 Tēnā koutou katoa, no mai haere mai, ne ratamihi koutou, o te whare whananga o tamaki ma koro, ana waka, ana hoa e fa, ana mana, ana iwi, ana manu korero o te marae. Tēnā koutou, tēnā koutou, tēnā koutou katoa. Our guests, this special contribution is the 50th anniversary lecture series of the Faculty of Medical and Health Sciences. Thank you for coming out on an evening like tonight. I'm Alan Merri and I'm Head of the School of Medicine here. I will be the Master of Ceremonies tonight. But before we start the main part, I'd like to introduce Sir Brewster to speak about AMRF. Good evening everybody and I'll just echo Alan's words. Thank you so much for coming out this evening. It's cold and it's rainy, so you are the brave frontier that has come out tonight and you will not be disappointed. We've got a fantastic range of presenters talking tonight about a whole host of subjects. So I am from Auckland Medical Research Foundation and we've been very fortunate to partner with the Faculty of Medical and Health Sciences for this lecture series. It's their 50th year celebration, so I'd actually just like to acknowledge distinguished Professor Ian Reid and also Professor John Fraser and thank them very much for our partnership and the opportunity to be involved. It's been absolutely invaluable and the six lecture series we've had have all been different but immensely worthwhile in terms of knowledge and information that's been imparted, so thank you. And I'd all just so like to say that tonight's lecture series includes a whole range of subjects, one of them being diabetes, and if I reflect on where research has taken diabetes over the years, it's been hugely significant in terms of understanding both Type 1 and Type 2, but I think I also saw something recently which showed how insulin used to be injected. So the things that we used to take, we take for granted is the way that even we administer medication these days in pharmacology as one of the subjects tonight has changed so immensely and that is due to research. So for all of our supporters here tonight and everybody who makes that research possible, thank you so much because it does change lives and it brings massive advancements in medicine. And last word on Auckland Medical Research Foundation, for those of you that don't know, we fund medical research and that's our sole purpose and due to a generous benefactor giving us all of our administration expenses, 100% of your donation can actually go into medical research, so that's something that people really value for our organisation. So thank you very much for coming tonight, thanks for the opportunity to say hello and I'm sure you will enjoy all of the wonderful presenters here tonight. Thank you. Thank you very much and I would just reciprocate with the thanks of the faculty for the support of the AMRF and my own personal thanks because I have been a recipient of some of the grant money from time to time. Now the format for this evening is that we have four very distinguished speakers who will each present quite different talks actually, but I think it will work best if we take the four talks and then they'll come up as a panel and we'll have a chance to have questions on any of them at the end. So if you have burning questions during any of the presentations, just make a note of them and we'll deal with them at the end. So the first of our speakers tonight is Professor Sally Merrie. Professor Merrie is a child and adolescent psychiatrist, the Cure Kids Duke Family Chair in Child and Adolescent Mental Health and the head of the Department of Psychological Medicine in the Faculty. Professor Merrie is interested in the development and implementation of effective therapies in child and adolescent mental health including computerised mobile phone based interventions and she's going to talk to us on bits, bots and beyond the promise of challenge and technology in improving mental health. Sally. Thank you, Alan, and greetings to everybody. Tana koutou katoa, talofa lava, maloile lei, warm Pacifica greetings, warm Maori greetings and warm greetings to all our varied population in New Zealand. It's a great pleasure and honour to be here tonight and I'm going to talk to you about bits and bots and the promise and challenges of using technology and I guess one of the questions that people say to me is you're a child psychiatrist, you shouldn't be using technology. We're supposed to be getting our kids off phones, we're supposed to be getting them off computers, we're supposed to be getting them to exercise more to interact more. Aren't you worried about the difficulties about that? For me technology is a two-edge sword and I think the first question is why use technology anyway and I've been an advocate for this for many a long year and for me the reason is that 13 to 20% of young people have a mental disorder in one year and less than half of us gets treated. Imagine if less than half of our young people with asthma or with diabetes was treated. Imagine the outcry and yet we leave our young people with mental health problems without the help they need. We've got US figures on the lack of treatment but this is also borne out in New Zealand and in New Zealand the secondary mental health services are funded only for the 3% of young people with the most severe mental health problems. On the other hand New Zealand is an early adopters and by the middle of last year there were 3.8 million mobile phones with active internet connections and we know that young people are on phones, we know because it's driving us crazy because we keep telling them to switch their phones off. We also know that it's spread around the country and that it's actually spread very widely so including for Māori and Pacific people some of the people who have the biggest disparities in mental health. So my story with this and I'd like to share a little bit about this, it actually goes back to 2003. I had a conversation with a GP friend of mine many years ago who was picking up mental health problems in her general practice and couldn't find therapists to see the young people she was seeing and she said to me, I think you should take cognitive behavioural therapy, one of the evidence-based therapies particularly for depression and anxiety and put it onto a CD-ROM so that I can run it in my office and I had a PhD student who's now Dr Caroline Astasiak who's a very able and quite charismatic researcher and she set out to make a very early prototype using a flash-based program to put CBT onto a CD-ROM and she also created an education program and she did a randomized control pilot trial to compare the two and showed that the journey worked. All well and good, except that she got feedback from the young people who said well this is okay but actually it's quite boring compared with the games that we play and they had a whole list of things that they thought that they wanted us to do to improve it. So we're very fortunate to be able to then have this to take to the Ministry of Health who then funded the development of a serious game and we set out to create sparks and what we wanted to do here was to address some of the difficulties that they had identified. So we wanted to make it immersive, we wanted to make it like the games of the day, we wanted to use a fantasy game format, we wanted to make it very engaging. We drew not only on gaming technology but also on e-learning theory and we particularly drew on something called a bicentric frame of reference which was proposed by Didi which actually says that you can learn by emotion but you learn better still if you can actually step back and make sense of it. So we landed up with a two-phased game and you can actually see that this here you will be looking at the guide and the guide is looking straight back at you. So this is a first-person game and the guide interacts with the young person and he will provide opportunity for screening, he will provide psychoeducation, he will provide challenges in the real world, he also provides choice so that young people can screen to see whether or not they've got problems that are likely to be helped by sparks and then he offers them a choice would you like to play this game or would you like to do something else and offers options if they do. If they choose the game it then goes into a third person format so you can see here they can actually choose the avatar, the avatar is customizable by skin colour hair, colour hair styles, the trim on the clothes and so on and then the avatar enters a fantasy world in which there are a number of challenges and the goal in this world is to the world is beset with gnats which are gloomy negative automatic thoughts and they need to be guarded by a circle of power. The circle of power has been destroyed, the gems are scattered to the four corners of the earth and your job is to go and find the gems and restore the circle of power and to do so you go through different provinces and each one of these is loosely linked to the cognitive behavioural therapy construct so you deal with unhelpful thoughts and with unhelpful emotions you overcome problems. Along the way you find some gnats which are gloomy negative automatic thoughts and you get to fight those, the young men that we were co-designing with really wanted to shoot stuff, we didn't want anybody to die in a game for depression so we thought that they could shoot the gnats and also catch sparks, smart, positive, active, realistic, expector thoughts. Having developed this we then wanted to test it to make sure it worked and so we did a randomised control trial and we were very thrilled, we have quite a small research team were then and were very thrilled when it was accepted by the British Medical Journal and they liked us so much they put us on the front cover. Now I think until that point we'd really thought that you know we're in a tiny little country at the end of the world and Silicon Valley is probably doing it better but we attracted a huge amount of international interest and we actually realised at that point that we were a bit ahead of the curve. We won some international awards, we got quite a lot of media coverage and we were feeling like the bees' knees. However, no sooner had we done this than the technology started to date and we had to move it very quickly from the CD-ROM, does anybody remember those even, onto the internet particularly because at the time the Prime Minister John Key had a youth mental health project and he wanted to launch it as a national programme and it was launched in April of 2014 and has been running and is available free of charge in New Zealand just on the internet, you can get it by just searching for sparks. And since then we've been collecting data on its usage and since it was released more than 18,000 people have accessed the website and we've been able to keep those web views going because we've been iterating as we've actually been going and built into sparks is a system to actually see whether or not it keeps working. So this is the PHQA which is a measure of depression that's built into sparks. We built this from people with mild to moderate depression. We thought that people with moderately severe and severe depression should actually go and see somebody but you can actually see here that the no symptoms don't change much, you would expect that and neither do the mild. The people with moderate depression improve, the people with moderately severe and severe depression improve the most which was a bit of a surprise to us and a bit reassuring because at least half our users are in the moderately severe to severe group. So that was all great and if you remember when I started when we set out to develop this we wanted something that would be really exciting and fuse young people and we wanted this sort of reaction. The sad news is that we didn't quite get it although we got really good completion rates within the trials in the wild it doesn't it isn't the same and we get quite a big drop-off at each module so about two-thirds of people who do each module do the next one so that by level four we've got about 11% of people completing and I guess perhaps we shouldn't have been surprised at this if you think about the number of people who take up gym memberships and don't follow through the number of people who don't finish the antibiotic courses and so on but I think that's one of the challenges is going forward to make it more sticky to use the parlance. The other big challenge is the design cycle so we started in 2003 we actually designed SPARX in 2008 we were going quite fast to get the national rollout in 2014 but we've had to really work hard to try and keep up with technology and we released a mobile phone version now but we're getting a lot of feedback that this is looking like a 2008 style game and the way that you interact on on phones is actually really quite different from how you interact on computers and so I'd like to spend the second half of the talk actually talking about where are we going to go to from here and what might we think about and we've been very fortunate to be part of one of the national science challenges very fortunate and also somewhat challenged because it's quite a difficult funding process but it's actually given us access to funding to allow us to think longer term and these these challenges are funded by the Ministry of Business Innovation and Employment and the idea here is that researchers from across New Zealand get together to collaborate to tackle some of the big problems in New Zealand the problems being tackled here in Abeta Staate, Tu Pu Eirea, obesity, literacy and youth mental health and the use of big data to inform better care and so we've got in this habits health approaches through behavioural intervention technologies and our vision is that we would create a go to IT ecosystem to improve health and well-being for young people a sort of trade me of health and well-being for young people that's known within New Zealand as the place to go we've got the important thing from this is the platform and this hosts things like online screening to see if people have actually got difficulty that could then provide ongoing referral to face-to-face therapy or could provide a range of apps a smorgasbord of apps that might help various problems that could then be monitored to combat the problem of rapid development we could do rapid online RCTs and then we can also link to the national databases particularly the integrated data infrastructure which has been created by Stats New Zealand to look at the longer term impact of some of these interventions. Co-design is really important and we started off co-designing with young people but we now realise that co-design is a much wider process and it's really important to be thinking about how does it sit in current health services what are the government priorities what about families and communities and that we need to really co-design with developers and learn from them. This is a little group from a lovely group of young people from Wontree Hill College who've been helping us with the design of our new apps and in the corner there is Tony Patola who's a Pacific Research Assistant we've got two Pacific and one Maori so we're also trying to support development of the workforce in one of our co-design workshops we've decided we've discovered that young people are different users so depending on how old they are and whether or not they have symptoms they want different interfaces so we've actually got players or gamers young people who would look who are pretty much engaging you know like 11 12 13 year olds pretty happy to engage as long as you've got a game interface in contrast older adolescents who might have symptoms who say cut out that game rubbish we don't want any games just tell us like it is and then we can put some help and then we know what to do so what we're working on is youth chat for screening this is an online screening that can be used in schools to identify young people with difficulties and we've carried out a feasibility study comparing it with heads which is an interview and we've actually shown that it's a very effective and efficient young people like it so do school nurses it helps them to triage better we've actually built we're on our second prototype of the platform and we've got a lot of functionality in there and we're looking to link it to the big data project and to this integrated data infrastructure and we've got this whole suite of apps here we've got play kindly and super kids for parents of young children preschoolers we've got kakano which is a project in christchurch following the difficulties some of the young children there have ongoing mental health problems and the parents want extra help it's five to 12 year olds we've got an app and a chatbot for mental health and an app to decrease risky behaviour and these are all being developed and we're trying to run clinical trials for these over the next 18 months or so to give you an idea about what it looks like te fitiyanga the quest is our app for emotional health and this is the relaxation module in this you go from island to island again doing various things that you can actually do on your phone and earning money and being on a leaderboard and things not real money money in the game this is headstrong which is a chatbot and I didn't even know what chatbots were but apparently you access you can get you can download these on your phone but they can also enter things like messenger so tracking where young people are and what they're using is actually quite a challenge and so we're using chatbot for 15 to 18 year olds they're sort of the more sceptical young people with a cast of characters to represent young people in New Zealand and this will give us in the future the opportunity to use machine learning and artificial intelligence to further develop these things this is play kindly which is a project that we've been doing linked in with the pacifica group and I don't know if you'll recognise but this is actually Oscar Kitely who's been involved in this project and this is actually to support parents of young children and this is kakano this is the Christchurch project that we've actually been doing we need to integrate it into services which I've talked about before and we've been thinking about how's this going to link into communities how's it going to link into health services how will it link into schools so what I'd like to do is finish by actually showing you a little video that we've actually got that gives you an idea about how we see it in practice in schools using our youth chat screening and I hope it's common for young people to feel stressed out or down mental health problems affect at least one in four young people there's about seven students in an average size New Zealand class over half of these young people don't get the support they need because they find it hard to ask for help and access services habits is a secure web and mobile space where young people can access digital screening and intervention tools for mental health and well-being it's based on proven strategies that work for young New Zealanders so how does it work meet Edina she's just started high school Edina is nervous about being at a new school Edina lives at home with her whanau like many families they don't always see i to i and Edina finds it hard to talk about what's going on all of these worries are adding up and she feels down a lot of the time sometimes she cries in her room alone at night she doesn't know what to do and where to go for help so where does habits come in Edina's school has signed up to use habits and all year nine students are trying it out Edina starts with check it answering a few questions about how things are going for her once she's filled it all in habits responds with feedback on her scores and gives her some options to move forward the school nurse gets reports on all the year nine to have completed check it Edina's results show that she's feeling down and so the school nurse makes a time to see her the nurse and Edina have a talk about what's going on at home and school they work together on what might help including choosing some support people Edina chooses to tell her dad about habits Edina agrees to try one of the habits apps they start the app together it looks helpful and Edina decides to keep using the app at home on her phone at the end of the activity Edina has the option to share her progress with her support people Edina likes using the app and decides to check out what else is on habits site she finds other apps that look helpful when bit by bit she starts to feel better by using habits Edina's school have been able to identify other students who are having a hard time and support them to get help via the apps the school nurse and other options the research from the habits team can use anonymous data to improve the apps that way they can help more and more young people to flourish with the support of digital technologies obviously I haven't done this on my own I'd like to acknowledge our comata Rauri Faramate who has stepped each step of this way along with me and my wonderful research team who are enormous and I'd just like to acknowledge all our funders and what isn't here but we actually have a a co-funding project with AMRF as well within this so thank you very much thank you Sally that's a great start to the evening our second speaker tonight is Associate Professor Rinki Murphy Rinki Murphy is an endocrinologist who works in Auckland and County's DHB she's an Associate Professor in Medicine at the University of Auckland and a principal investigator at the Morris Wilkins Centre for Molecular Biodiscovery a national centre of research excellence. Rinki's research in diabetes and obesity spans genetics, physiology and clinical research. Rinki is going to speak to us tonight on diabetes and obesity when one size does not fit all. Rinki Murphy. Thank you very much Ellen, tena koutou, tena koutou, tena koutou koutoua, malo alele, namaste, greetings to you all. I'm delighted to be able to speak with you tonight on diabetes and obesity two of the biggest health challenges to face New Zealanders. If I could just turn the projector on. So we all are aware of obesity we're not particularly proud of being on the top of the leaderboard for obesity around the world we are third in place second to Mexico and United States this is in selected countries in 2009 and since then our obesity rates have actually continued to rise from about 10% in the late 1970s to almost a third of our adults being obese in recent times. We're concerned about obesity because of all the host of medical complications from lung disease fatty liver coronary artery disease diabetes and certain cancers and the impact that has on quality of life health care and quantity of life as well so we're aware of the environmental drivers of obesity in terms of the availability of high caloric density of foods and mechanisation and automation in the home and in the workforce that mean that displaces the need for human labour transportation communication and electronic devices that all favour us to consuming more and spending less calories to some extent those of us who are financially better off are able to shield ourselves from this obesogenic environment to some extent by making time for physical activity and and being able to prepare nutritious foods of lower caloric density however it's not a level playing field for other reasons in terms of obesity in that there is alterations in our genetic susceptibility to obesity such that from various international studies of hundreds and thousands of people who have had genetic analysis of their genes show that people who are obese tend to have variation in their genes that control satiety or that feeling of fullness in the brain and so what we can conclude from that is that certain people are more predisposed genetically to overeating in the same environmental influences when we look at obesity treatments for for quite some time we're focused on personal efforts to exercise and to eat differently and in order to lose weight there are several commercial weight loss programs like um genie craigs and weight watches there's also a range of very low calorie diets and meal replacements that can help as well as medications and bariatric surgery so these are two of the common forms of bariatric surgery where you can see that the stomach is either disconnected from the passage of food called the ruin wide bypass or a sleeve gastrectomy where the majority of the stomach is removed and most of these obesity treatments unfortunately are very difficult to sustain and maintain and achieve weight loss and this is because of the strong biological mechanisms that we have to defend weight loss and to some extent the master regulator is in the brain in terms of integrating signals from the gut from other organs such as the pancreas and the fat itself that tells us when the fat stores are adequate and any efforts to decrease meal frequency and size are met with a whole host of adaptations that serve to gain weight back to what what it was and to some extent that is mediated by genetic influences such that some people have stronger adaptations to defending weight loss than others so I think obesity can be should be seen as a disease and it's not simply a lack of willpower that means that some people aren't able to lose weight and it should have the same degree of empathy as we have for other diseases and so with that I'd like to turn to diabetes and and the prevalence of that in diabetes in New Zealand which is also rising at a similar rate to obesity so in the last 12 years it's increased from about 140,000 people in New Zealand to well over 250,000 in New Zealand in most recent times diabetes is defined as a blood glucose above a threshold at which the blood vessels are likely to get blocked and hence the organs that they supply are at risk of complications so the cut-off for diabetes is fasting blood glucose above 7 or a random marker of glucose in the blood called HBA1C and a level above 50 and beyond that there is a risk of microvascular complications that lead to retinopathy or blindness, kidney disease, neuropathy and medium-sized blood vessels in the brain causing strokes, heart disease and peripheral vascular disease and the and the good news though in diabetes is that there are several glucose lowering treatments such that people who are able to control their blood glucose are able to lower their risk of these complications pretty effectively. The range of treatments however in terms of diet exercise a whole host of tablets and insulin and even bariatric surgery their effects vary by the types of diabetes and it's important to distinguish between type one and type two diabetes as the two main subtypes and type one diabetes which is actually causes about five percent of adult cases of diabetes and the predominant cause of diabetes in childhood is due to a loss of insulin production in the pancreas so this can occur at any body weight not linked with physical activity or diet and really the replacement of insulin is the only treatment. For type two diabetes which affects the majority 90% of adult cases with diabetes the risks of these increase with age and increase with increased body fat. Gestational diabetes has a similar etiology to type two diabetes affects five to eight percent of women in their pregnancies and it's generally associated with excess body fat. The diabetes generally goes away after the baby is born but those women are at a higher risk of having developing type two diabetes later in life. There's a number of other very rare specific types which we don't have time to go into but it's important not to think that everyone and adults has type two diabetes. Just a bit of physiology on how blood glucose is regulated here the master regulator is an organ called the pancreas and this senses blood glucose high blood glucose particularly after a meal and so that it releases insulin in response to the glucose insulin being the key hormone that signals to the muscle and fat cells to take up the glucose and restore normal blood glucose levels. In type one diabetes specific insulin producing cells in the pancreas are destroyed usually through an autoimmune process and there's a genetic susceptibility with certain HLA or other autoimmune type genes as well as a second trigger usually a viral trigger is thought to to destroy those those beta pancreatic cells and and that leads to progressively high blood glucose which is treated by insulin that needs to be injected intermittently or infused through an insulin pump and one of the difficulties with insulin treatment in type one diabetes is the need to sample blood glucose in order to judge the right amount of insulin to give and with recent advances in technology there are some better ways of monitoring diabetes and administering those however these are very expensive at the present time and we do hope that that will reduce over the years. In contrast type two diabetes is actually affects the muscle and fat cells in there and which become more resistant to the effects of insulin and hence they don't take up blood glucose the glucose well. There are also other defects in the pancreas for example and other organs in terms of controlling blood glucose levels and these multiple defects arise largely from an excess of fat cells and they have again a genetic predisposition with reduced pancreas function to produce insulin as well as environmental causes that determine weight gain and to treat the multiple defects in type two diabetes we have a range of medications to lower blood glucose as well as insulin and bariatric surgery which are very powerful ways of treating type two diabetes. However at this point we don't have any tailored treatments for the type two diabetes medications and what we are thinking about currently is that whether certain medications such as valedagliptin might be more effective in people who have a weaker pancreas and ability to produce insulin in type two diabetes whilst alternative medications such as piaglitazone may be more effective in people in whom are more obese and have high blood lipid levels or cholesterol levels and we're aiming to test this and by recruiting people who with type two diabetes who are willing to try these two different medications in succession to measure how well they control blood glucose according to characteristics measuring insulin production and lipid levels and body fat mass so we're aiming to work out whether we can predict glucose lowering response to certain diabetes medications using these characteristics and to compare them with various genetic factors as well as variation by ethnicity and in order to improve the ability to treat people with type two diabetes in a more personalised way and one of the interesting factors by ethnicity is how obesity and diabetes differs in New Zealand in different ethnic groups so in this graph here you can see that obesity prevalence is highest and Pacific people in the green bar here where almost two-thirds of adults have obesity whereas in the yellow bar here you can see that Asians and Indians have the lowest prevalence of obesity in about 12 percent we have intermediate levels in Māori at almost 50 percent and 25 percent in Europeans however when we turn to type two diabetes which we know is related to body fat the levels increase with age but we see the highest prevalence of diabetes is affecting Pacific and Indians in the orange so green and orange refer to Pacific people and Indian people and the lowest risk is that in New Zealand Europeans the red bar refers to those of Māori ethnicity and it's interesting as to why this might be and and much of this is thought to be due to ethnic differences in body fat so when we talk about obesity we usually talk about a BMI or a weight adjusted by height measurement of 30 and this corresponds in Europeans in the blue line to a body fat of 28 percent so basically this is a graph inviting people of different ethnicities and measuring their body fat and relating it to their height and weight measurements and you can see in the blue cluster that refers to Europeans there's quite a lot of variation from one individual to another but overall the 30 the threshold of height to weight of 30 corresponds to about 28% body fat when we look in other ethnic groups particularly Asian Indians this threshold of 28% body fat is reached at a much earlier or lower BMI so lower weight for height in contrast Pacific people have reached 28% body fat at a much higher BMI weight for height and this is likely to be genetically determined and there are individual variations according to how well people are able to store body fat versus muscle mass versus bone mass at any particular weight this highlights the limitations of measuring obesity and how we define it and simplistic terms we use weight and height which are easy to measure and you can each work out your own BMI by taking your weight and kilograms and dividing it by your height and meters squaring that and if your BMI is over 30 that's an estimate of obesity that just indicates that you're likely to carry excess body fat however this doesn't apply to all ethnicities and the and whilst we may use judgments on the street of who might be obese and who might not these aren't always reliable in terms of metabolic health many of our all blacks if we use the same weight who in height threshold of 30 to classify obesity they would be obese but in fact the body fat percentage would actually is actually quite low and and that determines metabolic health and type 2 diabetes which is not easy to measure without doing more expensive tests ideally MRI scans or body fat scanners in contrast this woman here probably if you met her on the streets you'd think she was quite slim but she happens to have a genetic defect that means that even at a low BMI she has very high liver and pancreatic fat and has developed type 2 diabetes at a very young age so so there are some important caveats to how we assess obesity one of the things that we've been looking at in our research is is to look at the genetic susceptibility to obesity and Māori and Pacific people living in New Zealand and just over 2,200 people have donated blood samples to look at genetic variants that predispose to obesity and what we've identified recently is that a particular coding change in a gene called creviref where there's an A instead of a G is present in 30 percent of Māori and Pacific people this gene variant is not found in any other ethnic group that's been studied across the world and what this A instead of G gene change means is those carriers are heavier approximately four kilos per copy of that gene and surprisingly even though they're heavier they have a 40 percent lower risk of type 2 diabetes so that is really interesting it brings us to doing further studies which are currently underway to assessing what this creviref gene variant means in terms of muscle mass in terms of hormones regulating appetite in terms of body composition and so forth so we hope that this information will help us tailor the BMI guidelines and weight and type 2 diabetes risk for populations in New Zealand so to summarise I'd like to leave you with the message that not all people of the same body size have the same risk of diabetes and that there are genetic differences between ethnicities and between individuals as to how much and where we store our body fat and in terms of what types of diabetes we are at risk of so thank you very much for your attention fantastic lecture thank you very much Winkie and I'll just be careful not to suggest to one of the all blacks that they're obese this is quite a quite an insightful point our third speaker is Associate Professor Jeff Harrison Jeff is a hospital pharmacist by training laterally specialising in cardiovascular intensive care medicine originally from England Jeff was awarded a PhD in surgery quite an unusual path for a pharmacist perhaps but went on to train in evidence-based medicine at McMaster University in Canada he moved to New Zealand in 2001 taking up the post of senior lecturer at the University of Auckland in 2005 and became head of school of pharmacy in 2016 his primary research interests are cardiovascular disease diabetes comparative effectiveness research and pharmacoepidemiology and he's going to talk tonight on people not potions the re-professionalisation of pharmacy thanks Aaron I'm delighted to be speaking to you today today of all days actually Ian you probably didn't realise that today is world pharmacist day so couldn't be more appropriate just in a little bit of a change of pace what I'm going to talk to you about today is about the profession of pharmacy but I will towards the end be talking a little bit about research and arguing that the profession itself is the intervention that we should be interested in in applying to our patients so when I say pharmacy you probably think of this the dude maybe he's not a dude the gentleman standing behind the counter handing out pills or maybe for some of the old people in the audience maybe you think of this but there's a serious point behind that particular slide as well so what I'm going to talk about today is where pharmacy came from where we are now and where we should be going as as an intervention to improve the health and wellness of New Zealanders so hold that image in your mind so pharmacy and medicine have a long and interdependent history and in fact that was recognised by Professor Lewis when first setting up the medical school on all those years 50 years ago when he envisioned that the faculty would have a school of pharmacy and a school of nursing that unholy alliance but this pairing of medicine and pharmacy has been around since prehistoric times prewritten history times and in fact this stone that you see here is found in a thesis in Turkey and dates from the 10th century and what you're looking at here is actually a mortar and pestle and there is a matching stone on the other side which represents the staff of escalopes which is the symbol of medicine and so they're often seen as a pair and I've heard an economist in the last two weeks argue that without pharmacy medicine wouldn't exist but I think that might be stretching a little far in this audience but pharmacy has been around for a very long time the first prescription first written prescription was recorded in 1550 BC and if you look at different parts of the world similar timelines of the evolution of pharmacy have been recognised and in fact the state's been involved for a very long time as well the first record of a state controlled pharmacy um heralds from Baghdad in Iraq so a long history of medicine and pharmacy together so where does pharmacy come from so the modern pharmacist as we know them has taken over the role of the apothecary as was who was a medical professional who formulated and dispensed products from materia medica that is the the herbs the plants the roots that were then used by the physicians the surgeons and their patients so as well as dispensing herbs and medicines the apothecary also offered general medical advice there's a story developing and a range of services that are now we see performed by doctors in a british view of this there's an event in 1704 where apothecary apothecary is divided into what we now know as general practitioners who treat patients and what we now know as pharmacists who prepare the medicines and the case went that an apothecary was sued by the college of physicians in the high court for having the brass neck of visiting a patient at home prescribing and dispensing medicine for that patient the college of physicians felt that this was completely inappropriate and and took the apothecary to court unfortunately for the college the court agreed with the apothecary largely on the basis that this was custom and practice that physicians were rare and charged too much there's an interesting parallel with today where pharmacists are now working in general practices seeing patients prescribing treatments and dispensing medicines not this time because general practitioners are too expensive but they are too few so this is one of the emerging roles of the modern pharmacist so what then happened so we had apothecaries pharmacists emerge from that what's happened since then well there's been technological change when we think about medicines we no longer think most of us no longer think about compounded herbs we think about the tablets that Rinky showed you the injections so industrial pharmacy led to the creation of pharmaceuticals into those products as we know them to be distributed by pharmacists that specialist knowledge that pharmacists held about how to make drugs became lost from the high street where it had been remember thinking back to the Victorian pharmacy that was where the pharmacist compounded products for an individual patient they made a consultation decided what the patient needed compounded it there and then and sold it to them a professional service whereas now increasingly pharmacists were seen as distributors of products that were ready prepared pharmacists remain the medicines expert but their daily activities the daily activities of being a pharmacist are perceived to be the distribution of a product disunfortunately hides the real role because what goes along with handing that box of medicine to you is the assessment of whether that's the right medicine for you whether it's the right dose whether it is in the right formulation for the individual but i would argue that the profession has had a little bit of a crisis of confidence around its professional identity and what it's there to perform and i think some of the profession and some of the the public's perception of what pharmacy is has been has been caught up in that so when i say pharmacy what i think is this and you'll notice in these images yes in one of the images there's a product or a row of products behind but what i actually see is pharmacists interacting with people and i think this is really what we're seeing starting to emerge again is the value of the pharmacist and the pharmacist knowledge no longer about the product but about the interaction with the person and about ensuring that the right individual therapy for that patient and i see one of my colleagues in the room who's a brilliant example of a community pharmacy a high street pharmacy that provides all of these services right now the value of this emerging role has been recognised by governments they've started to talk about not valuing the distribution of medicines you may know for those of you who read the papers that amazon has just spent a billion dollars in acquiring a distribution network for pharmaceutical products in the us it was interesting to read sydney mourning herald's response to that which was there's going to be a crisis in australia in australian pharmacies and amazon is going to take over there are two reasons why that's not going to happen one of which is to do with gst being charged in to amazon in australia and the other is the fact that australia and new zealand have fundamentally different healthcare systems to the us and there's less money to be made from the distribution of medicines in that way but that sort of technological change i think will be empowering for pharmacists pharmacists are now moving to and this is the research part of the presentation pharmacists are now moving to providing patients professional services extended services and i'm just going to talk to you a few examples from my own area of interest cardiovascular disease and diabetes so they've now been 39 randomized controlled trials pharmacist led management for hypertension as opposed to general practitioner led management of hypertension when comparing those two interventions with a pharmacist without a pharmacist you see an average systolic blood pressure reduction of 7.6 millimeters of mercury that's better than any single drug where pharmacists are able to not only just assess the patient to make recommendations to the general practitioner but they're actually able to enact that change themselves you see an average reduction in blood pressure systolic blood pressure of nearly 20 millimeters of mercury that's extraordinary so this big change in in in blood pressure how does that translate in terms of patient outcomes so there've been some studies done looking at how many strokes that would save how many heart attacks that would save and also whether that would be cost effective clearly you've got to pay the pharmacist to run this service right and you're already paying gps so by adding a layer of cost that's going to cost more but what that analysis shows not only is the treatment being the pharmacist more effective it's actually more cost effective as well and it's been said that it would be unethical not to fund this if this was a drug we would have general practitioners lobbying the Minister of Health we'd have the general public in the street demanding that pharmac paid for it and yet it's not funded here and it's considered to be something that we don't necessarily want to do again i've heard it said it would be unethical not to fund a service like this similarly there have been randomized controlled trials of pharmacist led care versus usual care for diabetes management specifically around glycemic control using existing treatments so not new treatments just using the treatments we have better and an average reduction in that study of nearly one percent or 10 millimoles per mol in the HBA1C and as Rinky showed you that translates directly into reductions in retinopathy reductions in nephropathy cardiovascular events there was also an attendant reduction in blood pressure and associated lipid levels LDL cholesterol and triglycerides that often go alongside poor glycemic control as well and that directly translates into improved patient outcomes again this is just adding the pharmacist as an intervention to the existing healthcare system and then talk a little bit about anti-colegulation management so many of you will have come across you'll know somebody on warfarin might even have taken it yourself or used it to kill rats one or the other is a commonly used medicine it has some interesting pharmacokinetics and interesting pharmacodynamics so different people need different doses but the same person will need a different dose from time to time as well so they're quite comp it's a quite a complicated drug to use when pharmacists and Marie was one of them in the pilot study when pharmacists see patients and manage warfarin as opposed to general practitioners outcomes improve what this graph shows is this is the distribution of blood test results so you may have seen or heard of an INR so an INR we if you're not taking warfarin your INR would typically be about one so normal clotting the higher the number the longer it takes your blood to clot ideally when you're treating somebody with warfarin you should be aiming for an INR about two and a half somewhere between two and three is acceptable above three the patient is at risk of bleeding side effects below two they're at risk of of clotting abnormal clotting which might cause a stroke heart attack or or a blood clot in the leg of DVT so this is the distribution of the amount of time that an individual spends in the correct range in that range of two to three this is usual care what happens in most of New Zealand this is what happens when you put a pharmacist in charge of selecting the dose and tailoring the dose to the individual ideally the international gold standard would be to spend more than 60% of time in the correct range so what you see here is turns out pharmacists are quite good at this there's an increase in the time in therapeutic range of nearly 17% importantly there's a 15% increase or sorry 15% decrease in the amount of time a patient spends below the required therapeutic range at risk of stroke but also there is a reduction in the amount of time that the patient spends in the bleeding risk in the above three level as well so why is it that pharmacists are good at this turns out we're pretty good at pharmacology now there may be a hematologist in the room there's not a lot that I could tell a hematologist about how warfarin works you know that's that's their area of expertise they will understand that there is genetic variation in v-core c1 particularly amongst Asian populations which means that the variation in dose is about 30% due to that one gene alone they'll also understand that the way warfarin is metabolised through 2d6 has a genetic variation that's responsible for about 10% of that change in dose I'm not going to tell a hematologist much about how warfarin works turns out though warfarin has lots of drug interactions it also interacts with lots of foods including turmeric which probably not a lot of hematologists would know just off the top of their head turns out pharmacists are pretty good at pharmacology and that's why when things go wrong or when the patient has complicated drug therapy we are in a position to perhaps make better judgments about whether to adjust the dose or whether not to it may be to do with the fact that we also have more time we don't just have those six minute consultations GPs unfortunately seem to have to manage through this service has been funded across New Zealand and there are about 8,500 patients that are currently in this service but there are about 30,000 patients on warfarin so there is a shortfall so there are a number of people that are not getting this service again I would argue Marie I'm sure has got a waiting list for her CPAM service and I certainly know there are areas in the country that are not served in this way so everything old is new again pharmacy is in an exciting transition phase pharmacy profession is always talking about being at the crossroads I sometimes feel that it's around about rather than acrossroads but there has been a shift from a product focus to a patient focus pharmacies are harnessing technologies to automate some of those processes around dispensing so dispensing robots that can reduce time and cost in getting the product to the patient which then allows the pharmacist to spend time talking with the patient identifying their problems and individualising their therapy the profession is also recapturing its base as the medicine's experts we've talked a little bit about potentially different responses to different treatments based on individuals genetic profile or predisposition integrative medicine I don't know whether you know what that means integrative medicine is really combining traditional therapies maybe traditional chinese medicine wrong or pacific medicines with what we lovingly term as western medicines often patients want to be able to take both together in order to be able to do that safely we need pharmacists and pharmacologists to be able to understand how those two approaches to treatment interact pharmacists therefore become those knowledge brokers there to support their medical and nursing colleagues and others and specifically their patients understanding and using existing therapies better just very briefly what to pharmacist study when I went to university I studied all the things on the left we did a lot of physiology immunology pathophysiology pharmacology in spades I did two solid years of pharmacology what I didn't do I didn't do any patient assessment I didn't learn clinical reasoning until I was treating patients and having to work it out critical thinking I could think hopefully I did a bit of critical thinking I didn't learn anything about communication skills I didn't learn anything about behavioural therapies we're actually starting to teach our students right now these skills I didn't learn anything about teamwork until a Thursday night in the butter market in Shrewsbury when I had to interact with my medical and nursing colleagues over half a pint of mild we do I did learn about evidence-based practice and I did learn about research methods but mostly that was looking down a microscope or in a test tube rather than clinical trials with patients our 40 students are leaving university with all of these skills equipped to deal with the general public and with patients to understand their needs and ensure that they're getting the right treatments so just to finish on the place of pharmacy in the future is very much in a one-team approach working with doctors nursing nurses other pharmacists providing person-centred and interdisciplinary healthcare I think we do have a role in managing long-term conditions I think we can reliably and I've demonstrated through evidence that we can at least as well as is done now pharmacists can take on that role and arguably do better I think we can harness technology to individualise health solutions across the country but only as part of that integrated team and sharing information so thank you for your time another remarkable lecture thank you Jeff I am a user of community pharmacy in this respect and I can confirm that it's a fantastic way to deliver medications our last speaker is professor John Fraser John Fraser is Dean of the Faculty of Medical Sciences at the University of Auckland formerly Head of the School of Medical Sciences is a graduate of Victoria University and gave a PhD in biochemistry from Auckland University in 1983 following postdoctoral research into immunology at Harvard University he returned to New Zealand as the inaugural welcome trust UK senior fellow in medical science he received a personal chair in molecular medicine in 2000 and was made a fellow of the Royal Society of New Zealand in 2005 for his work on super antigens John has a long-standing interest in immunity and infectious diseases and particularly the mechanisms of virulence and pathogenicity of gram positive organisms he's published over 150 peer-reviewed publications and books and has supervised 35 postgraduate and doctoral students John is a strong advocate for the role of science and society and the importance of research led teaching in medical education his lecture tonight is entitled new initiatives in rheumatic fever and I think he's also going to tell us about superbokes John Fraser Anna mana nereo ana hawa efa tena koutou tena koutou tena koutou katoa thank you Ellen uh slightly long-winded introduction I think that was taken from a bio I had many years ago yes I am indeed the Dean of the Faculty and it's my very great pleasure to pretty much finish this wonderful lecture series that we've had as part of our 50th anniversary celebrations before I start I'd just like to acknowledge all the work that's gone into this lecture series and the work that distinguished professor Ian Reed has put into what I have believe has been an outstanding lecture series in tonight's lectures notwithstanding my lecture which I haven't given yet I think have been outstanding and I hope that I can at least express a little bit of my interest in a field which I feel doesn't get a lot of attention in New Zealand infectious disease but is equally important and of course I'm hopefully I'll be able to convey some of that importance to you tonight so although my talk is entitled new initiatives in rheumatic fever it really is only a part of my talk I'm really going to talk about a more general topic and that is superbugs superbugs have always been an interest to me they are a fascination maybe somewhat ghoulish fascination because they do cause a great deal of concern they are the cause of a considerable disease quite disparate diseases across New Zealand and of course in this country we have a very significant disparity in the diseases that these bugs cause between Māori and Pacific particularly in our young as opposed to non-Māori and non-Pacific and rheumatic fever is a very very good example of how as a country we still have a major third world disease problem which has essentially been eradicated in other countries first world countries such as the UK North America and Europe both Australia and New Zealand have a very significant problem still in the high rates of rheumatic fever that occur in a young Māori and Pacific children so what is a superbug superbug is not every bug there are some very nasty bugs out there that cause very serious illness but they're not superbugs because they're easily treated you can drink foul water estuarine water and end up with cholera caused by an organism that lives in the water you probably find it in the estuary of Auckland but it's not a superbug because cholera is very easy to treat it's easy to identify and it doesn't occur in epidemics or pandemics superbugs really are characterized by bugs that are able to change their makeup the genetic makeup to resist any attempt to try and destroy them of course we all know that antibiotics have been the mainstay of the treatment of organisms such as the ones i'm going to talk about tonight but at the those antibiotics are beginning to fail more and more and of course just recently you will have noted those of you who've been listening to the news the appearance of a new form of drug resistant entracoxi in New Zealand which is essentially resistant to all major forms of antibiotics and that organism is essentially here to stay although it's in a relatively small number of our population it will continue to grow over the decades and the question is how fast will it grow and how much disease it will cause it will we will be unable to treat with our current repertoire of antibiotics so superbugs typically are recognized by their ability to to resist antibiotics they are very difficult to treat i'm going to talk about one organism particular which is probably the most difficult to treat they have high rates of community transmission which means that they are in the community already people in this room will be carrying these bugs without knowing it and for most of us they don't actually cause any illness it's when the immunity barrier is broken down and those bugs are able to establish a colony or an infection within the body and then that affection is not controlled by our immune response that it then becomes a flurid infection and causes very serious disease and often death they are the constant cause of disease the ones that i'm going to talk about these two organisms here staph aureus i'm sure you've heard of staph aureus and strep pyogenes constantly cause disease in New Zealand and this one in particular causes a widespread variety of diseases and is the organism which probably is best suited to change its genetic makeup to be resistant to pretty much all forms of antibiotics and of course New Zealand we are unique we have certain strains that are prevalent in this country that you don't see in other countries which makes it slightly more difficult to develop strategies to combat these particular strains this organism here is another grand positive organism it's called strep pyogenes it typically lives in the throat in the nasal passages and sometimes lives on the skin it's a another grand positive organism and this is the one that causes rheumatic fever but it also causes a number of other conditions so this is really just a summary some of the nasty conditions that these organisms cause staph aureus causes a number of this is probably the most common these two here abscesses and in particular the predominately skin infections the organism gets under the the upper layers of the skin and causes an infection so in here you'll have a small colony of staph aureus growing and you can see the immune response around this is becoming quite prevalent so it becomes hot and hot to touch very sensitive and that simply means that your immune response is trying to rid the body of that growing colony of staph aureus the problem of course is that organism has defense mechanisms to stop your immune response from working and in individuals where that immune response fails that organism can then become systemic it can get into the blood stream and you can experience a very severe often fatal condition called septicemia septicemia in particular we see on children it's really just a skin infection which is relatively easy to treat but the way in which we treat it has caused a very significant problem which i'm going to talk about in the next upcoming slides toxic shock a relatively rare condition which is caused by staph aureus not limited humans cows get mastitis that's also caused by staph aureus but the strains that cause mastitis are different from the strains that infect humans and cause disease cellulitis is really a more severe form of this where the organism has started to spread into the the lower forms of part of the skin and into the soft tissue underneath and into the muscle and that is a very very severe condition and if left untreated the patient is very likely to die this is the guy that worries us the most it's called MRSA MRSA stands for methicillin resistant staph aureus and it's a strain of bacteria which has become very prevalent worldwide which is really the poster child for superbug it is the one drug one organism that has become very difficult to treat and of course the rates of MRSA infection in New Zealand becoming increasingly problematic particularly those infections that occur in what we refer to as community acquired so they occur out in the community rather than in the hospital hospital acquired infections are slightly different from those that occur in the community settings such as aged care facilities wow and those community acquired infections are often much more difficult to treat but this little bug here MRSA is a major cause of morbidity and mortality worldwide now in US a very very severe problem and it's got that way because it's become resistant to the mainstay of antibiotics which the penicillin based antibiotics of which methicillin is a classic form we have high antibiotic high antibiotic resistance in staph aureus and of course the problem is that it has a very high asymptomatic carriage which means about 20 to 30% of the people in this room at the moment are carrying staph aureus in the upper areas the anterior nares of the nose up in here so it's a very very easy to spread this organism is the one that causes rheumatic fever strep pyogenes rheumatic heart disease you're probably familiar with strep throat i'm sure many of you have had a strep throat often really easy to distinguish between a standard viral infection because it hurts like mad and that's because your tonsils swell up to such a size that you can really have it's almost impossible to swallow but of course you get a systemic effects you get a high fever you feel very unwell and that's because the organism growing in these tonsils is releasing these virulence factors which are causing quite significant systemic effects that make you feel very unwell also causes scarlet fever less common in New Zealand that it used to be like rheumatic fever this is a particularly nasty form of strep infection where it's got into the soft tissue and into the muscle cellulitis and necrotising fasiatis often referred to as flesh eating bacteria the only solution here is really amputation because the soft tissue has really just been destroyed by this infection and rheumatic fever is one of the significant problems that we have in New Zealand because it is a disease of poverty and overcrowding so most of the cases of rheumatic fever in New Zealand are associated with one young Maori and Pacific children who live in low socioeconomic areas such as South Auckland and other areas where the transmission rates of this organism are very high and the treatment rates are very low and often the condition is left until the rheumatic fever has developed to a point where there's been permanent damage done to the heart valves of the valves of the heart thankfully strep pyogenes is still fully sensitive to penicillin so it's relatively easy to treat you just give a dose of penicillin and within 24 to 48 hours the the infection has has been eradicated i rhu the day when we discover a antibiotic version resistant version of strep pyogenes i hope i'm not around when that day comes so mrsa is the classic poster child of the superbug family methicillin resistant staph aureus we know it arose sometime in the 1970s from brazil we have records that date back that way and of course now genetic techniques and careful screening we can go back and look at the genomes of the organisms that arose so it often is associated with infections in the lung and on the skin causes inflammation of that heart muscle bone and joints and also causes particularly in the us for some reason a very severe severe form of necrotising pneumonia so it gets into the lungs and it starts to eat away the lung tissue and that's a very very severe infection so half of staph lacoccal infections in the usa now are due to methicillin resistant staph aureus and they are resistant to penicillin, methicillin, tetracyclin and erythromycin so really they've only the only way you can treat them is with long treatment severe antibiotics antibiotics that are only used as last resort community quiet mrsa is on the rise in new Zealand quite significantly and it is a problem one of the great mysteries of course is that some people develop mrsa and if only forms a mild treatable skin infection where as others succumb to a very severe invasive form and it's almost impossible to treat those of you who understand microbial genomics and genetics the classic strain in the us is called usa 300 it has some certain prototype genetic features that we refer to and these are often what we look for when we screen new infections in New Zealand to see if this prototype mrsa has made its way to New Zealand shores and really one of the great questions is what is it about this strain which makes it so infectious it's not just that it's able to resist methicillin it carries a gene which actually destroys penicillin based antibiotics that's not the reason why it's so severe and we still don't understand why an infection of mrsa causes such invasive difficult to treat well of course it's difficult to treat because it doesn't respond to antibiotics but the types of infections that cause are particularly severe so i'm going to get to the New Zealand situation now and this is research that was done by a group particularly by a phd student who was working in our group in the from 2012 through 2015 Dave Williamson and this is really a study which looks at what types of staph aureus clones are appearing in New Zealand and what are the predominant disease causing strains now i realize that this is probably a complex slide it's not meant to be it's really just to reflect that Debbie looked at over 3000 disease causing strains or clones that have been isolated from various patients around New Zealand and she did a genetic analysis of all of those clones and she was discovered that in fact 36 percent of them and this was across the entire population in New Zealand were represented by only three particular unique clones one two and three here in the aspartites this is just a way in which we identify and you can see that each of the three clones are different this this particular clone which is the most common thankfully it's still sensitive to methicillin this is methicillin sensitive staph aureus which means it's still easy to treat with standard antibiotics this is also sensitive but this one here MRSA is resistant to penicillin based antibiotics the most important discovery that Deb made was the fact that each of these three strains was resistant to another antibiotic called fucitic acid so 36 percent of the strains in New Zealand are now fucitic acid resistant now fucitic acid is not a particularly important antibiotic in the hospital setting we don't use it in the hospitals we use penicillin and tetracycline and erythromycin all the powerful antibiotics fucitic acid is an antibiotic that's used particularly to treat mild skin infections so most of you will have had a skin infection where you've gone to the general practitioner and he's prescribed anointment where you rub on the infection and that treats it and that's usually fucitic acid 20 years ago these three clones did not exist in New Zealand so where did they come from and why well the simple fact is that 20 years ago January 1998 fucitic acid was first prescribed as a treatment for skin infections and this is the prescription rates of fucitic acid in New Zealand you can see a steady climb so this is community dispensing rates per a thousand population per month is now up to by January 2012 and this has continued to climb this is a tube of phoban i looked in our cabinet at home and we have a tube of phoban sitting in the cabinet this is fucitic acid so the reason why these three clones have appeared and these are three very difficult to treat clones is because we've been using fucitic acid too much it's been used prescribed for skin infections that has caused the staph oris on our skins to develop fucitic acid resistance and that has caused the establishment of these three strains and now they have become the predominant disease causing strains in New Zealand so this is a clear lesson in how over prescription of antibiotics for really treatments that probably could have been treated in other ways has led to a very significant problem this is a lesson in how fast antibiotic selection and resistance can occur in a population such as New Zealand this is another antibiotic new person which is also used for skin infection and interestingly the rates of prescription have stayed relatively the same in fact they've gone down a bit so really the reason why this has increased was really marketing drug companies have marketed this to general practitioners general practitioners have seen patients have had a mild skin infection the practitioner has decided well i'm not going to test to see if it's staph oris or something else i'll just prescribe phoban and you can get it across the counter as well and people have used it and the consequence has been that within about 20 years we've got three strains which are all resistant to fucetic acid so that is a lesson in in how quickly antibiotics can cause these very significant and very problematic strains to appear and they're now essentially here to stay so one of the questions we have and i'm an immunologist by trade is whether vaccines are a logical solution to treating antibiotic resistance because of course antibiotic resistance has been around for millions of years bacteria antibiotics essentially have come from fungi fungly get infections just like we do and fungi over millions of years have produced these molecules which interact and destroy the bacteria or destroy the ability of the bacteria to grow we've used these compounds for the last 60 years very effectively but of course they're starting to fail us so what is the other solution well the only other solution we have because infectious disease is not going to go away is to look at the vaccine approaches because vaccines are still very effective in treating infectious disease however with staph oris it's been a bit of a problem because staph oris also doesn't respond particularly well to staph vaccines that's not to say that i don't believe staph a vaccine for staph oris might work it's just that the number of vaccines that have been tried clinically have all failed and this is really just a reflection of the failure of a number of very important vaccines that were developed to these two by a company called Narby Staph Facts failed even though it showed very good promise in animal studies the Staph Facts which is based on a cell surface molecule on the surface of of staph oris really showed no effect in clinical trials and they modified that and that was also failed and shelved another vaccine that was tested in clinical trials around the world called Pagimaxabab Mab was failed really didn't show any efficacy another company in Hibatex or Axis produced another vaccine which again failed in clinical trials and the most publicly or the one that caused the greatest interest was this very publicly touted vaccine called v7 110 by the company Merck which looked like it was really going to work all the animal studies appeared to be very effective it was based on a single molecule on the surface of staph oris called the ISDB protein which is on all strains of staph oris and in animal studies it looked like if you're vaccinated with this particular protein and got good antibodies against it then the animals were entirely protected from from infection by staph oris so it went into phase two and phase three clinical studies particularly in the US and cardiac units whereas cardiac units have problems with staphococcal infections most surgical units have problems with the staph oris infections but cardiac units are in particular notable for the problem in having post-surgical infections due to staph oris the trial was ended when it was discovered that the vaccine actually increased the death rate amongst those who were vaccinated by a factor of five fold so that told us that vaccines don't always work in fact they do quite the opposite they actually enhance the ability of the organism to grow because the vaccine we now know actually protected the organism rather than caused it to be more susceptible to immune attack unsurprisingly that study was halted immediately has that put an end to vaccines for staph oris i don't believe so and certainly my group has a real interest in developing alternative vaccines which don't actually work the same way as that that merc vaccine based on virence factors that we know through a lot of work that we've done are very very important in the initial colonisation of tissue by staph oris so the idea is that by vaccinating with these immobilised virence factors there's a quite unique to staph oris that you can deliver an antibody response that then protects the patient from further infection from colonisation so my vision is that a vaccine will be useful in all surgical settings people who are going in for elective surgery or cardiac surgery would be vaccinated two to three weeks or a month before the surgery so that they are at less risk of developing that post-surgical infection which is such a problem around the world so we are actively working on this and we have a project grant from the health research council to develop such a vaccine so i did want to talk a little bit about rheumatic fever it is still a problem in New Zealand we are working very hard to develop strategies to deal with rheumatic fever you are probably aware that over the past 10 years we've had a very major program run by the Ministry of Health which was really to screen a primary prevention program in high-risk areas where young people if they had a sore throat they would be seen by the the public health nurse in the school the nurse would swab the throat and give prophylactic antibiotics to those children who presented with a sore throat it was a very expensive exercise i think the government spent about 80 million dollars in total on this prevention program and was really to try and stop the infection of the throat by strep pyogenes before it occurred using penicillin as the prophylactic antibiotic i have to say that it wasn't particularly successful because the the rates of transmission in those communities is too high and unless you get every single child that is carrying strep pyogenes then really a primary prevention program as expensive as it is to run really does not provide the efficacy in small communities it's been shown to work because you can get every child in that community but in larger communities such as South Auckland unless you vaccinate every child at risk sorry if you treat every child with penicillin prophylactically over a long period of time those rates of rheumatic fever are not going to go away or are not going to produce so we have been working with our colleagues in Australia to look at the development of a vaccine for strep pyogenes this is a little bit more developed than the vaccine for staff for us and this is really just a slide looking at all of the partners that are involved in this very significant program which has been named canvas it's the coalition to develop novel vaccines against strep pyogenes it's primarily involved ourselves university of Auckland myself and jonathan carapetus who's the director of the telethon institutes and kids it was really started by former prime minister john key who asked me one day at a meeting what it would take to develop a vaccine against strep pyogenes i said 10 million dollars and he went away and said well i'll see what i can do so he then spoke to the prime minister of australia at that time and they developed a program which was funded on both sides of the tasman to look at fast tracking vaccines that was four years ago and after a lot of work we've identified a number of vaccines that we think should be likely ripe for clinical trials and the one that we are looking at most seriously is this a vaccine that's been developed by a company glaxosmith climb which is a complex vaccine which has been well developed through their developmental program it's a vaccine which has four components to it and we've been working very closely with gsk with the intention of a clinical trial beginning in australia and new zealand hopefully within the next two years so that the vaccine is currently under development to gmp manufacturing stage at that stage we're hoping that new zealand and australia will be the first sites for this clinical trial for this vaccine that's not to ignore the fact that that uh associate professor thomas profftett in orcland here is also developing an alternative vaccine based on another potential antigen which i think also has significant development so there's a lot of work going on looking at a vaccine approach uh my future for new zealand and australia will be that a simple vaccination of children at risk and we know where these children are they're in south orcland they're in porirua they're in the western part of the north island and northland they're in schools we can identify them and we can vaccinate them relatively easily so uh we are hoping that uh the the trials that are due to the start of the next two year will show that this vaccine is at least someway efficacious in reducing the rates of streptococcal infection that would suggest that it will also be effective in reducing the rates of rheumatic fever in this country so i've presented a somewhat uh grim tale of antibiotic resistance in superbugs uh my two favorite organisms strep pyogenes and staph aureus there is really no solution yet uh particularly in rheumatic fever with strep pyogenes but there is a shining light in all of this uh you're probably all all worried like everybody else about antibiotic resistance and the development of superbugs and what we're going to do about it uh the one problem we have is that over the last 60 years there'd been no new antibiotics that have been developed all the antibiotics that have been developed are different modifications of the same old antibiotic so the classic penicillin that was first discovered by alexander fleming has simply been modified over and over again to try and overcome the resistance that's developed against it so most of the antibiotics that are used today are still based on what we refer to as the lactam antibiotic molecule that's been a problem of course because we haven't discovered any new types of antibiotics just recently however and this was a very celebrated paper that occurred in nature was a very clever fellow called kim louis decided to look for organisms that had never been seen before uh and what he did was he made this little cell and he planted it in mud in his back garden and in these cells he made the summary that the organisms that they'd never seen before would only grow under the conditions that they were used to i.e. in mud and so he actually cultured these things in these cells in the conditions that they were most used to growing and he discovered this new organism called eleftheria tirai tirai being earth and it produced a new compound called tikiobactin and this is the compound for those of you entered a molecular structure it looks nothing like the lactams it's a completely new structure and it is very powerful against all grand positive organisms including MRSA and vancomycin resistant staph oris so this is a real shining light for the future and of course there's a lot of work going on now to try and repeat these this work in other areas to identify other new organisms that are producing other very interesting antibiotic molecules that in theory should have no resistance against them because they are so completely new and quite rare so with that i'd like to finish i'd like to thank you all for coming along tonight and i guess now is the time for a few questions we are out of time so i would like to just acknowledge that over the years we've had very generous support from the health research council and of course the Morris Wilkins Centre that i've been a member of many years of course the canvas funding that we received from both Australia and New Zealand has really supported a lot of the research that we've done over the last 10 years thank you thank you John i think that was a remarkable final closing lecture in this 50th anniversary series of lectures we do have gifts for the for the speakers i think we've had remarkable presentations tonight all of them very professional very interesting and very varied but i think more importantly than the gifts if you could join me in again expressing our appreciation for what i think has just been four fantastic presentations i'd also like to thank jasmine barba for the organisation where are you jasmine other you're at the top for the organisation tonight thank you for that and again thank you all for coming take care good night to all of you