For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you some insight into these issues. This week: (3.14) Jeff Aronson from Oxford University explains why remdesivir is a potential therapeutic, but is pessimistic about the quality of the studies being done on it (13.22) Carl explains why smoking cessation is still a key public health priority under covid-19 (16.30) Helen talks care homes, and interviews Mona Koshkouei, from Oxford University, about the research which shows staff are the main vector of infection. (27.20) David Spiegelhalter, professor of public understanding of risk, looks at the new data on excess deaths in the UK - and the difficulties with reporting that underlie it. Carl explains how deaths track infections, and why uncertainty there makes it hard to calcuate the case fatality rate (And why that is not a good measure to use in a pandemic) Reading list. Compassionate Use of Remdesivir for Patients with Severe Covid-19 https://www.nejm.org/doi/full/10.1056/NEJMoa2007016 How can pandemic spreads be contained in care homes? https://www.cebm.net/covid-19/how-can-pandemic-spreads-be-contained-in-care-homes/ Covid-19: Death rate in England and Wales reaches record high because of covid-19 https://www.bmj.com/node/1024784.full
Chapter 1: What is the main topic discussed in this episode?
Welcome back to your now weekly talk, Evidence, which we're recording on a beautiful sunny afternoon on Wednesday the 15th of April. As always, in this new world of coronavirus, we're focusing on that. Last week, we talked about hydroxychloroquine as a potential therapeutic, prognostic models and face masks.
Chapter 2: What is remdesivir and why is it considered a potential therapeutic?
Today, we're going to talk about remdesivir, another potential therapeutic, smoking, care homes, and what the latest data on mortality is in the UK. I'm Duncan Jarvis, multimedia editor here at the BMJ, and as always, I'm joined by our two favourite EBM nerds, Helen MacDonald and Carl Hannigan. Helen, can I get you to introduce yourself?
Yes, I'm Helen MacDonald, UK Research Editor at the BMJ. And Carl.
Hi, I'm Carl Hennigan. I am Professor of Evidence-Based Medicine at the University of Oxford and Editor-in-Chief of BMJ EBM.
So as it's been such glorious sunny weather here, it got me thinking, Carl, is there any evidence yet that warmer weather is having the effect that we hope that it might reduce coronaviruses spread?
Well, there's lots of evidence about seasonal viruses, particularly the ones that have a lipid envelope. ones like RSV and normal coronaviruses, that three things really have an impact.
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Chapter 3: Why is smoking cessation important during the COVID-19 pandemic?
As the temperature goes up, the humidity goes up, and it seems the humidity has a significant impact on the stabilization of the lipid envelope, which is highly fragile and can break down quite easily if you wash your hands. And the other factor is UV light seems to be important.
So being outside is actually a good thing in that UV light and a higher temperature should, if it operates like all the other respiratory viruses, actually destabilize the virus, if you like, make it more fragile, and we should see a seasonal dip occur.
Chapter 4: What research shows about infection spread in care homes?
There are just some slight concerns because with MERS and SARS in the past, that didn't quite happen in the same way. Nobody's quite sure about that. But actually, as we seem to warm up and go above 14 degrees C, which it is today, we should see an impact on the virus and its ability to transmit.
So fingers crossed there. And I suppose we might see that in a few weeks time when the numbers come in then. And that takes us on to what we're talking about later on about the latest figures on death. But before that, it's time to look at what to start and what to stop. So last week, we looked at hydroxychloroquine as a potential antiviral agent.
Now, one of the other ones that has been tested, and there was a new paper of slightly dubious quality in the NEJM, looking at remdesivir. And Helen, you've been reading about this.
Yes, indeed.
Chapter 5: How do excess death rates in the UK relate to COVID-19?
In my chat with Robin Ferner last week about hydroxychloroquine and chloroquine, he mentioned having greater hope for this drug remdesivir. So I was quite interested when I saw this research paper on remdesivir in New England Journal of Medicine a few days ago. It described compassionate use of remdesivir for patients with severe COVID-19.
Chapter 6: What are the challenges in interpreting COVID-19 death data?
But to be quite frank, it didn't really bring me any clarity. It was A descriptive paper of 61 or so people in a whole variety of settings in many countries around the world that didn't have any kind of comparison group. So it sort of left me back at square one.
So instead, I called Robin's colleague, Jeff Aronson at the University of Oxford, who together with Robin Ferner has been taking a broader look at the evidence around this drug. So I think we should hear from them.
Hi, yes, I'm Jeff Adamson. I'm a physician working in Oxford, and my specialty is clinical pharmacology, which means I'm interested in, well, anything to do with medicines, really. If they move, I shoot them. I think to understand why a drug like this might be beneficial, you need to know something about how the virus works. And there are two major
Dr. Michael Gomez- Aspects of that one is how the virus gets into your cells in the first place. And the second is once they're in your cells. How does it reproduce Dr. Michael Gomez- And overwhelm your body. So for me, those are the two major points that would offer targets for drug therapy. And the drug you want me to talk about today called remdesivir attacks the second of those.
It potentially stops the virus reproducing in the cells.
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Chapter 7: How does the quality of clinical trials impact COVID-19 treatments?
So the theory is very interesting, but what do we know about the reality in humans who are actually infected with the coronavirus or might become infected?
We only have one report now of its use in humans. And it's a study that's been published, which was just a look-see to give it to 60 or so patients to see if they got better in any way. And one can't really interpret the data from such a study. So what we are waiting for now is the results of proper trials of this medicine in humans.
From its use in other conditions, do we know anything about the harms that this drug might cause in humans?
Harms are often neglected in clinical trials because people are so interested in benefits. But it is important to collect harms. What we know...
Chapter 8: What role does hand hygiene play in preventing infections in care homes?
is from the use of this drug remdesivir in a previous viral infection with Ebola virus. And in that case, the incidence of adverse events, that's just bad things happening, which may or may not be due to the drug, of course, was about 60%. 60% of the patients in relatively small trial had one or more adverse events. And those adverse events were serious in 23%.
Most commonly, they involved abnormal liver function, diarrhea, rashes, renal impairment and low blood pressure. So it's not clear that this drug is necessarily harmless. One has to look out very carefully for adverse reactions. The importance of doing
proper double-blind randomized study in such a case asserts itself because if you don't do the double-blind randomized study then you won't know which adverse events were actually due to the drug and were actually adverse reactions so it's important not only to look for benefits but to look for harms and
and to use proper controls, double-blind, to show you the extent to which the adverse events you're seeing can actually be attributed to the medicine. And we don't know anything about that just yet. All of this stresses the importance of doing proper, double-blind, randomized, controlled trials.
After my conversation with Jeff, what I took away was there's perhaps a need for less speed or more careful thought around these trials. And it was surprising again, to pick up on some of the themes that Robin had mentioned the previous week, that there are a lot of small trials registered, which might give us quite shaky or low quality evidence.
And it really got me thinking around how much we know about wasted research in a pandemic. And it would be interesting for us to pick up on that theme, I think, and discuss that more next week.
Yeah, definitely. And especially interesting given that hydroxychloroquine is a fairly old drug. It's been around for a long time. So you would expect, you know, there is a generic version of it. But this one is a pretty new drug. It was developed for Ebola. So you would have thought it would be in there and organising this better themselves.
It's not often I am sort of short of words, but I am feeling incredibly disheartened and disillusioned by what's going on. It's sort of amplifying all the problems that we've observed for the last 20, 30 years are coming right into a funnel to show 90% of the data going, patients going into trials are wasted. The trials are done badly. They're not asking the right questions in the right way.
There's no standardization. And we're sat here wasting an opportunity to understand what's going on. I think it's incredibly important we really grasp this message. I saw a report that came out of a few case series claiming remdesivir worked. And this was in five patients, of which three of them had remdesivir.
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