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👇EPS and Ventricular Stimulation Testing in the Diagnosis of Narrow Complex Tachycardia: Understanding VA Conduction👇 For #EP_Fellows — simple tricks packed with valuable information! Electrophysiology is logical. Understanding is better than memorizing!!! 👉 Ventriculoatrial (VA) Conduction Patterns: A. VA Dissociation (even with isoproterenol) → Rules out AVRT and AVNRT... show more
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How Computer Cardio-Diagnostics Improve Outcomes in Cardiovascular Care #Cardiology #HeartHealth #Cardiovascular #HeartDisease #CardiologyNews #HealthyHeart #CardioCare #CardiovascularHealth #HeartAttack #Cardiologist #HeartFailure #ECG #CardiacHealth
![My cousin, Jonathan Ord asked me to teach the Come Follow Me lesson to his mission yesterday over zoom. This is the video I did and the full text. Hi. I am Brad Smith. I have ALS, which is a really weird disease that kills the motor neurons in my body. That means that I lose the connections between my brain and my muscles. My mind is still running at the normal rate. So, I can understand everything you say to me, but I can’t respond very quickly! I am getting faster, though. Last November I was the 3rd person in the world to receive the Neuralink brain implant. So I am controlling this computer with my brain. This is my old voice, recreated by AI from just two hours of me talking to my phone. I have come to see ALS as a calling, and I am trying to magnify it. I used to talk easily, but now I have to choose my words carefully, because it is hard and slow to type what I want to say. I joke that the Lord gave me ALS to get me to shut up. Those who knew me when I could talk laugh the hardest. President Ord is my first cousin. So we share grandma and grandpa Smith. Our grandma Smith was a character. When she taught at church, she would put a sign up that read: “thus saith the lord:” so I will try to keep this within what the Lord has actually said, while trying to teach you to look at a basic principle of the gospel in a different way. Ironically, the first verse of Doctrine & Covenants 93 starts with “Verily, thus saith the Lord”. This is an amazing section of scripture, Jesus Christ telling us to step up and be better! You should study it often. I will start with a story. I asked AI to make a video to dramatically tell the story. During college, I lived in Damascus, Syria, for a semester. It was a fantastic and wonderful experience. I especially loved exploring the Old City of Damascus. The Old City is built around the huge beautiful Umayyad mosque. Within the walls of the old city is a maze of narrow, winding, confusing streets and one really long straight street, as Saul found out in Acts 9:11. One day when a group of us were trying to get through this maze from the mosque to the Christian quarter of the Old City, we asked a man for directions. He thought for a second, then pointed and said, “Go left and then right, and then left and then right, and then left and then right, and then left and right, and you’ll be there.” Aren’t those the most ridiculous directions you have ever heard? We could have ignored him. But, we thought, he did know the city better than we did. So, with some laughter, off we went. Left. Right. Left. Right. And so on until, much to our surprise, we popped out at our destination. Life is a confusing maze. We face difficult choices, unexpected events, surprises, sorrows, opportunities, roadblocks. The Lord has given directions on how to get through to where we want to go. Sometimes the Lord’s directions seem odd, and we may struggle with the decision to follow. The Lord will not force us. It is our choice whether to choose and follow him. Wasn’t that fun? AI is getting crazy! I will be much less entertaining for the rest, but hopefully the spirit will teach you something new. The phrase “keep the commandments” (or “keepeth my commandments”) appears at least 4 times in Doctrine and Covenants Section 93, in verses 1, 20, 27, and 28. There are other references, like “keep my sayings” in 52 and “obeyeth my voice” in 1. So, commandments are really important in this Revelation. I suggest that making the gospel a more central part of our lives depends largely on how we look at commandments. When you think of commandments, do you think “I can’t. I’m Mormon”? (That was a popular T-shirt slogan during my college years.) Although, with the recent guidance from President Nelson, it probably should be “I can’t, I’m a member of The Church of Jesus Christ of Latter Day Saints”. It’s a common reaction: “Thou shalt not do Cool Things.” People LOVE to focus on all the things we CAN’T do, as if we are trapped and deserve pity for our beliefs. No pity is needed. Commandments are opportunities, not constraints. Commandments are awesome! Allow me to illustrate. Imagine a spectrum between Good and Evil. Somewhere in the middle is “the Line” that divides Good from Evil. As a teenager, I wanted to know where the Line was, so I could get close to it without going over it. I wanted to be on the “Good” side but still be able to do as many “Cool Things" with my friends as possible. From my experience, I believe God gives us two types of commandments: 1) Get Back over the Line commandments and 2) Come Further into the Light commandments. Type 1, the Get Back over the Line commandments, could also be called “Misery Avoidance” commandments. They are designed to keep us out of misery or, if we’ve crossed the Line, to bring us out of misery and back into the Good side. These are generally commandments with a clear and defined point of success, such as “Thou shalt not kill.” You will know, at the end of each day, whether you have successfully followed that commandment. I think all of the Ten Commandments fall into this category. The law of Moses was very black and white. The children of Israel had been in Egypt without a prophet for a long time when Moses received the law, and they needed to work on the basics. So, if you follow the Type 1 commandments, you will refrain from doing things that make you miserable. You will know you are in the Good if you can answer the baptismal interview and temple recommend questions honestly and faithfully. If you can do that, you have taken the basic steps necessary to avoid misery and are on a solid foundation for the next type of commandment. Type 2, the “Come Further into the Light” commandments, are the really cool commandments. Once we are out of the misery category, we can really start to pursue joy. So, God commands us to do things that he knows will make us happier and more like Christ. These commandments are the principles of eternal development, such as “Love thy neighbor” (Matthew 22:39). There is no clear end to loving our neighbor—it requires positive and eternal progression. We can always love more, and we can always find another neighbor who needs our love. It is an eternal principle taught by Jesus Christ. And if we truly love our neighbor, refraining from killing him becomes pretty easy. It is through these commandments that we find joy in Jesus Christ. Elder Christofferson taught about this spectrum in the October 2018 general conference: “Most of us find ourselves at this moment on a continuum between a socially motivated participation in gospel rituals on the one hand and a fully developed, Christlike commitment to the will of God on the other. Somewhere along that continuum, the good news of the gospel of Jesus Christ enters into our heart and takes possession of our soul. It may not happen in an instant, but we should all be moving toward that blessed state.” Our goal is to go THAT WAY (toward Christ) as much as possible. So first, get back across the line and stop doing things that will make you miserable. Then make every effort to try and be like Jesus, to “love one another as Jesus loves you.” The gospel of Jesus Christ is more than just “not doing” stuff. It is about coming unto Christ, being perfected in him, and denying ourselves of all ungodliness. Discuss with your companion what commandments and mission rules are for “Misery Avoidance” and which are “Come Further into the Light”! And, remember, commandments are ALWAYS connected to huge blessings. The Lord promised, “There is a law, irrevocably decreed in heaven before the foundations of this world, upon which all blessings are predicated—and when we obtain any blessing from God, it is by obedience to that law upon which it is predicated” (Doctrine and Covenants 130:20–21). Whenever we obey any of God’s commandments, we will get the blessing associated with that commandment. Elder David A. Bednar said: “The gospel of Jesus Christ encompasses much more than avoiding, overcoming, and being cleansed from sin and the bad influences in our lives; it also essentially entails doing good, being good, and becoming better. Repenting of our sins and seeking forgiveness are spiritually necessary, and we must always do so. But remission of sin is not the only or even the ultimate purpose of the gospel. To have our hearts changed by the Holy Spirit such that “we have no more disposition to do evil, but to do good continually” (Mosiah 5:2), as did King Benjamin’s people, is the covenant responsibility we have accepted. “This mighty change is not simply the result of working harder or developing greater individual discipline. Rather, it is the consequence of a fundamental change in our desires, our motives, and our natures made possible through the Atonement of Christ the Lord. Our spiritual purpose is to overcome both sin and the desire to sin, both the taint and the tyranny of sin.” I LOVE this concept—and as I have paid attention, I feel like apostles are trying to teach us this all the time. Are we listening? Let me repeat what Elder Bednar said. He said that the commandments help us change what we WANT. Why is that important? Remember my teenage desires? I wanted to be as close to the line as possible so I could still look cool for my friends. That is a good example of the “tyranny” of sin. Even though I was not actually sinning (probably because I was afraid of my mother), I still had some small desire to sin. I said, “I can’t. I’m Mormon” with many dramatic sighs. Overcoming the tyranny of sin is getting to the point where the sin no longer looks remotely interesting or fun because we are too busy loving our neighbors and trying to be like Jesus. Elder Dallin H. Oaks said: “The Final Judgment is not just an evaluation of a sum total of good and evil acts—what we have done. It is an acknowledgment of the final effect of our acts and thoughts—what we have become. It is not enough for anyone just to go through the motions. The commandments, ordinances, and covenants of the gospel are not a list of deposits required to be made in some heavenly account. The gospel of Jesus Christ is a plan that shows us how to become what our Heavenly Father desires us to become.” This talk was given when I was on a mission, before most of you were born. It completely changed my perspective on the gospel of Jesus Christ. It is called The Challenge to Become” and I recommend that you study it. When the Lord says keep the commandments, he isn’t just telling us to stop sinning—he wants us to become like Christ and to have joy. Take a moment and think, Where am I on this continuum? Remember that none of us is perfect like the Savior, and we all need to lift one another. That is why we worship together. That is why we have priesthood quorums and the Relief Society, Primary, and youth organizations. The Lord taught us that truth when he said we all have different gifts: “To some is given one [gift], and to some is given another [gift], that all may be profited thereby. To some it is given by the Holy Ghost to know that Jesus Christ is the Son of God, and that he was crucified for the sins of the world. To others it is given to believe on their words, that they also might have eternal life if they continue faithful” (Doctrine and Covenants 46:12–14). The Savior is still WAY over there: a thousand miles away somewhere. That is why we have quorums. We all have a long way to go. Let’s link arms and run together. Let me finish by telling a story from my mission to support my testimony of Jesus. Years ago my mission president said something interesting: “Either the Church of Jesus Christ of Latter-day Saints is truly the kingdom of god on the earth... or it is the greatest fraud ever in history.“ It is audacious to claim to be the true Church of Jesus Christ—but let me explain exactly why I know that to be true. I always BELIEVED that I was raised in the gospel of Jesus Christ. My parents taught me well and I felt good following the commandments and studying the scriptures. That led me to serve a mission in Brazil. My turning point of testimony came when I was 20–at least 2/3rds through my mission. We were invited into a house in the “fundos” of a property—a small structure built behind a larger house. The man was polite and allowed us to share our message. As I had done hundreds of times, I shared the story of Joseph Smith, a boy who sought the truth through prayer. I recited Joseph’s own words in response to his prayer: “I saw a pillar of light exactly over my head, above the brightness of the sun, which descended gradually until it fell upon me... When the light rested upon me I saw two Personages, whose brightness and glory defy all description, standing above me in the air. One of them spake unto me, calling me by name and said, pointing to the other—This is My Beloved Son. Hear Him!" I felt the strongest feeling I had ever experienced—an undeniable confirmation that what I said was true. It hit me in a way I can never forget! I knew that Joseph Smith was truly a prophet, and therefore the Book of Mormon was the word of god. What about the man we were teaching? How had he responded to my life-affirming spiritual experience? He shrugged and politely thanked us for the message. I was stunned. I felt like the windows of heaven opened on me—and he felt nothing. I learned that receiving answers to our prayers is like tuning a radio: not everyone is on the right frequency. For some reason, the Lord decided to broadcast on my frequency that day. I received the undeniable confirmation that the Church of Jesus Christ of Latter-day Saints is true. I have built on that foundation brick by brick since then. And every time someone has challenged me on Joseph Smith, I go back to that day in Brazil. I know that he was a prophet. My life has been blessed in ridiculously good ways since then. As I have tried to follow Jesus Christ, great things have happened to me. Even my hardest and most frustrating times have turned out to have a purpose. God has upturned my best laid plans over and over. But I look back and realize that I could never have planned any better. With the prophet Nephi I say: “I know that [God] loveth his children; nevertheless, I do not know the meaning of all things." (1 Nephi 11:17) When I say that the Church of Jesus Christ of Latter-day Saints is true, that does not mean we have a monopoly on truth. I know Christians and Muslims who teach me to be better—and Members of the church who are far from disciples of Christ. We just have more truth: scriptures, living prophets, ordinances, personal revelation, and answers to many of life’s biggest questions! That is pretty cool. But we can’t be prideful about the truth we have. You have all probably met people to admire both inside and outside of the church. So, I am all in. The Church of Jesus Christ of Latter-day Saints is true—not a big fraud. And we are all trying to get closer to Christ. I know that Heavenly Father has a plan for me. Life has not been what I expected, but I trust him! I know that Joseph Smith is a prophet of Jesus Christ and that the Book of Mormon is true. This is “intelligence, or, in other words, light and truth. Light and truth forsake that evil one.” With that knowledge, keep the commandments! In the name of Jesus Christ, amen .](https://image.24vids.com/tw-1961133396144656751/amplify_video_thumb/1961127653798547458/img/nIvUNxNHuUcT9YLP.jpg)
![An interview by VERY DARK AND CORRUPT Wall Street Journal aired today [1] WSJ's terrible "journalists" (and I use that term lightly) made many false statements about Sarepta's worthless, dangerous drug and Vinay Prasad's firing [1,2] I explain how the FDA sausage is made in excruciating detail Buckle up To get readers up to speed -> In June, corrupt pharma company Sarepta Therapeutics paid $40,000 to lobbying group Michael Best Strategies (MBS) to deal with a problem [3] -> MBS had recently hired Chris LaCivita, who had close connections with "MAGA" influencer Laura Loomer [4] -> With stock down 88%, Sarepta needed to sell their very bad, very dangerous drug or the company would go bankrupt [5] -> After several deaths from the drug this year, FDA official Vinay Prasad said "no way" and kicked the drug to the curb [2,6] -> Sarepta panicked and paid MBS (we believe) to deal with Prasad [3,4] -> If this story is right, LaCivita recruited Laura Loomer to take down Prasad [4,7] -> Loomer said she was defending Trump, but she was lying [7] -> She was defending taxpayer-funded payouts to a worthless, corrupt company [7] -> Laura Loomer so brave A history of bad drugs and regulatory failure -> This is one of the worst pharma scandals in American history and corrupt mainstream media isn't covering it -> Sarepta has a very long, troubled history [8] -> For more than a decade, every major Sarepta FDA drug approval has required INTENSE political intervention [8,9] -> Scientists at FDA have been repeatedly overruled [8,9] -> Many scientists have resigned, very publicly, over these POLITICAL decisions, some writing scathing public criticisms of these terrible decisions [10,11] -> The most recent resignation by Vinay Prasad is not something new; it follows in a long tradition [2,10] -> In fact, standards have dramatically deteriorated since the first controversies about the company's drugs in the 2010s [8,9] -> Prasad was trying to hold the line in the face of rapidly deteriorating standards at the agency [2,6] -> For that, pharma launched a coup--a literal coup of a drug regulator [4,6] -> This is unprecedented -> Banana republic sht, unbelievably corrupt 2016: first Sarepta drug approval and the "highly unusual" decision -> The first Sarepta drug approved by FDA was called Exondys 51 [8] -> This drug was for patients with mutations in dystrophin, a muscle protein [8] -> This is a debilitating and fatal disease affecting children [8] -> Exondys 51 increased dystrophin by 0.2% of normal levels [8,12] -> Unsurprisingly, there was no good evidence the drug worked [8,12] -> Why would it? It increases the protein from zero to 1/500th of normal levels -> One reviewer wrote: "I can find no precedent of an accelerated approval for a marketing application where the effect size on the surrogate endpoint is as small as 0.3%." [12] -> The study submitted by the company included no proper control group [12] -> The techniques used were so bad not even a first-year PhD student would do a study that way -> This the level of work you would expect from a mediocre undergraduate with no guidance -> It's almost like it was so bad on purpose -> (Narrator: it was on purpose) -> Nerd time: -> One reviewer wrote: "The Western blots submitted by the applicant for Study 201 were oversaturated, unreliable, and uninterpretable." [12] -> Another wrote: "Because CDER also determined that the conditions under which the original IHC analysis was performed were inadequate, including that the reader was not masked to sequence and time, the Center requested a re-reading of the stored images by three masked pathologists under different conditions. The IHC results from the reread were not nearly as favorable, as compared to the initial IHC results reported by Sarepta." [12] -> "The lack of concordance between the IHC and the Western Blot results is 'striking'" [12] -> "Study 201/202 had fundamental flaws, including baseline biopsies from external controls who could differ in unknown ways from study subjects, Week 180 biopsies from different muscles than baseline, and potential protein degradation in stored baseline samples." [12] -> And on and on. -> FDA commissioner Robert Califf wrote at the time: the submitted study was "characterized by major flaws in the clinical study design" and "Blinded experts assembled by the FDA fundamentally debunked this study, which has yet to be retracted and continues to be cited" [9,12] -> That's right, the FDA commissioner expressed dismay that the study that the company used to gain approval hadn't yet been retracted, it was so bad [9] -> Senior FDA official Janet Woodcock decided to approve before scientific review team had even voted [9,12] -> Woodcock be like: yeah i'm going to decide before you guys can because i know what you're going to say lol -> Despite external intense pressure, FDA scientists voted against Exondys 51's efficacy [9,12] -> They then voted against its accelerated approval [9,12] -> The review team filed an appeal with FDA commissioner after "passionate" disagreement with Woodcock [9,12] -> One reviewer called Woodcock's decision "unprecedented" [12] -> In a 126-page report, FDA commissioner Califf called Woodcock's decision "highly unusual" [9] -> The FDA board wrote: "[Woodcock's] involvement here appears to have upended the typical review and decision-making process. ... Care should be taken to avoid the appearance of interfering with the integrity of scientific reviews at the lower levels of a Center." [9] -> Again, the data were unbelievably bad, literally every technique in the study was inappropriately used [12] -> I would fire an undergraduate student who did science like this, immediately -> FDA's chief scientist accused Sarepta of "serious irresponsibility" for selectively publishing only some of the data [9] -> Even Woodcock, who approved the drug, called the research "seriously deficient" [12] -> Yes, even the person who approved the drug over the heads of FDA's scientists said the research was horrible [12] -> Still, FDA tried to bury their heads in the sand and beg that, basically, Sarepta pretty please do a better job next time -> FDA commissioner: "The utmost attention should be paid to optimizing the methodological rigor of [future] trial[s]" [9] -> FDA also demanded a clinical trial "to verify the benefit" of the drug [8] -> Welp, this was in 2016 [8] -> The trial results are supposed to be available in 2026, maybe [13] -> Or maybe later, depending on how much money needs to be made first -> As an article published in Nature three years later despaired of the decision: "The approval was conditional on the company agreeing to conduct a two-year post-approval trial to show Exondys 51’s efficacy. But by August 2019, the company had yet to begin such a trial and in the meantime had profited from sales of $300 million in 2018." [13] -> If it sounds like Sarepta used political pressure to get its drug approved and then tried to avoid actually publishing the study showing it didn't work, it sounds that way because that's exactly what happened [13] -> FDA commissioner after deferring to Woodcock: "I am confident this unique situation will not set a general precedent for drug approvals under the accelerated approval pathway, as the statute and regulations are clear each situation must be evaluated on its own merits based on the totality of data and information." [9] -> This statement was profoundly naive, and the historical record bears this out [8,14] -> Three FDA scientists resigned, including the lead reviewer of the drug, understanding the grave implications of the collapse of scientific standards and where they would lead [10,11] -> One was John K. Jenkins, M.D. Director, Office of New Drugs Center for Drug Evaluation and Research/FDA [10] -> In a presentation given just before his resignation, he wrote: -> "Path taken by Sarepta NOT a good model for other development programs" [10] -> Crucially: -> "Upholding statutory standards for approval in face of hopes and desires of patients, families, sponsors, and investors is a very difficult job" [10] -> "Personal attacks on FDA reviewers creates an atmosphere of distrust and isolation rather than collaboration" [10] This brings us to WHY Sarepta's drug was approved Facebook FDA -> So why did the drug get approved? -> Basically, Sarepta propagandized extremely desperate patients [9,15] -> They used miraculous snake oil promises and patients believed them -> Remember that this is life or death for patients, and they are extremely vulnerable -> Sarepta also professionally trained some patients to give testimonials to FDA and congress [15] -> The patients then went to congressmen who don't have time to understand the science [15] -> They gave emotional stories to congressmen [15] -> The result: -> Letter from 109 House members [15] -> Letter from 24 Senate members [15] -> And a media circus documented in the New York Times [16] -> Patients screaming at scientists during meetings [9] -> 2,792 emails written to FDA urging approval [12] -> One of them: "Dear Dr. califf: How is it that everyone in and around DMD understands this simple Idea and the science geniuses at FDA don't? You stupid fckers are costing each and every DMD kids days of their lives with your Moronic Dystrophin dance. Time to get a fcking clue" [12] -> Upon approval, a journalist for Reuters wrote: "owing to pressure from patient advocates, the U.S. Food and Drug Administration on Monday approved a treatment for Duchenne muscular dystrophy even though an outside panel of experts and the agency's own reviewers questioned the drug's efficacy" [17] -> A commentary in Nature Medicine was also published called "Railroading at the FDA" [9] -> Its author wrote: "In the words of one FDA committee member, Exondys lowers the agency's evidentiary standard for drug effectiveness 'to an unprecedented nadir.'" [9] -> A highly critical commentary was also published in Science, titled "Sarepta gets an approval - Unfortunately" [18] -> The article's author pharma veteran Derek Lowe wrote: "The company... called up Duchenne-affected boys and their families to plead with the FDA, and won over Janet Woodcock, and that appears to be enough. Is this going to be the new way to get a drug approved? Run a trial in a dozen people, generate unconvincing data, and then lobby Janet Woodcock? I share the worries that this might open the floodgates, because after all, Sarepta got their drug through." [18] -> One FDA reviewer ended in an equally grim note: ". Approval of this NDA would send the signal that political pressure and even intimidation – not science – guides FDA decisions, with extremely negative consequences. The public is well aware of this development program: the meager size of the study population, the marginal (at best) effect size, the Division’s dim view of the efficacy data, and the robust activism of some members of the DMD community. Many would be amazed at an approval action, because other DMD drugs, recently turned down for approval, appeared to provide stronger evidence of efficacy. ...The ramifications here are profound. The public will perceive that it was their unprecedented lobbying efforts that made the difference and earned eteplirsen its accelerated approval. For the future, this will have the effect of strongly encouraging public activism and intimidation as a substitute for data, which is one of the worst possible consequences for communities with rare diseases. This type of activism is not what was envisioned for patient-focused drug development." [12] -> A new era was born -> Activism had replaced data -> Facebook had fried people's brains -> And now Facebook-fried brains had fried FDA too -> FDA's credibility as a regulatory agency would now be hollowed out -> FDA's Facebook age had begun -> But the worst was yet to come Sarepta approvals: 2016 to present -> Three more drugs were approved from Sarepta on the same shoddy basis, proving Califf's promises that Exondys 51 was an isolated case empty [8,14] -> But things would take a turn for the worse with Sarepta's newest drug Elevidys in 2024 [19] -> At last a rigorous clinical trial looking at actual clinical outcomes was published [19,20] -> All would be put to rest -> At long last the issue could be resolved with HARD CLINICAL DATA -> There was only one problem -> The trial failed to show any benefit according to the primary outcome [19,20] -> The surrogate biomarker of micro-dystrophin meant absolutely nothing; it wasn't actually helping patients [19,20] -> What did FDA scientists do? They voted against approval. Of course [19] -> How could they not? The drug didn't actually work in the clinical trial [19] -> It's the only thing that made sense, since FDA is a scientific agency -> AND THEY WERE OVERRULED AGAIN BY PETER MARKS [19] -> YES THAT'S RIGHT, OVERRULED YET AGAIN -> PHARMA WINS AGAIN -> HAHAHAHAHAHA PHARMA ALWAYS WINS YOU FOOLS -> What happened is that Marks crossed his eyes somewhat, trying to make the words on the page blurry -> He prayed really hard, "my god please give me a sign, something, anything, I need this for my career" -> lzzosolsolzzolzozlslzolosllslozllzlzl -> Marks was trying really hard to see SOMETHING, come on come on, give me SOMETHIGN he said -> And he said: wait, look, there are these secondary, exploratory endpoints and a two of them look pretty good, I'LL APPROVE [19,20] -> AHAHAHHAHAHA YES PHAMRA WINS AGAIN -> And Marks said, "Thank you pharma go- I mean god, not pharma god, why did I just say that, FCK" -> The trial was explicitly designed for what Marks did NOT to happen [20] -> Once the primary endpoint was not met, the secondary endpoints couldn't even be statistically tested [20] -> And the trial explicitly said that they could not be interpreted the way Marks interpreted them [20] -> They were not adjusted for multiplicity and they were, like expression of dystrophin, simply bad endpoints [20] -> These two secondary endpoints were time to rise from lying on the floor and the 10-meter walk/run tests [20] -> Subjects who received the Elevidys performed, on average, about 0.5 seconds better than placebo recipients on these tasks [20] -> However several facts must be borne in mind when interpreting these: -> 1. At the time of testing, patients receiving the drug were receiving more corticosteroids than placebo patients, biasing the results [20] -> 2. Blinding might have been broken because those receiving the drug experienced lots of nausea and vomiting from the drug (~70%) [20] -> 3. These differences were tiny and may be attributable to chance, since the natural course of the disease varies widely [20] -> Marks knows this but who cares? Pharma I mean Facebook needed to be placated Elevidys: the drug -> To understand why this is so messed up, one must understand a few things -> On a Bayesian basis, one must assume that Elevidys is harmful until proven otherwise, for two reasons: -> 1. All drugs are potentially "toxic", but some toxins heal: by default you must assume it is a toxin that does not heal because this is what is actually usually the case; you need evidence that it actually heals -> 2. Elevidys IN PARTICULAR must be assumed to be harmful until proven otherwise because of the very nature of the drug -> Let's do a breakdown of the basic science of Elevidys that supports this (Bayesian) hypothesis: -> Gene therapy that permanently integrates into human genome [21] -> Meant to replace dystrophin, the protein that these patients cannot produce themselves [21] -> Preferentially targets muscle but gets expressed everywhere [21] -> Killed three people this year [6,21] -> Costs $3.2 million per injection [21] -> Truncated version of the protein it is supposed to replace [21] -> 3X shorter than the real protein [21] -> Has to be truncated because the technology cannot create the full protein [21] -> Because it's an abnormal protein, it's foreign, so immune system attacks it [21] -> Patients injected with drug are basically given an autoimmune disease [21] -> Patients have to be given anti-inflammatories to fight the disease that the drug causes [21] -> Causes terrible muscle inflammation [21] -> Inflames the heart, heart walls thicken because of the inflammation [21] -> Blows up the liver, causes acute liver injury and death [21] Drug should actually be assumed harmful, not beneficial -> Given all of the above, since the drug failed to meet its primary endpoint, it should actually be considered harmful by default, not beneficial [19,20] -> In other words, what we would actually expect if we added more patients and did an even larger study... -> Is that the drug would do worse than placebo, i.e., patients taking the drug would do worse than those taking placebo -> Why isn't this the default interpretation? -> They are reading the study with an intervention bias -> An intervention bias is natural, which is why "do no harm" is such a central tenet of medicine -> If I may put forward a thesis: most of Vinay Prasad's 500+-paper body of work has been dedicated to demonstrating the "do no harm" principle empirically [22] -> Rose-colored glasses study interpreters are simply not applying this principle properly and are thus failing scientifically in the most fundamental way -> Incomprehensible -> Back in 2016, scientists were adamant that the approval of Sarepta's first drug indicated the profound deterioration of scientific standards [8,9] -> But this latest approval is even worse: actual clinical data is now being overruled -> No standards at all are being enforced anymore; anything can now be approved based on any evidence whatsoever -> What Vinay was trying to do was simply to stop the unrelenting downslide -> And his firing punctuated that downslide for what it was The WSJ segment -> When Elevidys was approved, former FDA chief scientist and one of the original reviewers of Sarepta's first drug Luciana Borio said: -> "I don’t know what to say. Peter Marks makes a mockery of scientific reasoning and approval standards that have served patients well over decades. This type of action also promotes the growing mistrust in scientific institutions like the FDA." [23] -> To return to this video, these two WSJ reporters show an incredible level of ignorance and arrogance -> Finley says that the drug is "clearly" beneficial by misreading the secondary endpoints, just like Marks did -> An FDA memo from last year says about these endpoints: "Under these circumstances, they are misleading and cannot guide any stakeholders—including patients, family members and caregivers, and prescribers—in making informed decisions about the potential benefit of treatment with ELEVIDYS." [20] -> It really doesn't get any clearer than that -> But these two journalists are overruling the actual scientists, just like Marks did -> One of the most incredible comments during this interview was the complaint that "90% of clinical trials fail", as if that's bad thing [1] -> It's actually a good thing; most drugs suck; failing in clinical trial actually allows us to use only the drugs that don't suck -> These people don't understand the most fundamental purpose of the clinical trial -> They think clinical trials failing is a bad thing, as if it means that patients now won't get to use a useful drug -> No, it's a good thing, because it means that patients won't be exposed unnecessarily to a useless drug that might harm them -> The level of ignorance really is unbelievable -> What's worse is that these "journalists" defend their decision -> But what they did is exploit social media hysteria caused by Laura Loomer [1,7] -> Following up on her heels with editorials, using her as pharma attack dog [1,4] -> This is a huge blow to WSJ's credibility, and they know it -> Unbelievably shameful Where do we go from here? -> The Vinay Prasad firing creates a serious crisis of credibility at FDA [2,6] -> Up to this point, we could call these approvals a difference of opinion, but as we've seen, that's a huge stretch -> But any illusion of that is now shattered: the firing shows that drug regulation is explicitly political -> Janet Woodcock: approve, keep job -> Peter Marks: approve, keep job -> Vinay Prasad: block, transparently fired -> Make a decision that is anti-pharma and lose your job: that's the message -> Who can trust any decision at FDA anymore? -> RFK Jr. and Marty Makary both stand behind Vinay Prasad [24] -> Trump went along with lockdowns, he went along with mask mandates, he went along with all of the Covid pseudoscience that he now decries -> He should reverse course and not go along with this -> Trump has created a profound crisis of credibility at FDA and needs to fix it](https://image.24vids.com/tw-1952294845248114806/amplify_video_thumb/1952292444621451264/img/SPXp7ZpvQZ3FQV7_.jpg)
