People are citing reports of declining #COVID cases or deaths after mass #ivermectin distribution.
This is the scientific equivalent of “the rain stopped after I bought an umbrella.”
A short thread about why these “studies” are NOT very compelling.
1/
As cases rise, schools & businesses close, people stay home, nursing homes restrict visitors, masks are mandated, etc

A few desperate governments worldwide distributed ivermectin too

In an uncontrolled situation, why should ivermectin get “credit” for reducing cases/deaths?
2/
This is a classic POST HOC ERGO PROPTER HOC ("after this therefore because of this") fallacy.

Ivermectin distribution is usually a last-ditch effort, like buying an umbrella as you are getting soaked.

But the natural history of pandemics is to peak, then decrease.
3/
This pattern of rapid peak followed by decline is what we saw in areas that are overwhelmed, such as during the tragedies in NY & Italy during the first wave of the pandemic.

Ivermectin wasn’t used in either of these cases, but mortality declined rapidly form a high peak.
4/ ImageImage
Now let’s turn to the dubious AJT paper

Honestly, there’s so much wrong with this paper: it’s a narrative review pretending to be a meta-analysis that
picks small, poorly designed studies & excludes better ones

See @bmj_latest's actual meta-analysis bmj.com/content/373/bm…
5/ ImageImage
The dubious paper shows mortality in 8 provinces.
Oddly, it only looks at mortality in people >60yo.

They claim that deaths went down after ivermectin distribution.

Though L & R axes are slightly different, their data show that the mortally rate is ≈ or even > case rate?🤷‍♂️
6/ Image
Let’s look at mortality using JHU data.

We see deaths before (🟨) & after (⬜️) ivermectin.

In some cases deaths rose despite ivermectin; in other cases mortality was already falling (& continued to). In no case did ivermectin distribution appear to prevent future waves

7/ ImageImageImageImage
Summary:
* beware post hoc ergo propter hoc arguments
* the claim that mass ivermectin prevents COVID mortality is not supported by clinical trials (see BMJ's living meta-analysis)
* the claim that ivermectin prevents disease spikes is not supported by population evidence

8/8

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More from @nickmmark

8 May
A few years ago I wrote about the problem with vitamin C in sepsis.

It’s not that vitamin C is harmful (it probably isn’t) or that it’s ineffective (it almost certainly is) but that embracing pseudoscience undermines evidence based practice.

1/
pulmccm.org/critical-care-…
It took a half dozen high quality RCTs to refute one uncontrolled study of 47 people.


Most have given up on the “metabolic cure for sepsis” (with notable exceptions).

Why are “simple, cheap” therapies so alluring? and what can we learn about COVID?
2/
These pseudoscientific “miracle cures” exploit our desire to help our patients and appeal to several common cognitive biases and delusions.

🚩 Let’s run through some of the red flags of miracle cures:
3/
Read 16 tweets
19 Mar
#INSPIRATION RCT comparing intermediate vs standard dose DVT prophylaxis, just published @jama:
-no benefit to additional anticoag in ICU patients w/ #COVID19:no reduction in mortality, MV, LOS or any 2° endpoint
-time to rethink COVID #anticoagulation?
1/
bit.ly/3vCluqK ImageImageImageImage
INSPIRATION was a 10 site open-label RCT in 🇮🇷 comparing intermediate vs standard dose prophylaxis in ICU patients with PCR-confirmed #COVID19.

LMWH was the primary intervention (~40 mg vs 1mg/kg daily), dosed appropriately for weight; UFH was used if the GFR was too low.
2/
Overall the groups were balanced (total n=562) & were fairly representative of US ICU cohorts with COVID19.

The use of HFNC was very low (~3%) compared to in the US, which may reflect different practice patterns/availability.

Most patients (>90%) received corticosteroids
3/ Image
Read 9 tweets
12 Mar
Pre-print of the @remap_cap RCT of #anticoagulation for ICU patients w/ #COVID19 adds details but confirms what we learned from the press release:
- no improvement in survival or organ failure w/ therapeutic (TA) vs prophylactic anticoagulation (PA)
- medrxiv.org/content/10.110…
1/ ImageImageImage
This study is the amalgam of 3 large platform RCTs of TA in COVID19: @remap_cap @ACTIV4a & ATTACC.

Each trial was administered separately but as much as possible they harmonized the design so the results could be analyzed together. (a pragmatic way to enroll more pts faster)
2/ Image
There were some differences:
-REMAP enrolled suspected & confirmed infxn; the others only enrolled confirmed
-choice of anticoagulant varied
-most importantly, the definition of prophylaxis: ~1/2 the sites used standard low-dose heparin, the remainder used “intermediate dose”
3/ Image
Read 9 tweets
5 Mar
Following @remap_cap & #RECOVERY #Tocilizumab results, @NIHCOVIDTxGuide has updated guidelines:
-#Toci + #Dexamethasone now recommended for all ICU pts on IMV, NIPPV, or HFNC
-Toci + Dex recommended for non-ICU pts w/ rapidly increasing O2 needs & elevated inflammatory markers
1/
You can read the updated NIH COVID19 treatment guidelines here: covid19treatmentguidelines.nih.gov/statement-on-t…

IMO, this change makes sense based on the published & pre-published data, which I discussed last month:
2/
There are some caveats:
-Toci must be combined with dexamethasone (not given alone; ? harm signal)
-It should be given early (w/i 3 days)
-Toci should NOT be given to people who are already immunosuppressed or who have “an uncontrolled” infxn (e.g. getting worse despite Abx)
3/
Read 5 tweets
11 Feb
🚨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/
Read 13 tweets
5 Jan
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)

Fill in the blank
Read 14 tweets

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