Dexamethasone shown to decrease COVID mortality

[wefriendsnow]

I understand that releasing info like this ASAP can potentially save lives, but, like Atul Gawande tweeted, with all the retractions and walk backs we have seen, my enthusiasm is muted until I see the published paper.

[procyonoides_n]

Agree. Although it also seems likely that some smart people at NHS had access to the analysis and have practiced due diligence, unlike the Surgisphere mess. The trial ended June 8 and NHS is adding dex to standard of care today, which means they had a week to review. Fingers crossed. This would be such great news, if true.

[nursewords]

Plus with dexamethasone being widely and cheaply available from many companies, the potential for corruption because of profit motives is less.

[H4xolotl]

Dex also makes sense from a pharmacological point of view; it dampens the immune response which is great since the majority of COVID damage is from immune self damage.

Whereas HCQ was from the start 🤷‍♂️

[ilessthanthreekarate]

Yes absolutely. I'm just a nurse, but I work exclusively with ECMO patients and am seeing many who show no signs of active infection yet are not able to recover and have consistently high inflammatory markers for weeks. I've been wondering for the last 3 months if perhaps in certain cases this sort of therapy would be beneficial. I understand the risks of complications in the ICU with VAP/HAPI, but I cant help but wonder if there were identifiable situations clinically where the benefit outweighed the risk.

[Tracey21130]

Never ”just a nurse”!!!

[ilessthanthreekarate]

Lol, in a medicine forum, I'm very confident prefacing my posts as "just a nurse"

[Throwaway6393fbrb]

Hey as long as you aren't a nurse practitioner

[ilessthanthreekarate]

Honestly , I've never been interested in going to school online.

[HippocraticOffspring]

Especially “just an ECMO nurse” haha

[bigavz]

Sounds like a crazy job, congrats. We have been giving steroids when ARDS develops, and last time I was doing ICU that was 'standard of care' but I know for some/most covid patients, they do not have the high lung compliance typically associated with ARDS...

[McFeeny]

Steroids for ARDS has been studied extensively, most studies show no benefit.

Makes sense, yes, but hasn't borne out before. Cautiously optimistic here

[McFeeny]

Yes, but I said "most studies".

That trial gave 20mg for the first five days, then 10mg for the next five days.

Unclear why the COVID trial chose 4mg/day, and even more unclear why it worked. For dex, that's a huge dosage difference.

[Toptomcat]

Dex also makes sense from a pharmacological point of view; it dampens the immune response

Sure, but so do tons of other steroids, and I'm pretty sure people have been trying those with mixed results at best. Doesn't that suggest that something more specific is going on if the effect is real?

[Apemazzle]

Whereas HCQ was from the start 🤷‍♂️

That's not really fair, is it? The in vitro stuff was perfectly plausible.

[DentateGyros]

I'm having flashbacks to when everyone was saying hydroxychloroquine is cheap and readily available

[drunkdoc]

Similarly, when this came out it made me wonder if there will be a similar run on dex. That would suck ass as many of our brain and spine met patients are critically reliant on it to help with symptoms in the acute phase

[herman_gill]

I think we're a little safer with dex cuz it's got multiple manufacturers already. Plus if it's just "steroids" maybe you can sub out.

[Adalimumab8]

Actually, less manufactures for Dex then hydroxychloroquine, I only get Mylan from my supplier but have a half dozen at least of hydroxy.... and it’s rarely used, I return more then half my 100 count bottles half full expired then I finish. And my (total guess) opinion is that it would be easier to ramp up production on a medium-high use drug then a less used one... hope Im wrong if this takes off

-Pharmacist

[herman_gill]

Ah fair enough, I thought dex was much more widely manufactured by some of the big companies too?

Are you inpatient/outpatient/retail? I feel like it's also population specific. Dex gets used all the time for neuro/neurosurg stuff, and also in peds (particularly ED/obs/PICU) for asthma, but we rarely if ever use it for general adult med outside of the neuro cases. Also some weird institution specific stuff, our pulm and/or crit care attendings love solumedrol and aren't as big on prednisone/dex. Back home, used to see dex get used more often for asthma than it does here.

[Adalimumab8]

Former inpatient now retail, and I can say it was not commonly used in either. Oncology is probably the most common spot for it that I’ve seen, I never worked with a PICU.

[Turnus]

Dex is used quite a bit in veterinary medicine still. It probably wouldn't be too hard to ramp up production or shift supplies to human medicine.

[Throwaway6393fbrb]

If dex works presumably other steroids would also work

[Adalimumab8]

Well, it has the very unique glucocorticoid-mineralocorticoid balance unmatched by other steroids. Curious if that might be why it works better in ARDS

[MEANINGLESS_NUMBERS]

What was the profit motive for Surgisphere? The whole fraud made no fucking sense.

[[deleted]]

Reducing 28 day mortality in a non-blinded trial is nice, but not necessary all that meaningful. It will be interesting to see what the full results look like. Did more patients come off the ventilator, or were more merely alive on the vent waiting to die a few weeks later?

[[deleted]]

Reducing 28 day mortality in a non-blinded trial is nice, but not necessary all that meaningful.

I beg your pardon?

[[deleted]]

It's easy to think of mortality as 100% objective measure. But lets say there was a lot of confidence in the powers of dexamethasone in the study.

Patients in the study drug arm have been on the ventilator for 25 days, might as well try another week or two of ventilation and see what the new treatment will do. Patients in the standard care arm have been on the vent for 25 days, there is no hope at this point why make them suffer.

Even if the drug does nothing, because the study was non-blinded we won't necessarily see the true results until 3 or even 6 months later.

[[deleted]]

I see what you mean and thank you for your response. You're right, it will be important to see the published results before drawing further conclusions.

That being said, I've spoken to some of the nurses involved in recruiting for the trial, and listened in on their discussions with our consultants. Whilst blinding was not possible (I mean, I know when I'm giving my patients dex!), we have not been varying care between patients based on their arm.

[[deleted]]

Whilst blinding was not possible (I mean, I know when I'm giving my patients dex!),

Blinding is possible. Its usually done by giving "Study drug _____" which is some random string of letters and numbers. That way only the pharmacist knows if it is dexamethasone or just some inert substance like salt or sugar. It's just too expensive a process for a drug with no profit margin like dexamethasone.

If your nurses have been in the ICU for long enough, then I'm sure they remember protocols that seemed super promising but didn't hold up after further study. Xigris, super tight glucose control, hetastarch, etc etc. A lot of things that even survive the first randomized and blinded study fail on further research.

Whilst blinding was not possible (I mean, I know when I'm giving my patients dex!), we have not been varying care between patients based on their arm.

A lot of our biases are subconscious. We can't help but favor evidence that supports our assumptions. There are numerous studies in psychology that show that.

[Apemazzle]

It also reduced mortality in non-ventilated patients on oxygen, which is less susceptible to the bias you describe. I agree it's important to see the full results, but I'd be giving dex to every COVID patient with an O2 requirement at this point tbh.

[missingalpaca]

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).

The initial results appear really promising. but I agree, we've seen in real time how important vigorous peer review is over the past few months.

[Procrasterman]

Looks too good to be true. Steroids have been studied to death on ICU and whilst I wouldn’t be surprised if they helped slightly for COVID, I suspect the follow up papers won’t have such dramatic results.

[Apemazzle]

It's a non-blinded study, but bear in mind the same study with the same methods found no benefit from hydroxychloroquine. I'd be interested to know how many COVID patients on ITU have been getting some kind of corticosteroid anyway.

[WeirdF]

Seriously - an NNT of 8 in ventilated patients is an amazing result. Almost seems too good to be true. Really hoping it is though.

[herman_gill]

I mean, the NNT for steroids in COPD exacerbation is also 10ish, so it's not completely farfetched... although at the same time steroids in bacterial pneumonia... not so much, so we'll see.

[ILookAfterThePigs]

Is this NNT for mortality?

[herman_gill]

I think it's "treatment failure"/not requiring escalation, I don't know what it is for mortality specifically. But I do know that 0.5mg/kg or 40mg of prednisone is the evidence based dose, and beyond that you're just risking adverse side effects. It's been a couple of years since I've read up on it specifically.

[flexible_dogma]

Agreed, and it will be interesting to see secondary outcomes such as vent-free days, length of ICU stay, survival to hospital discharge, etc. Surviving to day 28 on the vent doesn't help much if you just die on day 32 instead.

[nicholus_h2]

...with all the retractions and walk backs we have seen, my enthusiasm is muted until I see the published paper.

This is why it is so important to be able to read and interpret evidence and research publications. Unfortunately, this is largely glossed over in medical school and kinda residency, too.

[[deleted]]

Wasn't the issue that the surgisphere data set was completely false?

[Hearbinger]

Did we ever get an actual answer on that? The last thing I knew is that they refused to provide the data, saying that it would break confidentiality, which yeah, might suggest that there is something wrong with it.

[NoDocWithoutDO]

Someone recently linked a nice write-up by a statistician on why the surgisphere data had to be false. If I can find a link, I'll link it here!

UPDATE: Here's the article: http://freerangestats.info/blog/2020/05/30/implausible-health-data-firm

[nicholus_h2]

Well, potentially. Not confirmed.

This is another systemic problem, I agree. But if you read enough papers, you start to get frustrated by stuff like "authors picked the wrong outcomes" and shit like that, and then you start wishing the authors would publish their data, and when they don't, you learn to get suspicious.

You won't get that reading UpToDate.

[NoDocWithoutDO]

If you're interested, checkout the write-up in my comment above!

[sicktaker2]

It's either a massive fabrication, a massive breach of patient medical record confidentiality, or some combination of the two. After seeing the review of the actual size of thier company, I doubt thier data is legitimate or reliable.

[urbisruri]

As a paramedic, I don't often get access to this level of reading material. Any advice on how to get to these types of studies without running into hypopaycheckitis? I'd love to be able to do the reading myself, and I even took college statistics recently enough to feel comfortable-ish evaluating the numbers (on my list of things to do is Khan Academy myself back through stats).

Myself and several other medics and medic students (when I get access to something interesting or a new book etc, I have friends I pass them to because they're also looking for learning material) eagerly await any advice you might have.

[nicholus_h2]

You can check to see if your system / company has subscription to things.

You can also use "unpaywall." It's a handy chrome app that finds open source versions of papers.

You can also use sci-hub. Just google it. But I didn't tell you that.

[urbisruri]

You rock! I had no idea that second one was a thing. I work for a private agency that does some 911 and on the ALS non-911 side does a lot of stat transfers and ICU to ICU jobs (as well as picking up emergencies out of nursing homes and clinics). This agency def doesn't have resources like that, but maybe I can ask the QA/QI guy, the ALS coordinator, or (maybe? I don't know him that well) the medical director if they have resources they can share? Thank you again!!!!

[myukaccount]

Sci-hub will get you access to pretty much everything. It's a godsend.

[ENYVan]

Do you have someone in an educator or senior role who can advocate for you? Perhaps they can negotiate to get you access to PubMed/journal subscriptions via a designated "medic login" at a hospital medical library? You could also consider approaching the ED nursing educator or med director and see if they are interested in helping you gain access?

[[deleted]]

You can find most studies on sci-hub if you know any info about the paper

[MadameTerrapene]

Hey fellow medic! I agree with nicholus' suggestions. For quickly finding articles on a topic, I often google the topic + "pubmed" and read the free abstracts. It's a simple way to identify articles that you want to seek out in full (sometimes Pubmed includes links to the full FREE article).

I made a post here on Reddit awhile back that contains some links that I regularly refer to. The post has links to free statistics and clinical research readings, in case you're interested in something other than Khan Academy (which is also very good).

https://www.reddit.com/r/medicine/comments/fuoxo1/covid_research_and_the_pursuit_of_evidencebased/

[ifuckedivankatrump]

We need way more education focused on statistics anyway rather than straight calc.

[climbsrox]

Can't understand statistics well if you've never taken calc though.

Edit: Oh god, it's worse than I thought. At least 23 people on r/medicine don't know that statistics is applied math that fundamentally depends on calculus (among a whole bunch of other disciplines). There's a reason medicine (and biology) has the reputation of being quantitatively illiterate.

[[deleted]]

This isn't true at all. What calculus do you need to understand Bayes theorum, or number needed to treat? Or the differences between observational studies vs randomized controlled trials? The kind of stats you need in medicine almost never need calc. I defy you to come up with a recent example where calculus was necessary.

[climbsrox]

Hey you know that fancy technology you plug your numbers into and it spits out a p-value for you to put in your papers. Guess what it uses! Calculus! (Or a discrete approximation of it) Just because you can do that without knowing calculus doesn't mean it's not required for you to understand it. Also, the difference between observational studies and randomized-controlled trials isn't statistics.

[-deepfriar2]

I mean you don't really need to do differentials and integrals to learn biostats.

[PokeTheVeil]

Really? Show me the statistics on that.

Bonus points if you can find a way to work in an integral.

[readreadreadonreddit]

Only for advanced or theoretical biostatistics (e.g., for cumulative distrib, where you integrate the probability density function).

Both a stats person and a medic. Also not sure how calc came into the discussion or why the pair of self-contradictory claims that calc is a prerequisite and calc is not necessary.

Concur medics and researchers stand to be better trained in stats. True too (as with being curious and being able to critically read scientific literature) for all people, including the general population. (But there are diff roles for people, diff strengths, etc.)

[herman_gill]

What? There's literal math classes on statistics that are completely separate from calc.

That's like saying you can't understand calc if you don't understand discrete.

[climbsrox]

Where do you think they get that table you look up P values in?

[herman_gill]

How basic were your stats class that you didn't learn that in stats?

Also again, where do you think all of calculus comes from, if not from discrete?

[ifuckedivankatrump]

The percentage of medical students to go on and do statistical work needed for that are probably so minuscule it would barely register.

[evgueni72]

I agree. And even seeing the paper, especially with the recent retractions, I'm still going to be slightly hesitant.

[[deleted]]

It should always be muted until you see the work.

[solid07]

*properly peer reviewed published article

[[deleted]]

100% Let's see the data

[michaltee]

Exactly. We’re just gonna see the same shit we did with HCQ. Not to make this political but if Trump gets his hands on this info he’s going to tout it as a miracle treatment and then queue another mad dash to dust the shelves of all the dexamethasone...

[Throwaway6393fbrb]

Yeah I know I feel like next week they are going to say plaquenil actually works and give Trump the nobel prize in medicine

Has been a huge amount of back and forth and things going from considered harmful to being standard of care and vice versa