Welcome to the latest issue of The Krembil.
The Krembil is the official newsletter of the Krembil Research Institute (formerly the Toronto Western Research Institute). Research at Krembil is focused on finding innovative treatments and cures for chronic debilitating disorders, including arthritis and diseases of the brain and eyes.
Stories in this month’s issue include:
● Krembil Welcomes New Director: Neuroscientist Dr. Jaideep Bains will take the reins at Krembil.
● We Are Krembil: 2022 Annual Report: Read the latest report to learn how we are working together to improve lives.
● Improving Health for All: Researchers identify the main causes of neurotrauma burden in Indigenous populations of Canada.
● Patiently Waiting: UHN study identifies key causes of long wait times for rheumatology consults in Toronto.
● Maintaining Immune Balance: A cellular balancing act keeps people with antinuclear antibodies from developing autoimmunity.
● The Other Eye: Researchers discover that NAION vision loss can go unnoticed until it affects both eyes.
Following an extensive international search, neuroscientist Dr. Jaideep Bains has been named the new Director of the Krembil Research Institute.
Dr. Bains joins UHN from the University of Calgary, where he served as the Scientific Director of the Hotchkiss Brain Institute, a centre of excellence in brain and mental health research and education. In this role, he chaired the Institute’s Strategic Research and Innovation Committee, establishing short- and long-term research priorities and managing a multimillion-dollar annual budget.
Dr. Bains is a highly respected neuroscientist who has spent the last two decades characterizing how the neural circuits that regulate our internal states store information in response to challenges such as stress. His discoveries have advanced our understanding of the roles of particular neuron populations in stress and how animals communicate stress through social interaction and chemical signals. He has an exceptional record of publications and funding acquisition and is a sought-after speaker worldwide.
This appointment follows the nine-year directorship of Dr. Donald Weaver, who will remain at the Krembil as a Senior Scientist researching Alzheimer disease.
“When I began my tenure as Director almost a decade ago, my goal was to foster a team-based approach to research and clinical care that would help to translate discoveries from bench to bedside,” says Dr. Weaver. “Today, I am incredibly pleased with what we have achieved.”
Dr. Bains brings a wealth of experience to the role, not only in scientific research but also in institute management and advocacy. He was selected because of his ability to foster cultures of diversity, collaboration and innovation, and to transform research organizations.
“The Krembil Research Institute is in an excellent position to become a research power internationally,” says Dr. Bains. “We will do this by building a diverse and inclusive culture of excellence, supporting individual investigators while also creating a rich environment where synergy can occur.”
“Our international search attracted a pool of exceptional candidates from around the world,” says Dr. Bradly Wouters, Executive Vice-President of Science and Research at UHN. “The interest in this position is a testament to UHN’s outstanding global reputation for research excellence, and we are extremely excited to attract someone the caliber of Dr. Bains.”
Congratulations, Dr. Bains!
A research team led by Dr. Edward Margolin, a Clinician Investigator at the Krembil Research Institute, has found that a particular form of vision loss known as NAION occasionally occurs in both eyes, despite seeming to affect only one.
NAION (nonarteritic anterior ischemic optic neuropathy) occurs when blood flow to the nerve that connects the eyes to the brain becomes reduced, specifically at the point where the nerve meets with one of the eyes. The loss of blood flow causes nerve damage that typically results in a sudden but painless loss of vision in the affected eye.
Although NAION episodes only affect one eye, approximately 15% of individuals who experience one episode will experience a second that affects their other eye within five years. Intriguingly, when doctors assess patients after a single NAION episode, they often detect minor vision changes in the unaffected eye that the patients had not noticed.
“We wanted to determine whether a substantial portion of the NAION cases that we see in the clinic could be second episodes, with a previous episode having already affected the other eye but going unrecognized,” says Dr. Margolin.
To explore this idea, the research team reviewed nearly 140 past cases of NAION diagnosed in Toronto. In each case, the team reassessed previous eye exams, and medical images and records.
The team found that 10% of these patients had experienced unrecognized episodes in the other eye, accounting for almost 60% of unnoticed vision defects. Interestingly, all the unrecognized episodes had caused defects in the patients’ fields of view that overlapped with those that were later successfully diagnosed.
“Redundancy in our vision could explain why patients often do not notice a problem until NAION episodes affect both eyes,” says Dr. Margolin. “There is considerable overlap in what each eye sees.”
Repeat episodes in the same eye are rare, so knowing whether the other eye has already undergone a NAION episode is important for deciding whether significant preventative action should be taken.
"Our study highlights the importance of carefully examining each eye after a NAION episode," says Dr. Natalie Brossard Barbosa, a former clinical fellow of Dr. Margolin and the first author of the study. "Modifiable factors such as a history of smoking, diabetes, high blood pressure and sleep apnea elevate the risk for NAION, so lifestyle changes or medications can be used to minimize a patient’s risk of experiencing additional episodes."
This work was supported by the UHN Foundation. Edward Margolin is a Professor of Ophthalmology and Vision Sciences at the University of Toronto.
Brossard Barbosa N, Donaldson L, Margolin E. Asymptomatic Fellow Eye Involvement in Nonarteritic Anterior Ischemic Optic Neuropathy. J Neuroophthalmol. 2022 Jun 23. doi: 10.1097/WNO.0000000000001644.
Science is a team sport.
Every discovery and clinical breakthrough that comes out of the Krembil is a direct result of teamwork.
We attribute our success to many people with unique ideas, perspectives and skills coming together with a shared goal of improving lives.
In the 2022 Krembil Annual Report, we want to introduce you to some of the people who make our Institute what it is—from our dedicated staff who support research and patient care, to our passionate patient partners who inspire us to keep going.
This report highlights a selection of the research achievements that we have made together over the past year, including:
● developing a model for early-stage Parkinson disease with the potential to accelerate drug discovery;
● optimizing an innovative tool for testing drugs to treat eye diseases such as glaucoma; and
● discovering a possible treatment target for a severe form of arthritis
The report also highlights some of Krembil’s recent outreach events and initiatives, including a new podcast geared towards making science accessible and engaging to everyone.
Click here to read the report.
Researchers at the Schroeder Arthritis Institute have identified immune system factors that prevent and promote the development of systemic autoimmune rheumatic diseases (SARDs).
SARDs are rare inflammatory conditions, including lupus and Sjögren’s disease, that are associated with the production of high levels of antinuclear antibodies (ANAs)—antibodies that attack the body’s own tissues.
A positive ANA test—meaning that ANAs have been detected in a patient’s blood—typically indicates the presence of an autoimmune disease; however, healthy individuals can also have positive ANA tests and ANAs can be detected years before the onset of autoimmune symptoms.
“It is largely unknown what immunological changes promote symptom development in SARDs and what factors prevent autoimmunity in asymptomatic individuals who have a positive ANA test,” explains Dr. Joan Wither, a Senior Scientist at the Schroeder Arthritis Institute and the senior author of the study. “A better understanding of these factors can help clinicians identify patients who are at risk of developing symptoms in the near future.”
To determine the factors that promote or prevent SARD symptoms, Dr. Wither’s team characterized the amount and activity of immune cells in the blood of individuals with and without symptoms that took an ANA test. Twenty of the individuals with no symptoms at the time of their ANA test went on to develop a SARD over the two-year study period, providing an opportunity to identify critical differences that may point to the risk of SARDs.
The team discovered that people with a positive ANA test had high levels of particular immune cells, such as antibody-producing B cells and T helper cells, compared to individuals who had a negative ANA test. People with symptoms had higher levels of pro-inflammatory cells than those without symptoms. In those who progressed to develop SARD symptoms, the researchers identified higher levels of particular inflammatory and regulatory immune cells.
These findings suggest that the key difference between symptomatic and asymptomatic individuals with positive ANA tests lies in the balance between pro-inflammatory and regulatory immune cell activity. This delicate balance is disrupted in SARDs in a way that favours inflammation.
“Our discovery of immune system features that contribute to the development of SARD symptoms can guide the development of improved tests to diagnose SARDs and predict symptom progression,” says Rashi Gupta, a master’s student in Dr. Wither’s lab and co-first author of the study. “We may also be able to eventually target these features to slow or prevent symptom progression.”
“SARDs affects about 0.5% of Canadian adults and the symptoms can be debilitating,” adds Emma Vanlieshout, a PhD student in Dr. Wither’s lab and co-first author of the study. “If we can diagnose these conditions early, before symptom onset, we have a better chance of treating them and improving patients’ quality of life.”
This work was supported by the Canadian Institutes of Health Research, the University of Toronto Pfizer Chair Research Award, the Arthritis Centre of Excellence, Arthritis Society Canada, the Schroeder Arthritis Institute and the UHN Foundation. Dr. Linda Hiraki holds a Tier 2 Canada Research Chair in Genetics of Rare Systemic Inflammatory Diseases. Dr. Joan Wither is a Professor of Medicine at the University of Toronto.
Gupta R, Vanlieshout E, Manion K, Bonilla D, Kim M, Muñoz-Grajales C, Nassar C, Johnson SR, Hiraki LT, Ahmad Z, Touma Z, Bookman A, Wither JE. Altered Balance of Pro-Inflammatory Immune Cells to T Regulatory Cells Differentiates Symptomatic From Asymptomatic Individuals With Anti-Nuclear Antibodies. Front Immunol. 2022 Jun 30. doi: 10.3389/fimmu.2022.886442.
Researchers at the Schroeder Arthritis Institute have uncovered key reasons why patients are often unable to see a rheumatologist at the Toronto Western Hospital Psoriatic Arthritis Clinic within the recommended time from their referral.
Psoriatic arthritis is a severe form of arthritis that is linked to psoriasis, a chronic inflammatory skin disease. The Canadian Rheumatology Association and the Spondyloarthritis Research Consortium of Canada recommend that individuals with symptoms of psoriatic arthritis be assessed by a rheumatologist within six weeks of their referral.
“Even short delays in diagnosing psoriatic arthritis can lead to worse outcomes for patients, including the development of irreversible joint damage,” explains Dr. Dafna Gladman, a Senior Scientist at the Schroeder Arthritis Institute and the senior author of the study. “Patients regularly face long wait times to see specialists in Toronto, and this is a major issue for the Toronto Western Hospital Psoriatic Arthritis Clinic. We wanted to get a clear picture of the percentage of our patients that are seen within the recommended time frame and identify reasons for delays.”
The team reviewed medical records and referral letters for 168 patients who were seen at the clinic between January 2013 and May 2019. “Using these data, we dug deep to examine what happens from the time that a referral is received at the Clinic to when the patient first sees a rheumatologist,” explains Dr. Gladman.
The team discovered that the average time from referral to rheumatologist consult was approximately 11 weeks. Only one quarter of patients were seen within the recommended six-week period.
The team determined that the primary cause of delays was a lack of spots at the clinic, suggesting a lack of resources and availability of clinicians who specialize in psoriatic arthritis.
The researchers also found that there was a disparity in wait times related to the location of referring physicians. Patients whose physician worked closer to the hospital were more likely to see a rheumatologist within six weeks from their referral than those whose physicians worked farther away. One reason for this might be because, if a patient lives further away, they may have less flexibility in terms of when they can make a scheduled appointment. This finding highlights the inequities and barriers to accessing care faced by individuals in rural communities.
“The Psoriatic Arthritis Clinic is a leader in arthritis care in Canada, but we need to do better to ensure that patients can access our services in a timely fashion,” says Dr. Gladman. “Our findings support the value of ongoing efforts to reduce wait times, such as implementing alternative models of care including specialized physiotherapy assessment, telehealth or establishing early arthritis clinics as intermediate points of care.”
This work was supported by the Canadian Institutes of Health Research, the Krembil Foundation and the UHN Foundation. Dr. Dafna Gladman is a Professor in the Faculty of Medicine at the University of Toronto. She is also the Director of the Psoriatic Arthritis Program, Co-Director of the Lupus Clinic and Deputy Director of the Centre for Prognosis Studies in Rheumatic Diseases at the Toronto Western Hospital.
Park S, Silverberg OM, Moez E, Chandran V, Gladman DD. Investigation into the wait time for consultation in the psoriatic arthritis program. Clin Rheumatol. 2022 Jul 22. doi: 10.1007/s10067-022-06288-8.
During the COVID-19 pandemic, health care workers have had to face exceptionally stressful, uncertain and demanding work conditions. These burdens have elevated the risk for anxiety, depression, insomnia, post-traumatic stress and burnout.
Early during the pandemic UHN’s Centre for Mental Health designed and implemented a program called UHN CARES (Coping and Resilience for Employees and Staff) to provide mental health support to everyone working at UHN. Drs. Kathleen Sheehan, Susan Abbey and Suze Berkhout, investigators at TIER and the Toronto General Hospital Research Institute, were behind the creation of this program and have recently reported on its development and success.
“Throughout the pandemic numerous studies have investigated the burdens on health care workers, yet few have explored how to best provide support,” says Dr. Abbey.
“We aimed to not only support UHN staff, but also establish evidence and guidelines that could be used elsewhere,” adds Dr. Berkhout.
The team of psychiatrists and psychologists at the Centre for Mental Health decided to implement a stepped-care approach through UHN CARES, in which users would be able to access and request the help they felt best met their needs. Three main ‘steps’ of care were made available:
Upon launching UHN CARES in April 2020, the team began collecting data on the program. Through interviews, surveys, forums and feedback reports, they were able to track the evolving needs of UHN health care workers in real time and adjust the delivery of care accordingly.
At the beginning of the pandemic, staff highlighted stresses from the home and workplace intersecting, challenges due to anxiety and depression, and fears of inadequate support. As the pandemic continued, responses shifted towards themes of fatigue, demoralization and burnout, as well as a need for support to be flexible and diverse.
The program’s dynamic structure enabled this feedback to be incorporated, making it more relevant and effective.
By November 30, 2021, UHN CARES program information had been downloaded nearly 1,000 times from UHN’s internal website, and the self-referral form for accessing the program’s resources had been downloaded more than 500 times. Many of the self-directed resources were subsequently accessed hundreds of times—more than 2,600 altogether—and around 1,100 psychological or psychiatric appointments were provided.
The services were also positively received: 93% of users said they benefited from the program and 95% said they would recommend it to a colleague.
“With UHN CARES, we have demonstrated that mental health support programs for health care workers can be highly valued and feasible,” says Dr. Sheehan. “The success of such programs depends on actively engaging health care workers throughout design and implementation, ensuring that resources are high-quality, and having program providers who understood the context of care.”
UHN CARES resources are currently available to Team UHN through the corporate intranet.
This work was supported by the Mount Sinai Hospital – University Health Network Academic Medical Organization Innovation Fund, The Princess Margaret Cancer Foundation and the UHN Foundation. Drs. Kathleen Sheehan, Susan Abbey and Suze Berkhout hold faculty appointments in the Department of Psychiatry at the University of Toronto.
Sheehan KA, Schulz-Quach C, Ruttan LA, MacGillivray L, McKay MS, Seto A, Li A, Stewart DE, Abbey SE, Berkhout SG. "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. Can J Psychiatry. 2022 Jul 19. DOI: 10.1177/07067437221111372.
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