Three-minute thesis competition video transcripts
Project Title: Towards optimising use of colistin against Pseudomonas aeruginosa
Supervisor: Professor Roger Nation
Research theme: Drug delivery, Disposition and Dynamics
The patients you see on the left represent actual patients. The patient top left developed a severe infection after undergoing a liver transplant. Penicillin antibiotics were commenced and blood cultures taken. Tests revealed the presence of a bacterium in the patient's blood, but it was susceptible to all usual antibiotic treatment. However, his condition continued to deteriorate, and after several changes of therapy tests revealed the bacterium was now resistant to all standard antibiotic treatments.
This scenario is increasingly common. All over the world bacteria are developing resistance to drug therapy, with outbreaks of MDR bacteria, or superbugs, now commonplace; this has caused some to suggest we may soon enter a post-antibiotic era. Fortunately, many of these superbugs remain susceptible to one particular antibiotic, colistin, which was added to this patient's antibiotic regimen. Within 5 days his condition dramatically improved, and within 2 weeks no bacteria remained in his blood.
Colistin is an old antibiotic, virtually abandoned as therapy for more than 20 years. However, as resistance has rapidly developed to the newer agents that replaced it, it is now increasingly used as the agent of last resort to treat these otherwise untreatable infections. Colistin was never subjected to many of the standard drug therapy tests required of more modern drugs, and we simply don't know how to use it optimally. This first patient was fortunate. Many recent studies have shown that colistin concentrations are often too low to be reliable effective. This provides the perfect opportunity for resistance to develop, and worryingly, that is exactly what we are starting to see. As colistin may cause reversible but severe damage to the kidneys, simply increasing the dose is not an option in many patients.
Our lack of understanding of how to best dose colistin is perfectly illustrated by the patient bottom left. This woman was on haemodialysis, contracted an infection with a MDR bacterium, and received colistin as last-line therapy. It was only after she died that the concentrations of colistin were found to be extremely low, rapidly removed from the blood by hemodialysis. Clearly, the colistin dosage regimen administered to her was inadequate, but we still don't know how best to dose colistin in patients on hemodialysis.
The research undertaken in my PhD seeks to fill some of these gaps in our knowledge. I have undertaken many of the types of tests performed on more modern antibiotics with the aim of learning how to administer colistin most effectively, maximizing bacterial killing while simultaneously reducing the emergence of resistance. I have investigated such things as the optimal dosing frequency, strategies to predict the extent of bacterial killing, and examined colistin combination therapy against MDR organisms.
So, why the empty bed on the right? This bed awaits a patient sometime in the near future. It could be waiting for you, or someone you love, whose only treatment option is colistin. Until recently, it would be administered based more on tradition and guesswork than scientific evidence. This time, I hope that with the knowledge gained through my research, it can be administered in a way that is safe, effective, and without resistance developing, giving this, and subsequent patients, a fighting chance at life. And hopefully, it will keep the postantibiotic era at bay a little longer.
Project title: Understanding allosteric modulation of GPCRs
Supervisor: Professors Peter Scammells and Arthur Christopoulos
Research theme: Medicinal Chemistry / Drug Discovery Biology
The entire human body is made up of cells. These cells are like light bulbs, flashing on and off at different times in order for our bodies to function correctly. For example, the muscle cells in our legs flash when we are walking, cardiac cells within the heart flash on and off with every beat, and cells within the problem-solving regions of my brain were definitely flashing when I was trying to come up with a clever way to explain my research in just three minutes.
The receptors on these cells are like electrical wiring, whilst the active sites present on receptors are like light switches. Finally, the natural chemicals travelling through the body act as microscopic specialised "hands", flicking the switches on and off as required. The body is healthy when these many "hands" are making light work, so to speak. But when they are malfunctioning, the result can range from a minor illness to a debilitating disease state.
Many drugs are designed to act as substitutes for these hands, but because they are not nearly as specialised as the natural "hands" present in the body, and because the light switches in different areas of the body often look very similar, drugs frequently switch lights on and off too rapidly, too slowly or in the wrong places, often generating severe side effects.
An exciting discovery is that the wiring of our cells is also connected up to the physiological equivalent of dimmer switches.
Because these dimmer switches provide a whole spectrum between light and dark, and happen to be more unique in appearance than the on/off switches throughout the body, the differently-shaped "hands" that target them are able to generate more fine-tuned lighting, whilst avoiding the undesirable effects of flicking the on/off switches. In real terms, this equates to drugs that have the potential to be more selective and therapeutically effective whilst producing little to no side effects.
My research involves designing, making and testing molecules which are able to act as "hands" at the dimmer switches of brain cells shown to have a role in the progression of Alzheimer's disease. The development of such a drug may not only be able to treat the symptoms of this devastating condition but to slow or halt the degeneration of the cells involved.
Now that's certainly something worth shedding some light on.
Project Title: Promoting Evidence-Based Weight Management Recommendations for Women Pharmacy Consumers
Supervisors: Associate Professor Jennifer Marriott and Dr Safeera Hussainy
Research theme: Centre for Medicine use and safety
Imagine you are a 40 year old overweight woman, sitting watching television after a hard day at the office, you flick through the channels wanting to watch something decent only to find commercial breaks. To your amazement every commercial is focused on one thing...weight loss. Quotes such as "lose 10kgs in 10 weeks" , Set yourself free" and "Start losing weight today" have been stamped in your mind. Being a researcher you think of one thing...which of these products and programs are evidence-based, which product or program is going to give you the best result and which health care professional can help you make that decision?
Good morning everyone and welcome to my three minute thesis. Currently in Australia over 60% of males and females are considered overweight or obese. There are numerous health risks of being overweight and obese including increased risk of heart disease, diabetes, stroke and in women increased risks of infertility, pregnancy complications, and certain cancers. And even with half of the population attempting to lose or maintain their weight at any given time and consumers spending 790 million dollars annually on weight management programs and product, the prevalence and cost of overweight and obesity in Australia continues to rise.
Undoubtedly better access to overweight and obese treatments are needed and that's where pharmacies can play a significant role.
Pharmacies are where women go to join weight loss programs, to get meal replacement products, to pick up vitamins or prescription medication to help them with their weight loss journey. Currently, however, resources to assist pharmacy staff in making evidence based weight management recommendations are limited and needs to be addressed.
So that's where my project come in; My PhD project aims to develop women specific weight management guidelines and educational resources for community pharmacies. I'm going to develop these resources using results from 6 different phases as outlined in this slide.
Phase 1 asked the sometimes dreaded question "what do women want". This phase has already been conducted in Nottingham, in the UK and Victoria and aimed to survey women pharmacy consumers to obtain information about women's attitudes and experiences to current weight management products and programs and to find out what they would want in their ideal weight management program.
Phase 2 explores pharmacists and pharmacy assistant's current knowledge and recommendations and what further information they require to better respond to their consumer requests.
Phase 3 involves using mystery shoppers to enter a pharmacy and find out what advice pharmacists and pharmacy assistants give their patients about weight management in a real-life setting. The draft pharmacy weight management guidelines and educational resources specific to women will be developed.
Phase 4 involves receiving advice from pharmacists, dietitians, doctors and specialists regarding the draft guidelines and educational resources before they are finalized, implemented and evaluated and finally given to key stakeholders such as the pharmaceutical society of Australia or the Pharmacy Guild in the hope that they will be implemented Australia wide.
These guidelines and educational resources will aim to facilitate weight loss and weight maintenance in overweight and obese women, they will give pharmacists and pharmacy assistant's clear directions on what to recommend and as for the ultimate goal they will help Australia become a healthier country.
Project Title: A review of dose administration aids: Improving medicine management
Supervisors: Associate Professor Jennifer Marriott and Dr Safeera Hussainy
Research theme: Centre for Medicine use and safety
Now you are probably looking at my project title and thinking, "Julia, what is so interesting about dose administration aids (DAAs)? Isn't it a bit dry and boring to be investigating the blister packs and sachets that organise medicines and assist in medicine administration at aged care facilities?"
Well, I'd like you to think about a few things. Australia's population is ageing. Reports have shown the number of those over 85 are going to more than quadruple in the next 40 years, and aged care facility populations are on the rise. Unsurprising with this ageing population. With this in mind its likely each one of you knows someone in an aged care facility. And it is unsurprising to know that a key factor maintaining their health are their medicines which are commonly supplied by pharmacists in DAAs.
Now what if I told you that studies in NSW and QLD have shown an error rate of these DAAs around the 3-4% mark? What if I followed that up with the findings of a Victorian pilot study error rate of around 11%? Now that's alarming, and it makes research just a little bit more interesting and certainly very relevant in this day and age.
I wanted to investigate the accuracy of DAAs prepared by pharmacy for Victorian aged care facilities on a large scale. By comparing DAAs with resident medicine records I could ascertain if they were packed accurately and appropriately (DAA audit). These pictures show you some things I found and these case studies illustrate the findings in two facilities.
Now you might be thinking, the facility would pick up on the error when it arrives. But you've got to remember around 60% of residential aged care workforce are carers and are not trained med experts and not required to identify medicines before they are administered. So, pharmacists really can't afford to be making these errors as they are potentially the last person who checks the packs before your elderly relative is taking those medicines.
With this in mind, the next stage of my research is to consolidate my findings and develop a quality improvement toolkit to target pharmacies and aged care facilities and reduce the incidents of errors in DAAs. This has the potential to also help community dwelling users of these devices. The success of the intervention will then be evaluated with a follow up audit of DAAs.
We don't live in a perfect world. People make mistakes but I'd like to think this research can make it just a little bit more likely that person you know who lives in an aged care facility is getting what they should, while they are relying on someone else entirely to manage their medicines and their health.
Project title: Investigating Cannabinoid Receptor Interacting Protein CRIP1a as a novel therapeutic target
Supervisor: Dr Daniel Malone
Research theme: Medicinal Chemistry
The image on the top left corner is that of a sea squirt which is in fact a marine animal that anchors to the sea floor. These little creatures have been around for 500 million years and have more in common with us than you might think. As with all animals, the sea squirt and us have what's called a nervous system which is basically a control center of the body. Within it you have cells that carry signals or messages. Where ever these cells meet, the signal is passed to a receptor in the next cell by a chemical known as a neurotransmitter. For example sometimes these messages can be telling your body that it's feeling pain.
What's fascinating is that millions of years ago the sea squirt evolved a set of new receptors known as the cannabinoids receptors which we also evolved to express. In us there are two receptors CB1 and CB2 with CB1 found highly in the brain in neurons that release the neurotransmitter glutamate and GABA.
The cannabinoid system in our body acts as a regulator of neurotransmitter release, making sure the body on functioning at the correct balance of chemical signals. Chemical messages need regulating in our body for good reason. If you have too much of a signal it can actually be toxic to the body and brain cells. For example in epilepsy there is excess of the neurotransmitter glutamate being released. But when the cannabinoid CB1 receptors are activated they cause the nerve cell to reduce the amount of neurotransmitter being released
The main aim of my project is to better understand CB1 mediated effects in the brain. Specifically I'm studying a cannabinoid receptor interacting protein called CRIP1a, which communicates with CB1 to increase neurotransmitter release. CRIP1a is unique in that it's only expressed with CB1 on glutamate neurons, cells where activation of CB1 is linked to positive effects like providing neuroprotection, reducing anxiety and also reducing pain. While CB1 activation on GABA neurons are linked to detrimental effects. To study CRIP1a a technique known as siRNA knockdown, this basically interferes and reduce expression of CRIP1a in the brain. We think that by decreasing CRIP1a positive effects seen with CB1 activation will be enhanced.
We are hopeful this work will provide evidence for CRIP1a as a potential therapeutic target for individuals suffering from epilepsy and anxiety-related disorders.
Project Title: Pacemaker 'waves' and 'sparks' in the Prostate
Supervisor: Dr Betty Exintaris
Research theme: Medicinal Chemistry
The male prostate is located beneath the bladder and surrounds the urethra. Its function is to produce prostatic fluids that optimises fertilisation but commonly undergoes changes that can lead to BPH. BPH is the enlargement of the prostate which can constrict the urethra and push into the bladder, ultimately resulting in lower urinary tract symptoms that lower the quality of life and while current pharmacotherapy can treat the symptoms, there are associated side effects so there is a need for an alternative treatment to get to the root of the problem. Part of BPH is caused by an increase in smooth muscle tone which occurs due to changes in spontaneous contractions with age. The aim of my thesis is to investigate what is causing these spontaneous contractions and potentially, how we can stop these contractions from occurring in the aging prostate.
For the first time, we have identified that the source of spontaneous activity is likely to originate from prostatic interstitial cells as shown in the bottom picture. These cells act like pacemaker cells in the prostate, initiating constant electrical pulses that propagate in waves to neighbouring smooth muscle cells resulting in co-ordinated contractions. We have seen that an increase in spontaneous contractions occurs with age and this is due to a change in Ca2+ levels.
There are two sources of Ca2+ that contribute towards contractility: Ca2+ release from the mitochondria which constitutes Ca2+ sparks, and Ca2+ release from the endoplasmic reticulum which constitutes Ca2+ waves. I have found that an increase in Ca2+ sparks and a reduction in Ca2+ waves occurs with age so by inhibiting the enhanced Ca2+ sparks, this can reduce the spontaneous contractions in the prostate.
To summarise, the identification of prostatic interstitial cells not only provides a better insight into how the prostate functions with age but also provides a novel target for a more specific alternative treatment to relieve an enhanced smooth muscle tone as seen in BPH.
Project title: The development of dry powder influenza vaccine formulation
Supervisor: Dr Michelle McIntosh
Research theme: Drug Delivery, Disposition and Dynamics
Sneeze -> excuse me -> if I was an active influenza virus carrier, I've just successfully transmitted the virus to everyone here, especially to this group of people here at the front row. How good would that be if we can utilise this natural transmission mechanism of influenza virus to transfer immunity with airborne particles, but, without transmitting the disease at the same time? Isn't that great? This is exactly what this project is all about.
Influenza is a very common infection that affects almost everyone at some stage of our lives. From epidemiology studies, influenza causes on average 2000 deaths and 10000 hospitalisations in Australia every year. The infection can cause serious complications, not only in the respiratory tract, but also in different parts of the body. Cardiovascular complications such as myocarditis and pericarditis, CNS complication such as encephalitis, and respiratory complications such as acute bronchitis and secondary viral and bacterial pneumonia. These complications are life-threatening and are common in high risk groups, such as children and elderly, or patients who are immuno-compromised because of their medical conditions. Annual immunisation in these groups is therefore recommended in clinical practice guidelines. In fact, the H1N1 influenza pandemic only 2 years ago in 2009 reminds us just how important it is to have protection against this common infection.
The development of inhalable dry powder influenza vaccine formulation aims to simplify, and therefore improve access and uptake of immunisation, by utilising the natural transmission mechanism of influenza virus to transfer immunity with airborne particles. This approach can help to remove many of the problems associated with injectable liquid vaccine formulations such as the complications associated with handling sharps and needles, the risk of needle stick injuries and transmission of blood borne viruses, the cold-chain storage requirement for liquid formulations in transit, and the need for trained medical personnel for administration.
Eventually we want immunisation to be easy. We want everyone to be able to just breath in the vaccine without all the complications associated with injectable liquid formulations.
Project Title: A Team Approach to Optimising Medication Outcomes in Primary Care
Supervisor: Dr Johnson George
Research theme: Centre for Medicine use and safety
Some things in pharmacy just work better together. Vitamin D and calcium. Amoxycillin and clavulanic acid. Homeopathy and the placebo effect.But perhaps one of the most important pairings that work better together, is that of pharmacists and other health providers working together to provide optimal patient care.Pharmacists are the drug experts, and by combining their unique expertise with that of other health professionals, patients can benefit from improved medication use and an enhanced level of care.
However, at present, pharmacists exist on the periphery of the Australian primary health care team. The collaborative services currently provided by pharmacists and GPs are still limited by geographical isolation, poor access to patient information and inter-professional communication that is largely sporadic, fragmented, and problem focused. This is unfortunate given that Australia's population is getting older and sicker, and patients in the community are at an increasing risk of having MRPs. In fact, the literature shows that 1 in 10 patients who see their GP experience an ADE with over half of these considered moderate or severe, and a staggering 8% requiring hospitalisation.
Put simply: we need to work together to optimise medication use in primary care.
A possible solution, and the focus of my PhD, is the integration of a clinical pharmacist into general practice. Such arrangements have been implemented successfully overseas and it is envisioned that such a role can be developed within the context of the Australian general practice.
To address this issue, my study comprises two main phases:
In the first phase, I interviewed a range of stakeholders, including GPs, practice staff and pharmacists, to explore their views on this potential integration. We discussed the roles of the pharmacist working in Australian general practice and the perceived benefits and disadvantages of these. Participants also shared their thoughts on the challenges of integration and how these could be successfully overcome.
The findings from phase one will guide the development of the ideal practice pharmacist role. In phase two, I will pilot test this role in a sample of general practice clinics in Victoria. This new collaborative service has the potential to reduce medication errors, improve the quality of prescribing, and optimise patient health outcomes. Additionally, it will create new job opportunities for a profession that is currently undervalued and underutilised.
This is just an example, of one way we can potentially improve the care of patients in primary care. So, like Vitamin C and ferrous sulphate, let's work together towards a healthier, safer and better tomorrow.
Project Title: Competence Assessment in Australian Pharmacy Students
Supervisor: Associate Professor Jennifer Marriott
Research theme: Centre for Medicine use and safety
It's Sunday morning and you have just woken up with a terrible cold, you manage to drag yourself out of bed and go down to the local pharmacy to buy some cold and flu tablets. When you arrive James, the pharmacist, hands you a bottle of throat gargle and a box of cold and flu tablets and says "don't swallow it, no more than 8 a day, and that will be $20 thanks". You leave the pharmacy wondering what on earth you are meant to do, so you call your sister who is a pharmacist. She explains how to take the medicines and starts laughing, so you ask her "what's so funny?'. She tells you that James always beat her on every single exam at uni and always rubbed it in! So she was glad to see that success at uni clearly doesn't guarantee professional competence.
Pharmacists must be competent, to optimise the safety of their patients and the general public, and to uphold the highest professional standards. So how do we ensure that Monash graduates are competent by the time they start working?
Since competence is about the integration of knowledge, skills, and attitudes into overall suitable performance, no one single testing method can confirm competence. Currently we are good at assessing knowledge, and do a reasonable job of assessing certain skills. However there is clearly a need for other forms of assessment which test the incorporation of knowledge, skills, and attitudes to allow us confidence in those graduating. This is where the Objective Structured Clinical Examination, known as the "OSCE' for short, comes in!
The OSCE is a multi-station examination format in which all students rotate though the same series of stations where they face a different clinical task, patient and examiner at each station. It has been found that the OSCE is able to achieve very high levels of reliability and validity when appropriately designed, implemented, and evaluated. Consequently it is seen as a fair way of teaching and assessing not just what students know, but what they can do in realistic situations. Despite the major advantages of the OSCE format, use in Pharmacy is just in its infancy, with Canada leading the way, and countries like Australia yet to implement OSCEs in any significant way. This could be, at least in part, due to the costly and complex nature of the OSCE.
What I hope to achieve is a reliable, valid, cost-efficient, and acceptable OSCE which allows us to be confident in the competence of our graduates. I also hope that what students learn through our OSCEs will have positive flow-on effects where Monash graduates help to raise the quality of the overall profession, and that our work will produce a more widespread effect on the profession by inspiring other institutions to implement a similar system.
At this early stage in my candidature I am completing my literature review and planning the details of my project. I hope to implement the OSCEs in first semester 2012, with a second OSCE in first semester 2013. This will allow me to study predictive validity which is an area that has received little research attention in pharmacy yet is truly at the core of competence assessment since it asks the question "Do scores on an OSCE predict who will become a good or bad pharmacist?'.
I am very excited and grateful to be conducting research in this area, and cannot wait to see how it all plays out!