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Hi everyone. I'm Helen Ashdown, so thank you very much for staying on into the evening to listen to me.

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I'm aware that you've had a long day, so I'm very much going to be talking about the kind of the lighter side of diagnostic studies.

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You may think what could possibly be the link between Breathalysers babies and bombs,

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but as you probably guessed, it's that the link between them is the study methodology and the diagnostic studies.

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And what I really want to talk about is my experience.

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So happened that I ended up doing a few diagnostic studies, partly because I really enjoy them and I think they're really they're really good fun.

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And so I wanted to share with you the kind of the fun side of that and really convince you that diagnostic studies are great.

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And I think they're well, hopefully in that space of me saying that,

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I really I really do think that it's a really simple, straightforward sort of study methodology,

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which is, you know, once you put your head around, there is really you know,

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there's lots of studies that can be answered using diagnostic test accuracy methodology.

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So what am I going to talk about?

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Does these three studies that I've been involved in breathalysers immunisation history and speed bumps and appendicitis.

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Now, immunisation is obviously really, really important, but it's just slightly less exciting I think, than breathalysers and speed bumps.

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So I'm actually probably get to talk about that for a few minutes and mainly concentrate

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on what I've done with the Breathalyser Study and the Speed Bumps of Appendicitis study.

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And what I'm going to talk about is kind of a how the study was designed in relation to the designing,

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the designing the research question and formulating that and how we designed

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the study to answer the question with the kind of the bumps along the way.

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So things that things that came up which were unexpected or interesting, and then to also focus on the kind of the communicating the findings aspect.

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So particularly with breathalysers and speed bumps, they've, they've had quite a bit of media attention.

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And so I wanted to concentrate on the the sort of how you explain diagnostic studies to the public and how how to kind of sell diagnostic studies,

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because it's not necessarily something which is easily understandable by by non, you know, people that don't don't understand the methods.

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And so you can see here, this is a video and you have to also I'll talk about how these how these came about.

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But first, it's come out a little bit small.

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So I don't know if this will be possible, but I was going to test your Oxford knowledge and ask you, first of all, which pub is that?

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Does anybody know where say.

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No, but I think that's a good guess. Canal in the background. It's the Jolly Bateman and Swamp.

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There we go. And where abouts is that? Now it is.

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Say something. Yay! Yay! Well done.

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So, yeah, so how these two pictures came out, how they came about and the sort of the stories behind them.

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So I'm sure this is really you will have done this today,

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but I just wanted to put it there in case as anybody that hasn't been on the course and wanted a bit of background.

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So instead of thinking about this typical peak out with diagnostic studies, I always think of this instead as a sort of pit.

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I hope I auto thinking about the patients or participants.

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The index test, the reference test, and then what the target condition is.

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And then putting them together to give us a sensitivity, specificity, positive, a negative predictive value and likelihood ratios.

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Hopefully that should make sense to everybody. You probably all know this already,

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but basically in the UK there's an immunisation schedule where babies have have immunisations

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and it's the same in countries around the world but kind of differs between different countries.

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And this set points when children have it and they get a letter in the post inviting them and then they get

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follow up reminders and they also and it all gets recorded in this child health record that all children have.

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But there are some children who don't have the immunisations up to date or even with the immunisations and the reasons for that.

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You know, there's many reasons for that. It may be that the parents actively decide that they don't want their child vaccinated,

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or it may be that they or it may be that there's just reasons, you know,

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they've forgotten or the letters aren't getting through or they don't have the time to take the children to the doctor,

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you know, all kinds of reasons. But when children go to hospital, when they go to the emergency department, when they're not planning to,

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you know, when they're not planning to do so, obviously an unplanned admission.

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It's a good opportunity to ask parents about it.

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And that's both so that you could potentially identify if the child might have one of these diseases causing that presentation.

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You know, obviously, the chances of measles is higher if you haven't been vaccinated against it.

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But also as an opportunity to kind of give education about the importance of

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immunisation and even give the immunisation while the child is in hospital as well.

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So it's important in those respects. And what we wanted to find out was whether history taking, say,

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whether the process of the doctor asking at the initial clerking of the patient, is your child up to date with their immunisations.

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How accurate that was for telling whether the child is is actually up to date.

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So what we do is formulating the research question saying how good is it clocking at picking up children who are overdue with their immunisations?

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So we looked at children six months to six years presenting to the emergency department, looked at immunisation history.

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So for that, we went through the emergency department cast cards, which at that stage everything was done written,

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whereas now it's electronic and where people had written kind of up to date IM's or whether there was any kind of mention of it.

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And then combined compared that with a central primary care immunisations record database,

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which is a central local database where this sort of information is held and looked at to whether they were overdue with their immunisations or not.

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And what were our findings? So 76%.

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So about three quarters had had an immunisation history documented and that was lowest for the surgical and mine injury presentations.

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And also the older the child was 5% recorded as incomplete on the history.

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And then when we compare that to the primary care database, it was slightly higher.

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So 7% and we include excluded some children because of the if they were only just

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overdue or if they'd moved from out of area or if they didn't have an NHS number.

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So there were various reasons that that those numbers have sort of decreased down.

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And what we find so we found that the sensitivity of this immunisation history

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for picking up children who were actually overdue was eight was less than half.

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So it's only about 40% who picked up using the methods. But if they are picked up, it's a relatively specific method.

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So our conclusions, less than half of those overdue, are picked up by history.

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Taking the highest sensitivity was in the younger age groups,

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which kind of makes sense in that it's kind of closer to when parents are when the child is actually had that immunisations.

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But there is a limitation of this in that the primary care database may overestimate those who are overdue, for example, if stuff hasn't been updated.

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We did get that the the local PC, the Primary Care Health Trust,

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people who run the database actually very kindly phoned up every GP practice of the people we identified

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as overdue to check that it matched the GP records and say we're relatively confident that it's accurate.

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But at the same time it's possible that those original GP records in themselves weren't weren't necessarily up to date.

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Moving on, speed bumps. So since I started doing this project, I've been collecting pictures of speed bumps.

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And this was from our holiday in.

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Western Canada. So this is on Vancouver Island in British Columbia.

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Really good speed. But my husband's absolutely sick of me going places and saying, say, oh,

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there's a really good speedbump, please, can we get down this road and take a picture of it? And this was very recently.

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So this is hot off the press. So the first people see this particular speed bump.

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Anybody, any guests for it is islands in the background.

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It's the west coast of Scotland, and that's the show of egg and that's the island of Rum.

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And this was, I think, news day or something. Anyway, good.

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Particularly good speedbump signs.

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These slides are taken from a presentation I gave M.I.T. a few months ago, and I'll come into that onto the reasons for why.

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But one of the things throughout is that lots of people have asked me to define what is a speedbump,

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which I find a bit strange, having grown up with speed bumps. But it is a rich set at intervals in a road surface to control the speed of vehicles.

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And they are also called sleeping policeman, which is the British equivalent,

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which the Americans all found very funny when we were over there because of well,

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a few of them had come across the Thames sleeping policeman before, but not not many of them.

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And the reason behind this study was,

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say this started when I was a surgical house officer and we had lots of people coming in with suspected appendicitis.

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Now, just to give you a little bit of background of appendicitis, you know, for the non medics, you know, that, you know,

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appendicitis can be really classical and it's obvious even to, you know,

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the person next door or your grandmother is appendicitis, but often it is not quite so clear cut.

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So you use it. The doctors use a combination of symptoms and signs.

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So things like whether the pain moves, whether the patient has nausea and vomiting to try and work out if it is appendicitis.

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But it's good to pick it up early because if you miss it, then it can get more.

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It can get more serious and can it can cause sort of severe sepsis and even death.

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And the definitive treatment is is to remove the appendix surgically.

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But that's something which actually more recently is a little bit more questionable

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and certainly mild cases are now sometimes treated with antibiotics instead.

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So what we wanted to the reason this kind of came back was that we've noticed that

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quite a few patients in the hospital would say that the journey had been terrible.

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And I worked with one of the surgeons who said, oh, speed bumps. Absolutely.

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You know, if the patient says they've had pain on going over speed bumps,

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they absolutely must have they straight to theatre, they must have appendicitis.

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Let's not worry about any blood tests or scans.

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And obviously they were joking, but they'd noticed that there was this strong association and we thought actually that would be really easy to test.

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You know, it would be quite easy study to do. So what we did, we looked at patients who'd been referred with possible appendicitis,

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looked at the index test as pain over speed bumps, appendicitis on histology as our reference standard,

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say what it looks like under the microscope and if it's showing signs of being

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appendicitis and then obviously the target condition being acute appendicitis.

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And we did this at Stoke Mandeville, which is famed for its link with spinal injuries and and was the place that the first Paralympic Games were held.

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The reason that we well, it was a good place to do it because Aylesbury is a hospital that's got quite a few speed bumps and you know,

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that's a good reason to do a study, obviously.

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And what we did was we looked to patients who'd been referred with possible appendicitis by either the emergency department or via their GP.

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We gave them a questionnaire when they were first admitted to hospital.

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So before they'd had any, you know, before they'd had any treatment.

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And this questionnaire kind of asked about the journey to hospital and whether they'd travelled over speed bumps and if they had,

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whether it made the pain worse or better. And then we got their permission to follow them through and sort of see what happened in relation

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to whether they went on to have appendicitis or not and those who were discharged home,

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we telephoned them a month later just to check that they hadn't been admitted elsewhere,

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that they hadn't had a you know, they hadn't been diagnosed subsequently with appendicitis.

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And yeah, so we followed them very happily. Nobody, happily, nobody died in our study, which was very good.

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And we looked at the appendicitis histology to see,

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to see that and that was blindly assessed by somebody who hadn't been exposed to the who hadn't seen what,

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whether the patient had had pain, O2 speed bump.

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So it was an independent assessor of the kind of interpretation of the histology results and the pathology department.

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The hospital had no idea that we were doing the study, so in that respect it was quite good that nobody knew it was going on.

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It was published in the Christmas BMJ in 2012 and it had a particularly good cover image.

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So I put this on, it was the Sgt Pepper staff cover, which I think is great.

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These are the results. But I've actually because these are the slides that I used I thought would actually be interesting to

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explain the results in the kind of the way that I did it to the public audience a few months ago.

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So this is from the original paper and I think later this week, I don't know with the latest tweet,

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you're going to be looking at the speed of those papers anyway. I think Richard talks about it.

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And so 101 patients were recruited in the study, 64 who travelled over speed bumps were included in the analysis.

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So we excluded those that said they hadn't been over any speed bumps.

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54 of those who travelled to speed bumps had worsened pain and we called those speed bump positive 34 patients in total.

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All have confirmed appendicitis and three of them had pain over speed bumps.

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And that gives a 97% sensitivity.

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So only one person didn't have pain over speed bumps.

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And that is a better sensitivity than other symptoms and signs of appendicitis.

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So it scored better than migratory pain, nausea and vomiting, rebound tenderness.

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And having such a high sensitivity means that it's a really good rule out test, as you know.

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And so it's really good for saying actually, it's really unlikely that you have appendicitis.

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However, lots of those who were speedbump positive didn't have appendicitis.

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So just because you have pain over speed bumps doesn't mean that you necessarily have appendicitis.

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And that was the worst thing about the media associated with this, that loads of newspapers said, do you get pain when you go for speed bumps?

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If so, go to a hospital, you might have appendicitis.

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I was thinking, no, they want me responsible for these people going to the hospital on account of us, on account of our study.

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And yeah, as I say, there was lots of media attention at the time,

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but what I really wasn't expecting was to get a phone call last Easter from a guy in in London,

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a professor, saying, oh, I think I think you might want to give me a call.

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I'm at home painting. This is my home phone number. I looked him up and he seemed like he was a proper, proper professor.

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And and I kind of thought, well, what have I got to lose by giving him a giving him a call?

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Even though I was away on holiday in Scotland at the time and I phoned him up and he said, Have you heard of the IG Nobel Prizes?

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And I said, No, no, never heard. And he said, Oh, you've won one.

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And obviously it was slightly lost on me, the significance of this, having never heard of them.

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But I was saying with a group of friends who who had kind of like got off the phone and then immediately said, What are you running on prize?

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That's amazing. I think in non-medical subjects, they're very highly regarded and they're seen as the sort of greatest accolade that you

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can get in your scientific career if you're not going to win a proper Nobel Prize.

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So what they're sold, as is the IG Nobel Prize, is on the research that makes that first make people laugh and then make them then make them think.

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And Nature Magazine call them calls it the True Nature Journal, calls it the highlight of the scientific calendar.

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And it really was you know, they were awarded at Harvard and they really make a huge, huge thing over the over this out.

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You know, there was just a huge amount of media attention. There's lots of people to travel from all over the world.

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I was interviewed by of Japanese TV stations, Russian TV stations, and I never even heard of these awards before.

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People just really, really excited that I was one of the winners of these really most coveted prizes.

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But the ceremony is absolutely mad. I've never had such a mad evening in my life.

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It's got paper aeroplane fights and this guy stands on the stage as a kind of target and people throw paper aeroplanes at him.

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And as I was sitting directly behind him,

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you're just in the sea of paper aeroplanes and it's just a kind of public lecture thing as there was a guy swallowing,

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swallowing a sword and that so but it was in a sort of scientific way.

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I can't quite remember the details, but anyway,

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and then you win these prizes and they put a lot of effort into the prizes and I brought my prize along to show you because I would say I'm very,

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very proud of this. This is my IG Nobel Prize.

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And what's what's particularly great about this is that bringing it back from the States?

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I came I got my bags out of the, you know,

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of the baggage collection thing at the end and saw that my bag had been opened and my padlock had been cut free.

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And afterwards I thought actually that was kind of obvious that that was going to happen

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because it looks like this big sort of thing with all these wires coming out of it.

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And I thought, no, the people opened it and tried to find out what it was.

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Must have been it must have been really, quite, really, quite surprised.

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Probably had to go, what is it? What is an IG Nobel Prize? But I wanted to show you two bits from the ceremony, like, thank you.

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As you know, we used to have a problem at this ceremony.

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Many of these speakers would exceed their allotted amount of time.

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Here's how we now solve that problem. Please welcome the charming, the delightful, the ever so cute.

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Miss Sweetie. Who? The swimming pool is eight years old.

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Mr. Sweeting, how would you demonstrate what you will do when somebody exceeds his or her allotted time?

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Please stop. Oh, please stop.

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Oh! Oh! Oh!

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Oh! Thank you. I'm a sweetie.

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Thank you. Miss me? Thank you.

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So. So the ceremony is just full. That's just one example of what is a completely crazy ceremony.

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And remind me quite a lot of kind of Monty Python style style things.

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But I just wanted to end by showing you our acceptance speeches. Again, something I'm very proud of.

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My friend from Edinburgh actually wrote it for us because it was very difficult to try and think,

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how am I going to summarise my research to a non-medical audience in just one minute?

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So this is this is what we did, and we were actually allowed a little bit of time afterwards to do a demonstration as well.

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But it was really good because then the demonstration really caught the press's attention.

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And I never thought when I started my medical career and started an interest in kind of diagnostic

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studies that it would lead me to being on stage at the University of Harvard dressed as a speed bump.

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But it really was my proudest moment. This was the this was the win a date with a Nobel laureate competition that they had beforehand.

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And they were real Nobel laureates that give out the prizes. Diagnostic Medicine Prize.

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The IG Nobel Prize for Diagnostic Medicine is awarded to Diyala, Kareem of Canada and the UK after the harm done to New Zealand, the UK and the U.S.

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Nigel D'Souza. That's me. If you missed me in the middle of it, the speed bump happened.

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South Africa, the U.S. and the U.K. Andrew Wall of China and the U.K.

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Abdelkader Aloni of Syria and the U.K. and Helen Ashdown, Richard J.

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Stephens and Simon Krakower of the UK for determining that acute appendicitis can be accurately

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diagnosed for the amount of pain evidence when the patient is driven over speed bumps.

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We tried to give our speech too quickly. We're also awarded $10 trillion.

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I'll tell you better than this. This is less how this day.

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But first of all, we'd like to say we never achieved this perk without the other group as well.

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And so, you know what else is missed? We've got both sides, you know.

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Our moms and dads. Let's not forget. I hope they're watching on the net and all I can yell at.

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Answer J. Oh, my God.

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Oh, God. That's one of the professors of our department.

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He's. Just what the [INAUDIBLE] is wrong with him?

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Please cut off the grid. If it's a hostile.

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Brain disease, appendicitis. Could it be?

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It could be that. Now, let me see. But how would I have to see to you an ultrasound or an X-ray?

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Man, just read our paper. Then you'll know the speed bumps all the way to show.

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Just so I can quickly offer help. You know the paper.

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They can jump. Appendix cases that we sent was sensitive at 97%.

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It really is the simplest test. Their specificity is not best.

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So see diagnostic test accuracy to a wide audience, he states.

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Oh, my God. He's got appendicitis.

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He's not. Not normally like that.

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I'm sure we have a little demonstration. Is that correct?

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We have a demonstration. This was the moment I regretted wearing high heels.

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But. And you'll know Antony's appendix there was made out of tights.

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I happened to have a safety pin to. And then some lucky person in the audience, Joe, got got Anthony's appendix, another one.

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So, yeah, it was completely, completely mad. The $10 trillion are actually Zimbabwean dollars, which have a value of about 20 PPI or something.

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So sadly so I have been awarded $10 trillion.

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But that, yeah, sadly is not worth very much.

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I think that's all I wanted to say pretty much, other than I mean,

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we got lots of media stuff around the time and they loved all the pictures from it and it was really nice.

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It was really nice because it gave an opportunity to talk about kind of how much fun

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diagnostic accuracy research is and also kind of public engagement in science and things.

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And that's my final slide. I always like to put a picture of my cats in presentations.

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This is Agnes and Pippa, but they really like diagnostic accuracy studies, too.

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So, yes, that's all I want to say. Thank you very much.