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Talk Evidence

Talk Evidence - Sepsis, talc and blindsided by blinding

22 Jan 2020

41 min duration
6887 words
3 speakers
22 Jan 2020
Description

Welcome to the festive talk evidence, giving you a little EBM to take you into the new year. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford University’s CEBM and editor of BMJ Evidence)* This month: (1.20) Carl tells us about new research on treating sepsis with steroids that might inform practice. (4.58)Proscribing of prophylactic PPIs or H2-blockers for intensive care patients. (11.00) Carl wonders if we can actually rule out an increased risk of ovarian cancer with the use of talc. (17.46) Helen drops and EBM bombshell - is all the work needed to blind participants in a double blind randomised control trial actually worth it? (33.00) Helen is annoyed about a press release from the department of health, and kicks of 2020 by stealing Carl's rant spot. Reading list: Corticosteroids for Treating Sepsis in Children and Adults https://pubmed.ncbi.nlm.nih.gov/31808551-corticosteroids-for-treating-sepsis-in-children-and-adults/?dopt=Abstract Gastrointestinal bleeding prophylaxis for critically ill patients: a clinical practice guideline https://www.bmj.com/content/368/bmj.l6722 Association of Powder Use in the Genital Area With Risk of Ovarian Cancer. https://www.ncbi.nlm.nih.gov/pubmed/31910280 Blinding Fool’s gold? Why blinded trials are not always best https://www.bmj.com/content/368/bmj.l6228 Impact of blinding on estimated treatment effects in randomised clinical trials https://www.bmj.com/content/368/bmj.l6802 *quick note to say sorry about the sound quality on Duncan's microphone - we had a technical glitch (he was left alone to record).

Audio
Transcription

Chapter 1: What is the main topic discussed in this episode?

7.591 - 21.507 Duncan Jarvies

Welcome back to Talk Evidence, your monthly roundup of the world of EBM. I'm Doug Jovis, multimedia editor here at the BMJ, and I'm joined in the studio by Helen MacDonald. Helen, can I get you to introduce yourself?

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22.027 - 26.512 Helen MacDonald

I'm Helen MacDonald, UK editor at the BMJ and resting GP.

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27.573 - 36.163 Duncan Jarvies

And we are joined on the phone by Carl Hennigan, who is currently in quarantine in Oxford. Carl, can I get you to introduce yourself?

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36.211 - 48.831 Carl Heneghan

Yeah, I'm going to describe myself as an active GP because I've been working over Christmas, doing some urgent care work, and that's given me the lurgy. Thank you very much, Christmas. And I'm also editor-in-chief of BMJ Evidence-Based Medicine.

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48.851 - 55.982 Duncan Jarvies

Well, I hope you get better soon, and I'm sure everyone listening does as well. Maybe it'll keep him a little bit more quiet this week, Helen.

56.382 - 56.843 Carl Heneghan

I'll try.

57.124 - 58.826 Helen MacDonald

We can mute him more easily.

58.886 - 77.946 Duncan Jarvies

Yeah, we can. Saying that, we are about to go straight over to Carl to do our first start and stop. Carl, you've been looking at corticosteroids for treating sepsis in children and adults.

78.078 - 101.559 Carl Heneghan

Yeah, no, that was interesting. There's a Cochrane review update that was first published in 2004 and last updated in 2015 that examined the effects of corticosteroids on deaf and children and adults with sepsis. And what's interesting about this update is it included 61 trials and the new search revealed 25 additional trials. So this is quite some update.

Chapter 2: What new research is presented about treating sepsis with steroids?

445.816 - 462.68 Helen MacDonald

And they found that PPIs were probably better than the H2RA agonists. So the panel suggests that you use this particular tool to calculate the patient's risk of bleeding, and in people who have more than a 4% risk of bleeding during their stay, to use this treatment.

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462.76 - 483.637 Helen MacDonald

It's a weak recommendation, so there's still some room to personalise that and think about whether it's worth it in that particular person's case. And that suggests that around 23 per 1,000 fewer people will have a bleed if they have the drug, But with that comes the harm that around 50 more of those people per thousand will have pneumonia.

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484.539 - 495.265 Helen MacDonald

And overall, the authors suggest that there's still some work to do in this area, particularly around better characterising the absolute risk of C. diff infection and pneumonia in that group.

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495.515 - 515.16 Carl Heneghan

Interesting. I thought there were two really neat things about this. One is I want to just raise the importance of clinicians and using your experience and expertise and submitting responses, because there's a response that says, although this is high risk patients, that those with liver disease.

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515.596 - 531.975 Carl Heneghan

you should treat this issue with caution because although patients with chronic liver disease are at risk of peptic and stress ulcers, portal hypersension is responsible for about 70% of the GI bleeds, and this will not be affected by PPI.

532.015 - 552.435 Carl Heneghan

So there was a sort of caveat in the responses that I think is worth reading, which I think is that there is a dilemma when you're doing these rapid recommendations There will always be a notion that people with expertise and experience will come in and say, hey, there's other bits of evidence that inform the issues. And I think it's our responsibility to respond.

552.455 - 569.11 Carl Heneghan

I think that's what we should do more of. I thought that was interesting. But also, tell me about this. I'm very wary of downloading things these days onto my phone. But it says you can download the magic app. What's that all about? And should we do that as clinicians? And will it help us?

569.225 - 596.548 Helen MacDonald

So BMJ Rapid Recommendations are produced in conjunction with the MAGIC organisation and they are a not-for-profit group who have the MAGIC app. And if you go to the MAGIC app, what you'll find is a lot more detail than we can store on bmj.com. So you'll find all of the outcomes listed there. You'll also find the ability to click on the outcomes and to present it in a patient decision aid form.

596.528 - 610.889 Helen MacDonald

That may be less helpful in this situation because people who are very sick in ITU are probably not in a position or may not be in a position to look at that information with their clinician. But that's one chunk of information there that's the shared decision aids.

Chapter 3: How should prophylactic PPIs or H2-blockers be used in intensive care?

1529.873 - 1551.283 Carl Heneghan

But often a problem is you go into a trial, you get consented, and then people, randomised particularly in surgery, say you're not going to get the surgery, and then they withdraw. And you have a super, you have a big problem then in balancing the arms. So what Zelen does, and there's a paper back in the BMJ in 98, is randomise you before consent to see what will actually happen.

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1551.924 - 1552.625 Carl Heneghan

Interesting issue.

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1552.786 - 1570.842 Helen MacDonald

So we've put, I suppose, a lot of confusion in everyone's minds now, but this paper does go on to give us some potential solutions. And I guess it gives you a reminder that on one hand, you want an unbiased study. But on the other hand, you're also trying to get information that actually helps you make decisions in the real world for real patients.

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1571.664 - 1576.075 Helen MacDonald

And sort of describes that the treatment effect from blinded studies is

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1576.055 - 1601.623 Helen MacDonald

can be quite different to real world settings where things like the placebo effect in a way are relevant and perhaps useful and part of what you want to see so they suggest thinking of trials as a kind of continuum where perhaps the closer you get to big pragmatic trials perhaps the more acceptable unblinding is likely to be and talk about whether um

1601.603 - 1623.075 Helen MacDonald

there should be a stronger emphasis on the assessors of the outcomes being blinded rather than sort of everybody being blinded. They also come up with a nice or showcase a nice series of questions that you might ask as you're designing your study, which include, is blinding needed for a scientifically sound result, i.e.

1623.115 - 1644.321 Helen MacDonald

will there be a placebo effect of your intervention and do you think it's important to separate it out? How likely is it that patients and or clinicians will behave differently if they know what the intervention is and how might that bias the result? How harmful might blinding be to patients and is that harm excessive?

1644.341 - 1658.577 Helen MacDonald

And finally, this point, which I thought was quite interesting, I had never thought of this before, was does the financial cost of actually achieving blinding compromise spending on other methodological aspects of the trial's integrity? What do you think of those, Carl?

1658.793 - 1683.047 Carl Heneghan

Yeah, so look, I think this is a really interesting issue. So there are a couple of things that come to mind. There's a paper by Johnny in Ardis that said you can overcome small effects with any introduction of bias. So one of the most important aspects about any trial outcome is the size of effect matters. So if the effect is tiny... You really worry about any introduction of bias.

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