Covid19 - clinical / epidemiological thread

[dchz]

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Bingo! This is how a good miracle drug-candidate looks:

There is no control arm and this is nothing but sensationalism. it is ****ty science to quote 1 case.

Crap... is it too late to buy Gilead stock?

Don't. The article is used to drive up hype.

I have it on good authority that other centers showed no benefit.

 

[BLADEMDA]

There is no control arm and this is nothing but sensationalism. it is ****ty science to quote 1 case.



Don't. The article is used to drive up hype.

I have it on good authority that other centers showed no benefit.

My hunch is that the use of Remdesivir in the ICU simply won't show efficacy vs placebo. Remdesivir with an IL6 inhibitor would be a different story.

Remdesivir isn't the miracle cure but it will help. The drug is worth maybe $3 to Gilead's share price. The stock is up way more than that so far hence it is a sell not a buy at current levels.

The real "cure" is coming later this summer/early fall with the use of antibodies against Covid 19. Prior to vaccine release the antibody treatment will be the most effective. Even after the Vaccines come out we will still need the treatments because vaccine efficacy won't anywhere near 95%.

 

[jeterfan]

Highly doubt Gilead is going to start giving away Remdesivir because it might help their image.the drug is patented till 2034. One way or another they will Make billions.
Gilead is one of the shrewdest bios out there. They take all the credit for curing hep c a few years back. The real heavy lifting was done by a small company called Pharmasset which got the drug to p3 and Gilead bought out, renamed
the drug Sovaldi and turned it into 60 bil and growing hep c franchise...at its peak the most expensive drug ever. 88k? Per treatment cycle or something close..Whatever it was one of the the most profitable acquisitions ever.

Bill Gates Buying a software operating system from Seattle Computer Products in the early 80s for $50,000 tweaking it a little and licensing it as “ms dos” for the next 20 years would still hold the record. Pretty sure he also intends to profit one way or another from this. Looks like he is playing the mandatory billion dose vaccine angle this time.

 

[turkeyjerky]

Man, in 100 years the saga of remdesivir will be make for a nice book. I predict #3 on the nytimes bestseller nonfiction list.

I was wrong before. I thought it was designed for ebola, and failed at that. It turns out it was designed for hep C, but failed at that (then gilead buys the drug that actually worked). Then it fails at ebola. Now, despite no decent evidence for efficacy (and are you kidding me--with 2 million+ cases so far you're telling me they couldn't perform an RCT??) it's about to become the most profitable drug of all time.

 

[deleted171991]

There is no control arm and this is nothing but sensationalism. it is ****ty science to quote 1 case.

It may well be. But there is a good chance the drug may actually work, based on the story. When a patient goes from almost intubated to feeling much better after the first infusion, there is probably something there. Of course, I'd love to hear this kind of story consistently, but I have hope.

It's interesting especially in the context that other centers showed no benefit. Did they change the dose? Is it just cheap journalistic sensationalism? It will be interesting to find out. Btw, that's why I said miracle drug-candidate.

P.S. The story about Marik's HAT recipe in sepsis was similar in initial sensationalism (patients decreasing pressor requirements within hours after the cocktail). Still, nobody has been able to reproduce his results in the last 3 years or so. Food for thought.

 

[dhb]

When a patient goes from almost intubated to feeling much better after the first infusion, there is probably something there.

If the effect were so powerful you would see it in every patient

 

[nimbus]

One month ago, on March 20, we had 255 COVID deaths in the USA. Today we have >40000. We broke 20000 deaths on 4/11. 10000 on 4/6. 5000 on 4/1 and 2500 on 3/29.

The good news is that the doubling interval has started to lengthen and the daily death count has started to decline after peaking around 2600. Still we are dealing with much bigger numbers and will have to deal with a long tail as the best case scenario. Worst case scenario is that we could have another peak that’s worse than the first.

We can look at the worldwide figures to look into our future. The USA currently have 700000+ cases and 40000+ deaths. There are currently 2.4 million cases and 165000 deaths worldwide. That could easily be the USA in a month or 2.

We have the worst Coronavirus epidemic in the world by a wide margin. It’s fine to talk about how to reopen safely but I think we are still not close to reopening in densely populated areas.

 

[BLADEMDA]

A flood of new research suggests that far more people have had the coronavirus without any symptoms, fueling hope that it will turn out to be much less lethal than originally feared.

While that’s clearly good news, it also means it’s impossible to know who around you may be contagious. That complicates decisions about returning to work, school and normal life.

In the last week, reports of silent infections have come from a homeless shelter in Boston, a U.S. Navy aircraft carrier, pregnant women at a New York hospital, several European countries and California.

The head of the U.S. Centers for Disease Control and Prevention says 25% of infected people might not have symptoms. The vice chairman of the Joint Chiefs of Staff, Gen. John Hyten, thinks it may be as high as 60% to 70% among military personnel.


None of these numbers can be fully trusted because they’re based on flawed and inadequate testing, said Dr. Michael Mina of Harvard’s School of Public Health.

Collectively, though, they suggest “we have just been off the mark by huge, huge numbers” for estimating total infections, he said.

Reports suggest many have had coronavirus with no symptoms

A flood of new research suggests that far more people have had the coronavirus without any symptoms, fueling hope that it will turn out to be much less lethal than originally feared. While...

apnews.com

 

[BLADEMDA]

One month ago, on March 20, we had 255 COVID deaths in the USA. Today we have >40000. We broke 20000 deaths on 4/11. 10000 on 4/6. 5000 on 4/1 and 2500 on 3/29.

The good news is that the doubling interval has started to lengthen and the daily death count has started to decline after peaking around 2600. Still we are dealing with much bigger numbers and will have to deal with a long tail as the best case scenario. Worst case scenario is that we could have another peak that’s worse than the first.

We can look at the worldwide figures to look into our future. The USA currently have 700000+ cases and 40000+ deaths. There are currently 2.4 million cases and 165000 deaths worldwide. That could easily be the USA in a month or 2.

We have the worst Coronavirus epidemic in the world by a wide margin. It’s fine to talk about how to reopen safely but I think we are still not close to reopening in densely populated areas.

People are ready to go back to some routines. Surveys show that after we partially re-open in a few weeks many are going back to gyms, restaurants and stores. You can include me among them as well. Many people are willing to accept some risk to their health in return for the opening of the economy. Now, there will still be social distancing, face masks and other common sense precautions in place but IMHO many people are ready to go out.

 

[BLADEMDA]

 

[BLADEMDA]

Coronavirus could irreversibly change restaurants, with experts predicting customer temperature checks and new fears of crowds

Like September 11 changed the airline industry, experts say that customers' fears and new precautions will force restaurants to adapt to a new normal.

www.businessinsider.com

 

[deleted697127]

Coronavirus could irreversibly change restaurants, with experts predicting customer temperature checks and new fears of crowds

Like September 11 changed the airline industry, experts say that customers' fears and new precautions will force restaurants to adapt to a new normal.

www.businessinsider.com

Maybe but it didn’t change our break room...

Would be awesome if this translates to more outdoor restaurants for improved ventilation.

 

[Ezekiel2517]

The Economist: Official covid-19 death tolls still under-count the true number of fatalities (need subscription):

Tracking covid-19 excess deaths across countries

Official Counts Understate the U.S. Coronavirus Death Toll (Published 2020)

Inconsistent protocols, limited resources and a patchwork of decision making have led to an undercounting of people with the coronavirus who have died, health experts say.

www.nytimes.com

 

[Ronin786]

So I just got off a week in our COVID ICU, our population exploded overnight. Actually don't think I ever worked as much in a week in residency as I did this one.

For what it's worth, it's hard not to subscribe to the theory that this isn't typical ARDS when you have someone saturating 88% on 100% FiO2 but with a compliance that is through the roof. One patient was pulling in 1200 tidal volumes on a Pinsp of 5. APRV really works for some reason and I just started going straight to it rather than trying to find some holy grail of optimal PEEP.

Also **** the president for blasting HCQ. Most clinicians have no recourse except to use it because they're worried about the perception. Very terrible position to be in. I would just write something in each chart about why it's not a good idea and throw it away. I'll let you guys know if I get sued in a year.

Also, clotting is real. Arterial and venous. Lots of PEs and aortic thrombosis. And I dont think inflammatory modulation works, but who knows what does.

 

[dhb]

compliance that is through the roof

I heard it evolves into a classical low compliance ards later on.

 

[Ronin786]

I heard it evolves into a classical low compliance ards later on.

My hunch is that the low compliance ARDS is just ventilator induced injury from high PEEP. Who knows though.

 

[deleted270145]

So I just got off a week in our COVID ICU, our population exploded overnight. Actually don't think I ever worked as much in a week in residency as I did this one.

For what it's worth, it's hard not to subscribe to the theory that this isn't typical ARDS when you have someone saturating 88% on 100% FiO2 but with a compliance that is through the roof. One patient was pulling in 1200 tidal volumes on a Pinsp of 5. APRV really works for some reason and I just started going straight to it rather than trying to find some holy grail of optimal PEEP.

Also **** the president for blasting HCQ. Most clinicians have no recourse except to use it because they're worried about the perception. Very terrible position to be in. I would just write something in each chart about why it's not a good idea and throw it away. I'll let you guys know if I get sued in a year.

Also, clotting is real. Arterial and venous. Lots of PEs and aortic thrombosis. And I dont think inflammatory modulation works, but who knows what does.

We had basically everyone who wasn't intubated on a hydroxychloroquine/azithromycin combo as a let's-throw-everything-at-the-wall-and-see-what-sticks kind of methodology, unfortunately. Didn't seem to do jacks***, though. Of all the therapeutic options, tocilizumab seemed to have the most benefit, but obviously this is 100% anecdotal conjecture on my part.

Totally agree about the clotting. My first week, before we had much experience taking care of these patients, we had standard DVT prophylaxis in place for these patients. Within less than a week, we had started everyone on therapeutic dosing of lovenox or heparin drips because of the mounting evidence suggesting a propensity for clot formation in these patients. The neurointerventionalists told me the other day that they saw a huge surge in the number of stroke patients coming in as the COVID cases increased in the NYC area, and a vascular surgeon I was talking to last week also mentioned a large increase in the number of patients suddenly coming in with cold and ischemic limbs. Crazy stuff.

 

[deleted59964]

seems the death toll is quite a bit higher than being reported

The Pandemic’s Hidden Toll: Half a Million Deaths (Published 2020)

Far more people died in 2020 during the pandemic than have been officially reported, a review of mortality data in 35 countries shows.

www.nytimes.com

 

[dchz]

So I just got off a week in our COVID ICU, our population exploded overnight. Actually don't think I ever worked as much in a week in residency as I did this one.

For what it's worth, it's hard not to subscribe to the theory that this isn't typical ARDS when you have someone saturating 88% on 100% FiO2 but with a compliance that is through the roof. One patient was pulling in 1200 tidal volumes on a Pinsp of 5. APRV really works for some reason and I just started going straight to it rather than trying to find some holy grail of optimal PEEP.

Also **** the president for blasting HCQ. Most clinicians have no recourse except to use it because they're worried about the perception. Very terrible position to be in. I would just write something in each chart about why it's not a good idea and throw it away. I'll let you guys know if I get sued in a year.

Also, clotting is real. Arterial and venous. Lots of PEs and aortic thrombosis. And I dont think inflammatory modulation works, but who knows what does.

I've been going to pressure control without inverse ratio. It's about mean airway pressure, not PEEP. I also follow the Flow curve to make sure it gets back to 0 before the next breath starts again because I got burned with a clogged tube once. Keep an eye out for higher resistances.

How are you diagnosing the PEs? A lot of people are empirically doing heparin infusions for this reason.

I had a pt on Sarilumab. Definitely worked. White count went from 9 to 2 then bounced back a day later, lymphocyte % went from 8 to 25% in a matter of days, PF ratio went from 140s to 200+ in the same period. Still need to see the overall data and control arm. It is ****ty science to quote 1 case. But if i had to hang my hat on a miracle drug, it's Sarilumab. @FFP

 

[MoMoGesiologist]

I've been going to pressure control without inverse ratio. It's about mean airway pressure, not PEEP. I also follow the Flow curve to make sure it gets back to 0 before the next breath starts again because I got burned with a clogged tube once. Keep an eye out for higher resistances.

How are you diagnosing the PEs?

I had a pt on Sarilumab. Definitely worked. White count went from 9 to 2 then bounced back a day later, lymphocyte % went from 8 to 25% in a matter of days, PF ratio went from 140s to 200+ in the same period. Still need to see the overall data and control arm. It is ****ty science to quote 1 case. But if i had to hang my hat on a miracle drug, it's Sarilumab. @FFP

I have had a couple pts get acutely worse (clinical decompensation, skyrocketing inflam markers) who I just supported through it (started broad spectrum abx, pressors, high fio2 and proning, therapeutic anticoag) and their clinical course and inflam markers improve (no immune modulating meds). There are pts who I make NO interventions or changes on and their clinical status or inflam markers go up and down on their own. It’s very very difficult for me to pin point whether pts will turn around on their own as part of their clinical course vs it was an intervention I made that was life saving vs if I give an experimental med would they have improved. I’m starting to doubt any improvement is from my care vs it would have happened anyway. It’s kind of driving me insane...

 

[dchz]

I have had a couple pts get acutely worse (clinical decompensation, skyrocketing inflam markers) who I just supported through it (started broad spectrum abx, pressors, high fio2 and proning, therapeutic anticoag) and their clinical course and inflam markers improve (no immune modulating meds). There are pts who I make NO interventions or changes on and their clinical status or inflam markers go up and down on their own. It’s very very difficult for me to pin point whether pts will turn around on their own as part of their clinical course vs it was an intervention I made that was life saving vs if I give an experimental med would they have improved. I’m starting to doubt any improvement is from my care vs it would have happened anyway. It’s kind of driving me insane...

We are essentially supporting them until their own immune system kicks in.

But when I see timing relationships where the drugs is given and everything takes a sharp turn. It's hard not to be optimistic.

I'm still aware this isn't replacement for good science. Just optimistic.

 

[anbuitachi]

Anyone try TPA?

 

[nimbus]

seems the death toll is quite a bit higher than being reported

The Pandemic’s Hidden Toll: Half a Million Deaths (Published 2020)

Far more people died in 2020 during the pandemic than have been officially reported, a review of mortality data in 35 countries shows.

www.nytimes.com

I’ve always been suspicious of some of the numbers, eg Turkey.

 

[chocomorsel]

I've been going to pressure control without inverse ratio. It's about mean airway pressure, not PEEP. I also follow the Flow curve to make sure it gets back to 0 before the next breath starts again because I got burned with a clogged tube once. Keep an eye out for higher resistances.

How are you diagnosing the PEs? A lot of people are empirically doing heparin infusions for this reason.

I had a pt on Sarilumab. Definitely worked. White count went from 9 to 2 then bounced back a day later, lymphocyte % went from 8 to 25% in a matter of days, PF ratio went from 140s to 200+ in the same period. Still need to see the overall data and control arm. It is ****ty science to quote 1 case. But if i had to hang my hat on a miracle drug, it's Sarilumab. @FFP

We did tociluzimab on a young patient in her thirties. We Don’t think it helped.
I don’t think anything we are doing is helping really. Just buying them time to declare themselves one way or another.
Their body is going to do what their body is going to do.

 

[dchz]

We did tociluzimab on a young patient in her thirties. We Don’t think it helped.
I don’t think anything we are doing is helping really. Just buying them time to declare themselves one way or another.
Their body is going to do what their body is going to do.

How do you know she didn't get the placebo?

I know my pt didn't get a placebo because i FREAKED out because his WBC dropped from 9 to 2, and i thought i missed a huge infection. Clinically he didn't look that way so I ordered the broad spectrum abx (didn't administer it) and called up ID. The ID doc was like, yeah Sarilumab prob caused it, don't give zosyn. That's how I know the pt got Sarilumab.

 

[CopaceticOne]

More deaths, no benefit from malaria drug in VA virus study

A malaria drug widely touted by President Donald Trump for treating the new coronavirus showed no benefit in a large analysis of its use in U.S. veterans hospitals.

apnews.com

 

[chocomorsel]

How do you know she didn't get the placebo?

I know my pt didn't get a placebo because i FREAKED out because his WBC dropped from 9 to 2, and i thought i missed a huge infection. Clinically he didn't look that way so I ordered the broad spectrum abx (didn't administer it) and called up ID. The ID doc was like, yeah Sarilumab prob caused it, don't give zosyn. That's how I know the pt got Sarilumab.

Didn’t know the hospital was in a study. Maybe it is. It was in the plasma study which I knew about. ID just told us they gave her Toci.

 

[Ronin786]

How do you know she didn't get the placebo?

I know my pt didn't get a placebo because i FREAKED out because his WBC dropped from 9 to 2, and i thought i missed a huge infection. Clinically he didn't look that way so I ordered the broad spectrum abx (didn't administer it) and called up ID. The ID doc was like, yeah Sarilumab prob caused it, don't give zosyn. That's how I know the pt got Sarilumab.

Toci isn't part of a study. We've given it to a bunch of patients and it has done nothing. Makes me doubt Sarilumab is any better.

As far as PEs go, we trend D-Dimers and start empiric heparin if there's anything suggestive of clotting like a CRRT filter going down or hypoxemia worsening/not improving.

 

[deleted171991]

More deaths, no benefit from malaria drug in VA virus study

A malaria drug widely touted by President Donald Trump for treating the new coronavirus showed no benefit in a large analysis of its use in U.S. veterans hospitals.

apnews.com

A malaria drug widely touted by President Donald Trump for treating the new coronavirus showed no benefit in a large analysis of its use in U.S. veterans hospitals. There were more deaths among those given hydroxychloroquine versus standard care, researchers reported.

CONCLUSIONS:
In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.

P.S. Sorry, I've just noticed CopaceticOne's post above.

 

[Kevin Durant]

I actually think Remdesivir will show a statistically significant benefit per their endpoint measurements. The study without the control group and the Monkey study (Antiviral remdesivir prevents disease progression in monkeys with COVID-19) are pretty promising.

I saw their increasing trial size as indication that they've shown a benefit and are working to get the medication to more patients (Gilead stopped taking compassionate use requests Gilead Sciences Statement on Access to Remdesivir Outside of Clinical Trials).

As for their stock price, I shorted them after the pump up from the rumor and closed those positions today. They may have a bit more room to fall further, but I'm expecting another runup in price and IV before they release results. Hard to say if the actual release will bump it upwards more or make it tank. Buy the rumor sell the news?

 

[CopaceticOne]

P.S. Sorry, I've just noticed CopaceticOne's post above.

😉 beat ya for once. Also:

NIH Panel Recommends Against Drug Combination Promoted By Trump For COVID-19

The group of experts, assembled under the agency run by Dr. Anthony Fauci, warns that using a combination of hydroxychloroquine and azithromycin could result in potential toxicities.

www.npr.org

 

[deleted171991]

This is beyond dumb: Coronavirus Live Updates: Doctor Says He Was Removed From Federal Post After Questioning Hydroxychloroquine Treatment

This is Middle Ages level stuff. Burn the heretic!

 

[Ezekiel2517]

I actually think Remdesivir will show a statistically significant benefit per their endpoint measurements. The study without the control group and the Monkey study (Antiviral remdesivir prevents disease progression in monkeys with COVID-19) are pretty promising.

I saw their increasing trial size as indication that they've shown a benefit and are working to get the medication to more patients (Gilead stopped taking compassionate use requests Gilead Sciences Statement on Access to Remdesivir Outside of Clinical Trials).

As for their stock price, I shorted them after the pump up from the rumor and closed those positions today. They may have a bit more room to fall further, but I'm expecting another runup in price and IV before they release results. Hard to say if the actual release will bump it upwards more or make it tank. Buy the rumor sell the news?

Changing the design of a trial mid-course is highly unusual. If they were seeing a great obvious benefit, the study would actually be stopped early. This would be to allow people in society to benefit, since this is a novel virus with no known treatment. By continuing to increase the number of patients, what they're trying to do is compensate for the minimal effects they are seeing and the low power of their study.

 

[Beach bum]

This is beyond dumb: Coronavirus Live Updates: Doctor Says He Was Removed From Federal Post After Questioning Hydroxychloroquine Treatment

This is Middle Ages level stuff. Burn the heretic!

Is this reported anywhere other than the amazingly impartial and accurate NY Times?

 

[nimbus]

Is this reported anywhere other than the amazingly impartial and accurate NY Times?

Redirect Notice

Redirect Notice

www.google.com

 

[anes121508]

I've been going to pressure control without inverse ratio. It's about mean airway pressure, not PEEP. I also follow the Flow curve to make sure it gets back to 0 before the next breath starts again because I got burned with a clogged tube once. Keep an eye out for higher resistances.

How are you diagnosing the PEs? A lot of people are empirically doing heparin infusions for this reason.

I had a pt on Sarilumab. Definitely worked. White count went from 9 to 2 then bounced back a day later, lymphocyte % went from 8 to 25% in a matter of days, PF ratio went from 140s to 200+ in the same period. Still need to see the overall data and control arm. It is ****ty science to quote 1 case. But if i had to hang my hat on a miracle drug, it's Sarilumab. @FFP

can you elaborate for me please on the mean airway pressure vs peep?

 

[anes121508]

I have had a couple pts get acutely worse (clinical decompensation, skyrocketing inflam markers) who I just supported through it (started broad spectrum abx, pressors, high fio2 and proning, therapeutic anticoag) and their clinical course and inflam markers improve (no immune modulating meds). There are pts who I make NO interventions or changes on and their clinical status or inflam markers go up and down on their own. It’s very very difficult for me to pin point whether pts will turn around on their own as part of their clinical course vs it was an intervention I made that was life saving vs if I give an experimental med would they have improved. I’m starting to doubt any improvement is from my care vs it would have happened anyway. It’s kind of driving me insane...

Humbling. I applaud you for writing this. Many of us on here like to write about our tales of triumph and how good we are, but this post might be the cold hard truth at the moment.

Part of me feels like if we just stick to the basics of solid supportive icu care with preventative basics and not create iatrogenic problems, some people will pull through. I am seeing a lot of basics of care being missed due to a multitude of factors that end up being too much for patients to handle on top of fighting COVID.

 

[anes121508]

Anyone try TPA?

currently contemplating where it fits.

poll the audience....were would you set the threshold for pulling the trigger on tpa? hypoxia, deadspace, dimer levels, tte findings, hd instability, etc.....what objective markers specifically in what clinical scenario would you use to justify tpa in a covid patient?

same question about nitric?


how about this...

when is the right time if ever for (criteria based) to...

prone
remdesivir
IL-6 inhibitors
steroids
nitric
tpa
ecmo
trach

 

[Monty Python]

Is this reported anywhere other than the amazingly impartial and accurate NY Times?

Reuters.

U.S. official says he was ousted for urging caution on Trump-touted coronavirus drug

The ousted director of a key U.S. agency charged with developing drugs to fight the coronavirus pandemic said on Wednesday he was dismissed because he called for careful vetting of a treatment frequently touted by President Donald Trump.

www.reuters.com

 

[Kevin Durant]

Changing the design of a trial mid-course is highly unusual. If they were seeing a great obvious benefit, the study would actually be stopped early. This would be to allow people in society to benefit, since this is a novel virus with no known treatment. By continuing to increase the number of patients, what they're trying to do is compensate for the minimal effects they are seeing and the low power of their study.

I agree they would stop it early if they had an adequate supply to treat every patient and there was a clear benefit seen. But they don't. They only have about 30,000 treat course equivalents available worldwide. They've stopped taking compassionate use requests in lieu of directly enrolling patients into the study to get them remdesivir.

I'm not saying that you're wrong in fact many people are skeptical because of the big jump in study enrollment...but I think it's just as likely this is a move to provide treatment to more patients. The preliminary studies I linked show pretty clear benefit. Another question is why would Gilead already be ramping up production 30x by year's end if their data shows that the drug is a dud? All their actions, preliminary studies, and anecdotes point towards efficacy.

 

[Mman]

when is the right time if ever for (criteria based) to...


trach

never

 

[Ezekiel2517]

I agree they would stop it early if they had an adequate supply to treat every patient and there was a clear benefit seen. But they don't. They only have about 30,000 treat course equivalents available worldwide. They've stopped taking compassionate use requests in lieu of directly enrolling patients into the study to get them remdesivir.

I'm not saying that you're wrong in fact many people are skeptical because of the big jump in study enrollment...but I think it's just as likely this is a move to provide treatment to more patients. The preliminary studies I linked show pretty clear benefit. Another question is why would Gilead already be ramping up production 30x by year's end if their data shows that the drug is a dud? All their actions, preliminary studies, and anecdotes point towards efficacy.

You keep bringing up their "preliminary" studies as if they're impressive or something. It's a garbage study, that's why it's getting trashed. Not only is there no control group, but the patients in the study are not patients who would be statistically expected to die anyways. Based on the stat article, look at how they define the "severe" patients they are studying: "severe" excludes "patients w multi-organ failure, abnormal liver tests, moderate kidney disease, needing mechanical ventilation at time of first evaluation, needing mech ventilation for 5+ days." The patients they are studying are basically patients who have fevers lol. These are not sick patients. And since this isn't data from a controlled trial, there is literally 0 information you can gain from it about the drug's efficacy. A drug that is highly effective does not need a large sample size. Bigger randomized sample sizes are needed when you want to validate small differences. Another thing not mentioned is how they changed several endpoint goals in the middle of the study. This, like raising the sample size, is a move to compensate for low power. It's pretty obvious what they're doing. I'm not saying this drug can't work. You just won't be able to tell from this study.

Also, just from a logical standpoint, do ppl realize this drug was originally created specifically for a different virus, and it failed? Ppl are hoping this will be a miracle drug for a virus which literally did not exist when it was designed. Think about the odds of that happening. Has there ever even been a drug which has successfully been repurposed for a virus? I can't think of one.

 

[Kevin Durant]

You keep bringing up their "preliminary" studies as if they're impressive or something. It's a garbage study, that's why it's getting trashed. Not only is there no control group, but the patients in the study are not patients who would be statistically expected to die anyways. Based on the stat article, look at how they define the "severe" patients they are studying: "severe" excludes "patients w multi-organ failure, abnormal liver tests, moderate kidney disease, needing mechanical ventilation at time of first evaluation, needing mech ventilation for 5+ days." The patients they are studying are basically patients who have fevers lol. These are not sick patients. And since this isn't data from a controlled trial, there is literally 0 information you can gain from it about the drug's efficacy. A drug that is highly effective does not need a large sample size. Bigger randomized sample sizes are needed when you want to validate small differences. Another thing not mentioned is how they changed several endpoint goals in the middle of the study. This, like raising the sample size, is a move to compensate for low power. It's pretty obvious what they're doing. I'm not saying this drug can't work. You just won't be able to tell from this study.

Also, just from a logical standpoint, do ppl realize this drug was originally created specifically for a different virus, and it failed? Ppl are hoping this will be a miracle drug for a virus which literally did not exist when it was designed. Think about the odds of that happening. Has there ever even been a drug which has successfully been repurposed for a virus? I can't think of one.

The study which the Stat leak from UChicago refers to is a RCT with arms including both mechanically ventilated patients. Key inclusion criteria includes "Peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen at screening."

On the UChicago conference call they discussed "We have seen people come off ventilators a day after starting therapy. So, in that realm, overall our patients have done very well. Most of our patients are severe and most of them are leaving at six days."

These are more than just patients with fevers. They're patients that already have an oxygen requirement and +/- ventilation. They're not at multi-organ failure failure no, but I don't think there is any drug out there that can reliably treat patients who have progressed to that stage.

I don't think them expanding the study size is a definitive sign that studies have not demonstrated results. Gilead has stated in the past that they are stopping compassionate use requests and transitioning to expanded access programs (eg clinical trials). Why give out a drug for free and gain nothing in return if you can collect data at the same time?

 

[dchz]

can you elaborate for me please on the mean airway pressure vs peep?

Two factors we can do to manipulate gas exchange of oxygen without mechanical circulatory support: Mean airway pressure and FIO2.

If you look at a normal pressure vs time curve on a ventilator for volume control, and compare it to pressure control:

Assuming all other variables (Insp time, vent rate, PEEP) are all the same, pressure mode gives you a higher mean airway pressure for any given peak inspiratory pressure, which in turn gives you better oxygenation parameters.

The downside is that ventilation might be affected depending on the compliance of the lung, which can be attenuated by modes that use the pressure control wave form but guarantees a certain tidal volume (VC+ on covidian, Volume autoflow on drager, pressure control volume guaranteed on GE).

Looking at this, you realize there are several parameters you can manipulate to change the airway pressure: the I:E ratio can change the mean airway pressure as much as the peep.

Lastly, you can tell many of the modes can be manipulated to do the same thing. APRV (bilevel for covidian) can be achieved through pressure control and simply changing the I:E time. I used to troll people in the ICU when i dropped people off and put them on APRV mode but it's really pressure support or pressure control or I:E of 1:2.

Mastery of these different modes is vital to supporting your patient as they have increased need for oxygenation.

 

[dchz]

The study which the Stat leak from UChicago refers to is a RCT with arms including both mechanically ventilated patients. Key inclusion criteria includes "Peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen at screening."

On the UChicago conference call they discussed "We have seen people come off ventilators a day after starting therapy. So, in that realm, overall our patients have done very well. Most of our patients are severe and most of them are leaving at six days."

These are more than just patients with fevers. They're patients that already have an oxygen requirement and +/- ventilation. They're not at multi-organ failure failure no, but I don't think there is any drug out there that can reliably treat patients who have progressed to that stage.

I don't think them expanding the study size is a definitive sign that studies have not demonstrated results. Gilead has stated in the past that they are stopping compassionate use requests and transitioning to expanded access programs (eg clinical trials). Why give out a drug for free and gain nothing in return if you can collect data at the same time?

I'm also at a center that has remdesivir. it has no effect in our center.

They are expanding the size to show a small effect.

 

[deleted270145]

From NYC

just goes to show how little we knew about this virus and how we‘re literally rewriting the playbook on the fly

 

[dchz]

From NYC

just goes to show how little we knew about this virus and how we‘re literally rewriting the playbook on the fly

many use the elephant in a dark room metaphor. It's on point.

 

[dhb]

A drug that is highly effective does not need a large sample size.

I like an NNT=1

 

[deleted171991]

many use the elephant in a dark room metaphor. It's on point.

Again, history is very helpful. Just remember the AIDS epidemic, and all the initial misconceptions about it.

 

[Ronin786]

New data on Gilead's remdesivir, released by accident, show no benefit for coronavirus patients. Company still sees reason for hope

Gilead's antiviral medicine remdesivir failed to speed the improvement of patients with Covid-19 or prevent them from dying, according to results from a long-awaited clinical trial conducted in China.

www.statnews.com

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