“As you’re growing and trying to establish as a researcher, PSI is a very good ally for you as a physician to establish your research program. PSI funding is like a bridge between small departmental grants and large agencies. PSI funding can propel you toward establishing such a program and becoming a world leader in your area of research.” – Dr. Venkatesh Thiruganasambandamoorthy

A research program supported by PSI Foundation has become the world’s largest study on syncope (fainting) in the emergency department.

“As we built the program one step at a time, we have recruited close to 9,000 patients,” says Dr. Venkatesh Thiruganasambandamoorthy, an emergency physician and scientist at The Ottawa Hospital. “Just by putting one brick after another together, we have become the world’s largest program on emergency department syncope.”

About 10% of patients who come to the emergency department after fainting will have a serious outcome, such as bleeding, pulmonary embolism or heart conditions. In many cases, physicians can diagnose a serious cause of syncope after examining the patient. But for a small proportion of patients, the cause is unclear.

Working in the emergency department and seeing many patients who presented after fainting, Dr. Thiruganasambandamoorthy recognized that emergency physicians needed a tool to predict which patients are at highest risk of a serious outcome. He intended to do a small chart review of patients, but as he started reading the literature, he found that very little research had been done about the outcomes of syncope patients, despite about 160,000 syncope patients coming to Canadian emergency departments every year.

In 2009, Dr. Thiruganasambandamoorthy received a PSI research grant to develop a clinical decision tool to predict which patients who present to the emergency department after syncope are at highest risk of having a serious issue diagnosed within 30 days.

With the PSI funding, he and his team collected data from two emergency departments at The Ottawa Hospital a number of variables during a patient’s initial evaluation, and they reviewed patient outcomes for the 30 days after the initial visit to identify the variables strongly associated with serious outcomes. They then received CIHR funding to add more sites and increase the number of patients studied, ultimately developing the Canadian Syncope Risk Score.

After the tool was developed, they validated it in nine additional centres across Canada. The tool is now validated in eight countries and is recognized as the most robust and accurate of the available syncope risk scores.

PSI research award will pilot implementation of syncope risk score 

The Canadian Syncope Risk Score provides emergency physicians with the probability of a patient having a serious outcome within 30 days based on several factors from the physician’s clinical evaluation and investigations. It also suggests optimal timelines for patients in each risk category to remain in the emergency department for observation, thereby helping patients have the best outcomes and physicians allocate health-care resources.

With the design and validation complete, Dr. Thiruganasambandamoorthy received a PSI-50 Mid-Career Clinical Research Award in early 2020 to implement the Canadian Syncope Risk Score in 20 centres across Canada. The one-time award, which was established to celebrate PSI’s 50th anniversary, provides up to $300,000 over three or four to support mid-career clinician-researchers – who often need to balance additional academic and clinical responsibilities – by protecting 50% of their time for research.

Dr. Thiruganasambandamoorthy says that supporting mid-career investigators is critical to continue the momentum that can be built through the early career awards. “After you have developed a budding researcher who has established a program, you want to sustain that program so that they have an impact on the health of Ontarians,” he says. “This PSI award is an important supplement for clinician-researchers.”

Over the past year, Dr. Thiruganasambandamoorthy and his team have been working with implementation scientists and end users to lay the groundwork for implementing the tool. They hope to start a pilot project once the burden on hospitals from the third wave of COVID-19 starts to ease.

Dr. Thiruganasambandamoorthy says the first PSI grant was instrumental in his career. In addition to establishing a world-leading research program, he has authored a chapter in a premier emergency medicine textbook and has received a mid-career lecture award from the CIHR Institute of Circulatory and Respiratory Health and the Canadian Association of Emergency Physicians.

“By starting slow, and then building on the funding opportunities that are available for physicians, you can establish a large program and be recognized at the national and international levels,” he says.

Research funded by PSI Foundation is tackling diverse challenges in mental health, ranging from examining the neural networks underlying mental illness to finding ways to reduce stigma in the health care system.

For much of its 50-year history, PSI Foundation did not fund mental health research. But after extensive consultation with internal and external stakeholders, including the PSI Board of Directors and leaders at Ontario’s medical schools, it began funding mental health research in 2016 through a dedicated stream of operating grants. The change recognizes the strong link between physical and mental health.

“The body, mind and brain are very closely connected. It’s like dancing a good tango,” says Dr. Georg Northoff, a neuroscientist and psychiatrist at the University of Ottawa Institute of Mental Health Research, citing the close connection between cardiac activity and psychological function as one example. “If you are struggling with mental health, you often don’t feel physically well either.”

Dr. Northoff received one of the first PSI Mental Health Research Grants in 2016 to investigate whether brain imaging can help improve diagnosis and treatment of bipolar disorder, schizophrenia and major depressive disorder (MDD). These three disorders can be difficult to distinguish from each other based only on symptoms, but the treatments are quite different.

With his PSI grant, he and his team used fMRI and electroencephalography (EEG) to study neural network activity and imbalances in the brains of people with these mental illnesses. A better understanding of brain activity will help develop diagnostic markers and may even improve treatment through stimulating specific brain regions.

They identified that some patients with MDD have slower-than-usual activity in the visual cortex of the brain, resulting in blurry perception and slowed behaviour. Using this finding, they evaluated whether stimulating this region of the brain is an effective treatment for MDD. They intended to stimulate other relevant brain regions to treat the other illnesses, but the study was interrupted by the COVID-19 pandemic; however, early results from patients with MDD were promising and will be explored in further studies.

Dr. Northoff says that the PSI funding supported the groundwork of the study and may ultimately improve treatment for depression.

“We really want to make treatment more individualized. We could use the imaging and whether they have blurry perception or slow behaviour to determine the exact region of the brain and frequency at which we need to stimulate,” he says. “That’s a real result of the PSI funding.”

New PSI research award examines stigma in health care system 

In 2019, PSI incorporated the mental health funding stream into its regular operating grants. However, to commemorate PSI’s 50th anniversary and re-affirm its dedication to mental health research, it awarded two Mental Health Knowledge Translation Fellowships, one-time $300,000 awards to support new clinician-scientists conducting mental health research and protect 50% of their time for research.

Dr. Javeed Sukhera, a psychiatrist at London Health Sciences Centre and Associate Professor in the Departments of Psychiatry and Pediatrics at Western University, received one of the fellowships to examine structural stigma toward mental illness in health care and medical education.

While implicit stigma is reflected in individuals’ attitudes and behaviours toward people with mental illness, structural stigma is embedded in organizations through policies, practices and cultural norms. And it can greatly impact health, especially in populations who are already vulnerable and marginalized in health care.

“We know that stigma is a form of prejudice and discrimination that is directly linked with poor health outcomes. It leads patients to mistrust health care providers, adhere less to health care recommendations and seek help less, and it is even empirically linked with suicide,” says Dr. Sukhera. “Knowing that stigma interferes with patient outcomes and wellbeing, I felt compelled to look at effective ways to tackle it within the system.”

With the PSI fellowship, Dr. Sukhera is examining how stigma influences a patient’s experience in the health care system, as well as analyzing social media conversations about mental illness and stigma to learn how medical students and residents learn about these topics. Based on those findings, he and his team will develop a digital toolkit that will not only help health care professionals provide better patient care, but will also empower patients and caregivers with knowledge and skills to address stigma and seek help. Dr. Sukhera says that knowledge translation and mobilization are key in making change to policies and procedures at health care institutions.

“It’s not just knowledge to practice, it’s knowledge to action – in terms of education, policy and advocacy,” he says. “That’s the kind of meaningful change that our research can actually produce if we are intentional about mobilizing it.”

Dr. Sukhera appreciates that PSI has recognized mental health research and its influence on health care and health care providers by including the field in its areas of support.

“Mental health touches every aspect of care, not just for patients but also for physicians and health professionals who are struggling and affected by the same challenges in the health care system,” he says. “By deconstructing the stigma that exists in the system, we have a chance to start building something better.”

“PSI has been unbelievably supportive of my research. I feel incredibly honoured and privileged to have held one of their grants, not just because of the funds, but because of the retreat with the other fellows, their annual day, and other events that made me feel supported.” – Dr. Kerstin de Wit

As a specialist in thrombosis and emergency medicine, Dr. Kerstin de Wit saw a disconnect between the clinical practice guidelines and typical procedures for diagnosing pulmonary embolism (PE) in the emergency department. To Dr. de Wit, the disconnect clearly demonstrated the importance of knowledge translation research and considering the end user of research.

“The actual generation of the research information is only a small portion of evidence-based medicine, and research on its own doesn’t change practice,” says Dr. de Wit, who practices at Hamilton Health Sciences and Kingston Health Sciences Centre. “We need people to work on implementation and trying to fit the new information into our current processes and procedures.”

In recent years, researchers have studied and modified a variety of processes to diagnose PE in the emergency department with the goal of reducing the number of CT scans ordered. The guidelines recommend that physicians complete a Pulmonary Embolism Rule-out Criteria (PERC) score, followed by another risk measurement called a Wells score, followed by a d-dimer blood test. If these tests indicate the patient is low risk for PE, they should not proceed to a CT scan.

In practice, emergency physicians seem to order more CT scans than might be expected if they were following the guidelines, but evidence about this was lacking.

Dr. de Wit received the PSI Graham Farquharson Knowledge Translation Fellowship in 2017 to investigate how emergency physicians diagnose PE. The fellowship provides salary support for a new investigator to protect 50% of their time for research, focused on improving health system processes or health outcomes for Ontarians.

As part of the fellowship, Dr. de Wit and her research team interviewed more than 60 emergency physicians in five cities about the procedures they use and their thought processes when diagnosing or ruling out PE. They found that physicians felt anxious about missing diagnoses of PE and using the evidence-based tests, and that physician knowledge, time pressures of the emergency department and patient expectations were all barriers to using the tests.

“We have these evidence-based tools and tests, but it’s clear that they don’t fit into the emergency department,” she says. “So we’ve ended up in this situation where physicians talk about the tests like they’re using them, but they’re actually not using them.”

“In the emergency department, we shouldn’t be making our lives harder,” she adds. “There are certain qualities to tests and processes that help us in the emergency department and would be easier to adhere to, and some processes that are not easy to adhere to. I would place the current evidence-based process for PE testing as something that is not easy, and in fact it probably doesn’t help us.”

Dr. de Wit then used the themes that emerged from the interviews to implement a simplified diagnostic process that was meant to work better in the emergency department, testing the implementation in two emergency departments in Hamilton.

The new process was successfully implemented, but she found that it didn’t change the number of scans that physicians ordered. However, deeper analysis about the implementation is ongoing.

Dr. de Wit says that the fellowship has been “the success or failure of my research career.” Since receiving the fellowship, she has received two CIHR grants, published 16 papers directly related to the research, been invited to present at three conferences, and presented 18 conference abstracts about the work.

While there’s still more to be done before settling on an ideal PE diagnostic pathway for the emergency department, Dr. de Wit’s research has provided important information about the barriers and unique challenges that emergency physicians face and demonstrated the importance of considering end users in knowledge translation research.

“I hope that it will encourage thrombosis researchers who are not emergency physicians to think a little more deeply before they test an algorithm,” she says. “And I hope that emergency physicians are consulted about advances in care in the emergency department so that researchers understand the processes they go through and what would be helpful for them.”

The vast majority of health care research taking place in Canada is based at a limited number of large academic centres, even though most Canadians are cared for at community hospitals. Yet many community-based physicians are still interested in investigating specific questions related to their practice.

“You don’t have to practice medicine for very long to feel like it would be nice to be part of improving what we do rather just doing the same thing over and over again,” says Dr. Alexandra Binnie, an intensivist at William Osler Health Centre in Brampton. “And there are an impressive number of physicians who are willing to invest a lot of time doing it if they think it’s possible at their hospital.”

But these physicians often face several significant barriers in undertaking research, one of the biggest being financial. The research funding system in Canada makes it difficult for community physicians without an academic appointment to receive funding. PSI Foundation plays an important role in filling this niche with financial support for community physicians.

“PSI’s financial support of community research is both practical and symbolic,” says Dr. Binnie. “It places external value on that work, and it recognizes that people are doing very interesting things in community hospitals and they should be financially supported to do those things.”

This support mainly comes through the PSI Healthcare Research by Community Physicians grant, which supports community-based physicians to conduct research that reviews practice patterns and enhances their practice and improves patient care. The grant provides up to $250,000 for up to three years.

Dr. Binnie and co-principal investigator Dr. Jennifer Tsang, an intensivist at Niagara Health, recently received one of these grants to compare patient demographics and treatment approaches for COVID-19 at both academic centres and community hospitals. Because academic hospitals are typically in downtown urban locations, they may serve different a different patient population than community hospitals, and physicians at community hospitals may not apply results if they feel that studies don’t represent their patient population.

They will be using data from Critical Care Services Ontario about patients who were admitted to academic and community intensive care units with COVID-19 in 2020 to analyze whether there are significant differences in patient demographics and treatment approaches between the two types of centres. The COVID-19 pandemic presented an opportunity to study these differences with one disease.

Understanding any potential differences between academic and community hospitals will help researchers understand the current landscape and think about how studies are done moving forward. “There’s an argument that we can’t just confine research to a handful of hospitals that don’t represent the country and our patients as a whole,” says Dr. Binnie. “We need to expand our research footprint so that more physicians have access to research, and patients are better represented within these studies.”

Educational fellowships support specialized training for physicians in smaller communities

PSI also supports community-based physicians, especially those outside of major teaching centres, who want to undertake specialized training. The PSI Educational Fellowships covers the course fees and associated travel costs for training in a clinical skill that is lacking in the community.

Dr. Mike Ballantine is a physician based in Kincardine whose practice includes rural emergency medicine, primary care dermatology and occupational medicine. He has received two of these fellowships, in 2019 and 2020, which have provided financial support for specialized courses in occupational medicine through the University of Alberta.

Occupational health specialists are rare to begin with, even more so in the rural area where he practices. He was already working with suppliers to the region’s largest employer before taking the courses, providing pre-employment medical exams, injury management and medical guidance, but Dr. Ballantine says that the courses will provide him with specialized knowledge to improve his practice and network with other occupational medicine specialists. And the companies he works with appreciate having a local specialist.

“One of the main pieces of feedback I’ve had is how great it is that there’s a local resource who not only is able to provide the occupational medicine services locally but also has a much better awareness of the resources that are locally available,” says Dr. Ballantine.

He adds that it is important for PSI to support physicians in communities across the province. “Having an organization that is willing to focus on community health care and resources is hugely beneficial,” he says. “These courses have been very helpful to my career, and I’m appreciative of the support PSI has given me.”

Medical trainees looking to gain experience in independent research have few options for funding support. But education and training, not just in clinical practice but also in how to conduct research, are critical to ensure that trainees can confidently pursue careers as clinician-scientists and pursue research that will change clinical practice.

PSI Foundation’s Resident Research Grants, which award up to $30,000 for up to two years, provide key funding to support these young investigators. The grants are part of PSI’s vision to support new investigators and ensure that physicians are well-equipped to lead innovative research and provide excellent health care.

“There are not that many opportunities as a junior investigator to have your own funding before your first academic position,” says Dr. Jodi Warman-Chardon, Director, Neuromuscular Centre and clinician-scientist at The Ottawa Hospital (Research Institute) and Children’s Hospital of Eastern Ontario (Research Institute) (CHEO), who received a PSI Resident Research Grant in 2013. “The PSI funding is critical for creating the clinician-scientist leaders of tomorrow.”

For many trainees, a PSI Resident Research Grant provides invaluable experience in their training toward becoming an independent investigator. Residents lead the research and are the main contact for the grant, providing them with invaluable learning opportunities in every aspect of leading a grant, including administration.

Dr. Warman Chardon was completing a neurogenetics/neuromuscular fellowship at the University of Ottawa and CHEO when she was awarded a PSI Resident Research Grant. With supervisor Dr. Kym Boycott, Dr. Warman-Chardon studied next generation genetic sequencing to diagnose limb girdle muscular dystrophy (LGMD), a group of inherited muscle disorders. They were able to identify disease-causing variants in genes known to be important to the condition, and they discovered a new gene responsible for early-onset disease.

The work resulted in several publications (including Clinical Genetics and Current Neurology and Neuroscience Reports) and several national and international presentations, including a poster at PSI’s Annual General Meeting in 2016, for which she won the best poster award. “The generosity and ongoing support of PSI has launched many investigators’ careers and is a real capstone for a trainee,” she says. “These grants change your career trajectory.”

Based in part on the data from the Resident Research Grant, she received a PSI New Investigator Grant in 2019, with Dr. Boycott as co-principal investigator. This research project aims to integrate MRI, genome sequencing and RNA sequencing to improve diagnosis for genetic myopathies, thus improving care.

“These clinician-led projects are not always attractive projects for other granting agencies, but they do change care,” says Dr. Warman Chardon. “These grants help advance patient care that we would not otherwise be able to do, and on behalf of my patients with these rare diseases, I’m incredibly grateful for PSI’s support.”

Areas of non-support excluded from Resident Research Grants 

Dr. Bobby Yanagawa, a heart surgeon at St. Michael’s Hospital and Program Director in the Division of Cardiac Surgery at the University of Toronto, had already completed a PhD and a post-doctoral fellowship when he started his surgical residency in 2008. He received two PSI Resident Research Grants, in 2009 and 2012, to study two different proteins and their roles in cardiac injury and cardiovascular disease.

Dr. Yanagawa says that as a surgical trainee, he had a keen interest in research but limited time to conduct it, which made it difficult to secure funding from large agencies. PSI’s support was critical to helping him build a research program while completing his training.

“This funding is like a catapult,” he says. “It gives people who have a project of smaller scope the opportunity to publish some papers and generate some momentum.”

Importantly, while PSI does not typically fund research in certain areas, such as cancer and heart disease, these areas of non-support do not apply to Resident Research Grants. Dr. Yanagawa says this exception is critical for clinician-scientists at the beginning of their careers who may not yet have the track record to successfully apply for large grants from national agencies.

“There needs to be funding for the researchers who can’t compete at the national agencies and for pilot projects and innovative ideas that it’s hard to get the big dollars for,” he says. “Without this funding, the trainees in cancer and cardiovascular disease would suffer. It’s really important and very much appreciated.”

Dr. Yanagawa now supervises trainees leading their own research projects, including studies of rheumatic heart disease, training using surgical simulations, and gender equity in surgical training. He says that supervising residents is a way to show appreciation for the support he received during his training and share his knowledge with the next generation of clinician-scientists.

“It’s nice to be part of that continuum, and I enjoy being part of that process,” he says. “To have the opportunity to work on the project with a resident, get them to drive it, successfully get grant funding and eventually see the fruits of that research is very satisfying.”

“PSI has a long history of funding important clinical and practical questions that have a high potential to improve the practice of medicine.” – Dr. Kathy Boutis

As a pediatric emergency physician at Toronto’s Hospital for Sick Children (SickKids), Dr. Kathy Boutis has treated many children with minor musculoskeletal injuries. Her research program, with significant support from PSI Foundation, has helped to shape how physicians at SickKids and around the world treat and manage these common injuries.

“I am first a doctor and I love being a doctor,” she says. “I wanted to do research in an area where emergency physicians could lead the path to change using high quality evidence.” Hundreds of thousands of children present to Ontario’s emergency departments with minor musculoskeletal injuries every year, and Dr. Boutis recognized the impact she could have by studying them.

She began working with Dr. Suzanne Schuh on a project to predict the need for radiography in children with ankle injuries, the results of which were published in The Lancet in 2001. In 2002, she received her first PSI Foundation grant as a principal investigator, comparing a removable brace to a cast for low-risk ankle fractures. The results demonstrated that the brace allowed children to recover and return to physical activity quicker than casting, and was more cost-effective and preferred by patients. These two studies formed the building blocks of what was to become a successful research program over the next two decades.

Research aims to help physicians “choose wisely”

Dr. Boutis has since been principal investigator on three more PSI grants, all of which have focused on de-escalating interventions for minor musculoskeletal injuries in children. Casting and other interventions can occasionally cause complications, but the benefits of de-escalating the interventions go beyond reducing complications and include the potential to reduce health care costs and improve the quality of life for injured children and their families.

“Our overall goal is to optimize the diagnosis and management of pediatric musculoskeletal injuries. It appeals to the current interest and demand in choosing wisely,” she says. “We need to look at managing these common problems to be more resource-efficient and convenient for patients.”

She and her team received PSI funding to evaluate the Low Risk Ankle Rule, a clinical guideline for when children presenting with ankle injuries benefit from ankle x-rays. Implementing the rule safely reduced the rate of x-rays given to children by about 50%. This rule is now being adopted by emergency departments all over the world. She then noticed that one type of common minor ankle injury, presumed to be a fracture, was treated for weeks with a cast, which seemed unnecessary. PSI funded a project that studied this injury using magnetic resonance imaging (MRI) and found that most kids with this injury, in fact, did not have a fracture – rather they had ankle sprains that could be managed with rest, ice, and return to activities when the child was ready. Her most recent grant awarded by PSI in 2019 is extending these principles to a minor leg fracture in toddlers, with the hopes of creating an equally safe but more convenient treatment for these injuries. “Parenting a toddler is challenging enough without the addition of restricting their activity for weeks,” she says. “If we can make managing these injuries easier, it’s a win for parents and the health care system.”

Growing out of her PSI-funded work, it became obvious that emergency physicians found pediatric image interpretation challenging, which led to medical errors. As a result, Dr. Boutis also implements cutting-edge medical education theory into the teaching of medical image interpretation, such as that required for x-rays and ultrasounds. This research eventually led to the development of ImageSim, an award winning and nationally acclaimed innovative web-based image interpretation learning system.

Study results have changed clinical guidelines around management of minor injuries

Studying minor injuries in pediatric emergency medicine is a niche area of research that has limited funding opportunities, and Dr. Boutis says that PSI Foundation funding has been critical. “PSI has been pivotal to my work,” she says. “They have always been very fair and transparent. I feel very positively about the organization and their mission.”

PSI funding has allowed Dr. Boutis to complete high quality multicentre trials that have made a significant impact in the field. She has published in numerous high impact journals, and her work has caught the attention of leading textbooks in the field. These efforts led to the development of clinical guidelines around management of minor musculoskeletal injuries internationally – which helped her realize her goal of making an impact on emergency medicine practice. “If my work never got implemented at the bedside, it would feel like all the evidence I derived failed,” she says. “One of the best compliments I receive is from my colleagues is that it makes them better doctors. You could not get a better compliment than that.”

“PSI funds a diversity of different types of clinical research – the whole gamut of medical and surgical specialities. It’s amazing what PSI has been able to accomplish in so many different areas.” – Dr. Ian Gilron 

Dr. Ian Gilron, an anesthesiologist at Kingston Health Sciences Centre and professor at Queen’s University, credits PSI Foundation funding for advancing his team’s research on combination therapy for acute and chronic pain. “When I was first getting involved in this field more than 25 years ago, pain management was such a big area of clinical need and there were lot of unanswered research questions,” says Dr. Gilron. “That continues to be the case, although we have made much progress.”

Pain helps to protect the body and alerts it to harm, and because of this important role many different neural pathways transmit pain. As a result of the many mechanisms involved, treating pain is challenging. A single pain drug by itself is unlikely to be highly effective for many patients, but rather combinations of treatments that target different pathways are often used.

Dr. Gilron has focused his team’s research program on evaluating drug combinations to treat both acute and chronic pain. “The first three project grants we got from PSI absolutely advanced the field in understanding multimodal drug therapy for acute pain, and a lot of those principles are also being applied in chronic pain,” he says. “The work funded by PSI has really helped advance that field.”

In particular, Dr. Gilron’s PSI-funded research has focused on understanding the treatment and impact of movement-evoked pain after surgery. His research suggested that movement-evoked pain may have different mechanisms than pain at rest, and it often does not respond to opioids in the same way as pain at rest.

His first three PSI Foundation grants funded single-centre clinical trials of drug combinations to treat movement-evoked pain after abdominal surgery: a study comparing a two-drug combination of rofecoxib and gabapentin to either drug alone, a study comparing meloxicam and gabapentin together to either drug alone, and a study comparing a triple combination of acetaminophen, meloxicam and gabapentin to any two of the drugs together. In each study, pain levels and other measures of physical function were improved with combination treatment at various timepoints after surgery.

New research is evaluating antioxidant’s effectiveness for pain 

At the same time as Dr. Gilron was leading this work in acute pain, he was also conducting proof-of-concept clinical trials of drug combinations for chronic pain.

These clinical trials were published in high-impact journals, including The Lancet and The New England Journal of Medicine, and Pain, and they all showed that the combination therapies being evaluated were more effective than any one of the drugs alone. “The improvement we observed with the combination was statistically significant, but it was a moderate improvement. We were hoping for more,” says Dr. Gilron. He adds that the side effects of each drug being tested, particularly the sedative effects, limited the dosages and, therefore, the added effectiveness of the combination therapies.

His most recent research is evaluating a possible treatment that has no sedative side effects, making it an ideal “partner” to combine with other pain drugs that do have this sedative effect. Recent studies have suggested that the antioxidant alpha-lipoic acid relieves pain in nerve conditions such as diabetic neuropathy without a sedative effect, and it could potentially be used in combination therapy for other chronic pain conditions such as fibromyalgia.

Building on this previous work and the need to identify new non-sedating chronic pain treatments, in 2015, Dr. Gilron received PSI funding for a proof-of-concept clinical trial studying the effects of alpha-lipoic acid on pain relief in fibromyalgia. The results, recently published in Pain, did not suggest that alpha-lipoic acid is an effective treatment for fibromyalgia in most patients, although there was a trend for pain reduction in male patients with fibromyalgia. As such, this trial represented an important step in research to identify new treatments for chronic pain.

“PSI is willing to take chances on new ideas. It is very focused on funding high quality research and skilled investigators, so they don’t take a risk in that perspective, but certainly it is willing to support new ideas and innovation,” says Dr. Gilron. “For PSI to keep our combination research program advancing for so many years then give us the opportunity to bring our research in a whole new direction is something quite unique.”

“PSI Foundation really understands translational research and the idea of the clinician scientist. The Foundation has a unique position in supporting clinically relevant research, and this has been an important contribution to science in Ontario, and therefore nationally and internationally.” – Dr. Michael Fehlings, Toronto Western Hospital and University of Toronto

Dr. Michael Fehlings, a neurosurgeon at Toronto Western Hospital and professor in the University of Toronto’s Department of Surgery, was first exposed to the idea of translational research and the role of clinician scientists as a medical student. “I was impressed that by asking key questions related to medical practice, one could generate research that could change the way you treat a patient,” he says.

During his research career, he has focused on spinal cord injuries, specifically secondary spinal cord injuries – the biochemical processes such as inflammation and generation of reactive oxygen species that cause cell death following an initial spinal cord injury. Because these secondary injuries can exacerbate the initial injury, understanding these mechanisms is critical to develop new treatments. Dr. Fehlings says that PSI Foundation’s support of translational research has been critical to his research program.

PSI Foundation has funded his research for more than 25 years, from his early basic research on the mechanisms of secondary injury to more recent translational studies of biomarkers for degenerative spinal conditions. “PSI Foundation had the confidence to allow me to come forward with various ideas over the years,” he says. “A number of these strategies funded by PSI Foundation have now become translated into therapeutics or clinical trials.”
One of the first significant discoveries in his career, partially funded by PSI Foundation, demonstrated that when sodium enters nerve cells after an injury, it amplifies nerve cell damage. Based on this discovery, the sodium channel blocker riluzole, which is approved for treatment of amyotrophic lateral sclerosis (ALS), is now in phase 3 clinical trials to improve outcomes for traumatic spinal cord injuries.

Over the years, he and his team have studied whether intravenous IgG, approved for treatment of various inflammatory conditions, is effective in reducing secondary spinal injury, and in enhancing recovery after surgery for degenerative cervical myelopathy (DCM), a degenerative form of arthritis. This work is now in late preclinical stages. They also developed a novel bioengineered system to deliver drugs to treat spinal cord injuries, which served as a critical proof of principle for current delivery systems being tested in clinical trials.

Dr. Fehlings says that PSI Foundation support was essential to these discoveries. “In each case, we were able to leverage PSI funding several fold, bringing in additional grants and industry support to move it forward to clinical trials,” he adds.

Support from the PSI Foundation has been instrumental in a number of discoveries throughout his career that have garnered him international recognition. In 2009, he was awarded the Olivecrona Award, the top international award for neurosurgeons and neuroscientists awarded by the Nobel Institute at the Karolinska Institute in Stockholm, for his important contributions in central nervous system injury repair and regeneration. In 2014, Dr. Fehlings was elected to the Fellowship of the Royal Society of Canada and to the Canadian Academy of Health Sciences, and last year the Right Honourable Jacinda Ardern, Prime Minister of New Zealand, presented him with the Ryman Prize for his work enhancing the quality of life for older people.

His most recent PSI Foundation grant, awarded in 2017, is more directly translational. He and his team are studying whether genetic biomarkers in blood samples can identify individuals who are more susceptible to DCM. Identifying these patients would allow for earlier, possibly even preventive, treatment. Early results have been very promising, and the work will be published soon.

Dr. Fehlings’ research, directly or partially funded by PSI Foundation, has led to results that have influenced clinical practice guidelines and enhanced outcomes for patients. “Translational work is always evolving,” he says. “Being a clinician-scientist has allowed me to ask critical questions and make a positive impact to help with innovative treatments.”