TOGETHER enrolled high risk people with COVID from 12 outpatient clinics in Brazil.
Patients could be enrolled up to 7 days after symptom onset (more on this later).
They were randomized to either placebo or to ivermectin 0.4mg/kg daily for 3 days. (Also more on dose later) 3/
The primary endpoint was a composite of hospitalization or >6hr ED visit. (Not an awesome primary endpoint IMO 🤷).
Secondary endpoints included: time until hospitalization, hospital LOS, need for mechanical ventilation, duration of MV, and death. (All very reasonable 👍)
4/
It enrolled n=1358 people.
The patients were slightly younger (median age 49) with the expected mix of comorbid conditions seen in COVID (DM2, HTN, asthma).
The groups appear well balanced (see my prior thread about the likely fraudulent vitamin C paper for more on this.) 5/
The study was stone cold NEGATIVE.
There was NO statistically significant difference in the primary endpoint or *ANY* of the secondary endpoints.
Beyond the overall negative findings, there was no prespecified subgroup that benefited from ivermectin.
Roughly half the patients (44%) got treatment within 3 days. That’s early. Among the patients who were treated earlier they did… worse!
8/
Also if we look at the patients who *completed* the 3 day course of ivermectin (per-protocol analysis) they actually did *worse* than the intention to treat group.
If ivermectin really worked, you might expect the people who completed a course of it to better. They didn’t. 9/
“BuT mOrTaLiTy wAs LoWeR!”
A common misconception about stats.
Let’s look at the 0.88 mortality effect.
The confidence intervals mean there is a 95% chance that mortality is between 51% less OR 55% more with IVM.
Would *YOU* take a drug that might increase mortality by 55%? 10/
“tHe tRiAl WaS dEsIgNeD tO fAiL bY eViL pHaRmA!”
This was one arm of a *multi-arm study*. Another arm of #TOGETHER found that a repurposed cheap generic med (fluvoxamine) *improved* outcomes in COVID.
How (& why) would an evil cabal sabotage just one arm of a multi arm RCT? 11/
Related dumb criticism:
“ThE vAcCiNeS wOuLd LoSe tHiEr EUA iF iVeRmEcTiN wAs PrOvEn!”
This is nonsense. The EUA for *vaccines* to prevent severe disease has nothing to do with the absence of therapies. Otherwise Dex, Bari, Toci, etc would have already “voided the EUAs” 12/
On the other hand the *only* trials that have found *any* benefit to ivermectin are:
- fraudulent (Surgisphere, Elegazzar, etc)
- flawed observational studies that are likely biased
- tiny studies looking at non patient centered outcomes like viral load
Clinical 🥡 points: #TOGETHER is the largest RCT of ivermectin to date. It found that early high dose ivermectin did NOT prevent hospitalization, mechanical ventilation, or mortality in high risk outpatients with COVID.
All prior (non-fraudulent RCTs) have found the same.
15/
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.