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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Did he have a head CT? What did it show?
Did he have stitches? Tetanus shot?
The NYT ran nonstop stories about Biden’s health after the debate but can’t be bothered to report on the health of someone who was literally shot in the head?
To the people in the replies who say it’s impossible because of “HIPPA” 1. I assume you mean HIPAA 2. A normal presidential candidate would allow his doctors to release the info. This is exactly what happened when Reagan survived an assassination attempt. washingtonpost.com/obituaries/202…
My advice to journalists is to lookup tangential gunshot wounds (TGSW).
Ask questions like:
- what imaging has he had?
- what cognitive assessments?
- has he seen a neurosurgeon or neurologist?
- he’s previously had symptoms like slurred speech, abnormal gait - are these worse?
If you intubate you need to read the #PREOXI trial!
-n=1301 people requiring intubation in ED/ ICU were randomized to preoxygenation with oxygen mask vs non-invasive ventilation (NIV)
-NIV HALVED the risk of hypoxemia: 9 vs 18%
-NIV reduced mortality: 0.2% vs 1.1%
#CCR24
🧵 1/
Hypoxemia (SpO2 <85%) occurs in 10-20% of ED & ICU intubations.
1-2% of intubations performed in ED/ICU result in cardiac arrest!
This is an exceptionally dangerous procedure and preoxygenation is essential to keep patients safe.
But what’s the *BEST* way to preoxygenate? 2/
Most people use a non-rebreather oxygen mask, but because of its loose fit it often delivers much less than 100% FiO2.
NIV (“BiPAP”) delivers a higher FiO2 because of its tight fit. It also delivers PEEP & achieves a higher mean airway pressure which is theoretically helpful! 3/
Results from #PROTECTION presented #CCR24 & published @NEJM.
- DB RCT of amino acid infusion vs placebo in n=3511 people undergoing cardiac surgery w/ bypass.
- Reduced incidence of AKI (26.9% vs 31.7% NNT=20) & need for RRT (1.4% vs 1.9% NNT=200)
Potential game changer!
🧵 1/
I work in a busy CVICU & I often see AKI following cardiac surgery.
Despite risk stratification & hemodynamic optimization, AKI remains one of the most common complications after cardiac surgery with bypass.
Even a modest reduction in AKI/CRRT would be great for my patients. 2/
During cardiac surgery w/ bypass, renal blood flow (RBF) is reduced dramatically. This causes injury, especially in susceptible individuals.
But what if we could use physiology to protect the kidneys?
Renal blood vessels dilate after a high protein meal increasing RBF & GFR! 3/
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.