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087 | Shifting thoughts and actions     Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. This week sheds light on antibacterial resistance and how that will change the course of the world on a widespread scale if our patterns do not change, how pharmacogenomics has become a new era in precision health, and how there may be a link between poor muscle health and type 1 diabetes.   Listen on to find out more!  ++++++  Ever consider a world where surgery was no longer an option? It is the unfortunate truth that if society does not slow the progression rate of antimicrobial resistance, life as we have come to know it will no longer be our future.  Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi. Without such means of effective treatment, it will compromise therapies that have been used for decades in healthcare and puts society in a very precarious position. Treatments such as major surgery or chemotherapy may fade into the background.  As we stand on the precipice of a post-antibiotic apocalypse, this global concern has researchers all over the world clamouring to find a solution before this issue gets out of hand. Kevin Schwartz, an infection prevention and control and antimicrobial stewardship physician from Public Health Ontario is one of those researchers seeking a strategy.  Dr. Kevin Schwartz says, “Antimicrobial resistance is going to be one of the biggest future challenges and it really threatens the way that we practice medicine. We take for granted some of the modern advances of technology that we will really jeopardize if the trend of antimicrobial resistance continues.”  Antimicrobial resistance happens when microorganisms change from exposure to antimicrobial drugs. It is a natural process that happens over time, but, unfortunately, that timeline has been accelerated due to the misuse and overuse of antibiotics in people and animals. Whether it stems from prescribing patients’ antibiotics for things such as a cold or flu, or when they are given as growth promoters in animals or used to prevent disease in healthy animals, the truth is that we need to find a solution to contend with these “superbugs” – and fast.  Antimicrobial resistant-microbes are found in people, animals, food, and the environment (water, soil, and air.) They can transfer from person to person, from person to animal and animal to person – that includes food of an animal origin – and is present in every country worldwide.  It’s such a huge global overwhelming problem. From hospital settings to non-hospital settings, using more antibiotics than we probably need to. There are a variety of reasons for that. Antibiotics are effective and life-saving, and often patients present with unclear diagnoses so antibiotics are often used to be on the safe side and so we are not missing a potentially treatable illness.  Schwartz adds that the fields of antimicrobial stewardship are trying to develop ways to help physicians and prescribers use the antibiotics more appropriately. There’s probably depending on the study and the area being treated, inappropriately prescribed 30-50 per cent of the time. So, there is lots of room to improve our antibiotic use.   However, there isn’t one strategy that is applicable across all patient settings and types of conditions and there is a lot of variability as to how antimicrobial stewardship can be implemented. For instance, the approach to improving antibiotics is going to be quite different depending on the setting. Some examples would be the difference in the intensive care unit compared to hospitalized patients, compared to patients treated in the emergency room, compared to patients treated in family doctor offices.  Schwartz focus is mainly on the out-patient setting. So, how can we approach family physicians and community prescribers to use antibiotics more appropriately? Some of the strategies to do this would be to provide feedback to family physicians. Some of the stuff that they are scaling up to do is to be able to give doctors some comparisons and feedback. For example, how much antibiotics are they prescribing compared to their peers? Then by identifying those doctors that are high prescribers we can have a significant impact to decrease overall prescribing.  He goes on to suggest that there are other simple measures that can be implemented, such as a study done in the US that monitored how a poster mailed to family doctor clinics and signed by the corresponding physician with the intent to use antibiotics appropriately displayed in the waiting room affected overall usage. The study showed that even this simple measure decreased over-prescribing by 20 per cent.  Public Health Ontario have done something similar in Ontario over the last year, partnering with Choosing Wisely Canada, an organization aimed to decrease waste and improve healthcare efficiency. So, they sent the poster to about 13,000 doctors in Ontario to hang in their offices for a similar purpose.  There are discrepancies in the system across the country, however, about the amount of antibiotics being prescribed by population and contrasting health regions. This could be due to the variance of the practice of physicians in different geographical locations. Some prescribe more, while others tend to prescribe less – allocating education and feedback as one of the best means to observe overprescribing.  There are notable differences between urban and rural environments prescription and usage, but through multi-variable modelling incorporating these variables as predictors, it is still undetermined why some prescribe more over others.  Schwartz says, “We want to make sure people are using the appropriate medicine for the appropriate condition. So, we’re not using overly broad, overly toxic medication when we do not need to.”  A study that was done in the UK highlighted what would happen if the course of action did not change over time. They estimated that there are roughly 700,000 deaths a year from antibiotic-resistant infections and that if we do not do anything by the year 2050, that number could reach a high of 10,000,000. To put that number in another light, the death toll will surpass cancer and motor accidents combined.  By weight, most antibiotics are used in animals, not in humans, and there’s lots of antibiotics in the environment and in other parts of the population. So, there’s all these different approaches where we need to combine – animal veterinary health with human health with environment – and all these different things need to come together so that we can mitigate antibiotic exposure and an element of resistance.  The importance of this issue can not be understated. All the advances that have been accomplished in health care will be for naught if antimicrobial resistance continues down this path. Successfully taking care of premature babies, organ transplant, bone marrow transplant, and complex cancer therapies are all prime examples of procedures that will become incredibly difficult or impossible to achieve. They all rely on the fact that we can treat the complications that go hand in hand with the procedure – namely infections. These patients are more susceptible to bacterial infection, and without effective antibiotics the procedure may be too risky.  If you think back to the way things were during WWI when there was no antibiotics when even a small wound in battle could be life-threatening or limb-threatening. We really take for granted what we now consider a simple condition, where in the past was life-threatening. Schwartz says they will become life-threatening again in the absence of effective antibiotics for these problems.  Physicians and dentists are examples of prescribers that need to prescribe antibiotics appropriately, and for the public to have an awareness of the risks of taking antibiotics unnecessarily over time. This awareness needs to be spread before the world turns into a post-antibiotic era. Antimicrobial resistance is an inevitable process. The bacteria are alive, and they will evolve to survive.  ++++++  Genomics is driving a paradigm shift from a disease-oriented health-care system to one that is more precise, personalized, predictive, preventative and cost effective.  Advancements in technology are helping make genomics more affordable and accessible than ever before. Likewise, societal attitudes toward genomics in clinical care are shifting. We are no longer asking ‘if’ genomics should be integrated with clinical care. Instead we are asking ‘when’ and ‘how’ we can use genomics to benefit as many people as possible.  With a vision to advance the use and application of genomics in clinical practice, Genome BC has invested almost $370 million in over 160 research projects. Genomics research is already saving lives and improving health outcomes and disease management for patients touched by cancer, heart disease, autism, epilepsy, rare diseases and other debilitating diseases. As genomics research moves from the bench to the bedside, clinical applications of genomics will affect many areas of medicine over the next 10-20 years, improving disease prevention, diagnosis, and treatment, as well as informing our approaches to wellness, nutrition, and public health.  Genome BC has had a long-standing interest in, and support for, a particular aspect of precision health called pharmacogenomics. Since 2004 we have invested in a number of projects analyzing the unintended side effects of medication, known as adverse drug reactions (ADRs). The discipline of pharmacogenomics, identifying gene variants that predispose people to serious side effects of medications or that alter the way your body will respond to, or metabolize, certain drugs, is being applied to improve the safety and efficacy of many therapeutics and treatments. We are funding teams across different levels of research in this critical field: in the hospital alongside clinicians, in the pharmacy and with primary care physicians.  At the hospital level Dr. Bruce Carleton and his team are working to prevent ADRs by developing laboratory tests to predict the likelihood of a childhood cancer patient developing an ADR and tools to incorporate these tests into clinical practice. At the pharmacy level another group, led by Dr. Corey Nislow and the BC Pharmacy Association, has developed a community pharmacist-based approach to pharmacogenomic testing wherein a patient’s saliva is tested for genes that will predict adverse reactions to commonly prescribed drugs. Finally, at the family physician level Dr. Martin Dawes and his multi-disciplinary team of doctors, pharmacists, and epidemiologists have developed TreatGx, a unique medication decision support system. Using the highest levels of evidence, TreatGX identifies personalized medication options for multiple common conditions. The options are presented to the doctor in an easy-to-read format with helpful information such as dosing instructions, potential adverse reactions, and medication cost comparisons.  Each of these research teams are bringing new understanding to the table, as well as integrating their work for maximum benefit to patients.  The goal of pharmacogenomics is to improve patient outcomes. In order to implement this tool effectively we must:  Validate the efficacy of genomics applications in day-to-day patient care  Ensure we are increasing value to patients and lowering costs  Identify and provide information related to diagnostic criteria and provide the relevant pharmacogenomics test(s)  Develop guidelines to help clinicians use these tests  Change perceptions for healthcare professionals and patients  Genome BC is working closely with the provincial government, universities, clinicians and other stakeholders to advance the clinical use of pharmacogenomics.  Canada is not the only country working to implement precision health- there is a global effort working towards a common goal. Momentum is building and there are success stories of clinical implementation of genomics happening in real time around the world. In BC there has been a critical change in the Hereditary Cancer Screening Program at the BC Cancer Agency because of a gene panel test that enables clinicians to test for more than a dozen of the most common mutations all at once, rather than one-by-one. This test enables people to learn what cancers they may develop, how often to have medical follow-ups, what cancer screening to get and whether there are preventive lifestyle factors that might mitigate the risks. Wait times for this test have gone from several months to a few weeks and BC Cancer is even helping other provinces clear their backlog. The hereditary cancer panel is now being reimbursed by the BC provincial government and has been fully integrated in clinical practice.  Clinical practice has begun to incorporate genomics technology and applications. Ultimately physicians will have practice guidelines to best move patients along a treatment pathway that is best suited to their own genetic makeup.  +++++  A recent study coming out of the labs of McMaster and York Universities have found that there may be a link between poor muscle health and type 1 diabetes – even among the youth.  The research team analyzed muscle biopsies of young adults with and without Type 1 diabetes who exceed Diabetes Canada’s recommended weekly levels for physical activity.  The researchers found structural and functional changes in the power generation parts of the cell, or mitochondria, of those with diabetes. Not only were the mitochondria less capable of producing energy for the muscle, they were also releasing excessive amounts of toxic reactive oxygen species, related to cell damage.  These changes have the ability to affect metabolism – the chemical processes that occur within a living organism in order to maintain life – resulting in a greater difficulty controlling blood glucose, and if unmanaged, could accelerate to a disability. The study findings add poor muscle health to the list of better-known complications of Type 1 diabetes, including nerve damage, heart disease and kidney disorders.  Thomas Hawke, corresponding author of the study and a professor of pathology and molecular medicine at McMaster says, “Now we know that even active people with diabetes have changes in their muscles that could impair their ability to manage blood sugar. Knowing in the long term that this could contribute to faster development of disability, we can start to address it early on.”   Skeletal muscle is the largest metabolic organ and is the primary tissue for clearing blood sugar after eating a meal, so it is necessary to keep muscle as healthy as possible.  With regular aerobic exercise, mitochondria in muscle increase to therefore help muscle cells use more glucose and become more efficient.  The researchers believe these dysfunctional mitochondria are what’s causing the muscle to not use glucose properly and to also damage muscle cells in the process and were surprised to see the muscles were this unhealthy in young adults with Type 1 diabetes who were regularly active.  Researchers say while further study is needed, revising evidence-based exercise guidelines, specific for those with Type 1 diabetes, may be required to keep them in the best health.  ++++++  Well that wraps up another episode of Biotechnology Focus radio. Thanks for checking in! If you would like to read the stories in full, please visit our website at biotechnologyfocus.ca. From my desk to yours – this is Michelle Currie.