Interesting results from the #TOGETHER RCT of #fluvoxamine vs placebo in n=1497 high risk outpatients in 🇧🇷 with #COVID:
-people who received fluvoxamine were less likely to require extended ED visit or hospitalization (11% vs 16%, RR 0.68 CI 0.52-0.88) thelancet.com/journals/langl… 1/
TOGETHER was a large, multi-arm adaptive platform DB-RCT done in 🇧🇷 Brazil from June 2020 to Jan 2021.
Patients were identified after testing positive, stratified by age (>50 or <50 yo) & randomized to fluvoxamine 100 mg BID x 10 days vs placebo.
2/
It builds upon 2 studies:
-an observational study in 🇫🇷 that found better outcomes among inpts already taking SSRIs nature.com/articles/s4138…
-a small n=152 RCT done in 🇺🇸 showing a decrease in clinical deterioration among outpts randomized to Fluvoxamine jamanetwork.com/journals/jama/… 3/
The groups were balanced, with the exception of sex: 60% female in FLV vs 55% in placebo arm.
This difference isn’t significant (Fishers p=0.06 Chi squared p=0.06) but women do have lower rates of hospitalization/mortality so this *could* matter.
~40% had <3 days of symptoms. 4/
The 1' results were promising:
-in ITT analysis, pts in the FLV arm were less likely to have an extended ED visit (>6 hrs) or hospitalization: 11% vs 16%. This met pre-specified criteria for superiority
-this is ARR = 5% or NNT = 20 to prevent 1 hospitalization. Pretty good! 5/
Few of the 2' endpoints were significant, however:
- more pts discontinued FLV than placebo (26% vs 18%)
- there were numerically more COVID hospitalizations & deaths with placebo
- by PP analysis, there was a small reduction in mortality with FLV: <1% (1/548) vs 2% (12/618) 6/
This adherence issue is interesting. It could suggest that side effects may be limiting for some number of the participants.
(Notably, the UMN & ACTIV6 studies use 50 mg BID instead of 100 mg BID using in TOGETHER. This should elucidate if it's dose dependent intolerance.) 7/
Clinical 🥡:
-a large well designed RCT shows that early fluvoxamine treatment in high risk outpatients w/ COVID appears to decrease the risk of hospitalization
-multiple high quality RCTs are ongoing. We should have more data shortly (& see if there is a mortality reduction)
8/
Clinical 🥡 (cont):
-the effect size NNT=20 to prevent hospitalization is similar to that of monoclonal antibodies & inhaled budesonide
-fluvoxamine is a cheap, widely available medication. Even a relatively small decrease in hospitalizations would be a big deal worldwide
9/
Finally, for the #CultOfIvermectin:
TOGETHER was a multi-arm trial. If this arm shows that FLV is beneficial, you ought to accept that IVM isn't. (you can't argue it wasn't early enough or underpowered, etc).
I look forward to watching your new/bizarre cognitive contortions
10/10
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Tragic news today about former president Biden's prostate cancer diagnosis. I wish him well.
As someone who follows presidential health reporting, I noticed something odd: unlike his predecessors, Biden's physician's never reported PSA.
How to interpret this absence? A🧵 1/
There are two possibilities:
1️⃣ Biden’s PSA was never checked
2️⃣ Biden’s PSA was checked but it wasn't reported
Strictly speaking, not checking PSA could be a medically correct option. Whether or not to test PSA is a complex question and is not the topic of this thread.
2/
Like many VIPs, presidents tend to have excessive testing that is not always strictly evidence-based.
For example, Bush 43 had an exercise treadmill test and a TB test for no apparent reason.
In honor of #MayThe4thBeWithYou let's consider the most difficult airways in the Star Wars universe:
1. Darth Vader
Species: human
Vader presents several challenges: Vent dependent at baseline, airway burns from Mustafar, limited neck mobility.
Discuss GOC before saving him
2. Fodesinbeed Annodue
Species: Trog
All airways require teamwork, but intubating Fodesinbeed Annodue's two heads really will require two operators.
Consider double simultaneous awake fiberoptic intubation
Be sure to consent both heads.
You will never find a more wretched hive of scum & challenging airways than Mos Eisley (except maybe at Jabba's)
3.Greedo
Species: Rodian
Micrognathia, posterior airway, no nasal intubation, green skin so no pulse ox
Approach: VL + bronchoscope. Intubate quickly (shoot first)
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.
🧵
1/
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.
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.
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/
🚨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!