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Here's a question that you might not have considered: how did the dose for #sacubitril/valsartan in #HFrEF get chosen?

Out today is a paper in @JACCJournals led by @RezaMohebiMD that addresses some questions about sac/val dose in HFrEF.

a 🧵

jacc.org/doi/epdf/10.10…
It's a little known fact that prior to the PH3 PARADIGM trial, a PH2 study in HFrEF was not performed--normally PH2 studies provide target doses for the pivotal outcomes trials.

So how was the dose of sacubitril/valsartan chosen??
The target dose of 97/103 mg twice daily was selected to achieve serum concentrations of valsartan = to those in Val-HeFT and VALIANT while simultaneously achieving 90% neprilysin inhibition in normal individuals.
Read 17 tweets
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Grassley And Johnson Request FBI Director Wray Turn Over All FBI Records On Crossfire Hurricane

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saraacarter.com/grassley-and-j…
Read 25 tweets
#OSHO

#Intelligence is a response to a new situation, not out of your past memories but from your present awareness, this very moment.

Intelligence is a spontaneous #responsibility. It has been misunderstood. It has become almost equivalent to #duty. The #reality is different.
There has been a perennial conflict between #intelligence and #intellect.

The man of intellect thinks that he is #intelligent because he knows so much. He has accumulated a great heritage of #knowledge, he is burdened with all kinds of #information.
The man of #intelligence is innocent; he functions moment to moment, his functioning has a freshness and a beauty. But to find intelligence one has to go beyond the mind. #Meditation is the way.
Read 12 tweets

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