One of the concepts I try to keep in mind while thinking publicly, and speaking with patients, is that you have to be able to hold opposing viewpoints in your brain and still function

A brief thread Re -- therapeutics

Every thing we do for patients has potential benefits and harms

No intervention is inherently all good or all bad

Eg:

statin drugs are beneficial for reducing cardiac risk--on average--but they can also cause harm

#TWICPodcast update

You may have seen one of >3000k journal articles describing #obesity paradox: high BMI is protective in, say, AF or Heart failure

That is so weird, b/c exactly zero docs tell normal-weight pts with AF or HF to eat Cheetos or donuts

How can this be?
🧵 Well, here's the deal: there is NO paradox

It's all due to systemic bias

Like studying the r-ship of IQ and sports ability but only in students at an elite college. Here, you'd find an inverse r-ship

The problem is a form of selection bias called collider bias
2/

I want to highlight a recent meta-analysis of the sham-controlled renal denervation trials #hypertension

From @maahmed1218 @AndrewFoy82 and others at Penn State.

Free access x 40 days here: sciencedirect.com/science/articl…

Comments > They study the 10 sham-controlled trials of RDN. About 1500 patients.

Mean fu (and this is a limitation) = 4 months.

Primary outcomes of the meta-analysis: the *raw mean differences* in 24 hour ambulatory, daytime ambulatory, nighttime, and office SBP and DBP

My colleague has an interesting idea on vax persuasion

But... Scott Alexander IDs a problem. All 4 folks he suggests are super smart & competent but they aren't optimized only for being correct, they are also optimized for keeping power.

See astralcodexten.substack.com/p/webmd-and-th…
1/

https://twitter.com/JReinerMD/status/1416811058040344584

I discussed my experience in clinic with vaccine hesitant patients on This Week in Cardiology podcast
podcasts.apple.com/us/podcast/jul…

Point 1: ... patients don't make decisions like odds-ratio-calculating robots. People feel risk.

Some feel more risk from the vaccine than COVID

When sacubitril/valsartan crushed it in 2014 in PARADIGM-HF for HFrEF, there were a few voices of criticism.

At #ACC21 the PARADISE-MI of entresto vs ramipril in post-MI patients w heart failure failed to show significance.

My summary
medscape.com/viewarticle/95…

Thread/ The specific message is obviously that based on this study, sac/val has no role over ACE/ARB in post-MI patients with heart failure and LV dysfunction.

We cannot ignore costs of care. And low BP was worse in the ARNI group.

Pure gold in this convo on #covid19

Why has @youyanggu been so accurate modeling?

Go to 39-minute mark and replay his words 100x

“When the data do not fit what I expected, I change my beliefs”

If only this was allowed in COVID science!

Brief thread 👇

https://twitter.com/plenary_session/status/1370509641709359107

This principles in this podcast are so darn important for critical appraisal

@youyanggu lack of prior infectious disease knowledge is a feature not a bug.

It allows a dispassionate interpretation of evidence.

Say it w me: **content expertise is over-rated!**

2/

Excited to share our recently published point-counterpoint paper on halting implantation of the @bostonsci subcutaneous-ICD

The paper is now open access.

A brief thread

https://twitter.com/JACCJournals/status/1370457134194917381

Background:
I have used the S-ICD. It has *potential* advantages over the traditional trans-venous ICD system

But it is the newcomer. A #MedicalConservative believes proponents of new stuff must show more than *potential* benefits over the tried and true.

Ok at the request of @PerPersvensson let's do a
Bayes Analysis of the HERS trial circa JAMA 1999

Estrogen/progesterone vs Placebo for reduction of MI/CV death.

https://twitter.com/PerPersvensson/status/1355426831797772290

Here are the events to put in the 2x2 table and the published CI and RR

First just look at the data. No diff in outcomes and wide CI from 20% benefit to 22% harm.

Going to be hard for prior beliefs to budge our posterior

Posterior is jargon for after seeing the data.

NEJM published 2 RCTs of #AFib ablation vs AF drugs.
The rub was that the ablation was done EARLY in the course.
Practice had been to try drugs first then do ablation.
EARLY AF and STOP AF studied the procedure early.
#AHA20 Thread and my column >> Both trials used the Medtronic cryoballoon system.
Medtronic participated in funding both trials.
STOP AF was 100% an industry trial. See pic.
Early AF had funding from many other sources

Giving talks in which you don't have a slide deck already made is illuminating. Look what I found out about publication bias>
It was "discovered" in 1979 by Rosenthal content.apa.org/record/1979-27…
How did he do this?
Thread ... He used a variant of ...sit down for this...the Fragility Index, which we reported on in cardiology
ahajournals.org/doi/10.1161/CI…
The criticism was fierce. But I liked it. @ShahzebKhanMD

Thread: To me, the most stunning report from #ESCCongress thus far: RATE-AF trial
Older pts w/ permanent AF + shortness of breath. (there are lots of these pts).
Rate control is crucial
In 2020, most receive beta-blockers.
But BB can cause dyspnea.
What about dig?
Gulp! 1/ Rate-AF randomized these pts to bb vs digoxin. Here is the protocol paper: bmjopen.bmj.com/content/bmjope…
Crucially they looked at quality of life. That's a really important outcome.

Need help from trial methods people. I ran across this amazing paper by @phlegmfighter et al looking at consequences of recommendations in the design and interpretation of Non-inferiority trials. pubmed.ncbi.nlm.nih.gov/28875400/
THEY SUGGEST SYSTEMIC BIASES.
Thread If you put the new treatment on the left side of the interpretative diagram, there are four ways to make Non-inferiority. Scenarios 1-4. but....

Thread coming on one way docs might add value to the #COVID19 crisis: critical appraisal.
I wrote a critique of a flawed study published in a major journal. The study reported on the assoc of anticoagulant use and death in COVID pts.
medscape.com/viewarticle/93… It is an important topic b/c numerous studies have suggested a high rate of clot-related complications in acute #COVID19 illness. it makes sense to consider anti-coagulants...

Oh my, @theheartorg and @Medscape are crushing it with not one but two great columns on the limits of testing for #covid19 --This is important on many levels, not just for the virus but also for literacy of medical testing.
Very Brief Thread -- I am excited In the first column, my friend @anish_koka a doc w #SkinInTheGame writes on why we can't test ourselves out of the #COVID19 crisis. medscape.com/viewarticle/92…
He debunks the Hammer/Dance figures with help from @AndrewFoy82 who does an actual correlation line --

Short Thread on my latest column over at @medscape About #COVID19 -- My POV: I am a doc who treats real patients. Every Rx decision requires balances the risks of the disease against the risks and benefits of the intervention. 1/ But it is not pure arithmetic. You have to think about asymmetries --like a stroke is usually worse than a bleed (anticoagulation). You also have to consider different patients have different experiences and goals. (Eg. NY COVID not same Montana) 2/

Paper from Prof. Ioannidis et al. <preprint>
They study the risk of #COVID19 death in younger vs older age groups from hotspot areas across the world.
I like this paper b/c it’s data rather than anecdotes.
medrxiv.org/content/10.110…
Thread The authors take current data -- imperfect as it is-- and use it to compare death rates across geographically separate cities, states and countries. They divide COVID deaths by population to get absolute death rates. (low for all ages.) New York data interesting.

This may be one of the most important pieces of content @medscape has ever published. What if we are doing it wrong in the treatment of #COVID19? What if @cameronks is correct? medscape.com/viewarticle/92…
Thread It's not like the ICU mortality of intubated patients is good. In fact, it is terrible. There is no argument that #COVID19 behaves differently than other causes of respiratory failure.

I have heard concern from many doctors in the #COVID19 front lines about early intubation. It is telling that some are afraid to speak publicly. I am not an expert. But would like to relay the worry about interaction bias in this setting. #Foamed One intensivist told me he saw a patient with clear-cut heart failure (pulmonary edema and pleural effusions and known LV dysfunction) intubated immed and placed on isolation. The patient had no C19 signs and stayed on the vent for days waiting for the negative test.

Oh my. Important paper in JACC led by @GreggWStone
Events continue to accrue late after stent placement. Yes, even the anointed drug eluting variety. This is big because it provides plausibility to the lack of MI or death reduction in stent vs meds RCTs onlinejacc.org/content/75/6/5… 2/ the other notable feature is that it lends credence to the findings of NORSTENT nejm.org/doi/full/10.10…
which found no different in major adverse outcomes b/w bare metal stents and the more expensive drug eluters.

Thread on my latest column @theheartorg on the faulty communication of the 5-year results of the EXCEL trial of Left Main PCI vs CABG

medscape.com/viewarticle/92…

A reader of the highly-influential NEJM manuscript would think the two treatments are similar That's important because any human being given the choice b/w a PCI or open-heart surgery will choose PCI b/c it's far less invasive.

But are the two treatments similar at 5 years? I use the data in the paper to show that, no, CABG looks better in the long-term.

A few words on #prevention.
When I rail against prevention, some assume I am not interested in preventing disease.
This is not true. I am.
I found this paper from @JuanGrvas et al that helps explain my tension about prevention.
cadernos.ensp.fiocruz.br/csp/public_sit… This article discusses the precautionary principle as it relates to screening and prevention of disease. Here you have 2 concepts--additive preventive measures and reductive preventive measures--taken from G Rose.