Outstanding Canadian health researchers in the spotlight

First ever CIHR-CMAJ Top Canadian Achievements in Health Research Awards

OTTAWA, Sept. 28 /CNW Telbec/ - The Canadian Institutes of Health Research (CIHR) and the Canadian Medical Association Journal (CMAJ) today honoured eight outstanding Canadian individuals and teams with the first ever CIHR-CMAJ Top Canadian Achievements in Health Research Awards, which recognize and celebrate Canadian health research and innovation excellence.

The winners were selected by a peer-review panel of Canadian and international experts, who looked for the discoveries and innovations that had the biggest impact on the health of people in this country and around the world.

    
    The winners are:

     -  Drs. Paul Armstrong, Robert Welsh and Padmaja Kaul, of the University
        of Alberta, who trained ambulance crews to liaise with doctors and
        begin treatment of heart attack victims about one hour earlier on
        average, dramatically improving chances of a full recovery.
    -   Dr. Adolfo de Bold, of the University of Ottawa Heart Institute, for
        the revolutionary discovery of hormone secretion by the human heart.
        This knowledge now allows physicians to control water and salt levels
        in the body, reducing hypertension and helping the heart recover
        after heart attacks.
    -   Drs. Geoffrey Fong, Mary Thompson and David Hammond, of the
        University of Waterloo, for their outstanding work with the
        International Tobacco Control Policy Evaluation Project in assessing
        the effectiveness of various programs to reduce smoking around the
        world.
    -   Dr. Bob Litchfield, of the University of Western Ontario, for a
        ground-breaking study of patients with arthritic knees, proving that
        knee surgery provided no extra value over physiotherapy and patient
        education.
    -   Dr. Michel LeMay, of the University of Ottawa Heart Institute, who
        developed a new way to handle heart attacks that empowers paramedics
        to read electrocardiograms and identifies patients with blocked heart
        arteries who need to be fast-tracked for angioplasty surgery -
        reducing mortality by 50 per cent.
    -   Dr. Nizar Mahomed, of the University Health Network in Toronto, who
        led a team involving some 35 hospitals that introduced new procedures
        for hip and knee surgery. These procedures reduced wait times, cut
        rehabilitation stays and dramatically improved patient outcomes.
    -   Dr. Stephen Moses, of the University of Manitoba, who demonstrated
        the effectiveness of male circumcision in reducing the transmission
        of HIV in Africa.
    -   Dr. Fred Possmayer, of the University of Western Ontario, who
        developed a technique to purify and sterilize lung surfactant - a
        substance that allows lungs to expand and breathe - so it could be
        used in premature babies to greatly improve their chances of
        survival.
    

"It's no surprise to us at CIHR that Canadian health researchers perform so well and have made such a difference in the day-to-day health and wellbeing of Canadians and others worldwide," said Dr. Alain Beaudet, President of CIHR. "It's a great pleasure for me to see CIHR partner with the CMAJ in honouring these award winners and their achievements."

"Canada has tremendously talented researchers and we are celebrating this talent with these awards," said Dr. Paul Hébert, Editor-in-Chief of CMAJ. "This program is designed to highlight and promote top Canadian achievements, and to help physicians, researchers and Canadians know about these accomplishments. To work with Canada's pre-eminent research funder is also a great partnership."

"It's worth noting that all the winners of this new award have placed a strong emphasis on translating their research discoveries and knowledge into innovations that have resulted in practical ways to improve health outcomes," said Dr. Ian Graham, Vice President, Knowledge Translation at CIHR. "That's a crucial test for health research; how can it make a difference in people's lives."

A second round of the Top Canadian Achievements in Health Research Awards has just been launched, with a February 1, 2010 deadline for applications. CIHR and CMAJ welcome applications from individuals or teams working as health researchers, health professionals, policy makers, or administrators. For more information on this year's winners and the next round of awards, visit www.cihr-irsc.gc.ca or www.cmaj.ca.

The Canadian Institutes of Health Research (CIHR) is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to enable its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 13,000 health researchers and trainees across Canada.

CMAJ showcases innovative research and ideas aimed at improving health for people in Canada and globally. It publishes original clinical research, analyses and reviews, news, practice updates and editorials. CMAJ.ca, a full-text, free open-access website, allows everyone to use the latest health information. CMAJ has an impact factor of 7.5 and its website receives over 25 million requests a year.

    
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Saving Time Saves Lives

A heart attack does more damage every minute it's left untreated, so in Edmonton they created a shortcut by starting treatment at the moment the paramedic arrives.

In a heart attack, time is the enemy; every minute without treatment means more damage to the heart and greater risk of death. A research team in Edmonton has found a novel way to advance care of the most deadly type of heart attacks, acute ST elevation myocardial infarctions (STEMI).

Dr. Paul Armstrong, senior cardiologist at the University Hospital in Edmonton and a professor at the University of Alberta looked to Europe for inspiration to ensure that heart attack patients received speedy care even before they arrived at the emergency department.

"My colleagues in France have had a well positioned pre-hospital system for a number of years," said Armstrong. "In fact before we adopted this over 9 years ago I actually went to Paris and met with some friends and colleagues, and actually rode in their ambulances and stood in their call center and explored their system. The difference between France and Canada is that French doctors ride in the ambulances, whereas in our system is we can't spare doctors to ride around in ambulances. So what we've done is devolve and delegate the care in a team system that is seamless."

Armstrong's experiment commencing in 2000, conducted in collaboration with Dr. Robert Welsh and others in Edmonton, trained paramedics to do a 12-lead electrocardiogram (ECG) of the heart. In this way, the earliest point of care could begin to address the problem immediately rather than just transporting the patient to a busy ER. Using a cell phone, the paramedics could send the results of the ECG to an on-call cardiologist's laptop to confirm the diagnosis.

When a positive STEMI result was identified, the paramedic would give a clot-busting drug, in appropriately-selected patients that would restore normal heart function in just minutes. "Time is muscle, and muscle is life. That's the algorithm that we work on," said Armstrong. If a catheter-based strategy, such as balloon angioplasty, was deemed more appropriate, such patients could be more quickly triaged to the hospital best-equipped to perform the procedure.

This work led to better treatment options for the city of Edmonton. It has also provided a new understanding of how ECGs can help health care professionals determine how long ago a patient's heart attack happened and the extent of damage that has already occurred in the heart. This information helps physicians determine how best to treat the patient. In fact, Armstrong has found preliminary evidence that will be followed up in future studies that treatment within the first hour after a STEMI heart attack can actually stop the irreversible damage to the heart muscle that makes heart attacks so deadly. With the help of Dr Padma Kaul, a new understanding of how women with heart attack access the acute health care system compared with men has also been discovered.

Who - Paul Armstrong is a senior cardiologist at the University Hospital in Edmonton and a professor at the University of Alberta. Dr Robert Welsh is Chair of the Vital Heart Response Program and Associate Professor at the University of Alberta. Dr Padma Kaul is Associate Professor at the University of Alberta.

Issue - Heart attacks can cause major damage to the heart in just a few hours. Doctors needed to find a shortcut that could reduce the typical 2-3 hour delay between symptom onset and hospital arrival.

Solution - Edmonton provided its paramedics with electrocardiogram equipment that could send readings to cardiologists, getting a diagnosis and treatment started often before the patient even arrived at the hospital.

Impact - Armstrong's method has shaved approximately one hour off the normal treatment time. In some cases, patients treated within an hour after symptoms start are spared any permanent muscle damage to the heart.

The Heart - More than Just Brawny Muscle

Lovers know that the heart is a mysterious organ, but solving the mystery of what the heart does was a matter of life and death for doctors.

Your heart is a tireless workhorse, pumping thousands of litres of blood every day of your life. And, for many years this was thought to be its only function, until Dr. Adolfo de Bold, a professor of pathology and laboratory medicine at the University of Ottawa Heart Institute, discovered that the heart did much more.

In 1969, when de Bold came to Canada from Argentina to do his MSc and PhD, he begged to work on a dormant research project of his supervisor's, the study of the then unknown function of the heart's muscle cells. Of specific interest was a feature found within these muscle cells, storage granules that looked very similar to the ones that produce insulin in the pancreas.

His training in Argentina had been on a related topic, and he recalls he had "a big desire to discover something, although I didn't know at the time how much of a chance I was taking."

De Bold toiled away in isolation in the labs, but he began to understand that these granules did indeed release a hormone that de Bold named Atrial Natriuretic Factor (ANF) that controlled water and salt levels in the body. In essence, when the heart muscles were stressed they would release ANF which then told the kidneys to filter out salts and reduce the amount of fluids the overworked heart had to pump.

When he injected the substance into rats, it had a major impact causing them to excrete a very large amount of urine. Next he isolated and sequenced the peptide hormone that was causing the effect and named it Atrial Natriuretic Factor (ANF).

Once his work was published, it excited what has been called "a revolution in our thinking ... and a blizzard of papers that together educated a generation of investigators." The discovery of ANF showed for the first time this new function of the heart muscle, which could allow doctors to either increase or decrease the load on the heart, an essential process for reducing hypertension and helping the heart compensate after heart failure.

As well, measuring ANF levels in the blood is a widely-used diagnostic test that doctors can use to assess heart health. "It's a very precise measure of the health of the heart," said de Bold. "As I frequently say, if the levels of this hormone are normal in the blood then nothing is wrong with your heart."

Looking back, de Bold realizes just how lucky he was to be able to study what he wanted on his own, although his solitary research did present a huge challenge when it came to finding the necessary equipment and funding to keep the project running.

"I have many stories of how we were at the brink of losing everything at the very beginning," said de Bold. "We were lucky to run into some provincial funding to buy the protein sequencer which was just shear chance. The research that I witnessed myself doing has been heavily reliant on divine providence and serendipity."

Despite his major discovery, de Bold is still studying this mysterious protein and its many effects. He's found that ANF has effects even beyond what he originally imagined, guiding molecules in and out of cells on a pathway.

"It's a huge impact, this discovery of new systems and new cellular signals," said de Bold. "There are many things that are really just beginning with this finding. It's kind of like insulin, we still don't know the whole story about it, so it's a lot to be done still."

Who - Adolfo de Bold is a professor of pathology and laboratory medicine at the University of Ottawa Heart Institute.

Issue - Researchers suspected the heart had some mysterious endocrine function, but no one had studied the issue in depth.

Solution - De Bold discovered Atrial Natriuretic Factor (ANF), a hormone that regulates how hard the heart has to pump by communicating with the kidneys to control salt concentrations in the body.

Impact - The discovery of the heart's endocrine function literally rewrote the medical textbooks. It offered doctors a new way of easing the load on stressed hearts and provided a blood test to diagnose heart failure and assess the efficacy of its treatment.

    
    The Science Behind Combating the Greatest Threat to Global Health:
    Tobacco Use
    

37,000 Canadians die every year of smoking. Researchers with the International Tobacco Control Policy Evaluation Project are using research evidence to promote methods for reducing these preventable deaths-in Canada and throughout the world.

In the 20th century, 100 million people lost their lives because of tobacco-related causes. Today, smoking kills more people than AIDS, malaria, and tuberculosis combined. But the global tobacco epidemic will reach unprecedented proportions in the 21st century, because tobacco use is increasing in low and middle income countries. By the end of the century tobacco-related deaths are projected to grow as high as 1 billion.

To reduce preventable deaths from using tobacco, the nations of the world, under the auspices of the World Health Organization, created the first-ever health treaty: the Framework Convention on Tobacco Control (FCTC), which includes tobacco control policies that ratifying nations (now over 160) are required to implement, such as more prominent warning labels, smoke-free laws, and higher taxes. While many public health authorities hope FCTC policies will be effective, the International Tobacco Control Policy Evaluation Project (ITC), centered at the University of Waterloo, is providing evidence from a state-of-the-art multinational evaluation program to give strength and direction to those hopes. The ITC Project is the only research program that focuses on evaluating FCTC policies as they are implemented throughout the world.

As an example, when Ireland decided to ban smoking in public places, including their famous pubs, the ITC Project was on hand to collect data on public opinion and behavior before and after the change. Led by Dr. Geoffrey Fong, a professor of psychology, Dr. Mary Thompson, professor of Statistics and Actuarial Science, and Dr. David Hammond, Assistant Professor of Health Studies and Gerontology at the University of Waterloo, with colleagues in the United States, Australia, and United Kingdom, the ITC Project is the world's authority on the effectiveness of tobacco control policies such as smoke-free laws. And what they found in Ireland was significant for tobacco control throughout the world.

Compared to the United Kingdom, which did not implement a smoke free law, one year later Ireland saw a dramatic reduction of smoking in public places. In addition, smokers and non-smokers alike widely supported the ban. This set of findings from the ITC Project provided powerful feedback for politicians and public health officials, and has been the foundation for the many smoke-free laws that have been implemented throughout the world, including the UK, Thailand, Brazil, and even France and Germany.

Combining research methods from epidemiology, social psychology, health behavior, economics, and preventive medicine, Fong's group has been evaluating the impact of tobacco control policies on attitudes and behavior in 20 countries that make up over 50% of the world's population and 60% of the world's smokers, including China, India, Bangladesh, Mexico, Brazil, the US, the UK and Canada.

Closer to home, the ITC Project has documented the loss of effectiveness of certain policies over time. For instance, Canada was one of the first countries to put graphic warning labels on smoking packages in 2001. But, in the intervening eight years, ITC data has shown that the impact of those labels is declining.

In light of these ITC findings, Fong believes that Brazil, already into its third round of very powerful graphic warning labels, could be seen as an example for Canada and other countries in their use of research evidence. According to Fong, Brazil is a "world leader in the conceptualization of graphic warning labels that will create negative associations with tobacco products."

Perhaps just like our need to develop stronger antibiotics to combat more powerful bugs, Fong suggests that tobacco control measures need continual strengthening in order to keep them effective.

"Despite the fact that prevalence rates have dropped dramatically in Canada, smoking is still by far the number one preventable cause of death in Canada and around the world," said Fong. "The tobacco industry will challenge any tobacco control policy, especially policies that work. And so the presence of strong evidence to guide health policies is even more important in the case of tobacco use. That is our mission and what keeps us going."

Who - Geoffrey Fong is a professor of psychology and Founder and Principal Investigator of the International Tobacco Control Policy Evaluation Project at the University of Waterloo, Ontario, and Senior Investigator at the Ontario Institute of Cancer Research. Mary Thompson, a professor of statistics and actuarial science, and David Hammond, assistant professor of health studies and gerontology, are two principal investigators of the ITC Project, also at the University of Waterloo.

Issue - Smoking is the world's largest public health problem and this is particularly true in developing countries. But what can governments do to stop people from smoking?

Solution - By measuring changes in people's attitudes and behaviour after various tobacco control policies are implemented over time and across countries, the ITC Project can determine the impact of those policies.

Impact - Many countries, including Ireland, France, Malaysia, the United Kingdom, and China, have used findings from the ITC Project to shape their tobacco control policies.

How Do You Mend A Broken Heart? Fast!

Heart attacks are dangerous, but STEMI heart attacks can become deadly in a very short time. In Ottawa, a massive collaborative project is saving time and lives when every minute counts.

You're short of breath and there is a pain starting in your chest and shooting down your arm and side. You call 911, and when the paramedics arrive and load you into the ambulance they hook you up to electrocardiogram machine to get a quick look at your heart rhythm. They confirm that you are having a heart attack, and they mention a funny medical word: STEMI.

They've been heading to your local Ottawa hospital, but all of a sudden they change direction and take you to the Ottawa Heart Institute. The paramedic in the back pulls out a special cell phone and calls ahead, describing your case on a dedicated STEMI heart attack phone line to a waiting receptionist who alerts the angioplasty team.

When you arrive at the Heart Institute, the paramedics know to go directly to the STEMI room where the team is assembled. In a few more minutes you have been given stabilizing drugs and are being prepped for surgery. In less than 90 minutes, you have had angioplasty surgery to reopen and inflate the artery. The lasting damage and chance of death are minimal, and in a few days you will go home.

This entire sequence of events is the brainchild of Dr. Michel Le May, a cardiologist and director of the Coronary Care Unit Research Group at the Ottawa Heart Institute.

STEMI events, or ST-segment elevation myocardial infarction, were one of the most deadly forms of heart attack, where time to treatment must be measured in minutes. Then in the 1980s a new group of clot-busting pharmaceuticals were introduced to clear blocked arteries. However, these pharmaceuticals were not without side effects, not the least of which included bleeding in the brain.

So, doctors started opening the clogged artery by inserting a balloon, a process commonly called angioplasty, which is much more effective for overall health. But, threading a catheter up the groin and into the heart to open an artery requires a high degree of specialization and expertise, impossible to have at every hospital. Add to this the time constraint that treatment should be done within 90 minutes.

In Ottawa, the Ottawa Heart Institute is the only hospital that performs angioplasties, but getting STEMI patients there took too long. After doing several studies into what would work best for patient health, Le May forged a new way of handling heart attacks that empowered paramedics to read electrocardiograms and decide where a patient should be taken, something that previously could only be done by ER physicians.

Since July 2004, almost one STEMI heart attack patient a day has gone directly to the Ottawa Heart Institute, usually receiving care in less than the prescribed 90 minutes. Because of Le May's research, their risk of death has been reduced by half and patients are even able to leave the hospital faster.

"It's amazing. There's no going back," said Le May. "In a very short time we go from a completely blocked artery to completely open artery, and the patient feels better. Our mortality rate continues to be down by 50% and we've treated more than 1,500 patients, so we know that our results continue to prove this is the best strategy."

Who - Michel Le May is a cardiologist and director of the Coronary Care Unit Research Group at the Ottawa Heart Institute.

Issue - STEMI heart attacks are deadly blockages of the artery, and while clot-busting drugs are a common treatment method, angioplasty (inflating the artery with a balloon) is superior. Unfortunately, angioplasty also requires a team of experts available around the clock.

Solution - Le May championed the idea of giving paramedics the power to diagnose STEMI heart attacks. With this power, they could coordinate their action and bring the patient to the Ottawa Heart Institute where a team of angioplasty experts could always be found.

Impact - Because of the improved patient transfer measures, patients are being treated in less than an hour and a half, significantly reducing the injury and risk of death.

Think Twice Before You Cut

A group of Ontario orthopedic surgeons asked the unorthodox question: what if surgery didn't make arthritis of the knee any better?

About half of all Canadians will deal with arthritis of the knee whether because of age or injury, and arthroscopic knee surgery to remove small torn bits of cartilage or smooth rough edges of the joint surface have been the standard treatment for osteoarthritis. However, research at the University of Western Ontario has produced evidence that has completely altered traditional treatment strategies for this condition.

Based on preliminary research done on veterans undergoing knee surgery, UWO's Fowler Kennedy Sport Medicine Clinic decided to launch a major investigation. "A lot of what we do in medicine and certainly surgery are really techniques and thought processes that are handed down over the years, and when you look back you realize there isn't great evidence to support some of the operations we do," said Dr. Bob Litchfield, medical director at the Fowler Kennedy Clinic and an orthopedic surgeon.

The group did a randomized controlled trial where 200 patients received therapy and education, but only half the patients received surgery first. Then they followed the patients' recovery over a two-year period.

At three months time, the normal point for a follow up visit with a surgeon, the surgery group appeared to have a greater recovery. However, Litchfield suspected that this initial response to surgery was likely explained by a placebo effect.

"It's sort of an intuitive thing if there's areas of flaps of cartilage or pieces floating around by removing those pieces we maybe change some of the mechanical symptoms where people complain of catching and locking," said Litchfield. "Every orthopedic surgeon felt strongly that we were helping patients, but one of the problems with busy surgeons is we would probably follow a patient for only about 3 months. When you put it to the scientific test and follow these patients longer, you realize you really could have achieved the same result with an optimized non-operative program."

Every time they measured patient health and response to treatment up to two years later, they could find no difference between those who received surgery and those who didn't. The fact that surgery did not provide major benefits was shocking, and when the results of the study were published in the New England Journal of Medicine in September 2008 it prompted huge debate.

"Sometimes with surgeons it's easier to operate than to guide patients through a non-operative program. It's what we do and we like doing it and we believe in it, but sometimes some of the non-operative modalities get forgotten. So hopefully this study will encourage people to think about those options again," said Litchfield.

For his part, Litchfield has been practicing what the research evidence has taught him. In cases where he would have done surgery before, now he says he is much more likely to discuss this study with the patient and try other treatments first. And, if he does need to perform surgery, it is not just to remove debris, but to actually realign the ligament or replace cartilage.

Who - Bob Litchfield is the medical director at the Fowler Kennedy Sport Medicine Clinic and an orthopedic surgeon.

Issue - Arthroscopic knee surgery sends a small endoscope through a hole in the knee to smooth rough edges and pull out flecks of floating cartilage. But, does this really improve osteoarthritis?

Solution - Following a large group of patients for up to two years, Litchfield and his colleagues found that there was no difference between those patients who received surgery and those who just underwent normal rehabilitative therapy and lifestyle changes.

Impact - While the group believes there are still instances where surgery is justified, they are also hoping to encourage orthopedic surgeons to consider non-operative therapies before cutting in.

Go Home - It's Good for Your Hips and Knees

Surgeons perform about 50,000 knee and hip replacements in Ontario each year, and as the population ages that number will only go up. A multi-hospital collaboration in Toronto is helping lower the cost of this operation and improve recovery times.

Hospital bed spaces can be hard to find in Ontario, and this translates into long wait times for elective surgeries such as joint replacements. In 2005, 23 healthcare organizations in the Greater Toronto Area joined together to form the Total Joint Network. Their goal: reduced wait times, shortened patient recovery and savings for the taxpayer.

Led by Dr. Nizar Mahomed, head of Orthopaedic Surgery for the Toronto Western Hospital University Health Network, the group began streamlining patients into two recovery programs. One group spent 5 days in an acute care hospital then returned home and received regular visits from a rehab specialist. The other group received three days of acute care followed by seven days of inpatient rehabilitation.

Testing revealed clear advantages to the new model. Using the model, the number of inpatient rehabilitation days decreased by about 40%, and the acute care length of stay also decreased approximately 30%. Meanwhile, patient recovery and satisfaction was just as good as before, while saving more than $10 million annually in healthcare costs in the Greater Toronto Area.

"We ensured that patient safety and clinical outcomes were maintained, satisfaction was high, and system cost savings were realized," said Mahomed. "It was a nice example of how a significant number of organizations can work together in a collaborative fashion to lead to evidenced-based improvement in healthcare delivery."

Not content to just overhaul elective hip and knee replacement surgeries, the group then focused their attention on hip fracture patients who Mahomed said were "a marginalized and underserviced patient care area."

The success of their first project attracted more healthcare organizations for the second experiment, 35 acute care hospitals in all. And, they set aggressive goals to get the patient into surgery within two days, to in-patient rehab within five days, and have the total rehab stay not exceed 35 days. Previously the average wait to get rehab was 10-12 days and the average rehab stay was 42 days.

In the end, Mahomed's plan worked even better than expected. Because patients didn't have to spend days sitting in a hospital bed waiting for surgery, they were stronger and in better condition at the time of their operation. As a result, the group managed to reduce the overall rehab stay to just 28 days. This shorter and, ultimately more effective treatment period meant that 20% more patients returned to their pre-injury health status. Their return to health is saving the province about $17 million per year by helping hip fracture patients avoid long-term care facilities.

"The results were actually better than I had anticipated when we first started this," said Mahomed. "I was hoping that at least we could have some improvement in how we deliver care and hopefully have better access for our patients, but the outcomes were far better than that. It really is an example of how you can achieve a win-win for all of the stakeholders in this particular area of healthcare."

Who - Dr. Nizar Mahomed is the head of Orthopaedic Surgery for the Toronto Western Hospital University Health Network.

Issue - Hip and knee replacements currently require lengthy stays in hospital or in-patient settings to rehabilitate the patient, and as the number of hip replacements increases bed shortages will cause major delays.

Solution - Rather than rehabilitating patients in acute care or in-patient settings, thousands of patients were discharged into other care settings, such as their own homes.

Impact - Patient health outcomes actually improved, their hospital stays were shorter, hospitals were able to do more surgeries, and taxpayers saved millions.

An Ancient Medical Technique Fights a New Plague

Named by TIME magazine as the medical breakthrough of 2008, the ancient tradition of male circumcision is making a comeback as a way to prevent the transmission of HIV in Africa.

Africa has one of the highest rates of HIV and AIDS in the world. To respond to this challenge, numerous efforts have been made to stem the transmission of HIV in Africa. None has been as successful as male circumcision research done by Dr. Stephen Moses, a professor of medical microbiology at the University of Manitoba, and his colleagues.

In the late 1980s, Moses started working with the University of Manitoba/University of Nairobi research group at Kenyan medical clinics, which had noticed that circumcised males had lower rates of HIV infection than non-circumcised males. They did larger studies and published findings showing significant reductions of HIV among circumcised men.

However, despite similar studies in different countries consistent with Moses's research, many in the medical and public health community still had their doubts.

"It was very difficult to convince people that male circumcision was really associated with this reduced risk of HIV," said Moses. "Most of the studies were observational not experimental, and many people thought that it wouldn't be until the findings could be confirmed with randomized controlled trials that the evidence would be really convincing."

So, in 2002, after a few years of preparation, Moses and his group began a randomized controlled trial in western Kenya. They followed a large group of young men for several years, and they found that the circumcised men had a 60% reduced risk of acquiring HIV compared to the uncircumcised men. In fact the results were so convincing, the trial oversight board concluded that the study had to be stopped early, with circumcision offered to the control group.

Other groups in other parts of Africa have done similar studies and found the same range of reduced risk. As a result, the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAID) have both endorsed male circumcision as a method of reducing the spread of HIV.

"Many countries look to the WHO and UNAID to set guidelines and policy in this area," said Moses. "The fact that they've endorsed these findings and have recommended male circumcision in appropriate contexts, especially in areas where HIV rates are high and circumcision is not widely practiced, is very important for HIV prevention."

Many countries in central and eastern Africa where male circumcision is not normally practiced have already begun to offer the service with initial results showing a very large uptake, which should translate into a slowing of the HIV transmission rate in those countries.

"It's been very exciting," said Moses. "There aren't a lot of HIV prevention technologies that have proven to be effective. Over the last few years a number of things that seemed to have promise have turned out to not work really well, so it's quite exciting to be involved in research into an HIV prevention method that has been proven to be enormously effective, not just in our hands, but by others as well."

Who - Dr. Stephen Moses is a professor of medical microbiology at the University of Manitoba and is currently working on HIV prevention programs in India.

Issue - HIV is rapidly spreading throughout Africa with very few effective means to stop the spread.

Solution - Moses found that male circumcision reduced the risk of HIV transmission by more than 50%.

Impact - The World Health Organization and the United Nations have both endorsed male circumcision as an effective way to reduce the spread of HIV and medical services are being expanded throughout Africa to offer male circumcision.

Breathing Easy not Easy Work

Taking their first breath of air was a big challenge for premature babies until a London, Ontario scientist's discovery changed all that and saved thousands of newborns.

Until the 1980s, Respiratory Distress Syndrome (RDS) often claimed the lives of babies born even just a few weeks premature. Their tiny lungs could not inflate properly, and research had not found a solution to the problem. Some believed that premature babies couldn't produce enough of a natural material called pulmonary surfactant, which is needed to reduce the surface tension of water within the lung and enables the lung's surface area to expand.

Some investigators had tried blowing a surfactant-like lipid mixture into the premature lungs, but these tests were unsuccessful and were discontinued.

Dr. Fred Possmayer, professor emeritus at the University of Western Ontario's Schulich School of Medicine, was astonished by how many premature babies died of RDS in the neonatal intensive care ward at St. Joseph's Hospital in London, Ontario.

In collaboration with Dr. Goran Enhorning in Toronto, Possmayer demonstrated in tests with a fetal rabbit model that surfactant could help premature bunnies breathe easier and survive.

"We conducted studies where we actually showed that you could keep them alive. There was absolutely no doubt that this stuff worked," said Possmayer. "But the problem was you can't take surfactant out of a cow, or a pig, or a rabbit and put it into a premature baby."

Now Possmayer faced the challenge of extracting, purifying, and sterilizing the surfactant without destroying its protective effect. Previous attempts to sterilize the surfactant by a number of methods, including x-rays, ended up inactivating the surfactant proteins. Instead, he established methods using organic solvent extraction, which many had believed would completely destroy the surfactant's activity. Instead, the surfactant remained effective, while all microorganisms and nonsurfactant protein contaminants were eliminated.

Then, the group began testing the safe surfactant, named Bovine Lipid Extract Surfactant (BLES), in premature babies at Saint Joseph's Hospital and at the Hospital for Sick Children and Women's College Hospital in Toronto. Testing showed that, to be successful, the surfactant needed be given early and that the ventilator needed to be fine tuned or the infant's lungs would become irreparably damaged.

With the new protocol premature babies were given surfactant immediately after it was noticed there was an indication of RDS. The results were amazing. Within minutes, the baby's circulation improved and oxygen levels could be lowered in the ventilator.

Now, thanks to the surfactant and other new medical interventions for premature babies, the risk of dying due to RDS is much lower.

After saving the lives of countless babies, Possmayer's work on surfactant has shifted from children to adults. Thousands of people suffer acute lung injury every year due to pneumonia, near drowning, or even car accidents. In many cases, the lung's biodefense system responds by secreting cytokines that activate white blood cells to seek out and kill any invading viruses or bacteria. Unfortunately, those same cells can get carried away, attacking the lungs and other organs leading to multiple organ failure and death.

But surfactant can play a crucial role in preventing this destructive cell activation and could be a way to stop multiple organ failure. "If you could use surfactant early enough, you would stop that cytokine cascade, and if you could do that you could short circuit the system," said Possmayer.

And so Possmayer continues to work on fully understanding how surfactant does what it does. "You need to understand something to take advantage of it; otherwise it's really hit or miss. If you understand something a bit you can only use it a bit, but if understand something better then you can really use it."

Who - Dr. Fred Possmayer is Professor Emeritus at the University of Western Ontario's Schulich School of Medicine and Dentistry.

Issue - Premature babies suffer Respiratory Distress Syndrome (RDS) because they don't produce enough lung surfactant to inflate their lungs.

Solution - Dr. Possmayer showed that lung surfactant would help keep premature babies alive and purified the substance so it could be safely used in humans.

Impact - BLES, the surfactant Possmayer developed, is now manufactured in Canada and used by more than 99% of the neonatal intensive care units in Canada. Death by RDS is now a very rare problem for premature babies.

SOURCE Canadian Institutes of Health Research

For further information: For further information: David Coulombe, Media Relations, CIHR, (613) 941-4563 or media.relations@cihr-irsc.gc.ca; Kim Barnhardt, Communications and Partnerships Strategist, CMAJ, (613) 520-7116 ext.2224 or kim.barnhardt@cmaj.ca


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