I live in an island where during a viral outbreak some were advocating for chloroquine against the Chikungunya virus. The initial in-vitro tests were promising but it turns out during human trials it has a reverse effect and delayed adaptive immune responses (1). It's sad to see scientific method destroyed by politics and social networks.
> It's sad to see scientific method destroyed by politics and social networks.
If there were such a thing as phase 5 trials with at least a million participants, it would be completely insane to use anything that had only undergone phase 3 clinical trials. People should make rational decisions based on the best evidence that's available at the time. Whether or not it's rational to take HCQ, there's nothing magical about phase 3 studies.
Antiviral drugs only really work in the first couple days of the illness, and with this disease you usually don't get symptoms until at least day 5. And in the current environment, no one is getting put on prescription antivirals until at least day 10, and usually even later. To me this raises the question of whether clinical trials are really even possible right now in the first place, or whether making decisions based off in vitro data is the best we can do for right now.
>To me this raises the question of whether clinical trials are really even possible right now in the first place, or whether making decisions based off in vitro data is the best we can do for right now.
I don't think I understand this. We have a clinical trial with in vivo data right here though, right?
Yep I live on Reunion. I might be biased, as I was born there, but if you have a job, a decent house, and loves nature living here is quite pleasant. It's like France with less grumpy people, tropical weather but with some third-world issues. Problem is jobs are scarce and aren't well paid (unless you're a french expat) and rents are astronomical.
The sample size is 62 and the mortality rates are between 0% and 7% depending primarily on age and co-morbidities. I don't think we can draw any meaningful conclusions from this other than what we already know: seems worth looking into HCQ more.
They weren't looking at the effects on mortality. They looked at TTCR ("the return of body temperature and cough relief, maintained for more than 72 h") and radiological changes. They found a decently large effect in both of these.
The meaningful conclusion is "Considering that there is no better option at present, it is a promising practice to apply HCQ to COVID-19 under reasonable management."
Also, you don't need to decrease mortality to have a huge benefit from a treatment. If you just get people recovering faster, you've probably indirectly saved many lives!
The side effects were a headache and a rash, neither one serious. The worrisome side effects of HCQ are also given in the paper: "Retinopathy is one of the major adverse reactions of long-term therapy with HCQ. Besides, patients with rheumatoid diseases treated with HCQ occasionally experience arrhythmias."
Luckily, long-term use of the drug isn't necessary here because the immune system successfully responds with antibodies to fight of the virus, so retinopathy isn't an issue. Also, as the paper states, "Fortunately, deciding on individual treatment plans scientifically, monitoring adverse reactions timely, to avoid overdose, short-term application of HCQ is relatively safe."
I know someone with Lupus, as I'm sure many people do. This is really good news for most everyone right now. But for people who need these types of drugs to fight Lupus (and I'd assume many other diseases) this is really bittersweet because they can either not get it at all now, or only get a very small amount. It's good to see this is going to help people with Covid-19, I really hope the drug makers can get this production ramped up fast so others that need these drugs can get what they need again.
"Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 32) compared with the control group (54.8%, 17 of 32). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia."
So hate to ask this, can you explain this for non-medical spectators? Specifically what TTCR and is "absorption of pneumonia" a good thing (e.g. the body has absorbed the pneumonia and therefore it has gone away) or a bad thing (e.g. the body has absorbed the pneumonia and therefore has "collected" more)?
I have a feeling that this is a mistranslation, not jargon. Other similar usage of "absorption" that I can find was also written by Chinese researchers.
In pneumonia, areas of the lungs fill with fluid. This prevents the area from filling with air, which therefore prevents the exchange of CO2 and O2 between the blood and air.
I will assume that 'absorption' in this sense refers to the fluid. It's a good thing when this happens, because that that area of the lung can be accessed by air again.
I think this counts a double blind trial. From the top of page 4 in the article:
"Randomization was performed through a computer-generated list stratified by site. Treatments were assigned after confirming the correctness of the admission criteria. Neither the research performers nor the patients were aware of the treatment assignments."
Not sure they've been doing proper studies and such because they're so slammed, but it seems they've been trying it in Italy and... maybe it helps some, but doesn't seem like it works miracles.
In combination with antibiotics and (it seems) zinc it looks quite effective.
A doctor in NY has treated with that combination and is up to almost 700 COVID-19 patients without one dying _or needing a ventilator_.
Some relevant quotes:
>Dr. Zelenko said the whole treatment costs only $20 over a period of 5 days with 100% success. He defines success as “Not to die.” Dr. Zelenko first posted his Facebook video message last week calling on President Trump to “advise the country that they should be taking this medication.”
>There are many other success stories about hydroxychloroquine across the country. Last week, Dr. William Grace, an oncologist at Lenox Hill Hospital in New York City, said they’ve not had a single death in their hospital because of hydroxychloroquine. “Thanks to hydroxychloroquine, we have not had a death in our hospital,’ Dr. Grace said.
This story was reported by Laura Ingraham on Fox News. Her tweet promoting this as a "cure" was immediately withdrawn by Twitter as "misleading". The 40 minute video interview with Zelenko, again on Fox News, was conducted not by a medical reporter, but by Rudy Giuliani. Zelenko goes on to make numerous huge dire public health predictions -- none of which a family practitioner has any business suggesting, especially in public on a national news outlet.
As always, consider the source of the information.
It's also very important to note that Zelenko was treating 700 unhospitalized patients; these were not cases severe enough to admit to a hospital. He treated them from his home (since he lost a lung to cancer years ago). So he never actually physically met with any of those 700 patients to monitor their progress.
In fact it's likely that many of these patients never tested positive, but simply self-reported as positive, further diluting the 'trial'.
And because 80% of positive COVID-19 cases are minor or even asymptomatic, the number of his patients that really _needed_ treatment falls from 700 down to, at most, 140 (20% of 700). That's a much smaller treatment effect that a large number like 700 would suggest.
It's also important to note that, apparently, Dr Zelenko treated sick people with medications that were NOT approved for the target disease. And he did so apparently without approval from any higher public health authority. In short, it appears that he experimented on his patients without authorization to do so from a public health or research authority.
Zelenko is a family medicine doctor, not a specialist in infectious disease or research. Thus it's very unlikely he wrote up an experimental design with proper safeguards, much less got it approved. With such poor experimental controls, it's impossible to interpret his results. What's more, if any of his patients later incur harm (like heart attacks from the chloroquine), such a laissez-faire approach to medicine will invite lawsuits galore.
Some of the papers being shared on r/COVID19 seem to be indicating that perhaps it has little effect once the disease has gotten severe, but if taken early, may reduce potential severity and time to recovery. Still early, but it seems like, if the results end up being true, it could be helpful in stemming the tide of the disease.
In this situation, helping some might be working a miracle. If a treatment - and I have no idea if this is the one - can prevent 20% of patients from requiring a ventilator, that's the equivalent of having 20% more ventilators.
Readit News
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977261/
If there were such a thing as phase 5 trials with at least a million participants, it would be completely insane to use anything that had only undergone phase 3 clinical trials. People should make rational decisions based on the best evidence that's available at the time. Whether or not it's rational to take HCQ, there's nothing magical about phase 3 studies.
Antiviral drugs only really work in the first couple days of the illness, and with this disease you usually don't get symptoms until at least day 5. And in the current environment, no one is getting put on prescription antivirals until at least day 10, and usually even later. To me this raises the question of whether clinical trials are really even possible right now in the first place, or whether making decisions based off in vitro data is the best we can do for right now.
I don't think I understand this. We have a clinical trial with in vivo data right here though, right?
Dead Comment
The meaningful conclusion is "Considering that there is no better option at present, it is a promising practice to apply HCQ to COVID-19 under reasonable management."
Luckily, long-term use of the drug isn't necessary here because the immune system successfully responds with antibodies to fight of the virus, so retinopathy isn't an issue. Also, as the paper states, "Fortunately, deciding on individual treatment plans scientifically, monitoring adverse reactions timely, to avoid overdose, short-term application of HCQ is relatively safe."
From Paper:
TTCR: Time to clinical recovery
edit: got downvoted, so adding link to only other "absorption of pneumonia" use that I could find: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344839/
edit2: I could also find some usage of "absorption of inflammation", again also all Chinese researchers.
I will assume that 'absorption' in this sense refers to the fluid. It's a good thing when this happens, because that that area of the lung can be accessed by air again.
The French study, problematic in the extreme but still promising, claims a large synergistic effect of using both drugs in combination.
Also, unlike the French study, this one appears to be at least controlled, but possibly not blinded.
Not sure they've been doing proper studies and such because they're so slammed, but it seems they've been trying it in Italy and... maybe it helps some, but doesn't seem like it works miracles.
A doctor in NY has treated with that combination and is up to almost 700 COVID-19 patients without one dying _or needing a ventilator_.
Some relevant quotes:
>Dr. Zelenko said the whole treatment costs only $20 over a period of 5 days with 100% success. He defines success as “Not to die.” Dr. Zelenko first posted his Facebook video message last week calling on President Trump to “advise the country that they should be taking this medication.”
>There are many other success stories about hydroxychloroquine across the country. Last week, Dr. William Grace, an oncologist at Lenox Hill Hospital in New York City, said they’ve not had a single death in their hospital because of hydroxychloroquine. “Thanks to hydroxychloroquine, we have not had a death in our hospital,’ Dr. Grace said.
From:
https://techstartups.com/2020/03/28/dr-vladimir-zelenko-now-...
When people are dying in large numbers, sometimes "anecdotal evidence" (especially with large samples) is plenty.
This story was reported by Laura Ingraham on Fox News. Her tweet promoting this as a "cure" was immediately withdrawn by Twitter as "misleading". The 40 minute video interview with Zelenko, again on Fox News, was conducted not by a medical reporter, but by Rudy Giuliani. Zelenko goes on to make numerous huge dire public health predictions -- none of which a family practitioner has any business suggesting, especially in public on a national news outlet.
As always, consider the source of the information.
It's also very important to note that Zelenko was treating 700 unhospitalized patients; these were not cases severe enough to admit to a hospital. He treated them from his home (since he lost a lung to cancer years ago). So he never actually physically met with any of those 700 patients to monitor their progress.
In fact it's likely that many of these patients never tested positive, but simply self-reported as positive, further diluting the 'trial'.
And because 80% of positive COVID-19 cases are minor or even asymptomatic, the number of his patients that really _needed_ treatment falls from 700 down to, at most, 140 (20% of 700). That's a much smaller treatment effect that a large number like 700 would suggest.
It's also important to note that, apparently, Dr Zelenko treated sick people with medications that were NOT approved for the target disease. And he did so apparently without approval from any higher public health authority. In short, it appears that he experimented on his patients without authorization to do so from a public health or research authority.
Zelenko is a family medicine doctor, not a specialist in infectious disease or research. Thus it's very unlikely he wrote up an experimental design with proper safeguards, much less got it approved. With such poor experimental controls, it's impossible to interpret his results. What's more, if any of his patients later incur harm (like heart attacks from the chloroquine), such a laissez-faire approach to medicine will invite lawsuits galore.
No. Anecdotal evidence alone is NEVER enough.
Snopes has more details of side-effects etc: https://www.snopes.com/fact-check/zelenko-669-coronavirus-pa...
https://twitter.com/yishan/status/1244717172871409666
https://twitter.com/yishan/status/1245066858597761024
If true, this argues for giving HCQ immediately upon admission.
https://blogs.sciencemag.org/pipeline/archives/2020/03/31/co...
TL;DR: better than the French paper but that's a low, low bar