Nick Mark MD Profile picture
Sep 25, 2020 6 tweets 3 min read Read on X
🚨BIG NEWS: In January, the unpublished VICTAS trial of vitamin C in #sepsis was stopped after enrolling just 501 of a planned 2000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 results are incomplete & we will need to wait for the actual publication to get the full picture.

But what we can see doesn’t look good:
* similar mortality rate in both arms
* more vasopressor free days in the control group
* some adverse events in the vitamin C arm
4/ ImageImage
Even with this limited data and some simple stats, we can see that there is no significant difference in all cause mortality:
- HAT 22.2% vs Placebo 24.1% (RR 0.92 95% CI 0.67 - 1.27; p = 0.67)

There also isn’t a difference in vasopressor free days:
- HAT 25 vs Placebo 26
5/ ImageImage
When we think about these results in the context of the other published studies it 🎨a consistent🖼:
- *not one* study has replicated the effect seen by Marik et al

See my updated Forrest Plot (full blog post soon): The more studies we do the smaller the overall effect.
6/ Image

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More from @nickmmark

Jan 27
Damn. Under Trump the White House Medical Unit was a pill-mill. Thousands of ambien & provigil per month.

Worse, for a clinic that doesn’t typically do procedures w/ moderate sedation they sure are they ordering prodigious quantities of morphine, fentanyl, versed, & ketamine…? Image
Honestly, this reminds me of Norman Ohler’s Blitzed.
The AG report was largely concerned with the enormous cost of prescribing these non-genetic meds.

It’s worth pointing out that dispensing prescription meds without documentation is malpractice. In the case of controlled substances it’s also likely a crime.
Read 8 tweets
Oct 28, 2023
It’s October - hockey season - so let’s talk about a hockey/pulmonary case:

A previously healthy 17yo presents with dyspnea, frothy sputum, & orthopnea that began after playing hockey.

In the ED he is tachycardic, tachypneic, mildly hypoxic. He has crackles bilaterally.

Dx?
1/ Image
Before we get to the diagnosis, Inhalation of which of the following could explain his symptoms?

2/
The answer is ZAMBONI DISEASE!

Poorly maintained combustion engines produce carbon monoxide (CO), nitrogen oxides (NO₂), & other volatile organic compounds.

These compounds are heavier than air.

To avoiding melting the ice, there is often minimal ventilation in ice rinks.
3/
Read 10 tweets
Jun 19, 2023
Lots of inane comments from Elon/Rohan bros that vaccines don’t prevent disease.

Let’s debunk these claims:
1. Polio - vaccine introduced 1957
ourworldindata.org/grapher/report…

2. Measles - vaccine introduced 1963
ourworldindata.org/grapher/measle… ImageImage
3. Tetanus - vaccine 1938
cdc.gov/vaccines/pubs/…

4. Diphtheria
researchgate.net/publication/32… ImageImage
5. Hepatitis A - 1996
cdc.gov/mmwr/volumes/6…

6. Hepatitis B - 1982
cdc.gov/mmwr/volumes/6… ImageImage
Read 6 tweets
Jun 8, 2023
The long awaited #COVIDOUT RCT is now in @TheLancet:
- high risk adults randomized to either metformin (MET), ivermectin (IVM), fluvoxamine (FLV) or placebo.
- MET reduced the risk of long COVID (6.3% vs 10.4%; NNT = 24)
- no benefit with IVM or FLV

thelancet.com/journals/lanin…
1/ ImageImageImageImage
COVID-OUT was a large blinded multicenter RCT looking at repurposed oral meds.

The primary outcome was severe COVID; this was one of the *MANY* negative RCTs of ivermectin. (See 🧵👇)

The current study is a planned secondary analysis, looking at the incidence of long COVID.
2/
COVID-OUT was a factorial design enabling efficient evaluation of multiple oral medications in various combinations.

After diagnosis, subjects received meds by next day mail. They were followed up to 300 days (10 months).

Diagnosis of long COVID was made by a synonym survey
3/ ImageImageImage
Read 9 tweets
May 28, 2023
Pulmonary teaching case: you are called to the bedside of a 60yo man who was admitted for pneumonia a week ago. You were called because “he coughed and now his chest is PULSATING!”

This is what you see at the site of a previously removed chest drain:

What’s the diagnosis?
1/ twitter.com/i/web/status/1…
This is Empyema necessitans (EN):

EN is a rare complication of an infected pleural effusion where purulent fluid “escapes” the pleura and erodes into the chest wall, causing an extrapleural fluid collection that communicates with the pleural space.

From @Radiopaedia:
2/ twitter.com/i/web/status/1…
Because Empyema necessitans communicates with the pleural space, fluid can move back & forth with respiration, as seen here:

With inspiration, negative intra-thoracic pressure pulls the fluid into the chest. With expiration, positive intra-thoracic pressure pushes fluid out.
3/ twitter.com/i/web/status/1…
Read 7 tweets
May 25, 2023
Interesting RCT in @NEJM about platelet transfusions prior to CVC placement in people w/ thrombocytopenia (Plt 10-50k):
- higher rate of grade 2-4 bleeding w/o Plt transfusion: 11.9% vs 4.9%
- difference driven by much more bleeding w/ subclavian lines
nejm.org/doi/full/10.10…
1/ Image
This trial enrolled n=338 hospitalized people in 🇳🇱 with platelets between 10-50k, INR <1.5 (changed to 3.0). 57% were heme/onc patients & 43% were ICU patients.

Median Plt count was 30k

Most were getting a CVC for chemoTx. (Most weren’t exactly your “typical” ICU patient.)
2/ ImageImage
Importantly they placed the CVC within 1 hour or randomization. This means they probably didn’t transfuse then place a line, more like placed a line while transfusing.

(IMO this difference matters in situations where platelets are dysfunctional, like uremia)
3/ Image
Read 7 tweets

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