🚨Exciting results from the #RECOVERY trial #preprint of #Tocalizumab (Toci) in hospitalized people w/ #COVID19
-reduced 28-day mortality (29 vs 33%; NNT)
-decreased likelihood of requiring MV (33% vs 38%)
-shorter hospital stay (median 20 vs >28 days) medrxiv.org/content/10.110… 1/
They randomized 4116 pts to weight-based Toci vs usual care (UC):
-groups were balanced: mostly male (>65%), older (>60 yo), & w/ comorbidities (>55%)
-most patients (82%) also received dexamethasone
-they received Toci early in hospitalization but were 7-14 days after onset 2/
Notably, only 83% of patients in the Toci group actually received Toci (plus 2.6% randomized to the UC group got Toci); this would decrease the effect size and bias the towards null.
This means their ITT analysis is probably *underestimating* the true effect size somewhat.
3/
To their credit, despite the fact that intention-to-treat (ITT) underestimates the effect they don't waste even 1 second of my time with an "as treated analysis."
Even in the supplement. This is a mark of legit science.
Statistically speaking this is a "nothing but net" shot 4/
In terms of outcomes, pts randomized to Toci had clinically meaningful Δ:
-decreased 28 day mortality (29 vs 33%; NNT 25)
-lower likelihood of requiring IMV (12 vs 15%; NNT 33)
-lower likelihood of requiring RRT (5 vs 7%; NNT 50)
-shorter hospital LOS (median 20 vs 28 days) 5/
One concern is that Toci can cause arrythmias & increase the risk of secondary infections.
Notably there was no increase in cardiac arrythmias, unexplained mortality, or infection related mortality.
This suggests that a single dose of Toci does not have major side effects. 6/
"BuT wHaT aBoUt AlL tHe NeGaTiVe TrIaLs?"
There's definitely been a back and forth in the Tocilizumab/COVID19 literature. This is a situation where we really need to look closely at the individual studies...
(Shamelessly stole this GIF from my friend @NickJohnsonMD btw) 7/
I will do a blog post on this, but here's the quick version: These studies vary alot!
-Intervention: some gave 1 dose Toci, some ≥2
-Population: some include only ICU/MV patients, some exclude all ICU or MV patients, some gave Dex, some didn't
-Most are underpowered (n<300) 8/
The authors do include a Forest plot, but their methodology seems a bit sketchy...
Specifically, they double up the control groups in a couple studies & appear to use a fixed effects model, despite reasonably high heterogeneity.
To illustrate, compare their analysis to mine: 9/
Overall this is a rigorously done study & analysis. I'm curious to see how this section changes in peer review.
I'm also curious to see if they do a cost-effectiveness analysis. My hypothesis would be the big reductions in IMV, RRT, and LOS would more than pay for the Toci.
10/
🥡Takehome point: RECOVERY is a large well-done RCT that convincingly shows that #tocilizumab is beneficial given in combination w/ #dexamethasone in severe/critical #COVID19 infxn
Two large RCTs (REMAP-CAP & RECOVERY) replicate this finding. This should change our practice
11/
To put this another way; I've gotten on and off the Toci train 🚂 over the last year, but these latest studies are compelling and make me a believer.
If I got very sick with COVID19, I would want to receive #Tocilizumab (along with #dexamethasone of course).
12/
Disclosures: Sadly I receive no 💰 from the makers of Tocilzumab...
13/13
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It kinda irks me when someone describes a vital sign or lab value as “incompatible with life.”
Here’s a @tweetorial all about the extremes of physiology.
Case #1:
A 10 yo ____ presents with the following vital signs.
T 109F RR 30 HR 300 BP 142/116
Fill in the blank
Answer: 🐓
A chicken's "normal" Temp is 103-110F (w/ HR 220-360) & they live up to 11 yrs.
The Hummingbird would be quite bradycardia (“normal" HR 800-1200 when active)
The Desert ant (Cataglyphis bicolor) has a higher temp (up to 122F!) but doesn't live 10 yrs or have that BP
Case #2:
An *arterial* blood gas is obtained from a ___ showing
pH 7.37 / PCO2 50 / PaO2 20 / HCO3 26
(yup it really is arterial)
First, Abx prescribing was much higher earlier in the pandemic (January 86% vs April 63%) and higher in China (76%) compared to the US (65%) & Europe (63%).
This suggests that overprescribing may be less of an issue currently and in the US.
2/3
Second, only 5 studies (out of 154) reported the Abx duration. We don’t know if Abx was quickly de-escalated (appropriate) vs continued despite (-)cultures (inappropriate).
IMO It’s not wrong to start Abx in sick COVID pts so long as you promptly d/c when cultures are (-)
3/4
🚨BIG NEWS: In January, the unpublished VICTAS trial of vitamin C in #sepsis was stopped after enrolling just 501 of a planned 2000
Now data on clinicaltrials.gov shows why, and it doesn’t look good for #vitaminC. Is this the last🔩in⚰️of the ‘metabolic cure’?
A short🧵
1/
I’ve been hopeful but more than a little skeptical about the 🍹🍋 metabolic cocktail for sepsis (vitamin C + hydrocortisone + thiamine) since the original before/after case series.
I’ve followed this literature closely & have been waiting eagerly for the results of the RCTs.
2/
Thats’s why I was excited to see that VICTAS had posted results. bit.ly/3j3Iatl
The VICTAS trial is the largest (& arguably best) of the vitamin C RCTs: a placebo-controlled, Double-blind RCT done at 43 sites across the US. The 1° endpoint was vasopressor free days.
3/
The authors found that these apparently impressive ANNs were poorly generalizable (i.e., the performance was much worse on a new validation set compared to the training set).
Compare the red vs. green ROC curves. The performance drops from an AUC of 0.99 to 0.7! Yikes! 2/
There’s a reason for this: They used one dataset for all their positive images and a separate dataset for all their negative images.
This is risky for confounding because the model could pick up on any number of differences in CXRs that aren’t clinically meaningful.
3/
#CriticalCare non-COVID teaching case:
An elderly man is admitted to the surgical ICU for monitoring after an uncomplicated kidney transplant. You notice this funny pattern on his arterial line tracing. What’s going on here? #FOAMcc#FOAMed 1/
What’s going on here?
2/
This is pulsus alternans: an alternating strong & weak pulse.
Based on the A-line tracing POCUS was performed that reveled a markedly reduced EF. Coronary angiography showed no obstruction and a diagnosis of stress CM was made. The patient recovered with medical therapies.
3/
On 9/11/01 I was a senior in high school in Brooklyn. I had a front row seat as planes flew into the WTC, murdering thousands & altering the course of our country
19 years later as an ICU doctor I have again been on the front lines bearing witness to another historic disaster
1/
2977 people died on 9/11.
Every week for the last 24, more people have died from coronavirus.
This month we pass yet another grim milestone as over two hundred thousand Americans have died in the pandemic.
But the death toll alone doesn't capture the enormity of the crisis.
2/
Even in the ICU, where we care for the sickest people with COVID19, most patients survive.
Over the last 6 months we’ve made progress & gotten better at treating COVID19.
But based on our experience with ARDS, many survivors of severe COVID19 will not recovery completely.
3/