“This study helped us confirm that at a local level, consistent infection control, community protective measures and vaccines were effective at halting the spread of SARS-CoV-2 for almost a full year. It also reminded us that a pandemic respiratory virus can mutate and overcome many of the prevention measures we introduced as the Omicron variant did in late 2021. We are indebted to the PSI Foundation for funding this study which is unique in Canada”

-Dr. Jorge Martinez-Cajas

About Dr. Jorge Martinez-Cajas

Dr. Jorge Martinez-Cajas is an Associate Professor in the Division of Infectious Diseases in the Department of Medicine at Queen’s University, with a cross-appointment in the Department of Biomedical and Molecular Sciences. He completed a three-year CIHR Canadian HIV Trials Network (CTN) research fellowship at the McGill AIDS Centre, where he studied antiretroviral drug resistance.

Dr. Martinez-Cajas leads the Canada-Colombia Collaboration Against HIV and AIDS, a recently established network of Canadian and Colombian institutions dedicated to HIV and AIDS research and care. His research focuses on the treatment of HIV infection in resource-limited settings, the implementation of HIV pre-exposure prophylaxis (PrEP) in Latin America, and outpatient parenteral antimicrobial treatments.

About the Funded Study

At the beginning of the COVID-19 pandemic, Dr. Martinez-Cajas recognized the need to assess infection risk among Ontario healthcare workers and the patients they served. At the time, over 71,000 cases and more than 5,000 deaths had been reported in Canada, with the majority occurring in older adults–particularly in long-term care facilities. In Ontario, 13% of all cases were in long-term care residents, yet they accounted for 70% of provincial deaths.

The PSI-funded study examined how healthcare workers’ roles in long-term and acute care facilities in Southeastern Ontario shaped outbreak risk and antibody development. It also assessed risk and protective factors for SARS-CoV-2 infection, including whether vaccination correlated with reduced infection rates.

Dr. Martinez-Cajas and Co-Investigator Dr. Yanping Gong recruited 205 healthcare workers from four facilities, including one acute care hospital and three long-term care homes. With the arrival of the Omicron wave in fall 2021, the research team followed up with participants to track infection risk before and after Omicron. By measuring antibody levels in healthcare workers exposed during outbreaks; those who cared for COVID-19 patients; and control groups with no direct exposure, the funded study identified proportions of susceptible versus protected workers.

Impact of the Funded Study

This study’s findings established a cohort model that can inform not only COVID-19 research, but also preparedness for future influenza or respiratory outbreaks. Dr. Martinez-Cajas highlighted areas for improvement in building larger cohorts, strengthening infrastructure and healthcare system readiness, and prioritizing resources during pandemics. Using the data from the study, Dr. Martinez-Cajas and his team developed computer simulations to test how reorganizing care within healthcare facilities might reduce outbreak risk, particularly in long-term care settings.

Reflecting on the findings, Dr. Martinez-Cajas explains: “this report examines the risk of infection by SARS-CoV-2 infection in a cohort or healthcare workers in a low-prevalence region in Ontario,” says Dr. Martinez-Cajas. “Its findings include infections driven by occupational exposures before Omicron but driven by community exposures after Omicron, protective effect of booster doses of vaccines, and additional protective effects against community infection by consistent adherence to mask use and social distancing even during the omicron waves. These findings are relevant for future pandemic preparedness.”

The study’s impact extends beyond just a single project, supporting future research and strengthening future pandemic preparedness in Ontario and beyond.

“The funding we received from PSI has helped researchers in the community hospitals, like ourselves, to connect with each other, learn from each other and build research programs in our own respectively community hospitals. The data that came from the work that was funded by PSI were by and large drawn from frontline clinicians and researchers in community hospitals.”

-Dr. Jennifer Tsang

About Dr. Jennifer Tsang

Dr. Jennifer Tsang is a Physician Research Lead, Intensivist, and Co-Director of Critical Care Research at Niagara Health; Regional Deputy Research Director of the Internal Medicine Residency Program at McMaster University; School of Medicine Research Lead at McMaster University’s Niagara Regional Campus; and Associate Professor of Medicine at McMaster University. Dr. Tsang’s research focuses on research capacity building in community hospitals and community-based distributive medical education.

Her medical training began at University of Ottawa, where she completed her MD in Internal Medicine–followed by a Critical Care fellowship at the University of Toronto. In 2013, she obtained her PhD in molecular biology and completed the Royal College Clinician Investigator Program at the University of Toronto.

About the Funded Study

Working as a community physician in the Niagara region, Dr. Tsang noticed a disparity between community hospitals versus academic hospitals when it came to health research output and participation in the research world — especially within intensive care units (ICUs).

With her PSI Healthcare Research by Community Physicians grant, Dr. Tsang and Co-Principal Investigator Dr. Alexandra Binnie set out to break down these barriers and to learn how to engage community researchers. As the cofounders of the Canadian Community ICU Research Network (CCIRNet), the two partnered with the network with the end-goals of fostering a community of practice, offering mentorship and training, and building research capacity in community hospital ICUs.

Digging deeper, Dr. Tsang and her team wanted to explore the factors that influence community ICU research participation and program development; and what was essential for implementing and sustaining a community ICU research program.

Impact of the Funded Study

With support from PSI, the results of this qualitative, descriptive study produced a research toolkit to support community ICU physicians interested in implementing a research program within their hospitals.

Following the principles of integrated knowledge translation (iKT), Drs. Tsang and Binnie worked with physicians who represented the toolkit’s intended users, including: CCIRNet members, community ICU clinicians, research staff, and administrators. Drawing on members’ lived experiences in developing community ICU research programs, along with preliminary findings from participant interviews, they compiled practical recommendations for launching, implementing, and sustaining these programs.

Yet, Dr. Tsang notes there is more work to be done on a systematic level. “Findings from this study highlight the need for more support from leaders at policy makers at the local community hospital level, the provincial level and the national level,” says Dr. Tsang.

“While the current study identified key strategies for strengthening community hospital research at an individual and organizational level, less is known about the strategies required at a systems level. These gaps have highlighted the need to now explore the perspectives of leaders from community hospitals as well as those at provincial and national levels to inform policy recommendations for strengthening community hospital research capacity at a systems level.”

With the online toolkit now available for use through the Canadian Journal of Anesthesia, Ontario physicians and policymakers alike can have a helping hand in filling essential gaps within the medical research space of community ICUs.

“PSI Foundation support enabled us to better understand the impact of antibiotic treatment duration for bacteremia on the gut microbiome and antimicrobial resistance, and has helped us develop an ongoing clinical trial microbiome substudy pipeline which will continue to uncover important off-target effects of antibiotics on microbiomes and antimicrobial resistance in humans.”
-Dr. Nick Daneman

About Dr. Nick Daneman

Dr. Nick Daneman is a Clinician Scientist and Division Head of Infectious Diseases at the Sunnybrook Research Institute, Senior Adjunct Scientist at ICES, and a Professor of Medicine at the University of Toronto. He specializes in Trauma, Emergency, and Critical Care. Dr. Daneman’s research focuses on antibiotic stewardship and resistance; hospital-acquired and critical care infections; with a specific focus on Clostridium difficile and bacteremia. His training began at University of Toronto, where he completed his masters in Clinical Epidemiology and later completed his medical training with a specialty in Infectious Diseases and Internal Medicine.

About the Funded Study

With his research team, Dr. Daneman set out to address the healthcare needs of patients who needed to consume antibiotics to fight off infection, while facing the off-target effects of antibiotic resistance and potential damage to one’s microbiome and the healthy bacteria in the body. The ‘BALANCE of the microbiome’ study enrolled over 3,600 participants worldwide — the first to embed a microbiome and antimicrobial resistance outcome in a large international clinical trial of an antimicrobial stewardship intervention.

The results of the randomized controlled trial revealed that for those who need to take antibiotics to treat blood infections, 7 days of taking antibiotics was just as effective as 14 days — reducing the potential damage caused by long-term antibiotic use.

“PSI Foundation support has directly informed ongoing clinical trial and microbiome substudy design, in particular in trials designed and initiated by this group, such as the BALANCE+ platform and ARODECAMP trials,” Daneman says. “Our goal is to continue to embed microbiome and antimicrobial-resistance assessments into clinical trials, to determine not only the clinical outcomes of study comparisons, but also their biological effects.”

Impact of the Funded Study

Moving forward, this PSI-funded study allowed Dr. Daneman’s team to develop a platform for future microbiome substudies of large international trials, including the ongoing BALANCE+ adaptive platform trial of bacteremia.

“Our goal is to develop and implement the methods required for microbiome analyses in clinically-actionable time for scenarios where microbiome and resistance status can inform clinical decisions.“

The implications of this study for Ontarians are major reductions in antibiotic treatments and harms across Ontario. With the data from this research, Dr. Daneman’s final goal is to incorporate microbiome and resistome considerations into clinical and stewardship practices in infectious disease by generating the data required to do so from human studies.

“This was my first successful grant as a new investigator, so it really jumpstarted my research career.… Getting that first grant and being able to do this research led to other opportunities, and I’m very grateful to PSI Foundation for their support.” – Dr. Selina Liu, Western University, Lawson Health Research Institute and St. Joseph’s Health Care, London, Ontario

Recent estimates from Diabetes Canada indicate that 5.7 million Canadians are living with diabetes. Many of these people do or will experience eye damage, called diabetic retinopathy, which is a major cause of vision loss. As a result, practice guidelines recommend that people with diabetes undergo screening for diabetic retinopathy once a year.

People with diabetes have their eye exams covered through OHIP, but they may face other barriers to getting an exam, such as simply remembering to make the appointment, taking additional time off work for the exam, and taking eye drops that make it difficult to see and drive for some time after the exam.

“Prior research showed that about 50% of people with diabetes in Ontario weren’t having their eyes checked regularly, and that’s a major problem. We know that diabetic retinopathy is the main cause of blindness in working-age adults in Canada and has a drastic effect on quality of life,” says Dr. Selina Liu, Assistant Professor, Department of Medicine at Western University, Associate Scientist at Lawson Health Research Institute and Endocrinologist, Centre for Diabetes, Endocrinology and Metabolism at St. Joseph’s Health Care London, Ontario. “Vision loss due to diabetic retinopathy is preventable through early detection and treatment. Developing strategies to improve retinopathy screening seemed to be a major area that deserved further research.”

One strategy uses a new technology to potentially make screening more accessible.

Non-mydriatic ultra-widefield (UWF) retinal imaging, which uses a specialized camera to take a wide-angle image of the retina, offers a few advantages over the usual screening methods used by optometrists. It only takes a few minutes and does not require eye drops, and images can be taken by trained staff and provided to an ophthalmologist to be read later. For these reasons, UWF imaging has potential to be incorporated into the regular diabetes clinic visits.

“What if we could integrate screening into a diabetes clinic visit?” says Dr. Liu. “If we could screen for retinopathy on the same day and in the same location where our patients are already coming for diabetes care, some of the barriers to getting screening done would be taken away.”

In 2016, Dr. Liu and a multidisciplinary team received funding from PSI Foundation for a randomized clinical trial called Clearsight to examine whether UWF imaging could detect more patients with eye disease that needed closer monitoring or treatment compared to usual screening.

“As a new investigator, embarking on a full 740-person randomized controlled trial was a bit daunting at first,” she says.  “But having funding from PSI Foundation was essential for this trial and gave me confidence as I went down this path.”

The research team recruited 740 patients with diabetes to participate in the trial, with half being screened through UWF imaging and half receiving usual care. The trial mimicked how screening is or could be done in a real-world setting: the patients enrolled in the UWF group were offered screening at the same clinic visit with the images read by an ophthalmologist later, while those receiving usual screening were responsible for making their own optometrist appointment. Patients in the UWF group were also still advised to visit their optometrist for usual screening, as per standard of care.

The team found that on-site screening significantly increased detection of diabetic eye disease that required either increased surveillance (more than annually) or referral to an ophthalmologist for further assessment. They also found that on-site screening resulted in significantly higher screening adherence than usual screening. The study did not look at patients’ vision outcomes as a result of the screening (since a much larger and longer trial would be required), but they expect that if more patients who require closer monitoring or ophthalmology referral are identified early, the rates of vision-threatening diabetic eye disease would ultimately decrease.

While the results were promising, screening with UWF imaging does come with significant costs, and Dr. Liu plans to complete a cost-effectiveness analysis of the imaging compared to usual screening. She is also undertaking research on other approaches to identify patients at risk of diabetic eye disease, including the use of artificial intelligence to read UWF images and the use of blood biomarkers for retinopathy screening.

Ultimately, she hopes that the Clearsight trial and other related work will provide evidence that can be incorporated into diabetes clinical practice guidelines to improve screening and vision care for people with diabetes, in Canada and worldwide.

“We hope that having this study will provide the high-quality evidence that this approach can improve retinopathy screening and detection rates, and perhaps it could be implemented in clinical practice guidelines so that the diabetes clinic could be a one-stop shop for diabetes care, including eyes,” says Dr. Liu. “We have more work to do to get there, but we hope our work can influence changes to health policy and clinical practice in how screening for diabetic eye disease in Canada is performed.”

First Nations, Inuit and Métis people in Canada have poorer health outcomes than non-Indigenous people due to historical and ongoing systems of discrimination, and these disparities can start in childhood, with Inuit children experiencing higher rates of respiratory infections, iron deficiency anemia, and other conditions.

A team of researchers in Ottawa – home to the largest Inuit population in Canada outside of the traditional Inuit homeland of Inuit Nunangat – recently completed a study funded by the PSI Foundation that aims to arm caregivers of Inuit children with the knowledge they want and need to improve child health outcomes.

“Our colonial history, historical and ongoing systems of discrimination, and the unique challenges that Inuit people face when they have to move from the north to an urban Ottawa community result in a lot of cultural dissonance and tensions that are challenging for this community,” says Dr. Brian Hummel, currently a pediatric infectious disease fellow at the Children’s Hospital of Eastern Ontario (CHEO). “We wanted to better understand what those challenges are and what can be done to help support child health for this community.”

Recognizing the need for better knowledge sharing around child health, Dr. Hummel and co-investigator Dr. Daniel Bierstone, along with supervisor Dr. Radha Jetty, the physician lead for Inuit Child Health and the Nunavut Program at CHEO, partnered with the Inuuqatigiit Centre for Inuit Children, Youth and Families to better understand the experiences of caregivers of Inuit children related to child health.

Supported by a PSI Foundation Resident Research Grant, Dr. Hummel and the team conducted focus groups with 24 caregivers of Inuit children. In the focus groups, they discussed where caregivers go for child health knowledge, the topics they felt they needed more knowledge about, and how they prefer to learn about child health.

Dr. Hummel says that the qualitative approach to the study, as opposed to conducting a survey or other quantitative method, was essential to collecting data that would directly represent the voices of the caregivers.

“This approach allowed us to collect data that was more rich, raw and real, and it allowed Indigenous voices to be more directly represented in the research,” he says. “As non-Indigenous researchers, we viewed our role as being vessels to bring forward Indigenous insights, very much in the spirit of ‘never about us without us.’”

Knowledge-sharing programs should include both Indigenous and Western ways of knowing

In the focus groups, caregivers said they needed more support and information about parenting and development, adolescent mental and sexual health, common childhood illnesses, infant care and nutrition – topics where there can be tension between Indigenous and non-Indigenous ways of knowing.

Caregivers also said that they often turned to their families, friends, community members and Indigenous health services for child health information, largely because of previous negative experiences with Western medical institutions and lack of trust of these institutions.

While caregivers strongly preferred in-person knowledge-sharing sessions for their supportive environment and opportunity to build community, importantly, they identified that involving both Inuit Elders and health care providers in these sessions was important.

“One of the interesting themes that came out in the focus groups was this idea of synergy between Indigenous ways of knowing and Western medicine ways of knowing, and how those two things don’t need to compete with each other but can instead work synergistically together to support Inuit child health,” says Dr. Hummel. “There are things that are valued more in the cultural understandings of health, such as nutrition, child-rearing and development. But there were also things they valued about western medicine approaches.”

“Ultimately knowledge-sharing programs should include both Inuit and Western knowledge and traditions, while empowering families to engage in Indigenous child-rearing practices,” he adds.

The study is the first of its kind to explore caregivers’ perspectives on urban Inuit child health knowledge, and it has been presented at national pediatric and Indigenous health conferences and published in the peer-reviewed journal International Journal of Circumpolar Health. Dr. Hummel and the research team hope that these findings can now be used to help develop programs and other knowledge-sharing initiatives to benefit caregivers and ultimately improve Inuit children’s health.

As Dr. Hummel finishes his fellowship and moves to the next stage of his career, he plans to continue being involved in research and education on top of his clinical practice. And he says the PSI Resident Research Award has helped prepare him by giving him a rare opportunity to lead a larger project.

“As residents, there aren’t a lot of funding opportunities for these kinds of larger projects,” he says. “PSI funding is really important for those of us who want to do larger projects to have these opportunities.”

A clinical trial funded by the PSI Foundation is changing the management of a rare genetic condition found in the Amish communities of southwestern Ontario. A research team led by Dr. Victoria Siu, a medical geneticist at London Health Science Centre and associate professor at Western University’s Schulich School of Medicine and Dentistry, found that histidine supplementation was effective in reducing the complications in children with the condition.

“The positive effects of histidine supplementation in patients with this condition open up the possibility of an inexpensive treatment to prevent loss of vision and hearing,” says Dr. Siu. “It’s very difficult to find funding for a clinical trial of a natural health product like histidine. We couldn’t have done this trial without PSI funding, and I’m very grateful.”

Dr. Siu began her career in London, Ontario, which is close to the majority of Ontario’s Amish and Mennonite communities, and she often sees patients from these communities as part of her practice.

In the early 2000s, she and her colleague, Dr. Tony Rupar, received funding from the PSI Foundation to lay the groundwork for a newborn and early childhood screening program in the Amish and Mennonite communities that would test for four treatable genetic disorders. In addition to helping identify children who could benefit from early treatment, the newborn screening program also helped Dr. Siu and other researchers examine the genetic conditions that affect this community.

“In a way, that grant was really seed funding for many other new discoveries,” she says. “The community, the public health nurses and midwives, started letting us know about other children with medical conditions, which enabled us to identify several new genes that caused some of these disorders in the community.”

More than 15 years after her first PSI grant, Dr. Siu received another PSI grant to examine a potential treatment for one such genetic disorder ­– HARS syndrome.

HARS syndrome is an extremely rare autosomal recessive genetic disorder, but it is much more common in the Amish community in southwestern Ontario where approximately one in five individuals in in the Amish community is a carrier of the gene and approximately one in 100 babies in the community are affected.

The HARS gene codes for an enzyme that links histidine to transfer RNA (tRNA), a process essential for protein translation. When this gene is mutated, the enzyme’s function is altered.

Affected children are often somewhat smaller than unaffected children, but are otherwise healthy and develop appropriately; however, when the child is infected with even common childhood viruses such as influenza or RSV, they often need hospitalization and can develop acute respiratory distress syndrome (ARDS). Following infection, their balance becomes unsteady, and their hearing and vision deteriorates. Historically, the mortality rate for affected children has been quite high due to ARDS. Children who do survive often need cochlear implants for their hearing and continue to lose their vision.

Children in histidine study stayed healthy through COVID-19 pandemic

With PSI funding, Dr. Siu and her research team examined 14 children with HARS ranging from one to 17 years old who were given a daily histidine supplement to determine whether it could be used to keep these children healthy and prevent further hearing and vision loss. Histidine is a relatively inexpensive supplement, costing around $100 a month for the oldest participants and much less for the younger children taking a lower dose.

Over the three-year study, the researchers monitored the children’s growth and overall health and periodically assessed the children’s vision and hearing.

The research team found that none of the children experienced any significant deterioration in their vision or hearing over the course of the study. And, importantly, the children also maintained overall good health during the study period, which took place during the COVID-19 pandemic.

The children were not vaccinated against COVID-19 and researchers found antibody levels in the blood indicating that they had been infected with SARS-CoV-2, yet none of the children were hospitalized.

“We saw that the children stayed healthy through this study period, and that was quite incredible to us because it was during the pandemic,” says Dr. Siu. “When these children had influenza, rhinovirus, RSV or any of those common viral illnesses, they have historically been hospitalized in the intensive care unit and needed to be ventilated, and some of them have died. We felt that for these children to stay healthy through COVID was really quite remarkable.”

With the study apparently showing the benefit of histidine supplementation in these children, management of HARS syndrome has already changed. The children are continuing to receive daily histidine supplementation and, when they are hospitalized with illness, they receive extra histidine and anti-inflammatory drugs and reduced fluids, all of which seem to reduce the risk of ARDS.

“Most clinical trials have big sponsors, and there’s really no place for a small trial like this. We also had additional costs for transportation and medical appointments because of the nature of working with this community,” says Dr. Siu. “The funding from PSI was very important and much appreciated as it  allowed us to do work that will make a difference for these children.”