Osteoporosis is often referred to as the “silent thief”. The disease is caused by low bone mineral density (BMD) and can occur over a number of years without any symptoms. It is often diagnosed when the first fracture occurs and the disease is already fairly advanced and less treatable. At least one in three women and one in five men will break a bone due to osteoporosis in their lifetime.

Artificial intelligence screening tool, Rho, was developed by 16 Bit inc., a Toronto-based medical device company founded by Canadian radiologists Dr. Mark Cicero and Dr. Alexander Bilbily, radiologist and affiliate scientist at Sunnybrook Health Sciences Centre. The company’s mission is to create trusted AI-based medical software to improve the quality and accessibility of health care for all. Rho automatically screens patient x-ray scans for low BMD and alerts physicians of increased risk of osteoporosis which allows patients and physicians to work together to create preventative treatment plans.

We recently sat down with Dr. Bilbily to chat about how Rho is shaping the future of health care.

What inspired you to become an inventor and create Rho?

I enjoy my clinical work, but its impact scales linearly – I can only help one patient at a time. What excites me about software is it can scale exponentially, creating value even while I’m asleep, camping in the backcountry, or chasing after my toddler.

We created Rho because our health-care system urgently needs smarter, more sustainable solutions. With an aging population, rising costs, and limited resources, we have to find ways to improve care while reducing expenses. Rho identifies patients at high risk for osteoporosis using x-rays they’ve already had without extra imaging or added cost. This enables much earlier intervention which prevents devastating fractures for patients and reduces cost to the health-care system. We have successfully built and deployed the first tool of this kind which has already impacted the lives of over 300,000 Canadians.

What skills or traits have helped you the most in your journey as an inventor and entrepreneur?

Curiosity, the ability to learn quickly, and empathy have all been essential. As a physician, transitioning into entrepreneurship meant learning an entirely new language – product development, branding, market strategy and, regulatory affairs. My curiosity pushed me to dive in, and years of medical training helped me to quickly learn and adapt.

Empathy has been a key strength because it has helped me build a strong partnership with my co-founder, recruit a mission-driven team, and deeply understand the needs of our customers and patients.

What advice would you give to someone interested in launching a health-care company to commercialize their discoveries?

Start with something you think the world needs – something you’re willing to spend 10 years of your life building. Healthtech is hard. It comes with all the usual start-up challenges, plus regulatory, clinical validation, and compliance hurdles that increase cost, risk, and time. If your motivation is just financial, it’s hard to weather the storm. But if you’re mission-driven, that purpose will sustain you and attract others who share your vision like key teammates, advisors, and early customers.

How has Sunnybrook and INOVAIT enabled you to make your technology a reality?

INOVAIT, [Canada’s image-guided therapy and AI network led by Sunnybrook], has been essential at every step of Rho’s journey. Through the Pilot Fund in 2022, they helped support our AI model development, early user testing, and Health Canada approval. That funding and visibility gave us a critical boost to land our first customers. More recently, the FOCUS Fund has supported our commercialization efforts which included helping us expand Rho’s capabilities, build evidence through publications, and grow into international markets.

Sunnybrook has also played a pivotal role – from running Rho’s first prospective clinical trial with CAN Health Network, to supporting bold new research in my lab. That includes exploring next-generation AI use cases in medicine – some of which are admittedly a bit out there, but might just shape the future.

The post Sunnybrook Inventors: Dr. Alexander Bilbily appeared first on Your Health Matters.

That’s what some Sunnybrook scientists are questioning, and now investigating in a clinical research study to enhance bone fracture repair.

The “magic pill” in this case is a daily medication already scientifically tested and well established in clinical use known as lithium carbonate.

With timed administration at very low doses, lithium carbonate has been shown to enhance bone repair, and now, orthopaedic clinical researchers are testing it in injured patients with fractures.

The Sunnybrook-led study – Lithium for Fracture Treatment (LiFT) – is a randomized controlled multi-centre clinical trial investigating if lithium can improve long bone fracture healing in healthy patients from 18 to 55 years of age, who have a shaft fracture of the femur, tibia/fibula, humerus or clavicle. Participants take the medication for just two weeks starting 14 days after the fracture or surgery.

“Fracture healing in adults typically takes several weeks to months to heal – and in up to 10 per cent of cases, it can fail to heal completely despite appropriate treatment,” says Dr. Diane Nam, an associate scientist with the Holland Bone and Joint Research Program and orthopaedic trauma surgeon at Sunnybrook.

Dr. Diane Nam, Principal Investigator on the LiFT trial.

“Sustaining a fracture significantly impacts an individual’s function, such as the ability to work, drive or physically parent young children. We’re talking not only about the long time to heal bones, but don’t forget the pain and negative impact on a patient’s quality of life and mental health. If we can show that this safe and inexpensive ($1/a day) therapy works, it can potentially have a huge impact to globally change how we manage fractures.”

Dr. Nam was involved in the scientific research from “lab bench to patient bedside”. She led the team as its principal investigator in conducting the pre-clinical work and in translating the research through to the current clinical trial.

The first few patients in the initial pilot clinical trial showed a reduction in pain with the use of lithium, with no impact on mental activity or mood. In order to keep the highest standards for clinical research, the current study is blinded, meaning that patients and the research team who will analyze the data do not know who is receiving the actual drug or a placebo pill in order to control for potential bias. 120 patients have been enrolled in the study to date.

The trial has sites at Sunnybrook, St. Michael’s Hospital, McMaster University Medical Centre, Ottawa Hospital and Royal Victoria Regional Health Centre, and is supported through Sunnybrook’s Centre for Clinical Trial Support (CCTS) and the Canadian Institutes for Health Research.

A research participant from the LiFT trial comes in for one of his check-in visits at the fracture clinic and to have x-rays taken.

The research team will analyze and compare X-ray result scores assessing for bone union where three of the four outer layers at the fracture site are bridged. They will also factor in how the research participants are functioning in their day-to-day life, including accounting for pain levels.

The research is also considering potential barriers to the acceptance of lithium therapy for the purpose of fracture healing, from both the perspective of patients and care providers. Of note, the dose of lithium being used in the study is so low (300 mg or one-quarter of the dose amount used for other applications) that it’s not detectable in blood work at 12 hours after taking it.

“This important clinical trial is one of many promising investigations that have resulted from collaborations between surgeons and scientists in the Holland Bone and Joint Program,” says Dr. Cari Whyne, senior investigator involved in the trial and the Susanne and William Holland Chair in Musculoskeletal Research at Sunnybrook Research Institute and University of Toronto. “This aligns with my research focus in clinically-translational bioengineering research aimed at maximizing function among those who develop musculoskeletal disease or disability.”

For more information about participating in the LiFT trial, contact lift@sunnybrook.ca

The post Igniting Discovery: Can we speed up bone healing? appeared first on Your Health Matters.

“We’re here to support our Sunnybrook investigators in their leadership of clinical trials,” says Gail Klein, operations director for the CCTS. “We’re their right-hand people; providing internal supports and a full-service package to make things easier for them, while also acting as a partner to the partners – that is, other trial sites worldwide.”

Sunnybrook has a strong history of leading clinical trials locally, nationally, and globally. CCTS has expertise in the management and coordination of single-centre, multicentre, national and international clinical trials and research projects across any therapeutic area at Sunnybrook.

“This is an incredibly exciting time to be part of the clinical trials team at Sunnybrook,” says Dr. Paul Karanicolas, medical and scientific director for the CCTS. “Across our institution, there is a renewed and growing focus on innovation leading us to the forefront of inventing the future of healthcare. Our work is not only advancing medical science—it’s directly impacting patient lives in meaningful ways.”

Have a Sunnybrook-led clinical research project in mind (or in the works)?

Contact the CCTS at: ccts@sunnybrook.ca

The post Igniting Discovery: Where researchers go to get their research projects off the ground appeared first on Your Health Matters.

Big sister Debbie has always been there for Cindy; this time, as they scurry through hospital corridors, a little late for their first appointment of the day.

Together, the siblings navigate traffic, banter over the long drive from Brantford, and keep on top of appointments. Debbie is a little on edge, given the circumstances. She takes her support role seriously, as she – more than most, due to her career in nursing – understands its importance to patients; her sister, in this case. Cindy, as a result, comes across as laid back and has an energetic spring in her step.

Despite having left early as they always do, the heavy fog and wet morning meant road conditions were heavier than usual. But nothing was going to get in their way…

Cindy is part of a clinical trial, or research study, that is testing an investigative drug therapy for the prevention of Alzheimer’s disease. It is one of many dementia research trials from the Brain Lab in the Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Health Sciences Centre.

A volunteer participant for the study, Cindy is required to come in to hospital for regular visits – twice a month in her case, for now. This trip marked a year of visits; expected to continue another four years, for the duration of the five-year study.

Why would someone like Cindy – who shows no symptoms of Alzheimer’s disease – need or want to take that time to participate in such a research study?

When I first heard about this study, I knew right away I wanted to be a part of it. My mother had dementia, Alzheimer’s disease (AD). Seeing mom deteriorate mentally, it was difficult. She would have been in her late sixties, when she started manifesting confusion. She deteriorated; it was tough to see her go downhill. I wanted to learn what my risk was, to see if I could get more information, and what I could do about it”

Cindy Greatex,
clinical trial research participant,
68 years old 

Dementia is a term for several diseases that affect memory, thinking, and the ability to perform daily activities, with Alzheimer’s being the most common, contributing to about 60 to 70 per cent of dementia cases.

According to the World Health Organization, the illness gets worse over time and mainly affects older people. Having a family history of Alzheimer’s disease – in particular, if a biological parent or sibling has the disease – increases the risk of developing it.

As a part of the study, Cindy had the option to have her genes tested; she didn’t hesitate. The results showed that she has the strongest genetic risk factor for AD – which means she has a 15 times higher risk of developing the brain disorder than the average person.

As a medical doctor, Sunnybrook cognitive neurologist and brain scientist Dr. Sandra Black knows too well the devastating effects that diseases of the brain can have on patients, their quality and length of life, and their impact to families and loved ones.

Recognized internationally for her contributions to the diagnosis and treatment of vascular dementia, Alzheimer’s disease and stroke, Dr. Black has been compassionately providing care to patients and their families for most of her career, while working to advance research into what we know about the brain. This includes leading 88 clinical trials and training 110 trainees – new generations of clinicians and brain scientists, who have gone on to be leaders in cognition, stroke and dementia across the country.

While there are drug therapies available to help treat some of the symptoms of AD or other dementias (once those symptoms have already developed), there are limited medical options to address prevention, before the disease takes hold.

Yet Dr. Black has never been more optimistic.

Never before did we have the option or possibility of altering the pathway in which dementia develops. Now we’re actually looking at the pathology itself that leads to brain cell damage and cognitive decline. This is an emerging field and we’ve learned the sweet spot in preventing or slowing down Alzheimer’s disease is well before symptoms start.

Sandra Black,
Scientific Director, Dr. Sandra Black Centre for Brain Resilience and Recovery,
Sunnybrook Research Institute (SRI) and
Officer of the Order of Canada

She explains how the focus of therapies in their clinical trial research now is to intervene before the toxic processes behind the disease begin to form – a minimum of 10 to 15 years before symptoms kick in and “have a life of their own”, spreading in the brain.

“If we can do that, then you’re going to avoid it (dementia developing). It’s like stroke prevention: you get worked up, and put on prevention therapies, so you don’t have a stroke.”

The comparison should not go unnoticed, considering that she and her colleagues at Sunnybrook’s stroke clinic were one of the first to provide stroke prevention therapies in Canada in the 1990’s.

For the time being, volunteering to participate in a clinical trial is often the best option for patients like Cindy to access therapies that are not yet available “clinically”; in this case, a drug therapy in an effort to prevent or offset the very start of the disease process.

Receiving the drug, however, is not a guarantee as clinical trials are often randomized and blinded, which means volunteer participants are either selected for the drug therapy itself, or a “placebo” instead – the latter usually is just a saline solution – so Cindy and the research team don’t know which group she falls in.

“There has to be this placebo comparison in order for the study to be controlled, in order to validly test for any effects and differences – good or bad – of a drug being studied,” explains Halil Akbulut, clinical research coordinator in the Hurvitz Brain Sciences Program at Sunnybrook.

Without people like Cindy and her study support partner, we wouldn’t make any progress at all. They’re contributing to our understanding.

Cindy will continue to be closely monitored and tested for the duration of the study. Her sister Debbie is her “study partner”. In addition to providing a supportive role to Cindy, Debbie is part of her “team”, sharing any cognitive, physical or emotional changes she observes while outside the hospital setting. Changes to cognition can include thinking processes such as attention, learning and memory, language, remembering, reasoning, and problem solving.

If Cindy’s cognition or overall health declines, she will be pulled from the study. If it’s found that she was on the placebo, she will be offered the drug therapy as part of the agreement as a participant of the study. If she was on the drug arm of the study, she will continue to be offered it, for as long as she and her care team decide to use it.

I’m learning so much through this study, I’m learning how to eat better, how to sleep better, interacting more with people; so it’s giving me a lot of tools that I can put into place now while I’m going through the study, and I know it will make a difference in my life, to a better quality of life.

When asked if she had any advice to offer others who may be considering a clinical trial, Cindy added:

“If there are clinical studies available, sign up. It helps to find out as well genetically whether you have a predisposition – a higher probability of getting the disease – so there’s so many good points about being part of a study. I encourage people to find out if anything is happening in your community – I’m commuting myself – it’s worth the while to do that.”

The post Igniting Discovery: Can we stop dementia in its tracks, before it starts? appeared first on Your Health Matters.

Vitreous hemorrhage is a leading cause of severe vision loss worldwide. This condition, commonly caused by diabetic retinopathy, occurs when diseased retinal blood vessels rupture, rapidly filling the eye with blood and rendering someone blind within minutes. The traditional treatment for this condition involves a period of watchful waiting to allow for natural resolution, which can take many months. Patients suffer while waiting, facing limitations in physical activity, reduced work productivity and the fear of impending surgery or permanent blindness. If the hemorrhage does not clear, surgery is the only alternative.

Dr. Gary Yau, ophthalmologist and affiliate scientist in Physical Sciences and the Hurvitz Brain Sciences Program at Sunnybrook, is developing a non-surgical, office-based solution that uses the power of sound to restore vision loss caused by vitreous hemorrhage. The technology applies focused ultrasound waves deep within the eye to fragment the hemorrhage and accelerate its clearance, all without the need for incisions.

Partnering with SRI, Dr. Yau founded Vitreosonic, to accelerate the technology and its potential to transform the current treatment paradigm, having a significant impact on how patients may recover from this blinding condition in the future.

Dr. Yau sits with the Vitreosonic technology, which applies focused ultrasound waves to the eye non-invasively.

How did your training as a physician help you as an inventor?

Medical training is, understandably, centred around learning the craft of clinical care. While it may not explicitly focus on invention or product development, health-care professionals are uniquely positioned to contribute to innovation. We work on the front lines, encountering real-world clinical challenges and observe firsthand where current solutions fall short. Our research background trains us to think critically about evidence and improvement, and as end-users of medical technologies, we bring valuable insight into what works in practice, not just in theory.

What knowledge or skills do you need to become an inventor?

Perhaps the most essential skill I’ve observed in successful inventors is simply the ability to get things done.

Invention is about bringing an idea to life. It requires you to be both a dreamer and a doer.

As an inventor, you’re stepping into new territory, so you’ll inevitably hear phrases such as “this isn’t how things are usually done.” The ability to push forward despite those barriers is a necessity.

I certainly am early in this journey, and still have many walls to navigate, but this pursuit has been one of the highlights of my professional life. True invention doesn’t just advance care—it has the power to redefine it. I would encourage those that have a compelling idea to take this less travelled path, as its impact on patients can be profound.

What advice would you give to someone interested in launching a health-care company to commercialize their discoveries?

Absolutely go for it. Inventing and entrepreneurship aren’t the most common paths for health-care professionals, but they offer an incredible opportunity to make a lasting impact on patients’ lives.

I didn’t initially set out to start a company. It began with identifying a compelling clinical need, one that resonated deeply with me. Over time, it became clear that the only viable path to bring this solution to patients was through commercialization.

In that sense, forming a company wasn’t the goal, rather it was the necessary vehicle to move the solution forward.

Translating an idea into a real-world solution often requires knowledge beyond traditional medical training, such as intellectual property, regulatory strategy, and product development. For clinicians interested in innovation, being involved more upstream in the invention process not only broadens our perspective but also allows us to shape the direction and real-world impact of new solutions from the start.

As a health-care professional, your unique clinical insight is a major advantage that can help propel an idea forward.  Just as important, though, is knowing where your expertise ends and being resourceful in filling those gaps. It’s rare these days, especially in health care, to develop an impactful invention entirely on your own. I’ve been fortunate to collaborate at SRI with Dr. Kullervo Hynynen and an outstanding engineering team, Bohao Ning PhD and Christopher Hu MSc, whose expertise and partnership continue to be essential in moving this technology ever closer to the bedside.

The post Sunnybrook Inventors: Dr. Gary Yau appeared first on Your Health Matters.

Now, clinical researchers at Sunnybrook think they have a living example to support this theory.

A patient case study with brain network mapping, reported by University of Toronto Psychiatry resident and lead author Dr. Saarah Haque and colleagues, was recently published in the journal Communications Medicine.

The findings from this study provide additional understanding of the causes of substance use disorders and could be helpful for developing new treatments in the future.

Sunnybrook cognitive neurologist and senior author of the paper, Dr. Matt Burke, provides for us a summary of his patient’s case, and helps us to make sense of what it could potentially mean for the direction of research and the treatment of chronic, debilitating, and otherwise “treatment-resistant” alcohol use disorder (AUD).

Dr. Matthew Burke, cognitive neurologist and associate scientist in the Hurvitz Brain Sciences Program at Sunnybrook.

Can you provide for us an overview of the events that led to this case study?

A few years ago, a 42-year-old Toronto woman with chronic AUD (since her early twenties), experienced a traumatic brain injury (TBI) as a result of falling down stairs while intoxicated. She struck her head and lost consciousness, with no memory of the incident.

While in intensive care, brain imaging showed bleeding in in the left frontal lobe of her brain.

A few weeks after her injury, I first met with this patient through my work at Sunnybrook’s Traumatic Brain Injury (TBI) Clinic. She reported a good recovery in many symptoms but still had some insomnia, mild short-term memory difficulties, and loss of smell and taste. Interestingly, she also independently reported a dramatic reduction in her cravings and interest in drinking alcohol – leading to her being abstinent from alcohol for the first time in years.

Keep in mind that before the incident, she didn’t respond well to any treatments. Previous attempts to reduce her alcohol consumption went unsuccessful, despite trying multiple approaches including psychosocial treatments – such as individual counselling and group supports, and pharmacological treatments – where she participated in clinical trials testing medications aimed at minimizing symptoms, such as cravings and a strong urge to drink. But they didn’t work for her.

So, this patient had tried a number of other treatments for her alcohol addiction – with little to no success – and was now suddenly showing signs of remission, after her fall?

That’s correct. You could say her addictive behaviour stopped becoming as much of a problem for her – in a way that was not seen before with clinical treatment.

At a one-year follow-up appointment, she had reported one relapse a few months after the TBI that was triggered by increased workplace stressors, in the context of the COVID pandemic.

After the relapse, she had successfully abstained from alcohol in the four months preceding her one-year follow-up appointment in our clinic (early remission), and she was discharged from the TBI clinic.

How did this incident lead to a research study?

We were obviously fascinated and very happy to learn about the relief she was experiencing from her addiction, albeit it was unfortunately in the context of a TBI with other consequences that can come with such an injury.

We were curious as to whether the damage to the specific brain region seen on the CT scan could be the reason for her marked reduction in cravings and interest in alcohol. In order to do so, we knew we would need to collaborate with previous colleagues at Harvard Medical School to map the brain region and see if it overlapped with regions/circuits previously implicated in remission from addiction.

What did you find?

We were able to trace a focal lesion – damage to tissue created when an object penetrates the skull and directly injures the area. In this case, the location of the lesion was in the orbitofrontal cortex – a part of the brain’s frontal lobe.

This is the same area that previous research in pre-clinical models and humans has been telling us plays a role in addictive behaviour – including the regulation of urges, compulsions, and reward decision-making processes.

We then looked to see what parts of the brain this lesion is connected to in a process called lesion network mapping. This map revealed that the lesion overlapped with previously identified circuits implicated in addiction remission.

What does this tell us?

This case study provides us with information that we normally would never be able to ethically do – in that you would never intentionally disrupt or create injury to one’s brain – for obvious reasons, unless there is very specific evidence indicating a measured controlled way for healthcare practitioners to do so that is proven to show therapeutic benefit with minimal risk.

An example of this includes some of the proven therapies offered in medicine and research for some other brain conditions, where non-invasive or minimally-invasive brain therapies have shown to carefully and precisely create either some form of connection disruption, or in some cases, produce a controlled lesion or “injury” to very specific parts deep within the brain to create a therapeutic effect.

In this case, this unintentional TBI appeared to somehow, by fluke, disrupt a brain connection in perhaps a specific way and/or in a critical spot, that contributes to, or is responsible for, this patient’s AUD.

To the best of our knowledge, there have been no published reports of focal lesions resulting in remission of isolated alcohol use disorder (without the use of more than one drug).

What is the take home message?

We describe a patient with longstanding alcohol use disorder who reported reduced cravings and stopped drinking alcohol following a traumatic brain injury that damaged part of her left frontal lobe.

We performed analyses on this damaged brain region and found that this area overlaps with previously-identified brain connections involved in substance use disorders.

Our findings provide additional understanding of the causes of substance use disorders and could be helpful for developing new treatment strategies.

How unusual is this case?

This is a fairly extraordinary situation. I would say there are probably a handful of other cases I have seen where patients report a paradoxical improvement of pre-existing symptoms (e.g. low mood) after a major head injury.

When I was previously working down at Harvard Medical School, I was involved in research that collected such rare lesion cases from the medical literature and combined them with brain network mapping – and they garnered unexpected media attention, probably in part due to the unusualness of these cases.

Does this mean a potential treatment for alcohol addiction? What are the next steps?

Not yet. But it does shine a new light in this area of research and highlights how changes to brain circuits may impact complex behaviours (the crux of neuropsychiatry).

Our findings suggest that potentially just disrupting this brain network could possibly facilitate remission, however, the intersection of brain injury and AUD is complicated and requires more study.

Importantly, we couldn’t control for other possible factors that could have been potential contributors to alcohol remission in our patient. This includes negative psychological associations with alcohol (given that the trauma occurred in the context of alcohol intoxication), less social interaction, the role of psychiatric factors, such as depression or post-traumatic stress disorder, or reduced exposure to triggers for alcohol use in the context of a recovery from TBI.

We therefore need to do more research and proceed with caution in further investigating any potential treatment looking to modulate the brain circuit implicated in our article.

The post Brain injury paradoxically alleviates alcohol addiction in Toronto woman: Q&A with Sunnybrook neurologist Dr. Matthew Burke appeared first on Your Health Matters.

It’s this highly-specialized setting within an academic health sciences centre that lays the foundation for clinical research – the study of health and illness in people – that drives discovery, innovation and learning in the field of critical care, at home and around the globe.

According to the Canadian Clinical Research Network, for the second year in a row, Sunnybrook has enrolled the highest number of patients in Canada in critical care-related trials funded by the Canadian Institutes of Health Research (CIHR).

Two current Sunnybrook-led clinical trials – on the cusp of discovery – are expected to produce evidence that will change the way critical care is practiced, and impact outcomes for critically-ill patients:

The world’s largest clinical trial in critical care:

Using antibiotics to prevent hospital-acquired infections before they happen.

Dr. Brian Cuthbertston, senior scientist in the Evaluative Clinical Sciences, Tory Trauma Research Program at SRI, is the international principal investigator for a number of global critical care studies and collaborations, including the SuDDICU trial.

Critically-ill patients who receive mechanical ventilation (assisted breathing) in an intensive care unit (ICU) are particularly at risk for hospital-acquired infections – these are infections that can develop while patients are in hospital receiving care, and are a major cause of illness, sometimes death, and increases to the costs of care.

While the evidence supporting the preventative use of antibiotics is strong, many health care professionals around the world don’t use this approach, out of a concern of the effects of antibiotic resistance – when antibiotics are no longer effective.

Led by SRI in Canada and the U.K., and by The George Institute in Australia, the SuDDICU  study – Selective Decontamination of the Digestive tract in Intensive Care Unit patients – is a large, randomized controlled trial and international research collaboration, that was first established in 2009.

The researchers wanted to test:

• whether using antibiotics to prevent infections increases the number of patients who get better and go home after being critically unwell, and
• whether using antibiotics in this way affects patterns of antibiotic resistance – when antibiotics are no longer effective – in the ICU.

“The preliminary results are not only promising, but also came as a bit of a surprise,” says Dr. Brian Cuthbertson, international principal investigator of the trial, critical care physician and senior scientist at Sunnybrook.

This research aims to give health care professionals and patients data on the benefits so they can make informed decisions about providing preventive antibiotics as part of care.”

Publication of the study results are expected in the near future – stay tuned to SRI Research News.

The clinical trial ranked #1 out of hundreds of thousands of Health Canada pandemic study grant applications:

Swapping intravenous (IV) sedative for inhaled sedative for patients on a ventilator in the ICU.

This trial is homegrown within Canada (and includes a single U.S. site), but its potential for global impact is not any less significant.

A dose of isoflurane is prepared, as part of the SAVE-ICU trial designed and led by Sunnybrook. The inhaled sedative – known for its use in surgeries – has been tested for use with patients in the intensive care unit, versus traditional sedatives given through an intravenous (IV) line.

The SAVE-ICU study – SedAting with Volatile Anesthetics Critically Ill COVID-19 Patients in the Intensive Care Unit – is a collaborative, multi-hospital, randomized clinical trial testing:

• whether inhaled volatile sedatives – a more widely available anesthetic commonly used in operating rooms – can replace sedative drugs that are typically delivered intravenously (by IV) for patients in the ICU with respiratory distress requiring ventilation; and
• whether patients recover faster with this form of sedation.

“In order to tolerate the uncomfortable procedure of being put on a breathing machine, patients require sedation or sleep-inducing medications,” explains Dr. Angela Jerath, lead principal investigator of the study, anesthesiologist, and a scientist in Evaluative Clinical Sciences at Sunnybrook. “At the beginning of the COVID-19 pandemic, these drugs were in short supply due to the high number of patients needing ventilators.”

The investigators will compare the impact that inhaled versus IV sedation has on outcomes important to patients with respiratory failure, their ICU clinical teams, and health resource use; this includes ICU and ventilator-free days, quality of life, delirium and hospital mortality.

Adds Dr. Jerath: “There has been some evidence to suggest that these (inhaled volatile) drugs may also have properties that reduce lung inflammation, which may speed up recovery and reduce the time patients spend on a ventilator.”

The investigators are also continuing to look for any elevation in risk between the two methods of sedation, but there has been no indication to stop in the last few years, with no adverse events showing.

“As the inhaled sedative doesn’t have to be filtered through the body like the IV sedation does, there are benefits for the lungs, liver and kidneys, for cancer patients, and with no particular concerns over IV sedation seen,” explains Eily Shaw, the research coordinator on the trial.

“When you turn the dose up/down with an IV drip, you need to wait for the body to process it first, and there’s also a considerable ‘wash out’ period after with patients coming off the effects from the sedative days or even weeks later. It can be a long time before they feel themselves again which can be confusing and sometimes scary.”

Although volatile (inhaled) anesthetics are not new (as a standard of care for surgeries), “their use still had to be studied in the context of the ICU because the type of person coming in for surgery is different than the patient who is ventilated due to respiratory distress in critical care,” says Eily.

At the study start in 2021, it was initially aimed at patients with a COVID diagnosis, but has since expanded to include any patient in the ICU with any kind of respiratory distress (lung failure) requiring sedation on a ventilator.

Dr. Angela Jerath, scientist and anesthesiologist in the Schulich Heart Program, is the lead principal investigator of the SAVE-ICU study.

The goal of this study is to determine if inhaled sedation should be a standard of care in the ICU as well,” says Dr. Jerath. “This can be done differently between hospitals (with different tiers of care), and would also ease the pressure on IV sedation stock, in particular during heightened times of need, such as a pandemic.”

With over 750 research participants over the four-year study period, it will take another year or two to assess the data. In the meantime, members of the research team like Eily are left humbled with their own anecdotal personal observations and sense of what it means:

I’m always buoyed by how thankful our participants and their families are to be involved in our research. For me, the human component is what makes the work we do particularly special. Our team certainly can’t take all the credit but it’s so massively rewarding to see patients when they get better and they look totally different at follow ups and are so grateful, we understand the importance of doing this.”

The post Igniting Discovery: Clinical trials changing the trajectory for the critically ill appeared first on Your Health Matters.

The human brain is an extraordinarily complex organ responsible for our thoughts, memory, breathing and so much more. Its intricate networks, made up of billions of neurons working together, make our actions possible. Neurodegenerative diseases like Alzheimer’s and Parkinson’s disease can impact the patterns of these cells’ activity, and being able to map these networks and the cellular activity within them can inform potential treatments for these conditions.

Scientists have recently developed powerful microscopy systems and molecular techniques that create three-dimensional images of cells to study brain function and activity in detail. However, these images are exceptionally large and complex (with trillions of pixels), making it very difficult to detect changes in network activity patterns.

To address current gaps, a group of researchers in the Hurvitz Brain Sciences Research Program, in collaboration with teams in the United States and Europe, developed the AI-based Cartography of Ensembles (ACE) pipeline, a software that identifies patterns of brain cell activity in large volumes of brain data. A study describing the ACE pipeline architecture and its application in complex neuroscience problems was recently published in Nature Methods. ACE was designed using cutting-edge deep learning algorithms and trained on more than 30,000 3D images curated from microscopy images.

“ACE is capable of analyzing a wide variety of microscopy images, meaning researchers can use the pipeline to gain new insights into how specific populations of cells in different regions of the brain respond to disease,” says Ahmadreza Attarpour, the first author of the study and PhD candidate at SRI and the University of Toronto. “ACE goes beyond traditional methods relying on brain maps that divide the brain into pre-defined regions based on their coarse structural differences.”

Our novel pipeline acts as a detective, pointing out cell activity and patterns that would be otherwise difficult for even highly trained professionals to identify.”

The tool has the potential to accelerate discoveries in neuroscience because of its ability to help researchers accurately identify patterns of activity in specific cell groups and networks within every region of the brain. Researchers can monitor these patterns to better understand how neurological diseases affect brain activity and how treatments may normalize these activity patterns.

“Using ACE, scientists can evaluate the effects of experimental drugs on a particular population of cells across the brain or identify novel targets for neuromodulation therapies,” adds Dr. Maged Goubran, scientist in the Hurvitz Brain Sciences Research Program and Physical Sciences Platform and co-senior investigator of the study.

“ACE provides a powerful tool for mapping brain function and circuitry, paving the way for breakthroughs in neuroscience research and, ultimately, improved patient outcomes,” explained Dr. Bojana Stefanovic, senior scientist and director of the Physical Sciences Platform at SRI and co-senior investigator of the study.

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With no cure for the disease, scientists around the world are conducting research that is leading to breakthroughs in the diagnosis, progression and prevention of Alzheimer’s. Dr. Julie Ottoy, scientist in the Hurvitz Brain Sciences Program, is one of the many researchers at Sunnybrook Research Institute, studying the pathophysiology of Alzheimer’s and what impacts it has on patient outcomes.

Dr. Ottoy’s interest in researching the causes and progression of Alzheimer’s disease started from her personal experiences. Like many Canadians, she has seen firsthand how the disease can impact the lives of family members and friends. Her experiences with her own loved ones and conversations with individuals with lived experience have played a pivotal part in shaping her work.

They remind me time and again that the research we do is about people, their families and their futures.

Dr. Ottoy’s research is working to answer some of the most fundamental questions surrounding Alzheimer’s. Who is most likely to develop Alzheimer’s? In what cases does the disease progress faster? Can we detect changes in the brain before symptoms appear?

Her work specifically focuses on better understanding mixed dementia. This is when Alzheimer’s disease occurs alongside vascular brain damage, which occurs when the blood vessels in our brain are affected and the blood flow to the brain is disrupted. Although mixed dementia is common, it’s not fully understood, making diagnosis and treatment challenging.

Using advanced neuroimaging techniques, like PET and MRI scans, blood-based biological markers, computational biology and AI-based analysis tools, Dr. Ottoy’s research focuses on two overarching themes:

• Mechanisms: To better understand how changes in our blood vessels and immune system contribute to brain changes seen in Alzheimer’s and mixed dementia.
• Biomarkers: To investigate novel biological markers that can aid researchers and clinicians in predicting the progression of these disorders in their early stages.

Her research looks for signs of vascular damage on brain scans, patterns of inflammation and the presence of toxic proteins that form into amyloid plaques and tau tangles. By combining this information, researchers can group patients into more specific subgroups based on the biological changes driving their disease, in turn driving more targeted intervention.

Photo illustration. Kevin Van Paassen/Sunnybrook Health Sciences Centre.

“Alzheimer’s is a very heterogeneous disease, meaning there is a number of different contributing factors and causes for the disease,” explains Dr. Ottoy. “By identifying different subgroups of patients using biomarkers, we are a step closer to creating more tailored treatments that match the individual needs of each patient more closely.”

Another area of her research investigates how well different brain regions connect with one another. The abnormal buildup of tau, one of the toxic proteins in Alzheimer’s disease, leads to cognitive decline in Alzheimer’s disease. Some studies suggest the way brain regions connect with each other is a key mechanism for the spreading of tau. Dr. Ottoy’s work studies these highly-connected regions and tau epicentres, to predict where the tau will build up next.

By studying the interface between the vascular system, immune cells and the spread of Alzheimer’s-specific toxic proteins throughout the brain, scientists can identify novel treatment targets, determine the best time and approach for disease intervention and develop new biomarkers that can inform future clinical trials and potential treatments. Understanding immuno-vascular contributions to dementia is important because both vascular and immune factors are modifiable.

With the advent of disease-modifying treatments, we are closer than ever in meaningfully slowing the progression of Alzheimer’s disease.

Today’s research lays the groundwork for larger-scale initiatives, including multi-site collaborations, like Toronto’s first 7-Tesla MRI, housed at Sunnybrook and part of the Toronto Neuro-Immunology/Imaging Consortium (TONIIC), a multi-site collaborative research initiative focused on neuroimmunology and neuroimaging for diseases such as Alzheimer’s. These research efforts will deepen understanding of disease mechanisms and aid in identifying new biomarkers and therapies.

“My hope is that these advancements will drive the development of combination treatment strategies that reach the clinic and accelerate progress toward precision medicine for neurodegenerative diseases.”

Dr. Ottoy’s research in immune-vascular contributions to dementia is funded by the Alzheimer’s Association and BrightFocus.

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But researchers may have a whole new treatment therapy technique to target and treat hypertension that may be an option in the future.

Newly-published pre-clinical research from scientists at Sunnybrook Research Institute suggests that focused ultrasound – a breakthrough non-invasive surgical technique – when targeted to a specific location in the midbrain, can inhibit neuron activity to reduce blood pressure for potential long-lasting treatment.

When left untreated, hypertension (or high blood pressure) is a fatal condition. Currently, it is treated with diet and lifestyle changes, and systemically-delivered medications that act on the central nervous system to lower the heart rate, relax and open up the blood vessels, help rid the body of excess salt and water, or alter enzyme secretion.

For patients with drug-resistant hypertension, or for those who are pregnant, many treatment options are ineffective and unsafe.

Previous research looked at an alternative approach using deep brain stimulation – an invasive neurosurgical procedure – to stimulate a specific region of the midbrain in a handful of patients. The results were promising, but the procedure has been associated with potential infections and hemorrhage.

That’s where focused ultrasound comes in.

Acclaimed in the medical and scientific world as “scalpel-free brain surgery”, FUS has crossed over from research into successful clinical treatment of some brain conditions, non-invasively.

With its additional ability to safely open the blood-brain barrier (BBB) non-invasively – a world-first research breakthrough – scientists continue to plough forward in their investigations of FUS as a treatment option for other health conditions controlled by the brain, such as is the case in this new study published recently in the journal Brain Stimulation.

“We’ve shown in pre-clinical work that by targeting the periaqueductal grey (PAG) region of the brain we can cause direct neuromodulation of central brain activity, which reduces blood pressure for six hours following a single 10-minute ultrasound sonication,” says Dr. Harriet Lea-Banks, lead author of the study, and junior scientist in the Hurvitz Brain Sciences Program at Sunnybrook Research Institute.

“Lowering high blood pressure into the normal range was extended to nine days with the addition of a second component: introducing nanodroplets – tiny liquid droplets – containing anesthetic medication that are injected into the bloodstream, and triggered with five daily treatments of ultrasound to the brain,” adds Dr. Lea-Banks, also an assistant professor in the Department of Medical Imaging at University of Toronto.

Ultrasound causes the nanodroplets to evaporate, locally releasing the anesthetic drug in a time-controlled fashion, within that specific area of the brain. This approach was shown to extend the time that neuron activity was modified and blood pressure was reduced, and prevent off-target effects, such as general sedation; increasing its reliability.

“This work builds on our previous success with FUS and out of a need for a new alternative strategy for hypertension management,” says Dr. Kullervo Hynynen, senior author of the study, VP of Research at Sunnybrook Research Institute, and a pioneer of focused ultrasound.

This study has shown that transcranial FUS offers a non-invasive tool to stimulate the VLPAG and trigger the delivery of an anesthetic agent; both approaches show the ability to modify central brain activity to achieve sustained reduction of hypertensive blood pressure into the healthy range, while offering the potential for real-time treatment monitoring.”

Based on the results of the research, the authors suggest it may be feasible to develop a FUS device that would allow the control of hypertension initially in a hospital setting, and eventually in the patient’s home for cost-effective, long-lasting treatment.    

“This work has implications for developing a new non-invasive and long-lasting treatment for hypertension that has greater safety and broader applicability than current treatment options for vulnerable patient populations,” adds Dr. Hynynen, also a professor in the Department of Medical Biophysics at University of Toronto.

“We’re looking forward to investigating this option further, and are optimistic the results will add another tool to the clinical toolbox for controlling and reducing hypertension.”

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