an interest in patient- reported outcomes.

During my pediatric rheumatology fellowship, the more patients I saw in the SickKids Lupus Clinic, the stronger my interest grew in cSLE. In particular, I observed a gap in care regarding the detection and treatment of cognitive impairment and of psychiatric comorbidity in cSLE. I applied and was a successful recipient of the Geoff Carr Lupus fellowship award (Oct 2021-Sep 2022) with the support of Lupus Ontario, granting me the opportunity to further my rheumatology training in the field of cSLE, and begin investigation of cognitive function in cSLE. This research project leverages ongoing funded longitudinal studies examining brain function and development in cSLE, led by Dr. Andrea Knight, my primary mentor. So far I have gained experience with subject recruitment, data collection and management, and I have begun to work on data analysis. Our preliminary data shows a cross-sectional prevalence of cognitive dysfunction in youth with cSLE (n=24) of 42%, predominately in executive function and attention cognitive domains in addition to increased sleep disturbance, pain, and fatigue in cSLE patients to compared to age and sex-matched controls (abstract in preparation for submission to the 2022 American College of Rheumatology (ACR) Annual Meeting).  Despite these preliminary findings, there still remains a paucity of knowledge regarding the longitudinal prevalence of cognitive dysfunction in cSLE, and its relationship to disease and comorbid patient-reported outcomes.

During my lupus fellowship and time with Dr. Knight, I have also had the opportunity to pursue additional research and academic activities related to cSLE and mental health. I am a co-investigator for the Treatment and Education Approach for Childhood-Onset Lupus (TEACH) study, a multi-site randomized clinical trial in the US and Canada, funded by the CARRA-Arthritis Foundation (CARRA-AF), led by Dr. Natoshia Cunningham. This study tests a telehealth application of TEACH vs. standard medical care in youth with cSLE. SickKids is one of the key participating sites, and at this time, I am contributing to the disease-related data collection of study participants (Cunningham et al Pediatric Rheumatology 2019) . Focusing on health equity, I worked on a study examining the association of socio environmental factors with depression and anxiety symptoms among youth with cSLE, resulting in a co-authored abstract at the 2022 ACR meeting (Ostojic-Aitkens D et al, Arthritis Rheumatol, 2021; manuscript in preparation). I am also currently finishing a master’s program in quality improvement and patient safety via the Institute of Health Policy, Management and Evaluation at the University of Toronto. My master’s project focuses on improving routine mental screening for depression and anxiety in cSLE clinic, to ultimately optimize capture of mental health burden and ensure appropriate equitable mental health care.  This QI initiative highlights potential modifiable risk factors for cognitive impairment, and builds on the groundwork for designing appropriate patient-centered psychosocial interventions.

With this investigator career development award and multi-disciplinary collaborative team with expertise in cognitive function and neuropsychiatric lupus, I will build on my prior training and experience to develop the skills to independently conduct cSLE research. With mentorship from Dr. Knight and my multidisciplinary advisory team, formal coursework through SickKids Research Training center, and informal education, I will obtain further training in longitudinal assessment of cognitive function and its relationship to disease-related factors and patient-reported outcomes. This mentored award will enable me to maintain protected research time, gain the additional skills and experience necessary to conduct and publish original research, submit competitive grants, and achieve my long-term goal of becoming an independent investigator in rheumatology with expertise in cSLE research.

Project Summary

Lupus is a rare but severe chronic autoimmune condition that can affect any part of the body
causing inflammation and damage. Brain inflammation in lupus often strikes during an important period of brain development. Some children and adolescents with lupus have cognitive impairment like having a hard time remembering things, thinking clearly, multi-tasking, or even finding the right words. If left untreated, this can interfere with school performance, future work success and overall well-being. The exact causes of cognitive impairment are hard to pin down, but studies show other factors can play a role including depression and anxiety, pain, poor sleep, and fatigue. All of these factors together result in challenges detecting and treating cognitive impairment. The proposed research project will help us better understand cognitive impairment in children and adolescents with lupus, specifically learning about cognitive areas most affected and how people do over time. We will also learn about if other factors related to lupus and patients are linked to cognitive impairment. The knowledge from this study will guide future studies to come up with ways to detect this issue early on and create tailored treatments to improve overall quality of life.