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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77 yo with respiratory distress, RR 30, SpO2 80% on non-rebreather at 15 lpm
CXR & TTE are unrevealing
pH 7.58 / PaCO2 24 / PaO2 >500 / HCO3 22
MetHb 0% CarboxyHb 0%
The ABG looks like this:
The answer is sulfhemoglobinemia.
Sulfhemoglobinemia is a *permanently* modified hemoglobin associated with exposure to TMP/SMX, dapsone, phenazopyridine, & other amino & nitro compounds.
It has an altered oxy-hemoglobin dissociation curve.
2/
Sulfhemoglobinemia is easily confused with methemoglobinemia. Both have very dark colored blood & present with cyanosis. Diagnosis typically requires a specialized lab.
Spoiler: you may have heard that SulfHb is green. It isn’t really. You’re thinking of Vulcans’ blood.
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…?
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.
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