The COVID-19 interview – experiences from the front line!

The COVID-19 interview – experiences from the front line!

The COVID-19 interview – experiences from the front line

In this “COVID interview” episode I interview Dr Tom Fardon, consultant respiratory physician at NHS Tayside, honorary reader at the University of Dundee. Regularly called on by the media to explain what is going on with the COVID pandemic, we take time to explore aspects of the disease and how it is treated and cut through a lot of the misinformation out there.

Please find Tom’s latest Facebook post here
Music in the podcast is by Drew Worthly – Thanks Drew, please check out his music here

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Edited transcript of the podcast

In this episode of the Doctor Family podcast we feature an interview between me Dr. David Stokes and Dr. Tom Fardon. Tom is a respiratory consultant at NHS Tayside, and honorary reader at the University of Dundee. He’s been working at the sharp end of the COVID-19 pandemic.

We present some of the insights he’s gained from working with these patients and indeed, having caught the virus himself and recovered.

David:

So You’re now up in Scotland as a leading respiratory physician. And a lot of people may have seen that you’ve been writing some very informative posts on Facebook really sort of cutting through a lot of the misinformation, which is out there. Your posts have been very interesting to read. I thought it would be great to pick your brains a little bit today about your experiences with COVID.

Tom:

The Facebook stuff started off because I think right at the beginning of this, there’s so much information and what everyone now refers to as fake news. I think people are getting really panicky about what what to believe what not to believe, and I just wrote a couple of posts to my very small friends list on Facebook, of 30 or 40 people, and then it became evident very quickly that people were very interested in and now I have a frightening number of people find me on Facebook and that’s approaching 10,000 which is a weird, a weird situation to be in but but some people do seem to appreciate some level headed advice and opinions.

David:

It’s somewhat ironic that your posts have gone viral.

Tom:

Yes, it is a bit strange!

David:

You’ve been right there in the thick of it working on the COVID wards

Tom:

As a respiratory physician, we became sort of the front line in the COVID assessment unit very, very early on. In fact, I was looking back at that my diary I was on call the first weekend that we ran our COVID assessment unit.

We very rapidly converted our infectious diseases unit into a COVID assessment unit. I worked that first weekend, very challenging times, not knowing what the disease look like, what people would present like, having to be assuming everyone has the disease and trying to get the test done and try to manage people in a safe way.

I still work on the COVID assessment unit, but I also work on our COVID HDU (our high dependency unit) where people who are who are more sick than than could be looked after on a normal ward. So that’s where we’re doing the CPAP (continuous positive airways pressure) treatment, which people may have heard of, which is the tight fitting mask that blows air into the lungs to help ventilate people. So that’s where you go if you’re pretty sick, before going into intensive care for to need a ventilator.

David

so, I think for most people, It’s a either a mild to moderately nasty flu like illness with upper respiratory tract symptoms and the usual flus symptoms of fevers and myalgia (muscle pains) and some may have it without any symptoms at all. I understand you’ve had COVID yourself going through all of this. But obviously, for some, it is much more serious, what what is the sort of presentation for those patients that are coming into you who are sicker?

Tom

So I think the, as you say that there’s a really wide range of symptoms and the data we’ve got from the European studies now show that there really is a massive wide range.

The majority of people who, who are sick enough to come to hospital and then need to be looked after have fever, breathlessness and a persistent cough. Breathlessness on a short short amount of exercise. So walking from here to the kitchen and back again example when you wouldn’t normally be breathless that being that’s a prominent sign.

We’ve noticed this slightly unusual thing that that patients themselves often don’t notice that their breathlessness at rest, they are sitting, feeling okay, and it’ll be their partner or their children or their friends who say, ”you’re breathing very, very quickly. You look awfully breathless” and the patient says “I feel absolutely fine”. That’s a good trigger for needing hospital admission as well that people who are breathing at 40 breaths a minute and feel okay.

We put the SATs probe (oxygen saturations probe) on a finger and their saturations of a pretty very low and those are the people who we need to look out for in hospital. As you say the majority of younger fitter people are going to have a sore throat, a bit more breathless, headaches, flu like symptoms, as you said. Most people tend to get over that in four or five days and they’re feeling pretty much back to normal, by seven days back to work or back doing normal activities.

Then there’s people like me who sort of fall in the middle, where I got better after about four or five days, and then by day seven, I got a lot worse. For that second week was much worse than the first week. So we just have to caution people that if they’re feeling better by day five and six, then just take an extra couple of days just to make sure that everything settles down.

The people who are very, very sick and need high dependency care and intensive care, do tend to be people who are older, in their 70s and 80s. People who have other illnesses, heart disease, particularly poorly controlled diabetes, and also people who were overweight. We now know that obesity is a is a real risk factor for doing badly with COVID.

Those people can have a whole raft of different problems that start with the lungs and then can spread, like any severe illness, spread to affecting other organs, the heart, the kidney, the brain.

David:

So by that point, it’s pretty much like any other case we look after in high dependency in intensive care, looking after the whole person. It’s interesting, you talk about this second peak as in terms of the illness, for some people, they get better, and then they could get worse once more. Is that secondary infection? or is there just as a strange way the virus affects certain people.

Tom:

We think it’s this I mean, you heard this phrase of cytokine storm, is what we think happens. Because we don’t have really have any immunity to this at all. It’s a brand new disease. The way the immune system works, takes about five or six days to build up antibodies and the right kind of cells to fight an infection. And then after about day five or six, that the immune system starts to work very aggressively and releases lots and lots of chemicals and hormones which activates the immune system hugely. It’s that over activation of the immune system that makes you feel unwell on day 7,8,9,10. So we don’t think it is a secondary infection, we think it’s just the way the immune system is fighting the infection away, and that in all likelihood, you’re not infectious by that point. But you feel pretty awful.

David:

So the immune system seems to be the thing that’s causing the the symptoms and the damage to the to the respiratory system, rather than viral damage itself to the cells of the respiratory tract?

Tom:

I think so. And we’re backed up with that with quite a lot of evidence from the Far East. There’s a very nice study in Taiwan where they did a lot of contact tracing and looking at how long people were shedding virus for and the vast majority of people stopped being infectious at day five, but the symptoms went on for for much longer than that. So it’s not the virus itself that’s causing the problem.

And as you know, Dave that a lot of Symptoms we get from illnesses are not the primary effect of the bacteria or the virus but the immune system, the effects that causes the symptoms like fever, headaches. And I think this is just an extreme version of that, because this is a virus we’ve not come into contact with before.

We see this in people who’ve got mild to moderate disease like I had. And we’ve seen people have got severe disease, they come into hospital, I think they’re getting better. We hang on and by about day six or seven, suddenly, something happens where they get much much sicker. So we do like to be very cautious with people who have been more unwell in HDU, particularly waiting for that day 6,7,8 deterioration.

 

It’s interesting to talk about secondary infections, because in the Spanish Flu of 1918, Yes, a lot of people died of flu – but more people died of secondary infection. Two weeks after they had the flu, they got secondary bacterial infection in their lungs. Of course, in 1918, we didn’t have antibiotics, so there was no treatment. That’s really what caused the millions of people to die in that pandemic.

I was very worried. I think I wasn’t alone, that we what we would see people having COVID, and then two to three weeks later come back with a bacterial infection. Thankfully, we’ve not seen that. That when, eight weeks in now and we’ve not seen that second peak of bacterial infections, so that’s really reassuring.

David:

You mentioned that obviously a lot of the symptoms that talking about treating primary care with simple paracetamol or what have you for the fever. Are there any of the treatments that you’ve used in hospital for those sicker patients who are being affected potentially by this cytokine storm, their immune system going crazy.

COVID 19 treatments

Tom

the bottom line here is there’s nothing yet that has been proven to be of any benefit. The cytokine storm story leads us to think about drugs like tocilizumab, which is an IL-6 inhibitor, this is a drug which is widely available and used for people with rheumatoid arthritis. It reduces inflammation caused by this chemical IL-6 we’ve measured in people with bad COVID at day seven that IL-6 levels are very very high, off the chart.

It kind of makes sense to us that if you’re given give the inhibitor reduce those levels, then people might get better. But the data from the observational data from America where they gave people tocilizumab on a compassionate basis, it did nothing at all. And in the people given the drug or have they had to withdraw it because they had side effects. So tocilizumab doesn’t work as yet.

Of all the other drugs which may have read about in the news and bounced around, nothing has been proven to be beneficial yet. Remdesivir was not was shown not to work in the Chinese cohort. The Americans have told us that they have great data showing it does work but then haven’t published it. So you have to forgive my scepticism that in a way it shows the data or believe it, Kaletra the antiviral treatment for HIV doesn’t work.

The hydroxychloroquine data is not great. I’m afraid everyone really hoped it would work but it’s so far has not been demonstrated to do anything, and in fact, some of the graphs it looks like you’ll might do a little bit worse. The there’s the diamox (acetazolamide) story, this is a treatment for altitude sickness. Some people have said that the damage the lungs is very much like altitude sickness therefore to use altitude sickness treatment, but there’s a logical fallacy in there, just because it looks like it doesn’t mean to say it’s working in that way. And indeed, we’re not even doing a trial of diamox because there’s just no rationale for using it. So at the moment, the best the treatment for COVID is paracetamol for fever and also for any aches and pains and then treat the other things that go wrong oxygen, CPAP and support the kidneys.

CPAP

David:

With regard to the CPAP that you mentioned, I know you’ve mentioned in your post as well on Facebook, for those who don’t know is where there’s a tight fitting mask fitted over the face. The patient is generally still conscious, and the machine is just puffing air into the lungs.

Tom:

Yeah, that’s right

David:

Is that essentially because they’re getting too tired to breathe completely for themselves? Or what is what is the theory behind that? Is it keeping airways open? what was working in that case?

Tom:

So CPAP works in a number of ways. It certainly opens up airways as you described. So in people who’ve got collapsed bit of airway at the edge of their lungs, if you blow in that it opens up, it’s like this, like blowing a balloon, you get more and more lung opens up so you’ve got better gas transfer, and it certainly helps oxygenation.

When you have COVID lung disease so the chest X ray looks bad and you’ve got lots of fluid floating around in the lungs. The lungs become stiff and and don’t open properly. So helping by blowing air in it opens up the lungs a bit more allows more gas to be transferred.

So it’s that stiffness when we talk about lung compliance, nicely healthy lungs are very compliant, blow in and out really easily, unhealthy COVID lungs are very stiff, they lose that compliance. And that’s what CPAP essentially does most effectively, CPAP works even better and people who are overweight people, when they lay down flat, that the weight presses downwards squishes the lungs up and you end up taking small breaths. So CPAP helps open up the lungs even more. So no doubt some lovely listeners out there have CPAP at home all the time for their sleep apnea. And it’s working in a very similar way. It’s in fact exactly the same machines when we’re just using those machines that those masks for people in our HDU.

David:

I know, at the beginning of the the outbreak everyone was concerned about the number of ventilators that were going to be available. Is there a limit on the CPAP capacity or is that not been an issue either?

Tom:

It’s a great question. And so much uncertainty at the beginning of this of how many people will be getting affected how many people will need to come to hospital. So we modelled this across Scotland and we thought that the worst point of the pandemic Probably 500 people across Scotland would need to be on CPAP at any one time. So we put in orders for CPAP machines to make sure we’d have enough machines in terms of population for So that would mean about 90 people, which is three wards, which in itself was a challenge to try to work out how many how we do that. But in the end, we never had more than eight people on the proper one.

So we have we managed to get I think 35 or 40 machines all ready to go lined up, trained 150 nurses how to use them. And then we didn’t need to use them, which is great….

To have those machines ready was really important. And I know that in places of higher population density, so in London, Birmingham, Manchester, Leeds, etc, whether there was a lot more pressure, a lot more patients all coming at once, and numbers of ventilators were more challenging but certainly Scotland we’ve been okay.

COVID and BAME patients

David:

That’s great. There’s another question which a lot of my patients have been concerned about. And that’s this seeming increased risk for patients of black and minority ethnic groups where there seems to be an increased risk of having a severe infection with COVID 19. Is there any evidence that you’ve looked at in terms of how accurate that is? how big the effect is? or indeed why that might be the case?

Tom:

It’s definitely a thing. I don’t really have much personal experience because up in Tayside we don’t have a large black and minority ethnic population. So it’s not really been a large issue to me to deal with.

We have our immigrant population tends to be from Poland, Romania, Bulgaria, and they don’t seem to do any worse than than other Caucasian European people. But I do know that from the rest of it, mainly in England. Absolutely. Then the black and ethnic minority ethnic communities have been hit worst by this There was some initial postulation that it was due to population density. I think it’s reasonable to say that people from the Indian subcontinent that culture is to live it, families live together through multiple generations. And it’s not uncommon to find Great Grandma, grandma, parents and children living together. So it was, it was postulated that it was that it was contact with many people, which caused a problem. But that doesn’t seem to be the case, because it doesn’t seem to discriminate, particularly in terms of that.

There was some suggestion that people from BME backgrounds would be from a lower socioeconomic group. But again, that doesn’t seem to bear out either. They’ve been BME doctors and nurses, lawyers, business people who’ve had had COVID and done worse, it’s probably a genetic factor.

It’s probably to do with their ACE receptors, the receptor which the virus attacks and gets into cells. We know that people, that black people, particularly their ACE receptors are different. So we treat their hypertension differently with ACE inhibitors, etc. We haven’t proven that yet. There is a study that’s being led by a team in Edinburgh. It’s a UK wide study looking at the genomics that people have COVID. So that includes all comers to try to sample blood, extract DNA and look for common genes to see if there is a genetic linkage to doing worse and whether that is a BME specific thing or not? Hopefully we’ll find out.

David:

I think that was interesting. I thought about the ACE inhibitor idea before with, early on in the outbreak, people being concerned about people being on an ACE inhibitor and that turns out not to be such a concern.

Tom:

Yeah, and actually, some of the data from America is that being on an ACE inhibitor is protective against poor outcome is interesting, and very hard to explain. The thing is, they were able to show that things that lead to a poor outcome.

  • Having ischemic heart disease
  • Heart failure
  • Hypertension if it’s not very well controlled
  • Diabetes is not very well controlled
  • Smoking

But being on an ACE inhibitor was protective.

David:

The other theory as to the difference in outcomes for BAME patients that I have heard, which I again, has a degree of plausibility, but no evidence that I’ve seen is the vitamin D levels where, on average, between two levels seem to be lower in that group.

Tom:

Yeah, like you I don’t think I’ve seen any compelling evidence for it. There were some centres down in London who were pragmatically deciding to give people vitamin D, on the basis of “what harm could it do” but but actually, having too much vitamin D can be bad for you and can suppress your immune system, giving vitamin C, vitamin D, etc. doesn’t work for any other infection.

I think this is an interesting topic, actually. That there’s such a willingness and a desire to find a treatment here that we’re trying lots and lots of different things. But if you take one step back and say, well, “it doesn’t work for anything else. Why would it work for this”? If it doesn’t work for the common cold or doesn’t work for normal Coronavirus? Why would it work for this virus? So I’m not saying it’s bad that we’re trying lots of things that we absolutely should. But there needs to be a rationale, there needs to be a what is most likely to work?

What is our hitlist? What’s the first thing to do second, which is why diamox … We’re not even researching it because there’s just no rationale for it. So I think rushing around deciding to take massive dose of vitamin D, if your vitamin D level is normal. It’s probably no

David:

Although I have to say from from experience, whenever I test someone’s vitamin D, I’m expecting it to be low in this country unless they’re being treated.

Another question a lot of fear that some of my colleagues have expressed is the the infectious dose and your exposure to virus particles. So there was a real concern that medical staff and key workers were getting sicker potentially as a result of having a bigger infectious doses The first instance, I don’t know if anything has sort of born out from that that you’ve come across.

Tom

No and I think it’s important to distinguish between the two terms which are often conflated, which is viral load, and the exposure dose.

So viral load does seem to link with the most severe illness, and that came out of China very early. And that just makes sense. The more virus you have floating around your bloodstream, the more likely you are to have severe illness.

But there is no direct correlation between being exposed to a vast number of viruses in the air and having a very high viral load. There is a minimal infecting number, it’s unlikely that one virus I mean, literally one virus particle is going to cause infection, it’s likely more like thousands. We don’t know what that number is. Every infection has a different minimal infective dose.

It makes sense that if you’re in an environment with lots and lots of virus, you’re more likely to get it and that bears out with where there have been outbreaks that have been documented, churches, family gatherings, tight spaces. It’s far less likely to be infected if you’re in the open air, but in terms of your question is about health care workers all the time that I’ve been working in a COVID positive area I’ve had PPE (Personal Protective Equipment) to wear. And I’ve read it and followed the instructions from Public Health England and Health Protection Scotland of wearing the right PPE and doing good hand hygiene, and I’ve always felt well protected.

There is this argument that if you’re wandering around, and in a confined space, with no protection at all, in a low risk environment, how does that compare with being in a high risk environment, but with full PPE on? it’s going to take some time to tease all that out, but I think so long as you do have the right PPE and it works, which, in my experience it has done then, ….. We just I think just try to keep the message clear. “It’s (COVID-19) a it’s a droplet thing”. Use droplet precautions. hand hygiene is probably the single most important thing out of everything, Social distancing stay safe

David:

Oh, yes, not to get into the somewhat confusing recent messaging change from the government

Tom:

Not up here

David:

Yeah, not up there, apologies of course, very different.

COVID Testing

The testing which is going on for COVID obviously, the only test that I’m aware of for an acute infection sort of in the early days would be you’re looking for the RNA, the genetic material of the virus itself.

Doing blood testing for antibodies is only going to be useful after five to seven days (when the body has had a chance to produce antibodies which could be detected) of suspect of having having infection. What’s your experience of the testing how specific and sensitive visit in the test you’re using and seeing?

Tom:

So it’s another impossible question, or at least an impossible answer. There has been this worry all the time, all the way through this about what’s the false negative rate of the tests? How many people have a swab that says it’s negative, but actually they have the they have the disease?

As you well know, Dave, there is no test that’s 100% sensitive, there’s always going to be a false negative here or there. And working out how, how accurate it is, how many false negative there are is really challenging when there’s no gold standard test to compare it against. So I can if I have a goal set a test which is 99% sensitive, I can compare anything else against it, but I don’t have that.

David:

I think the thought that came to me is you’re obviously admitting patients who have got Symptoms And Signs of COVID, are you usually finding that many of those are coming back with an initial negative test? And then finding subsequently, they turn positive on retesting

Tom:

so that’s happened a few times. And I mean, fewer than 10. But more than 5. So we’ve had a number of patients. Yeah, maybe five to 10 patients who we’ve seen. We’ve thought, yeah,  I really think they’ve got COVID. The presentation seems like it they’re sick enough. They’ve got the right X-ray, the test comes back negative. So we’ve repeated it. And that repeat test has sometimes been positive. And we’ve had to stop and think well, why was the first test negative? And then on a couple of occasions, we’ve done three tests.

Now, this is not this is not unusual in medicine. As you well know that the pretest probability is really important. If you the clinical suspicion is very, very high. The test is a complementary thing. And if that test comes back negative, we don’t just stop and say, Oh, fine, I was wrong. You take stock Think well, the probability is still very, very high, that there’s something here, let’s redo the test.

It’s that balance of probability, the art of medicine that you and I have been doing for 20 years, that that we still do.

The test is obviously, critical thing. But when we think the test doesn’t fit with a clinical scenario, and then we then we repeat the test, and still treat people as though they have been that they do have it. ….

I think that testing is is quite dependent on who does the test. So you need to have someone who’s well trained, because you have to get the swab all the way down and all the right to the back (of the nose and throat). And so long as it gets right to the back and brings a tear to the eye, then you’ve probably got the right place. And by doing that, I think I’m pretty confident in our testing process.

I’ve so I’ve had the test done that made me cry. And and I was sure it’s in the right place and my test was positive. The challenge of course is how many tests can you do a day Can you do 300 tests, 3000 tests, 30,000 tests. And the more tests we have the capacity to do, then we’ll test more people. Yeah, absolutely.

David:

It’ll be interesting to see with the home testing quite how effective that is, I suspect it’s quite difficult to stick the swab quite so far into the to the nose to get that tear coming to the eye.

Tom:

Absolutely. And I think you know, some swabs and tests that you can do at home are actually very good. And that self swabbing for sexually transmitted infections, for example, is it’s been shown to be very effective, in some cases, better to do a self swab than a doctor swab. But for this, I have some concerns that it says to me a little tickle at the front of the nose and a little tickle around the teeth. But if you’ve got someone else in the house can do it for you. You’ve got a wife along to say to come and do the test. They’re going to be a bit more aggressive.

David

Absolutely. So I suppose the other thing that everyone is waiting for really at this point is a vaccine, seen as a way out of the lockdown and to bring back normality? Have you been following along with the research that’s been going on in the search for a vaccine

Tom:

Peripherally, and it’s not really my field, but it certainly is something I’m interested in and the the British society of Immunologists have been putting on some really, really interesting web casts and podcasts talk about the process of how you might go about making a vaccine. vaccine manufacturer is incredibly complicated, hugely complex.

What do you make the vaccine to do? Is it the spike protein, which is the protein that allows the virus to enter into cells to make it to a different bit of protein or on the cell? Spike protein seems to be the best candidate. Then when you’re making that vaccine, you have to make sure do the antibodies that we make against the spike protein, are they actually protective against the disease? Because they might not be. I mean, it’s very likely that they are but you have to be confident that it is and that requires testing.

Some of that testing may require re inoculation of people. That’s that’s actually quite a difficult thing to get your head around. The evidence is that reinfection doesn’t happen, that people who’ve tested positive with a PCR swab two weeks, three weeks down the line, it’s dead virus and it’s just hanging on from the previous from the single infection.

There are some researchers who’ve been bold enough in their papers to say reinfection does not happen. That’s very confident. And I think we’re moving in that direction. But what we need is we need a reliable antibody test that says to an antigen, which is we’re confident in the test works and that that antibody is actually going to give you immunity. So that’s the vaccine. Do you make a vaccine which is just the protein? Or is it do you give a the live bits of virus or an attenuated virus (a weakened version of the virus), a dead virus?

All these strategies have been used for vaccines for decades. So all these questions remain unanswered. There are scientists around the world feverishly trying to come up with a vaccine. I think realistically, you’re looking at 18 months.

David:

yes, absolutely it’s not a quick fix, although I know that a lot of people working on it very hard.

Could I ask a slightly different question? Obviously, the effect that COVID has had on on on all of healthcare, as well as the rest of society has been vast, and routine work seems to have gone out of the window in preparation for managing these very, potentially very poorly patients. And obviously to reduce the potential exposure of patients, particularly the cohort that you’ll be looking after and the respiratory clinics, who will be delicate, should we say or more prone to getting a very severe infection or a bad outcome with covert infection? How have you been managing your hospitals, outpatient clinics?

Tom:

This is the return to new normal question, what we’re not going to go back to what we had before. I don’t think it’s I don’t think hospitals are going to work the same ever again. The idea of bringing a lot of people who are frail fragile, as you described, into a waiting room where there’s 25 of them, traipsing in and out of one room coughing and spluttering in a respiratory unit is going to sound bonkers now, having had this kind of rapid viral spread.

What we’ve done across Scotland and I’m sure it’s happening in England as well is looking at digital solutions. So we started doing video conference style clinic appointments, everyone knows what zoom is now and everyone knows using these video conferencing type systems to have meetings, speak to their friends and family, etc, etc……

It coordinates well, so patients get a letter, here’s the URL, stick this in your phone, tablet, PC, Mac, whatever. And then you get put through to a virtual waiting room, the Virtual Receptionist meets them, and then as they would normally have, we chat, they wait in the waiting room, and then I come in and have my consultation. It’s actually very efficient, no travel time, I can do it from anywhere.

There are some things I can’t do. So I can’t examine people. So there was some time there’s gonna be some limitation in that. I can’t do tests, but there’s ways around that we can get people, bits of equipment to measure saturations, etc, blood pressure, blood pressure machines, etc. So we can refer to mentioned actually we can manage probably 80% of what we do. Through a virtual system, the remaining 20% of work. And a lot of this is more surgical work, where you have to examine the patient, you know, you need to lay a hand on a tummy and have a feel, or you need to have put a camera in a hole and have a look that still needs to be done face to face.

We’re looking at clean pathways or green pathways, as we call them. So how would you get people to have the confidence to come to a hospital? Where Yes, there are some people in one part of the hospital who have COVID, into into a clean environment where there isn’t any COVID and people can come in and be reassured that everything’s okay. And rather than sitting in a waiting room for two hours with another 20 people, you come in and you get seen it’s it’s more efficient, you need to come and get seen and go out again.

And just simple things like one way in one way out, so you don’t cross paths with people. These are logistic things which which every hospital is now thinking about so that people can have the confidence to come to hospital and feel safe.

David

Fabulous. I think we’ve we’ve seen that as well. In general practice this this is this is forced through a number of changes, it’ll be very interesting to see which of the changes are for the better and which we need to rethink once we’re able to.

So on that positive note, I just like to thank you very much for your time today. I wish you the best of luck and continuing your, your treatment of these, these patients. And I look forward to catching up with you again soon.

 

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