Nick Mark MD Profile picture
Jul 25, 2021 13 tweets 9 min read Read on X
Pre-print of the #COVIDSTEROID2 RCT comparing dexamethasone 6mg vs 12mg in hospitalized patients on high flow O2 or MV:
- no difference in survival or days free of MV with higher dose dex but…
- interesting “trend towards benefit” w/ higher dose dex
📄medrxiv.org/content/10.110…
1/ ImageImageImageImage
🔑 Question: we know from #RECOVERY that steroids are beneficial in severe COVID, but what’s the ideal dose?

#COVIDSTEROID2 was a large DB multi center RCT to answer this. It randomized patients on high flow O2 or MV to either 6mg or 12mg of dexamethasone for up to 10 days.
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The 1° endpoint was days alive free of lifesupport (MV, ECMO, RRT). 2° endpoints included 28 day mortality.

Based on prior studies, they powered for a 15% relative mortality reduction (ARR ~4.5%) combined w/ a 10% reduction in life support duration.

This is pretty ambitious.
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They randomized 1000 people (outcomes were available for 971). The two groups had similar baseline characteristics:
-mostly older (median 65), mostly male (~70%)
-comorbidities were frequent (DM, CHF, CAD, CHF)
~1/2 were on High flow O2, 1/4 on MV, & 1/4 on CPAP at enrollment
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The results were interesting.

Compared to 6mg, 12mg of decadron was associated with:
-numerically lower mortality (27.1% vs 32.3%, ARR 5.2%)
-more days free of support (22 vs 20.5)
-lower rates of SAEs (11.3% vs 13.2%)

However NONE of these reached statistical significance
5/ ImageImageImageImage
Slicing the data different ways yields similar findings: the higher dose of dexamethasone is numerically slightly better but doesn’t (quite) achieve statistical significance. ImageImageImage
What can we conclude?

It’s tempting to round “a trend towards benefit” up to “benefit” but this isn’t good science

If we round down a p=0.06 why not, for symmetry, dismiss a p=0.04 as “trending towards insignificant”?

Thresholds may be arbitrary but we shouldn’t just ignore
7/
Perhaps better to put this finding in context in two ways:
1) #RECOVERY demonstrated a huge mortality benefit by ICU standards (NNT 8); it’s hard to power a study to improve on this
2) prior studies (#DEXAARDS) had shown that a higher dose of dex (20mg/day) was safe/effective
8/
The differences b/w studies are germane:
#RECOVERY enrolled all hospitalized people w/ COVID & found a lower dose of 6mg dex was beneficial (but only in people with hypoxemia)
#COVIDSTEROID2 enrolled sicker people (all on O2) and found a “trend towards benefit” at 12 mg dex
9/
#DEXAARDS enrolled people who were even sicker, those on MV who already met criteria for ARDS

This study was pre-COVID but I think we have enough data to say, uncontroversially, that COVID ARDS is ARDS

Thus it’s reasonable to conclude that sicker pts “need” more steroids🤯
10/
Although #COVIDSTEROID2 doesn’t show a clear benefit for higher dose dex, it also demonstrates that 12mg isn’t worse than 6mg. In fact 12mg has numerically fewer serious side effects, including infxn

With diverging KM curves it’ll be interesting to see the 3 & 6 mo follow up
11/ ImageImage
Clinical 🥡:
- this is a *NEGATIVE* study…
- yet there *IS* reason to think that a slightly higher dose dexamethasone (12mg instead of 6mg) may be safe & beneficial in sicker COVID patients (such as those with ARDS on MV)
- looking forward to reading the peer reviewed 📄
12/12
Things NOT to do:
-go above #DEXAARDS dosing; older studies found HARM w/ higher steroid doses in ARDS
-continue for longer than 10 days; NO studies demonstrate benefit for this
-substitute another steroid (unless you need to); no mineralocorticoid effects w/ dex may help
13/12

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More from @nickmmark

Mar 9
Every year, there is a predictable spike in fatal car accidents, medical errors, & heart attacks.

It’s estimated that there are thousands of excess deaths, a 1% increase in energy consumption, & billions of dollars in lost GDP.

The cause? Daylight savings transitions.

🧵

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Earth's axis of rotation and orbital axis are not precisely aligned. The 23.5 degree difference - 'axis tilt' - gives us our seasons and a noticeable difference in day length over the course of the year.

2/
For millennia this seasonal variation was an accepted fact of life.

In 1895, George Hudson, a New Zealand entomologist, was annoyed that less afternoon light meant less time for bug collecting.

He realized that clocks could be adjusted seasonally to align with daylight.

3/ Image
Read 27 tweets
Feb 14
Musk is so stupid. Exhibit #10544

There aren’t thousands of 150 year olds getting paid social security. There are null values in a database he doesn’t understand how to read… Image
When unidentified people get admitted to the hospital the default DOB is 1/1/1900. The EHR shows their age as 125 yo.

But *almost* everyone is smart enough to understand this is just a result of missing data… Image
Nice summary here debunking Elon’s “duplicate SSNs” claim.

thedatageneralist.com/elon-musk-does…
Read 4 tweets
Feb 8
Important point re indirects:

Unlike other Trump moves, this is arguably GOOD news for researchers!

If the NIH budget is unchanged (a big if), this allocates more money to researchers; if you go from an indirect of 75% to 15% it means you can fund 3 grants instead of 2.
Some context:

Between 1947 and 1965, indirect rates ranged from 8% to 25% of total direct costs. In 1965, Congress removed most caps. Since then indirects have steadily risen.

2/
A lot of indirects go to thing like depreciation of facilities not paying salaries of support staff.

This accounting can be a little misleading.

If donors build a new $400m building, the institution can depreciate it & “lose” $20m/year over 20 years. Indirects pay this.

3/
Read 4 tweets
Jan 22
🚨Apparently all NIH Study Sections have been suspended indefinitely.

For those who don’t know, this means there won’t be any review of grants submitted to NIH

Depending on how long this goes on for, this could lead to an interruption in billions in research funding.
With a budget of ~$47.4B, the NIH is by far the biggest supporter of biomedical research worldwide.

Grants are reviewed periodically by committees of experts outside of the NIH.

When these study sections are cancelled, it prevents grants from being reviewed & funded.
Hopefully this interruption will be brief (days)

A longer interruption in study sections (months) will inevitably cause an interruption in grant funding. This means labs shutdown, researchers furloughed/fired, & clinical trials suspended. This will harm progress & patients!
Read 8 tweets
Oct 13, 2024
#HurricaneHelene damaged the factory responsible for manufacturing over 60% of all IV fluids used in the US, leading to a major national shortage.

As clinicians what can we do to about the #IVFluidShortage and how can we prevent this crisis from happening again?

A thread 🧵
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There are many things we can do as clinicians to improve ICU care & reduce IVF use.

1️⃣Don't order Maintenance IV Fluid!
Almost no patient actually needs continuous IV fluids.
Most either need resuscitation (e.g. boluses) or can take fluid other ways (PO, feeding tube, TPN).
2/
Frequently if someone is NPO overnight for a procedure, MIVF are ordered.
This is wrong for two reasons.
We are all NPO while asleep & don't need salt water infusions!
We should be letting people drink clears up to TWO HOURS before surgery, per ASA.

3/ pubs.asahq.org/anesthesiology…Image
Read 16 tweets
Oct 1, 2024
New favorite physiology paper: Central Venous Pressure in Space.

So much space & cardio physiology to unpack here including:
- effects of posture, 3g shuttle launch, & microgravity on CVP
- change in the relationship between filling pressure (CVP) & LV size
- Guyton curves!
1/

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To measure CVP in space they needed two things:
📼 an instrument/recorder that could accurately measure pressure despite g-force, vibration, & changes in pressure. They built & tested one!
🧑‍🚀👩‍🚀👨‍🚀 an astronaut willing to fly into space with a central line! 3 volunteered!
2/
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The night before launch they placed a 4Fr central line in the median cubital vein & advanced under fluoro.

🚀The astronauts wore the data recorder under their flight suit during launch.

🌍The collected data from launch up to 48 hrs in orbit.
3/
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Read 16 tweets

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