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There are wide discrepancies in the instructions for how deep the nasopharyngeal swabs used to test for COVID-19 are to be inserted up Canadian noses, new research from Western University and Lawson Health Research Institute has found.  

As an otolaryngologist Dr. Leigh Sowerby is an expert in the anatomy of the head, neck and inside of the nose. Using that expertise, he and his colleagues examined the COVID-19 testing instructions provided by provincial and territorial authorities and found wide variations. They reported their findings in the Journal of Otolaryngology – Head & Neck Surgery. 

“As a surgeon who works inside the nose all the time, I was surprised to find that most of the instructions in Canada aren’t effective to reach the nasopharynx; they just don’t go deep enough into the nasal cavity,” said Sowerby, an associate professor at Western’s Schulich School of Medicine & Dentistry and Scientist at Lawson Health Research Institute.

To perform a nasopharyngeal test, the swab must be inserted far enough into the nasal cavity to reach the nasopharynx, the upper part of the pharynx at the top of the throat behind the nose. Samples from the nasopharynx have been shown to be the most sensitive for COVID-19 testing, and are considered the gold standard. 

 

 

However, less than a quarter of provincial and territorial public health instructions tell practitioners to insert the swab deep enough to reach the nasopharynx, Sowerby said.

The research found that six provinces and territories, including the Northwest Territories, Nunavut, Ontario, Saskatchewan, Prince Edward Island and Alberta, recommended that the swab be inserted to a depth of four centimetres, or half the distance from nostril to ear. This depth only reaches the mid-nasal cavity, not the nasopharynx, he said. 

British Columbia and Manitoba recommended a seven-centimetre depth of insertion, which is still not enough -- only reaching the posterior nasal cavity but not the nasopharynx.

In Nova Scotia and Newfoundland, the recommended depth of insertion was two-thirds of the distance from nostril to ear, which would effectively reach the nasopharynx, as would following the instructions in New Brunswick and Yukon to insert the swab from nostril to external ear canal.

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“If we are doing what we are calling a nasopharyngeal swab, the technique for that should be standardized; there is no reason why there should be so much variability,” Sowerby said.  “The take-home message is that if we want the most accurate test results, there is room for improvement in the test instructions. Otolaryngologists have a role to play, as we can provide a great service by actively engaging with our local and regional health authorities to train on proper technique and anatomical knowledge.”

A Canadian consortium, which includes Lawson Health Research Institute (Lawson), TRIUMF, BC Cancer and Centre for Probe Development and Commercialization, is the first in the world to receive regulatory approval to produce the world’s most commonly used medical isotope, technetium-99m (Tc-99m), using small particle accelerators known as cyclotrons. 

Tc-99m is used in tens of millions of nuclear medicine procedures globally each year. These include cancer scans, cardiac tests, as well as several other diagnostic procedures. As the world moves away from uranium-based nuclear reactors, there has been growing concern in the medical community of a global shortage of these life-saving compounds. This development helps secure a domestic supply of Tc-99m for Canadian patients.

For over a decade, Dr. Michael Kovacs, Director, Lawson Cyclotron & PET Radiochemistry Facility, and Steven Foster, Business Manager, Lawson Imaging, have been working on research that has contributed significantly to this major development. They have demonstrated the successful production of Tc-99m on a standard hospital-based cyclotron at Lawson, confirming that this technology can be used by almost half of the world’s already installed cyclotrons. Clinical trials were conducted across Canada and locally at St. Joseph’s Health Care London.

“In 2011, we received federal funding to see if we could develop a technology to produce Tc-99m in hospital cyclotrons,” explains Dr. Kovacs. “Canada’s Chalk River nuclear reactor was one of the world’s largest suppliers, and it was set to close in 2016. Cyclotron facilities offer a greener, safer, more sustainable approach for producing critical medical isotopes. Our goal was to find an alternative to the traditional means of producing this isotope, and we have been successful.”

Nuclear medicine is a functional imaging technique, meaning that it images biological function. Medical isotopes are converted to radiopharmaceuticals which get injected into the patient during a procedure. According to the specific biological properties of the isotope, they move throughout the body, rendering a 3D map of where the isotope has gone. This gives researchers and medical professionals valuable information of how various physiological processes are performing.

“Canada is a global leader in nuclear imaging technology. With the help of our collaborators across the country, we have home-grown technology to produce commercial quantities of Tc-99m on common cyclotrons,” adds Mr. Foster.  “This technology has been patented and licensed to ARTMS Inc., a spin-off from the consortium, and is now being commercialized and sold throughout the world.”

The process was approved by Health Canada in November, 2020, and is expected to be deployed in British Columbia by 2022. 

An international team led by scientists from Lawson Health Research Institute and Cedars-Sinai Medical Center are the first to show that Magnetic Resonance Imaging (MRI) can be used to measure how the heart uses oxygen for both healthy patients and those with heart disease. 

Reduced blood flow to the heart muscle is the leading cause of death in the Western world. Currently, the diagnostic tests available to measure blood flow to the heart require injection of radioactive chemicals or contrast agents that change the MRI signal and detect the presence of disease. There are small but finite associated risks and it is not recommended for a variety of patients including those with poor kidney function. 

Standard methods 

More than 500,000 of these tests are performed each year in Canada. A patient suspected of coronary heart disease for example may have reasonably normal blood flow at rest but as soon as they exercise they have pain or feel out of breath. They need more oxygen delivered to the heart tissue but due to vessels being compromised that doesn’t happen. 

The standard technique is usually done in two days with the goal of seeing if the heart can increase blood flow when more oxygen is needed. The first test studies the patient at rest to see what the blood flow is like in the heart. This is a nuclear medicine imaging test that requires radioactive material to be injected and takes about an hour or more to complete.  

They next day, they come for the same test but with the introduction of a stressor. That can be physical exercise but more often they are given an injection of a chemical drug which stimulates the heart and increases blood flow. This is in addition to a second injection of the radioactive material. The heart is imaged to see the level of oxygen getting to different parts of the heart and whether there are obstructions or reduction in size of the surrounding arteries.  

A new stress test

“We wanted a non-invasive way to image the heart and replace the stress stimulus, and drastically reduce the amount of time needed for testing,” says Dr. Frank Prato, Lawson Assistant Director for Imaging. “This new method, cardiac functional MRI (cfMRI), does not require needles or chemicals being injected into the body. It eliminates the existing risks and can be used on all patients."

The team included researchers from Lawson; Cedars-Sinai Medical Center and University of California; King’s College in the United Kingdom; University Health Network and the University of Toronto; Siemens Healthineers; and, University of Edinburgh in the United Kingdom. 

“Our discovery shows that we can use MRI to study heart muscle activity,” explains Dr. Prato. “We’ve been successful in using a pre-clinical model and now we are preparing to show this can be used to accurately detect heart disease in patients.” 

To replace the stress test, this new technique uses repeat exposure to carbon dioxide to test how well the heart’s blood vessels are working to deliver oxygen to the muscle. A breathing machine changes the concentration of carbon dioxide in the blood. Levels are brought up for three minutes and then back down to normal four times. These changes should result in a change in blood flow to the heart, but does not happen when disease is present. 

The cfMRI method reliably detects whether these changes are present and is comparable to the information gathered from the current two-day technique – in much less time and without injections. Dr. Prato notes that “we don’t want to stress the heart. We want to see whether there is capacity in the heart to increase blood flow if the heart needs to work harder.” 

A brilliant discovery 

Other researchers have explored oxygenation-sensitive MRI but initial results contained a high level of ‘noise’ with blurry images. Project leader and partner Dr. Rohan Dharmakumar, Associate Director of the Biomedical Imaging Research Institute at Cedars-Sinai Medical Center, believed that the noise was actually variation in the heart’s processing of oxygen. He engineered a way to average this variation and through testing at Lawson the team discovered that the noise is actually a new way to study how the heart works. 

“We’ve opened the door to a new era and totally novel way of doing cardiac stress testing to identify patients with ischemic heart disease” says Dr. Dharmakumar. “This approach overcomes the limitations of all the current diagnostics – there would no longer be a need for injections or physical stress testing like running on treadmills.” 

Through investigating this technique, they learned that the blurry images were showing normal physiological variability. People often think of heart rate as being stable, but in fact a heart that is unable to keep up with stressors indicates that disease is developing. In a healthy heart, the oxygen distribution to the tissue needs to vary. 

“It’s a very exciting time. We had to bring all the technologies together to be able to image these kinds of changes in blood flow moment to moment,” says Dr. Prato. 
He adds that “using MRI will not only be safer than present methods, but also provide more detailed information and much earlier on in the disease process.” Following initial testing through clinical trials, he sees this being used with patients clinically within a few years.  

Moving forward 

In addition to studying coronary artery disease, the method could be used in other cases where heart blood flow is affected such as the effects of a heart attack or damages to the heart during cancer treatment. Due to its minimal risk, this new tool could be safely used with the same patient multiple times to better select the right treatment and find out early on if it is working. Dr. Prato notes that “with this new window into how the heart works, we have a lot to explore when it comes to the role of oxygen in health and disease.” 

The next steps of the research include a proof of principle study in London, Ontario with 20 patients. Following standard tests using the conventional technique at other sites, the participants will then come in for the experimental test to show that it produces the same result. The research would then move into a multi-centre clinical trial internationally. 

The study “Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using Magnetic Resonance Imaging” is published in Science Translational Medicine.
 

Researchers in London, Ontario have been awarded $1.345 million over five years through the second phase of the Canadian Consortium on Neurodegeneration in Aging (CCNA), announced today as part of Canada’s first national dementia strategy. CCNA is a collaborative research program tackling the challenge of dementia and other neurodegenerative illnesses. 

A Dementia Strategy for Canada: Together We Aspire focuses on preventing dementia, advancing therapies and finding a cure, as well as improving quality of life for people living with dementia and caregivers. 

Clinician researchers from across the country working together 

Dr. Manuel Montero-Odasso, Scientist at Lawson Health Research Institute, is world renowned for his findings on the relationship between cognition and mobility in the elderly, and gait as a predictor of frailty and dementia. He leads the Mobility, Exercise and Cognition (MEC) Team in London, comprised of top researchers in the areas of mobility, exercise and brain health.

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“Evidence from other countries with dementia strategies shows that coordinated, targeted efforts at the national level improves results for all aspects of dementia care and also for research,” says Dr. Montero-Odasso, also a geriatrician and Director of the Gait and Brain Lab at Parkwood Institute, a part of St. Joseph’s Health Care London. 

CCNA was purpose-built to synergize dementia research within the Canadian context. Phase I saw the creation of infrastructure fostering collaboration amongst Canadian researchers, and there are now 20 teams built around important research topics. 

“This kind of effective national collaboration by scientists and clinicians from many disciplines gives the CCNA a cutting edge in research, prevention, treatment and management of all forms of dementia,” explains Dr. Montero-ODasso. “We created a national network of researchers form west to east coast with a high level of expertise to deliver lifestyle interventions to improve cognition and slow down progression to dementia. I feel privileged working with such excellent investigators and leading this important endeavour locally.” 

Preventing dementia through lifestyle changes

The MEC team has several projects in the works, but the majority of the new funding is to complete the SYNERGIC Trial, SYNchronizing Exercises and Remedies on Gait and Cognition. 

This first-in-the-world clinical study is testing a triple intervention aimed at treating Mild Cognitive Impairment (MCI) and delaying the onset of dementia. The SYNERGIC Trial incorporates physical exercises and cognitive training, along with vitamin D supplementation to determine the best treatment for improving mobility and cognition. 

“We are looking at how interventions will work together and targeting cognitive decline at its earliest stage – individuals with MIC,” explains Dr. Montero-Odasso. “Both physical and cognitive exercises have shown promising effects for maintaining cognition, while vitamin D deficiency is associated with cognitive decline.” 

A professor at Western University’s Schulich Medicine & Dentistry, Dr. Montero-Odasso partners with researchers from across the city including Dr. Rob Bartha, imaging scientist at Schulich Medicine & Dentistry and Robarts Research Institute at Western University, and Dr. Kevin Schoemaker who leads the Laboratory for Brain and Heart Health. 

Study participants in the SYNERGIC Trial are asked to complete an individualized and progressive routine of exercises and cognitive training three times a week for six months, with one final assessment at 12 months. The main site for the study is Parkwood Institute with the physical exercises taking place at the Labatt Health Sciences Building on the Western campus.

To date, 138 research patients has been recruited across multiple sites in Canada. 

One participant’s experience 

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One day, Peter Saracino saw an advertisement about a research study. They were looking for participants who were a minimum age of 60 and had minor cognitive impairment. He felt he fit the bill and he was interested in this kind of research. 

“I have family members who suffered from forms of dementia and Parkinson’s Disease. I really understand how hard it hits and I liked that this study was about prevention,” explains Peter. 

Going into it, Peter thought he was in pretty good shape. He has two dogs and walks them regularly. “But by going to the gym and doing the exercises and faster-paced walking, I realized that I wasn’t in as good shape as I thought. My diet was under control but I was still taking blood pressure medication. I didn’t have much energy.” 

After 10 weeks in the study, he feels better than he has for over a decade. “I can garden for longer. I took two notches off my belt. I no longer take my blood pressure medication. I actually feel younger.”

He remembered that last year he slipped and fell four times, which was very unusual for him. Part of his cognitive impairment is that he had trouble with balance, and that has improved for him as well. 

Peter feels that “this is exactly the kind of research that the government should be investing in – an ounce of prevention is worth a pound of cure. This kind of research leads to keeping people independent and healthier as they get older. People are happier. They feel like doing more. There is no downside to improving someone’s health through lifestyle changes, and in fact it is cost effective and helps ease the burden on the health care system.” 

Looking forward 

“Our preliminary analysis from SYNERGIC is giving us a strong indication that a multimodal approach, combining physical exercise, cognitive training and supplementation, has a synergistic effect. It seems the whole is greater than the sum of its parts,” says Dr. Montero-Odasso. 

A major goal for the work of the MEC team in London is to translate their research findings into clinical guidelines that can be used at the front line of care. “Practitioners understand the overall importance of exercise and cognitive vitality, but we are missing more specific guidelines on what kind and how much will work for different patients. Basically, what is an effective lifestyle prescription.”

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Dr. Montero-Odasso adds that “as our population ages, a comprehensive strategy is vital to ensure the growing number of those living with dementia receive the care and support they deserve. Over half a million Canadians are currently living with dementia. By 2031, this number is expected to nearly double.” More than one third of dementia cases might be preventable. 

CCNA Phase II

In CCNA’s Phase II, researchers are working on analyzing the overall health of every patient in a large clinical cohort study, COMPASS-ND. This information will be used to enhance understanding of how changes in the brain affect dementia severity and ways to reduce and prevent this through lifestyle changes. Lawson is the leading recruitment site for COMPASS-ND and the London team will be instrumental in the larger lifestyle interventions moving forward. 

CCNA is funded by the Government of Canada, Canadian Institutes of Health Research (CIHR) and other funding partners. CIHR is providing $31.6 million, and partners—including provincial agencies and non-profit organizations—are providing an additional $14.4 million for a total investment of $46 million over five years. The research on dementia prevention, diagnosis, treatment and care as part of Phase II of the CCNA will support the national strategy.

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• Researchers testing triple intervention to combat dementia 
• Lawson and Western researchers suggest walking and talking can be an early predictor of dementia 
• How changes in the brain affect walking while talking in older adults