Researchers Under the Scope

Patients in intensive care units often move to a regular ward before they're discharged, and sent home.

But increasingly, hospitals are skipping that step, sending a handful of ICU patients directly home.

"We were really looking at analyzing the data of safety in terms of discharging patients home safely in terms of outcomes such as mortality, or a re-admission to hospital," said Ryan Donnelly, who's currently finishing his first year of residency in Regina.

He said for young patients without serious co-morbidities, direct discharges to home are an option.

"If you have a patient who's in the ICU who has been waiting for a ward bed and ends up getting well enough to go home, it kind of started that way," he said.

"The data analyzing it came after the practice started happening already."

Under the supervision of Dr. Eric Sy and Dr. Vincent Lau, Donnelly teamed up with Sehar Parvez, who's now in her fourth year of medical school at the University of Saskatchewan's Regina campus.

Their work was first published in September 2021 in the Canadian Journal of Anesthesia, with a subsequent article published in January 2023's journal of Critical Care Medicine.

Although the Covid-19 pandemic limited any direct interviews with patients, Donnelly and Parvez started by combing through more than 8,000 papers that mentioned direct to home discharges.

"The evidence that we've gathered from my meta-analysis is that it can be safe," said Donnelly. "It's something that is going to be happening more and more."

Their next step was to put together a questionnaire, and sending it to healthcare providers across the country. They received more than 350 responses.

"About a third of healthcare providers didn't know that there is an increase in the direct discharge home from the ICU," said Parvez. "I thought that was very interesting."

She and Donnelly found critical care providers were more likely to feel comfortable discharging an intensive care patient directly home, especially compared to healthcare workers who weren't as familiar with the practice.

Parvez went on to analyze outcomes for 120 patients who were in the hospital between February 2020 and May 2021.

Each one was discharged directly home after spending time in the critical care unit.

"We found that 32% of our direct discharges to home at that time were from substance overdose," said Parvez.

She and Donnelly studied the outcomes for patients, watching whether they had to be re-admitted to hospital within 30 days to a year.

Parvez said the practice is safest when a patient has health care support workers checking in with them, documenting and communiating changes immediately to their family doctor.

In this episode, both Donnelly and Parvez share what it was like to be a medical school student during a global pandemic, as they learned to do research under the supervision of veteran clinicians at the Regina General Hospital.

"We had to learn very quickly though how to do research in a virtual environment," said Parvez. "We didn't know how to use Zoom right away. We didn't know how to share a screen right away,

She now is looking at internal medicine as a potential career path.

"It informed my desire to want to work on being a mentor, being an educator, and continuing to practice evidence-based medicine," said Donnelly, a family medicine resident.

"It was certainly rewarding."

For decades, families have watched Alzheimer's disease steal their loved ones' cognitive function. It's the most common form of dementia; one that affects a third of people over the age of 85.

It's a disease Dr. Ron Geyer and Dr. Andrew Kirk want to tackle.

Right now, most pharmaceuticals target the symptoms of Alzheimer's disease, without addressing its root cause. Most lose their effectiveness after three months.

Geyer, a biochemist and professor of pathology at the University of Saskatchewan's College of Medicine, said a novel protein could change that.

"They did a first clinical trial with this drug and they showed pretty exceptional efficacy," said Geyer.

NeuroEPO, first developed by researchers at the Center for Molecular Immunology in Cuba, stimulates red blood cells in the brain. It's a recombinant form of the naturally produced erythropoietin protein (EPO), which stops neuron cells from dying, promoting their growth and communication mechanisms.

During its first round of human trials in early-stage Alzheimer's disease patients, 82 per cent of those receiving the treatment saw stabilization in their cognitive function. For more than half receiving the drug, cognitive function improved.

Alzheimer's disease progressed and worsened for almost everyone receiving the placebo.

"We decided to move this forward and do a Phase Two trial in Canada," Geyer said.

Once the study is approved by Health Canada, trials will involve between 80 and 100 patients. Geyer said so far, everything is on track to begin testing NeuroEPO this summer.

The trick, he said, is delivering the drug directly to the brain.

"It breaks down in the blood quicker than normal EPO, so that's good in that it doesn't cause side effects," Geyer said.

He said his research group has teamed up with Rocket Science Health Inc., a company that's developed a way to deliver NeuroEPO through the nose to the brain.

Compared to a Covid-19 nasal swab, Geyer said the delivery mechanism for this drug is 'much more comfortable'.

Working with the Sylvia Fedoruk Canadian Centre for Nuclear Innovation, Geyer said his team is also expanding PET scans and neurological diagnostic tools for patients taking part in the study.

"We're hoping that with that, with those diagnostic assays, including MRI to measure the total brain volume, that the clinicians can use this information immediately as the trial starts to better diagnose their Alzheimer's patients, provide more clarity on the diagnosis, let them develop a treatment plan earlier."

Geyer said patients and doctors in Saskatchewan have already contacted his team, trying to sign up.

"We want to make it as broadly available as possible," he said.

Still, NeuroEPO will not be widely available, until a third-phase trial in the future which proves the drug's efficacy, shows no adverse effects, and involves at least 300-500 patients with Alzheimer's disease.

Geyer said his team is up to the challenge.

"It's almost impossible to find someone who doesn't know someone who has some form of dementia," said Geyer. "The ultimate goal is to keep people out of the hospital."

Debra Morgan grew up on a farm and continued farming with her husband, initially working in nursing in the winter.

Nursing shifts took her from neurosurgery to pediatrics, to orthopedics, then to Saskatoon's geriatric units at City Hospital and Royal University Hospital.

"I just found that I really enjoyed working with older people," Morgan said.

She soon followed her passion for research, opting to study geriatric care as she earned her masters' and doctoral degrees in nursing.

Today, she's a professor and chair of rural health delivery at the Canadian Centre for Rural and Agricultural Health. Morgan also serves as the director of the University of Saskatchewan's specialist Rural and Remote Memory Clinic launched in 2004 as a research demonstration project and now funded by the Ministry of Health. She built and leads Saskatchewan's Rural Dementia Action Program (RaDAR).

"Twenty years ago when we started this, there was very little rural dementia research," said Morgan. "We didn't know if the best practices in the literature would work in rural settings, or how."

Early on, RaDAR team specialists observed a disproportionate number of rural patients referred to the specialist Rural and Remote Memory Clinic were for less complex diagnoses, where a specialist referral is not typically indicated.

Morgan wanted to know why those patients couldn't get care closer to home.

"Alzheimer's disease, which is the most common type of dementia, should usually be diagnosed by primary care providers in their community," she said.

Often, she found family doctors and nurse practitioners did not feel comfortable making a dementia diagnosis.

After a provincial consultation, Morgan realized rural and remote nurse practitioners and family doctors would benefit from working in an interdisciplinary team and from a standardized assessment tool, one connected to the patient's provincial health record.

"Rural primary care providers see so many different conditions in a day, they are generalists," said Morgan. "They don't see the number of people with dementia as they would someone with diabetes or heart disease, for example."

Starting from scratch, Morgan and her team put together a one-day interdisciplinary rural memory clinic for patients in the Sun Country Health Region, using the town of Kipling, Sask. as its initial base.

During periodic memory clinics in Kipling, she'd bring together patients and their families with nurse practitioners, occupational therapists, physical therapists, home care nurses, social workers and family doctors, along with a First Link coordinator from the Alzheimer Society.

That team would assesss one dementia patient in the morning, and another in the afternoon.

Morgan has been documenting their progress each step of the way and spreading the memory clinic model to other rural communities. Six rural primary healthcare teams are now delivering these clinics and more are planned.

"Our research, we try to involve the people who will be delivering or using the services in their rural communities, as they know best what is needed to improve the quality of life of people living with dementia and their families," she said.

"Families tell us they really value having that clinic close to home, with healthcare providers that they know," Morgan said.

"It reduces that feeling of just being very isolated and alone.

In this episode, hear why Covid-19 stalled expansion plans for more than a year, and next steps for expanding the services delivered by both the specialist Rural and Remote Memory Clinic at the University of Saskatchewan, and the rural primary healthcare memory clinics.

If you've ever sat through a bad date at a restaurant, unsure of what to order, you're still doing better than a typical zebrafish date.

Dr. Michelle Collins said without safety precautions, a zebrafish male and female left together overnight often eat their embryos.

The assistant professor of Anatomy, Physiology and Pharmacology at the University of Saskatchewan's College of Medicine has studied zebrafish for years, using them as a model to examine genetic factors in cardiac development.

"They're actually quite beautiful," she said. "The embryos look almost like a crystal ball."

In this episode, Collins takes us inside her laboratory, where she breeds both typical and genetically modified zebrafish, to better understand irregularities inside the human heart.

"We start to see some early changes in the developing heart that just get worse as the fish ages," she said.

"You start to see that the heart chambers aren't really contracting properly, they're very arrhythmic," said Collins. "They really model what a person that has something like atrial fibrilation would be experiencing later on in life."

In December, Collins published her most recent findings in the Journal of Cardiovascular Development and Disease, noting the public health implications for humans with similar patterns of abnormal heart development.

Her interest in calcium stores, and the way they're regulated in ion channels led her to Discovery Grants last year of nearly $200,000 from the Natural Sciences and Engineering Council of Canada (NSERC).

Collins' first microscope was a Christmas gift. By the fourth grade, she was running experiments at home, thanks to a book from her grandparents

"I had some really great science teachers that really helped propel me into scientific research," said Collins, who became curious about developmental biology.

Today, she works with real-time video feeds, using a high-powered microscope that allows her and her team members to observe zebrafish hearts at up to 150 frames per second, producing detailed video images of the vascular system in fluorescent colour.

"It's very gentle on live samples, which is really instrumental to what we do because we want to look at a beating heart. We don't want to blast it with lasers," said Collins.

"We have this sort of a spinning disc, which allows less phototoxicity from the laser, and it also can acquire movies really quickly," she added.

Her hope is to one day match mutations in the zebrafish genes with mutations in patients with genetic heart defects.

"Can we use these new genes that we've identified to screen patients and figure out if this could be an underlying cause of their cardiac arrhythmia?"

Diagnosing pulmonary diseases ilike asthma in young children is still largely a matter of trial and error, according to Saskatchewan's top pediatric respirologist.

As viruses and colds tear through schools and daycares across North America, Dr. Darryl Adamko wants to change that.

"If you have asthma this year and you're not taking your inhaled steroids, well you're rolling the dice," said Adamko, who's watched an influx of young patients over the past few months at the Jim Pattison Children's Hospital in Saskatoon.

In children, problems with breathing are the leading cause of hospitalizations.

Undiagnosed asthma and other pulmonary conditions in children mean small patients have a a much tougher fight when they're infected by Covid-19, RSV or influenza.

"You have to be taking those preventative drugs first before the virus finds you," said Adamko.

That's why he's pinning down biomarkers for pulmonary disease in a familiar tool for family doctors: urine samples.

"We still really don't have a great test for like preschool kids. It's just history for the most part," he said.

Using mass spectrometry and nuclear magnetic resonance imaging, he and his team have spent more than a decade analyzing urine samples and refining their methodology.

"Now that we've got enough urine samples analyzed that, I think we've got a good signal," said Adamko.

His research today is aimed at creating a urine test that would give giving family doctors and paediatricians a faster, more efficient way to diagnose pulmonary conditions long before kids arrive at the hospital.

In this episode, he explains why a resurgence of RSV after years of Covid restrictions has hit young patients hard.

"It's really bad for little babies. It loves the smallest little airways," Adamko said. "This year the problem is we've got a bunch of two-year-olds, and one-year-olds who have never seen these viruses."

May this holiday season find all our Researchers Under the Scope listeners feeling cozy, festive and warm.

In the spirit of giving, the Office of the Vice-Dean of Research at the College of Medicine has once again teamed up, to make a donation to students and staff at King George Elementary School in Saskatoon. This is where you can scroll down and find the details you need to make an e-transfer donation.

And in the New Year, we resolve to bring you an episode for parents of young children. With Influenza A, RSV, and Covid-19 ripping through schools, daycares and workplaces, we have a preview from our next episode wth Dr. Darryl Adamko. He's Saskatchewan's top pediatric researcher, and a pediatric respirologist at the Jim Pattison Children's Hospital in Saskatoon. Adamko is working on a prototype that would allow family doctors to screen young children for asthma and other pulmonary diseases far more quickly and accurately.

Thanks again for sharing your ears with us! We wish you a Merry Christmas and a happy New Year, and we'll meet up here again in 2023.

When Scott Widenmaier left high school, he wasn't sure what career path he wanted to pursue.

He grew up in Alameda, Saskatchewan, and soon found work on oil rigs. But by the time he was in his early twenties, he knew it was time for a change.

"I realized that winters are just too cold to continue doing that," said Widenmaier. "I wasn't sure what I was going to do with my life, but I was interested in biology and human physiology."

In his third year as a science major at the University of Regina, he became fascinated by a lab experiment examining how neurotransmitters control heart rates. He then moved west, to graduate studies at the University of British Columbia, studying endocrinology and its role in diabetes.

"I really like the elegance of the feedback circuits," said Widenmaier, who went on to land a post-doctoral position with Dr. Gökhan Hotamisligil at Harvard University's School of Public Health.

As he discovered the emerging field of immunometabolism, Widenmaier began to see links between the way the gut and the human immune system talk to each other, especially around obesity.

"That communication to the immune systems and the metabolic systems is dysfunctional and contributes to a lot of the diseases that we see linked to obesity," said Widenmaier, who studies the way the body manages cholesterol.

That's the focus of his work at the University of Saskatchewan as an assistant professor in the College of Medicine's department of Anatomy, Physiology and Pharmacology.

"There's this transcription factor that sits in a part of the cell and it recognizes when cholesterol's too high," he said. "It changes where it goes in the cell and it regulates a response by the cell to try to prevent the cholesterol from causing damage and stress."

Widenmaier has now landed a number of awards, including the Heart and Stroke Foundation's National New Investigator Award in 2020/21. Widenmaier was also named that year's McDonald Scholar.

"We've made a lot of progress with understanding the role of NRF1 and NRF2 in the liver," he said. "We've identified some molecules that may be important for protecting cells from too much cholesterol."

In this episode, hear how this work has implications for patients with heart and stroke disease, obesity, liver disease, degenerative brain conditions, as well as various forms of cancer.

"The issue with cholesterol is that we absolutely need it, but we also need it to be exactly the right amount," said Widenmaier. "There's lots of times where that that capacity gets stretched, especially under conditions of obesity."

"What are those natural adaptive systems? If we can find out what they are, can we make them work better?"

As a high school student growing up in Melfort, Sask.. Linda Chelico (PhD) knew she wanted to work in health sciences.

She enjoyed biology class, and took an interest in watching nature heal itself. She wanted to find environmentally friendly solutions to health problems.

Then, she read a National Geographic magazine about landfills filling up.

Chelico began thinking about the environmental footprint of garbage, and about the organisms that could help break down piles of refuse. The idea turned into her Grade 11 science project, where she showed ways micro-organisms could degrade some of the waste people produce.

"That's when I decided I wanted to be a microbiologist," said Chelico. Watching evolving life forms had her hooked.

She moved a two-hour drive west to Saskatoon, and enrolled as a microbiology student at the University of Saskatchewan. Within a year, she switched to an honours degree through the College of Agriculture's Applied Microbiology program. She earned her PhD in Saskatoon studying insecticidal fungal strains, with varied results.

"You could kill the insects without putting chemicals in the environment," said Chelico.

As she tested the fungus on arid prairie fields, the effects of its prolonged exposure to sunlight and irradiation intrigued her.

"Some of these fungal spores would survive a lot of UV damage," she said. "It would dry out, it would acquire mutations. And I was trying to formulate it with sunscreens and then in the lab irradiate it with UV radiation, like if you're going to a tanning bed."

Although mutations were generally seen as negative for cell health in her course work, Chelico realized they deserved a closer look.

"There's extreme stress on the organisms. They've acquired a lot of DNA damage from this UV irradiation," she said. "So how do they survive?"

In this episode, we hear how Chelico's interest in damaged, mutant cells morphed into a scientific Hollywood story, after she met Myron F. Goodman, at the University of Southern California's Los Angeles laboratories.

Chelico spent five years of post-doctoral work studying microcellular activity and biological responses to stress in Goodman's lab.

"Everything was unified by the benefit of mutations," she said.

By 2009, Chelico put Hollywood Boulevard in the rear-view mirror, returning to Saskatoon to accept a faculty position at the University of Saskatchewan's College of Medicine. Working as a virologist, microbiologist and biochemist, Chelico and her teams have landed more than $1.6 million dollars in three years, with continuing grants from the Canadian Institutes of Health Information.

Her laboratory is focused on what key enzyme mutations in viruses mean, particularly for patients with HIV-AIDS, other viruses, and cancer.

"In humans, when these mutations happen, usually we see it come out as a cancer," said Chelico. "It doesn't exist in all of our cells. It exists in the type of [immune] cells that react to environmental stress."

Colour-changing reactions and small explosions punctuated life at Dr. Oleg Dmitriev's home, when he was a boy. He loved trying out chemical reactions, and experimenting. As a teenager, he was fascinated by the science fiction novels his father brought home.

"It's all about strange worlds and unusual, strange forms of life," said Dmitriev, a protein biochemist. "I started wondering, why is the life on our planet is the way it is? And what is the chemistry of life?"

After earning his PhD at Moscow State University, Dmitriev went on to post-doctoral studies at the University of Osnabrück, followed by years of bench research at the University of Wisconsin. That's where he discovered the potential of nuclear magnetic resonance spectroscopy-- something he uses today to piece together the way copper moves through human cells.

"It still fascinates me," said Dmitriev, who moved to the University of Saskatchewan in 2005 to open his own laboratory. "It's a very, very important technical component of my research."

Today, as a professor of Biochemistry, Microbiology and Immunology at the U of S College of Medicine, Dmitriev has honed in on ATP7B, the protein that transports and regulates copper in human tissuess.

"Copper is a very important bioelement that is needed for supplying our cells with energy, but at the same time it also has a dark side," Dmitriev said. "If it escapes, it can start a cascade of damaging runaway reactions."

The Canadian Liver Foundation estimates one in 30,000 Canadians inherit a defective version of the protein, causing Wilson Disease. Without treatment, they suffer liver damage and a host of neurological symptoms from an over-accumulation of copper.

"There are many entry points for copper," said Dmitriev. "Where does it go from the point where it enters the protein? How does it go across the cell membrane? How is that activity regulated?"

Together with Dr. Scott O'Leary, a cell biologist, Dmitriev was successful in securing a $761,176 grant from the Canadian Institutes of Health Research in 2021 to explore those questions. He said understanding the 'cogs and wheels' of copper transport in the body may also help clarify the way other metals, such as platinum, move through human tissue.

Platinum compounds are frequently used in chemotherapy treatments for breast, colon, lung, and ovarian cancer.

"They're quite effective, but they're incredibly toxic," said Dmitriev. "They have a lot of really serious side effects."

Because platinum uses the same transportation mechanisms as copper, Dmitriev wants to know how to make its journey through the body less harmful.

"Can we manipulate those transfer pathways to make sure that platinum chemotherapy drugs get to their target, but do not go astray and poison the patient?" he said.

Looking back, Dmitriev said he's glad he landed at the University of Saskatchewan, as it gave him the chance to explore the areas he feels most passionate about.

"I would do it all over," he said. "Science is fun. Science is exciting. It's a good life."

Asmahan AbuArish grew up in Hebron, surrounded by military checkpoints.

She knew she wanted to help people, but she had to give up her dream of being a medical doctor early.

Fortunately, AbuArish is no quitter.

She discovered physics — and later its very real applications in curing inflammatory pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

Last year, Dr. AbuArish arrived at the University of Saskatchewan to open her own lab, landing $175,000 through the Canada Foundation for Innovation's John Evans Leaders Fund.

Today, Dr. Asmahan AbuArish is an assistant professor of anatomy, physiology and pharmacology at the U of S College of Medicine. She is a quantitative molecular biophysicist.

AbuArish admits she avoided biology and classes involving memorization during her studies, thinking she'd pursue a career as a teacher. But she kept asking questions during physics labs and eventually had to reconstruct two-dimensional images of the data she'd collected.

"This is when I thought, this is my data coming alive and I'm looking at it in 3D," AbuArish said.

"This was fascinating. This is when I realized I'm doing something nobody has done before."

From that moment, AbuArish said she was hooked.

In this episode, she explains why patterns, data modeling and fruit fly models, combined with a super-resolution scanning confocal microscope, will enable her to perform advanced biophysics analyses. Detailed imaging and fluorescent molecular tagging allow AbuArish and her team to figure out which pulmonary medications will — and won't work.

It's work that has immediate implications for patients with CF and COPD.

"I'm interested in understanding how does the healthy complete form of the molecule function, and then how does it function? How does the mutant function? How do they behave? What is the difference in their behaviors?"