Transcript:

[Michael] OK. Well, thank you for the invitation to speak. It’s always a real pleasure to actually be directly speaking to parents of people who’ve been affected by a condition because it’s an opportunity for me to learn from you as well.

So I’m a paediatric neurologist at the Evelina in London. And I don’t have any commercial interests at all.

My main research project that I’ve been doing in the last few years has been on autoimmune encephalitis. So the work on Sydenham’s chorea has been kind of a side project, but one that’s been really interesting and fruitful.

OK, from the medical perspective, how can we provide the best care for patients with Sydenham’s chorea? We need to know what the evidence is.

So this pyramid is a kind of way of visualising the different types of evidence that we can get from clinical research studies.

So at the bottom we’ve got studies which can still be very valuable, laboratory studies, but they don’t involve any humans. So we should always be quite careful about extrapolating from studies on animals to benefits in humans.

And then you’ve got an awful lot of case reports, especially for conditions which are quite rare now, like Sydenham’s chorea. We have lots of case reports in the literature, but that’s kind of anecdotal evidence, really. And then you have studies that are designed to compare children with Sydenham’s chorea to healthy controls. And then the gold standard for primary research is randomised control trials where for testing and interventions we’re randomising patients to receive the intervention or to receive the control. And there really aren’t very many of those at all in Sydenham’s chorea. In fact, there are three and they were small studies.

And then at the top of the pyramid we’ve got secondary research, which is kind of pulling together different aspects of other research projects that have been done, to try to synthesise that into a guideline or a summary across lots of studies, which we can use to inform our practice.

So as I’ve said, there’s very few of these in in Sydenham’s chorea. There’s not very many well designed observational studies either. There are quite a lot of case reports.

So in part one of this talk, I’m going to show some data from how we’ve pulled together all of these many small case series and case reports to analyse all of those patients together.

And then in Part 2, I’m going to give you an update on the progress we’re making developing an international consensus guideline, which pulls together data from that metanalysis (a metanalysis is an analysis across lots of previous studies and also all of the other high quality evidence that we’ve got) to try to produce a guideline to help clinicians give the best care for patients with Sydenham’s chorea.

OK, so I think that the areas of need in Sydenham’s chorea really are that some patients can relapse and we don’t understand well what the factors are that determine a relapse.

Most patients do recover from the chorea and have a good long term outcome, but there are a small group that don’t, and again it’s not that clear what determines that group.

And there is clearly consensus that the patients should receive antibiotics. But beyond that, there’s not a very clear consensus, and you’ll find different clinicians will do different things in terms of things like steroids and which symptomatic treatments they would give, the treatments that help to relieve the chorea symptoms.

So for this study, we pulled together lots of people from all around the world, including people associated with the Sydenham’s chorea association:  Adrian and Emanuela.

And this was finally published last month, and it’s Open Access, so you can go and read this paper if you want to some reading material to put yourself to sleep! But I’ll give you the summary of this paper.

So the aim was to describe the features of Sydenham’s chorea and what treatments patients are getting, and then specifically to address some of those questions which are unresolved. So what factors are associated with the duration of the chorea at the first episode? What factors are associated with patients going on to have a relapse?

And which factors are associated with functional outcome, and particularly a focus on the treatment factors that are determining those things.

So as I said, this is a study where we’re pulling together information that’s already been published from many, many small papers. So we did our systematic search and we found 2207 papers that were potentially relevant. So that’s why you need lots of people to work on a study like this. And we divide it all between us, extracting the data from those papers. So essentially what you end up with is a big spreadsheet where you’ve got one row per patient. So we’re only interested in papers where they provide individualised patient data.

There might be a series in a paper called “5 Children with Sydenham’s chorea” and they’ve given quite a lot of detail on each patient, and then we extract that to become 5 rows in our spreadsheet, and then the columns are all of the different factors that we’re interested in, and the outcomes.

So the outcomes that we’re interested in for this study, we are interested in patients who had a relapse and comparing those to patients who haven’t had a relapse, and two years of follow up were considered sufficient for that.

We were comparing patients with a good versus a poor long term outcome. So that long term outcome was at six months or later from the onset of the career.

You don’t need to know the details of this modified Rankin scale score, but a good outcome was essentially having no symptoms, or having some minor symptoms that don’t impact at all upon the activities of the child. There’s no disability, there’s no developmental impairment, there’s no behavioural impairment, even though there might be some very subtle findings when a doctor examines the patient.

And then we put all this together using multivariable modelling. So we’re looking at the independent effects of lots of different factors on these outcomes. And the other outcome was the duration of the chorea.

And so I’m not going to dwell on this slide because I’m going to talk about some of the different factors on the following slides. But we looked at lots of different clinical features and also lots of different treatments to see what their independent effects are on the outcomes, after controlling for the effects of the other factors, so we can isolate the impact of each individual factor.

Results

So we we end up in our big data sheet with one and a half thousand patients.

These are patients that have been reported since the 19th century with individual patient data. So for the descriptive part, we look at all of these patients, because I think it’s really interesting to see what the historical trends have been. So here you can see in this in this figure, we’re going from the 19th century up to the most recent patients. You can see that the age of onset of Sydenham’s chorea hasn’t really changed.

It’s tends to be 10-11 year old peak onset.

It tends to always have had a female predominance over the years.

But then interestingly, you can see here, that what used to be a predominantly febrile illness (it was very much part of a fulminant, acute rheumatic fever, has has now transitioned to becoming an illness where most children are presenting without a fever, and that probably relates to antibiotics now being available.

And then here we’re looking at the treatments. So you can see antibiotics massively coming online during the 20th century. And now almost all patients are receiving antibiotics.

And then other treatments become available at different decades in the 20th century, and more recently, other approaches to immune treatments. So in addition to steroids, IVIG and plasma exchange are becoming more popular recently, but still quite small numbers of patients.

And then here we’re looking at some of the different outcomes and tracking those across across the decades. Interestingly, the average duration of the chorea at the first episode seems to have got a bit longer in the most recent decades.

And that’s quite puzzling. It might be due to increased recognition. Perhaps listening to the families more about when they say that there’s still chorea there, even if it might not be present on the day of the clinic visit.

OK, so for the rest of this data, I’m just going to tell you about the patients who had their onset since the Second World War because those much older patients we weren’t quite so confident about how those have been reported. It was quite a different era, different investigations were available. So now we’re just looking at over 1000 patients who presented after the Second World War.

And the majority of those patients come from actually just four countries – Brazil, Turkey, Italy and the United States. So this doesn’t necessarily reflect the countries where the incidence is highest, but it’s a combination, and also I suppose, how likely doctors in those countries are to write papers and report these patients.

And then there’s that age distribution. So you can see that that peak age distribution around age 10 to 12 years old and that really hasn’t changed very much over the years. So this is a paper which I dug up from the archives in trying to find patients for this study, from actually the hospital I’m affiliated with, Guys Hospital, from 75 years ago. And you can see this age distribution at that time. It’s strikingly similar.

Clinical Features

OK, So what were the features that these patients had at their first Sydenham’s chorea episode? So about half of the patients had reported symptoms of an infection prior to the Sydenham’s chorea.

90% were admitted to hospital. The average length of stay in hospital is 3 weeks.

The most prevalent symptoms were difficulty walking, difficulty using the arms to manipulate objects and to feed.

Psychiatric symptoms

So this graph on the right is showing the most frequently reportedly reported psychiatric symptoms.

We know from the previous literature that these these are the things that are most frequently seen, so emotional liability, mood swings, anxiety, irritability, hyperactivity.

Not many patients actually were assessed by mental health specialists, though, which is something that we’re keen to encourage in our guidelines, which we will come on to later.

Speech impairment – most patients have impaired speech.

And a smaller but important minority of patients, perhaps even more severely affected, the coordination of swallow, and some of them requiring nasogastric feeding.

I’ll skip over that because the main focus of this is was on the neurological symptoms.

Treatment

So most patients receive antibiotics.

A quarter of all the patients in this measure analysis received immune treatments, and by far and away the most common was steroids – corticosteroids – Prednisolone.

So this was looking at what the clinicians had said about the symptomatic treatments. So these are the treatments that are directly treating the chorea itself or the psychiatric symptoms. Here in green for each of these drug classes, represents clinicians that said this drug worked to resolve this symptom. In red, clinicians said it didn’t work; and in grey, that it wasn’t clear to the clinician or it wasn’t clear from that report.

Sodium channel blockers – these are actually epilepsy drugs, like carbamazepine – were reported to be the most beneficial for symptom relief.

Benzodiazepines, that’s a drug that makes you quite sleepy but and can settle abnormal movements, were reported to be the least effective.

But this is very subjective, just based on the clinician saying what they found for their patient. And then this is [a list of] some of the adverse effects. Obviously the flip side of some of these drugs is that they can cause side effects, in particular some of the older antipsychotic medications – they can be very effective at treating the symptoms, but they can be associated with a high rate of side effects, compared to some of the more benign medicines.

Duration of first episode

OK, so one of the main outcomes we’re interested in was how long does the chorea last at the first episode? So this graph is showing you at each time point from zero to 18 months, what proportion of the patients have still got chorea. And then again, going back to that older paper, you can see some similarity, but also a difference here – this dotted red line shows the average duration of the chorea (where 50% of the patients have had their chorea resolved). It’s three months overall for this whole metanalysis, and that’s quite similar for this in this older paper.

But the difference you can see is that there’s about 15% of patients who have still got the chorea at 18 months in this more modern cohort – in the older cohort, it seems to be very rare for patients to still have symptoms even at a year. And again that’s quite interesting. And to what extent it’s due to increased recognition, it’s not completely clear.

Relapses

We looked at how how many relapses patients had.  So most most of the patients didn’t relapse. One third had relapses, and most often just one. It was a very small number that had highly recurrent relapses. Again, that was similar looking back at that older paper.

Final follow up

And there we’re looking at the final follow up, so what the clinician said about the very final outpatient visit and how the patient was doing.

And the average patient was doing extremely well and didn’t have any symptoms or signs on examination. And a minority were still having ongoing psychiatric behavioural symptoms or difficulties at school. I think this is almost certainly an underestimate because if it’s just not mentioned in a report, it’s quite hard to tell whether they’d actually evaluated for it or not. So I wouldn’t put a lot of emphasis on that part of the data.

Treatment Factors

OK, so the main the main thing we were doing was putting all of these different factors together and trying to work out which ones are important for these different outcomes. So I’m not going to get too much into the details of the statistical modelling, but I’m just showing you the results that were statistically significant.

So what we found was that immunotherapy was associated with a shorter duration of the chorea.

Patients with carditis had a slightly longer duration of chorea in the first episode.

This graph is showing something similar. So the green line here is where we’ve had steroids for more than a month and it’s the same figure that I showed you before, what proportion of the patients have still got chorea, so you can see that there’s a very significant shift there. If you give a longer course of steroids the the duration of the chorea is is shorter.

Relapse Factors

Then we looked at factors predictive of relapse. We found that the treatment factors that were protective against relapse were antibiotics, not surprisingly; steroids; and also sodium valproate, which was quite surprising because we think of sodium valproate as a treatment for the chorea. We wouldn’t think of it really as influencing the long term course of the disease. So that was quite interesting.

So we looked into the literature about that and it is plausible. Sodium valproate can modify the way that your DNA is turned into proteins, and I’m not going to go through this in too much detail, but this was just a study where they applied sodium valproate to the white blood cells from patients with lupus, which of course is another neuropsychiatric inflammatory disease. And they found that sodium valproate… the red bars here are the patient… sodium valproate led to an an increase in the anti-inflammatory immune cells, and a decrease in the inflammatory immune cells.

So extrapolating a bit here, but it is plausible that sodium valproate could be modifying patients’ immune systems in the long term to make them less likely to have a relapse. That was an interesting finding that we didn’t expect to see.

Poor functional outcome

And then finally, we looked at predictors of poor functional outcome. So that was defined as still having chorea or psychiatric symptoms at six months or later from the first onset of the illness.

And we didn’t find any treatment factors that were protective there.

And there were a few factors that were associated with the poorer outcome, like a very young age of onset, having other inflammatory diseases as well as the Sydenham’s, and having received plasma exchange (which probably just speaks to how severe those patients were, in ways that we can’t capture within the model).

And the other thing to mention here is that there are actually a very small number of patients who did have that poor outcome.  So that limits the statistical power here.

Summary of the evidence

OK, so in summary, from this study, before I move on to the guideline that we’re developing, so we found that treatment with immunotherapy was associated with a shorter duration of chorea.  Corticosteroids were associated with a shorter duration of chorea, and also less chance of having a relapse in the long term.

Antibiotics were also protective against a relapse; sodium valproate (surprisingly) was also protective against a relapse in the long term.

The bad – so Haloperidol was associated with increased relapse. Now there are various reasons why that might be. It could be that the patients who were given Haloperidol were different in some way… more severe in a way that we haven’t managed to capture and control for. It could be that haloperidol does actually modify the parts of your brain that produce abnormal movements. It’s a bit hard to resolve that just on the basis of this data.

 And so the good, the bad and the ugly…

The ugly is of course there are limitations to this – it’s quite “dirty” data. We’re just mining lots of data from the literature. There are all kinds of biases in the reasons why clinicians will report a particular case. It might actually be quite an unusual case, and that was why they reported it. But we’re trying to make the most of this large number of patients to get signal that we couldn’t get from smaller studies.

International Consensus Guidelines

1. So the second part of the presentation, I wanted to give you an update on how we’re progressing with our international consensus guideline, which is including summarising across lots of different sources of evidence and also expert opinion (clinicians who’ve managed a lot of patients with Sydenham’s).

So this is the group of of clinicians and other supporting team who are involved in this in this study. We’ve got representation from all the continents except Antarctica, I think there’s not much Sydenham’s in Antarctica!

So the aims were to affirm key statements on the history and clinical features of Sydenham’s chorea, and that’s not really controversial, but I think it’s nice to have it in a document that you’re going to disseminate out to people with less expertise, to provide guidance on what assessments should be done for patients with Sydenham’s chorea: who should be involved in their care? How should they be followed up? To make clear recommendations about which treatments should be considered in which types of patient.

And to identify things that we still don’t know that we think should be emphasised for future research.

So the way that we do this, it’s called a Delphi Process. That’s just the process whereby you offer lots of statements for all of this group to vote on. You have to have the agreement of at least 75% of the group for that statement to make it into the final guideline. And there’s multiple iterations of refining the statements to optimise the agreement among the whole group.

And where we’ve got to with this is that we have we’ve completed the final meeting now, and we’re just turning that into a guideline. So we’ve got the agreement on all the statements, perhaps with a few minor tweaks still outstanding.

This was a little screenshot of that final meeting, with some of the people that are in that final meeting. Adrian looks like he has a much better camera than everyone else!

OK, so these are all the sections that these statements get organised into. I’m not going to go through all of this. I thought I would just pull out some things that I thought might be of greater interest for for you as a group.

So who should be involved in the care of children with Sydenham’s chorea? A paediatrician or a paediatric neurologist.

We said that children should have evaluation by a cardiologist or a paediatrician with cardiology expertise.

As I mentioned before, we found a very low rate in the literature of people actually saying they got mental health assessment for patients. And so that’s a recommendation.

And the children should be screened for difficulties with learning, which we know can be a part of the persisting symptoms after the acute phase.

So I’m just showing you statements that the whole group has agreed on already.

And then some of the allied health professionals that we’re recommending should be involved. So if there’s an issue with using the hands or with mobility, you need occupational therapy, physiotherapy or rehabilitation teams.

And we’re saying that children should be screened for issues with feeding and swallowing and then speech and language therapist or a rehab team should be involved to support that.

And again, issues with speech and language, obviously speech and language therapists are important.

So we hope it’s going to be really helpful to have these kinds of statements in the guideline, because then that’s something that you can show to your local clinicians to say, look, actually there is actually an expected standard of care internationally.

That where there’s concern about speech, we should have the opportunity to see a speech and language therapist, for example.

So here are some of the different assessment scales and tools that we’re recommending. I’ve already mentioned the modified Rankin scale score. It’s quite coarse. It’s quite focused on mobility. It’s more of a research tool. So we’re also recommending some of the more detailed tools that clinicians might use to score symptoms and monitor the response to treatments.

And we’re suggesting that psychiatric and behavioural assessments should also be part of the standard assessment of these patients.  We’re recommending that psychiatric diagnosis should be used where appropriate, but also with consideration to the fact that symptoms in the acute phase may well resolve and it might not be appropriate to give a diagnosis for symptoms which are transient.

And we’re making a recommendation that video recordings are worth storing with the consent of the family. And that’s as a paediatric neurologist, that’s been actually one of the most transformative technologies of the last few decades, being able to see family videos of what the movements are. So that’s actually really useful.

We’re recommending cardiology evaluation, which I’m not going to focus on, it’s clearly important.

OK, so we thought it would be helpful to recommend investigations that are useful. Also the investigations that don’t add a lot and don’t always need to be done. So the main focus of investigations is looking for evidence of streptococcal infection and ruling out other possibilities for a child presenting with new onset of chorea.

We’re trying to design a guideline that’s going to be useful in developing world settings as well as in more well resourced countries, and so acknowledging that in countries where there’s a very high prevalence of Sydenham’s chorea (still, it might not be necessary to do so many investigations) that children in those countries might not need to have an MRI scan, for example.

But where a scan is needed and that would be the case in the UK, MR is preferred to CT scan.

We would mention that some of these other types of research imaging aren’t routinely necessary.

Other things that we don’t think are routinely necessary in Sydenham’s chorea, unless there’s a reason to suspect another diagnosis like encephalitis, would be lumbar puncture and antibody tests. So it isn’t necessary to do the full list of all investigations that can possibly be done. You can make a positive diagnosis of Sydenham’s chorea without all of these investigations.

So we’ve made some statements on what the general approach to management should be. So the aim of for treatment of Sydenham’s chorea is a return to functioning, and the emphasis is on return to previous functioning or to optimise the quality of life within the functioning that’s possible.

We’re making a statement that providing information to the family is an important part of the treatment.

And the behavioural problems and psychiatric issues and issues in school are also part of the range of things that should be managed.

And we’ve covered speech therapy previously.

We’ll do this quite quickly because antibiotics isn’t controversial at all for Sydenham’s chorea, but we’re providing some guidance on what forms of antibiotics can be used, in particular, in situations where there’s antibiotic allergy, and Emanuela has really been leading the group that’s been providing detailed recommendations on this, which has been really helpful.

So I’m going to skip past that, but that’s all going to be there in the guideline as a resource, yeah, we’ve actually done a lot of work on the antibiotic side of things.

And then the immune treatments. So we’re trying to get agreement from this whole group, when different people do have different opinions about this. So patients with mild Sydenham’s chorea might not need to have steroids, IVIG, et cetera. Patients with moderate and worse Sydenham’s chorea we recommend should be offered these treatments. It’s a discussion with the family about the risks and benefits.

I think we’ve found quite clearly from the metanalysis that steroids are likely to shorten the duration of that first episode of chorea, and steroids might also be protective against a future relapse. So steroids is the preferred first line immunotherapy, but other options include IVIG, and less often plasma exchange and the other immune treatments.

And then focusing on those symptomatic treatments – sodium valproate, carbamazepine, et cetera might not be necessary for children with mild symptoms, but should be offered to all patients with moderate or worse symptoms.

Sodium valproate is a useful symptomatic treatment, but there are other good treatments as well. Carbamazepine is another good one. There are some concerns around sodium valporate in children approaching reproductive age.

The older anti psychotics, while they can be effective in well selected children, are associated with more side effects.

And also that it might not be necessary to reach for the drugs and you need an expert to help evaluate the patient, and they might be able to deliver a psychological intervention instead of or as well as drugs.

1. And then the final final slide here before I summarise, these are some of the things that we’re recommending as needing future research, so hopefully this will be something helpful if you were putting in an application for a small grant for a research study, you could say actually this was highlighted in this international guideline as something that’s needed, that would hopefully help support these research studies to happen.

I’ve just highlighted in bold there some of the things that have come from the parent community, from Emanuela in particular.  That actually it can be quite difficult delivering these intramuscular antibiotics and we need more research to address how to do that whilst optimising comfort and compliance.

OK, so for the metanalysis, we found that these immune treatments, in particular corticosteroids, resolve their first episode of chorea more quickly, and antibiotics, steroids and valproate can be protective against relapse. And we’ve published that last month and it’s Open Access.

You can have a look the consensus guideline when we’ve collected all of the votes from these multiple iterations when I’ve consolidated that into a guideline, which should hopefully be out by the end of the year.

And thank you to all the people involved in that.

[Nadine] Any questions from the group?

[Lisha] Hi, I’m not sure if this is the type of question you can answer, so no worries if not. But basically I was only diagnosed last year, after a very long period of having no clue what was going on and the flare that I had when I was 15, which was like the biggest flare I had, was more relatable to Sydenham’s chorea and the kind of symptoms that people get, whereas before that point I had lots of different things, like when I was ten, I had been diagnosed as Henoch Schonlein Purpura, but we think due to the length of time it lasted, like 2 years, it wasn’t necessarily that. They think there was a lot of misdiagnosis going on when I was younger, so I was only diagnosed last year by Doctor Ubhi. Well, the question is, was it Sydenham’s chorea? So basically, I’ve been diagnosed with Sydenham’s chorea, but Dr Ubhi who diagnosed me last year said that because I’m 22 and I didn’t receive treatment when I was younger, it’s very unlikely basically that I’ll get better. And the way I’m experiencing life now is that I’ll kind of be normal like this for like a few weeks and then I’ll have a huge flare and like, lose mobility. I’ll have regressive, childlike behaviour and all the other symptoms and everything that goes along with that.

And I’ll have that for a period of time and then I’ll really, really slowly recover and then have a couple weeks where I’m pretty normal and can cope with life. And then I’ll go downhill again. So mine isn’t like a big flare and then I get better… It’s very, very up and down.

I don’t know if you can answer this, but what do you think? Even though I am a lot older, is it still possible to have treatment and kind of see a better future?

[Michael] It’s always possible to have treatment, for sure. The question is, which treatments are appropriate, and are likely to help, once you get into the more chronic phase.

I didn’t show it in the statements there, but I think there was agreement from this international group of experts that once you’ve got past about two years, probably immune treatments aren’t going to be the thing that’s going to really make a difference. But there’s still going to be treatments that are really helpful.

I imagine Michael Morton might weigh in on this as a psychiatric expert, but you know, there are all kinds of interventions that you can do for symptoms that are mainly psychiatric, which doesn’t necessarily mean drugs at all, but I might pass it to him for comment.

[Michael Morton] Yeah, I’d agree that immunotherapy is unlikely to achieve anything but you have symptoms which come and go, and so I would be looking for a discussion, either with a neurologist or possibly a neuropsychiatrist, a psychiatrist who understands neurological disease, maybe based in a General Hospital, about the possibility of one or other of the drugs that can manage symptoms of Sydenham’s chorea, and you know, in my mind, the anti-epilepsy drugs are the sorts of drugs which are sometimes quite good for stabilising fluctuating conditions. But I mean it’s wrong for me to make any more comment than that because I don’t know you, but I would certainly be pushing for a hospital based psychiatrist appointment or a psychiatrist who’s an expert in neuropsychiatry to give you some advice, a liaison psychiatrist, anyone working in a General Hospital would probably be able to be helpful.

[Nadine] And I would just add to that, be careful, it needs to be a neuropsychiatrist, because there are lots of psychiatrists working in hospitals now for crisis teams and crisis services, so you need somebody who’s got the experience that Michael’s described there, rather than just any psychiatrist based in a hospital, because some psychiatrists are there for a crisis purpose and not necessarily for neuropsychiatry.

[Lisha] Thank you. I’m going to see Adam Handel in July in Oxford [Autoimmune Neurology], so hopefully that is, with what you’re saying, on the right path.

And do you think they’ll help with the movement side of it as well, like in the seizures and stuff like that, is that still able to be helped, if that makes sense?

[Michael Eyre ] Yeah. And Adam’s very well placed as a neurologist to look at this kind of neuro inflammatory aspect. Yeah. Perfect.

[Lisha] Thank you.

[Sharon]  Thank you. That was very interesting.

Michael, I’m wondering. I have a few questions, but I’ll start with this one.  Is there any research or results into the long term effects of taking antibiotics, you know, so my son is 7 or 8 now, diagnosed with Sydenham’s, and they told us he needs to take antibiotics until he’s at least 18, twice a day amoxicillin (Moxipen, we call it here), and so I’m just wondering what, if any, long term effects there are from that?

[Michael] Yeah, good question. I mean, it’s not something that I’ve specifically researched, but just speaking as a sort of general clinician, I think that the main thing you would probably be concerned about would be the effect on the microbiome, like your gut health. because we know that antibiotics can modify that. That’s something that you can sort of try and find dietary optimizations for alongside the antibiotics. I think we we do know that once patients come off antibiotics, that tends to normalise.

So I don’t think there’s any evidence that that would be permanently altered and I think any theoretical side effects are definitely going to be less impactful than the very known effect of rheumatic fever itself, so I think you’re right to be concerned, and you can look into things like probiotics and things that can help your gut microbiome.

[Sharon] Also I know when I take antibiotics, I tend to feel a bit drowsy, and tired. I don’t know if that’s just me – I have concerns for my son, taking this so often, if that affects him.

[Michael] That’s not something I’ve ever seen in patients on prophylactic antibiotics. And the antibiotics that we use for prophylaxis tend to be quite well selected to be narrow spectrum, whereas antibiotics that you take when you’re sick, the doctor will probably give you a broad spectrum, then they can have more wide-ranging effects. So amoxicillin is quite narrow spectrum.

[Sharon] Thank you.

[Nadine] And I think a key thing is to keep reminding yourself why he’s taking the antibiotics. So keep reminding yourself that it is there for a reason and you’re not just giving them daily because the doctors told you to. You need to remember what you’re treating with the antibiotic and the rationale behind it. So then if you balance those scales together, the side effects and the worries sometimes come down, because you realise, actually, you know, just taking something for the gut within your diet is much less restrictive than not having the antibiotic to treat the symptoms, so just remind yourself why.

[Sharon] Yeah, that makes sense.

[Emanuela] Yes, I wanted to add to that, doses of prophylaxis as are not doses for treatment of infections. So they are impacting less, less likely to have side effects with the lower doses.  And also penicillins are less disrupting in macrobiota than other antibiotics.

So they are well tolerated generally.

[Adrian] Yeah, I thought Emanuela would probably be saying the same things as me..  Of course Emanuela and myself, our children have been taking these antibiotics for 10 years now. And (Emanuela can say for herself), but my son is a very healthy young man. He’s now 15, and on balance, of course it’s much more important that he doesn’t get a relapse in his valve disease or his abnormal movements.  He has done absolutely fine, if that’s any reassurance, going forward for the next 10 years.

[Nadine] I just want to say thank you very much. That was really, really interesting. And we can’t wait for the for the final publication. I think it’ll be really worthwhile,  going to really make some significant changes in the world of care and treatment for Sydenham’s chorea, which is what this charity was originally set up for. We just wanted to make a real difference to the experiences that Andrew and Sam and some of our other parents had at the time when we had the outbreak in Glasgow.

So thank you for coming along today and all your hard work.