Coronavirus thread

[MickAK]

I'm of course familiar with the Wakefield scandal, but a retraction doesn't really reflect at all on the quality of the journal - more the character of the author. There is a degree of good faith that has to be assumed by the editors of any academic journal, because often there is no way to detect academic dishonesty on their behalf. Literally every well respected academic journal has retracted at least dozens, if not closer to hundreds, of articles over the course of their history (in the case of the Lancet, almost 200 years).

While not perfect, the Lancet remains a premier medical journal, and the authors of the study are medical faculty at premier medical schools. Their findings should be taken seriously.

The issue is not the retraction but their history of publishing shoddy work. I provided a source for that. They, of course, publish good work too. I don't think it's unreasonable to be skeptical of a medical journal that essentially started the modern anti-vaxxer movement.

As to how the study was conducted, it's pretty easy to understand. They describe their methods fairly succinctly. Per below:



They used a multinational, 3rd party database - the Surgical Outcomes Collaborative - to find inpatients around the world with COVID-19 and to examine their hospital stay to see what factors about the patient or the care they received predisposed them to morbidity or mortality.

They specifically had an eye for HCQ/azithromycin use and cardiac arrhythmias. They found that these drugs increased patient mortality and were associated with an increased rate of ventricular arrhythmia, a predictable consequence of inappropriately prescribing a drug that prolongs your QT interval.

The issue there is not the collection of data but the conclusions drawn by people who didn't author the study and the way it's being presented. The study only involved people that were hospitalized and treated within 48 hours. This of courses predisposes towards more severe cases and cases where a medicine that interferes with viral replication is already fighting a losing battle. The case fatality rate of the patients in the study was 11.1%. This is far higher than even the most liberal estimates of the CFR of COVID. This is a study of people predisposed to dying of this. Those people are also predisposed to HcQ complications. That was known and understood before the pandemic.

Your reply makes it clear you didn't really read or understand the article I linked.

I read it and I understand it just fine.

I don't know why you have such a strong belief that HCQ is an appropriate treatment for COVID-19, or what you do for a day job. However, it does seem quite clear that this belief is based in emotion and/or social/political identity and not in a nuanced understanding of the medical literature.

I have no idea if HcQ is useful as a prophylactic/early treatment or if they are useless fluff pills. A strong amount of anecdotal studies and trials suggest it is useful in that setting. When this was about flattening the curve and not overwhelming hospitals that was very hopeful, as even something with a slight effect of stopping people from developing to severe was a game changer. Additionally, Plaquenil is a safe and well understood medicine that is cheap and easily mass produced. The side effects and contra indications are well understood. It's an over the counter medication in many countries.

There is lots of room in medicine for debate, uncertainty, and disagreement. However, this conversation is underpinned by rational and lucid examination of the evidence in published literature. In the last two months, we have rapidly advanced our understanding of this disease and produced an astonishingly large body of knowledge in a short period of time. The lion's share of that evidence suggests that HCQ +/- azithromycin does not provide any benefit to patients with COVID-19, and more than likely predisposes them to worse outcomes.

All the evidence against it's usage as a prophylactic/early treatment is based on its use as a last ditch effort in severe/hospitalized cases. The only evidence that it would ever work in that setting was it killing SARS in vitro in 2005.

If you'd like to explain your position more carefully, using the findings presented in medical literature, I'm more than willing to listen. However, given that this doesn't seem to be within your wheelhouse, I'd instead suggest you keep a much more open mind on the subject and perhaps re-examine the reasons you believe so strongly in this drug.

I'm using the exact same study that you posted so I don't get the implication that I'm getting my information from PaTRIOt FoLK FREEDOM MEDICINE!!!
In that study it says:
Our study has several limitations. The association of decreased survival with hydroxychloroquine or chloroquine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured confounding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred.

Is this the kind of material or debate you would normally spend a lot of time thinking about prior to the pandemic? If not, why is this of sudden importance to you now?

I've been following it since the 2014 Ebola outbreak because that affected me personally and I got interested. I don't claim to be an expert, just an interested layman.

I trust and respect individual doctors. Medicine as a whole is incredibly untrustworthy. It kills more people than Covid every year and it's held to a lower standard of diagnosis than certified auto mechanics.

I don't know if HcQ will work and I'm not the person to ask. However, I can recognize when there's a narrative being pushed and I'm capable of looking at the data and seeing if it's horseshit. If someone who went to medical school tells me that it's actually Equine Fecal Matter for Fertilization I don't just step in it, because the experts have been dragging us through horseshit the entire pandemic.

Maybe it's helpful and maybe it isn't. Doing proper trials is going to be challenging because the disease is so mild in so many people. I don't see any reason not to continue those trials and I'm suspicious of the efforts to stop them.

[Nephrology]

The issue is not the retraction but their history of publishing shoddy work. I provided a source for that. They, of course, publish good work too. I don't think it's unreasonable to be skeptical of a medical journal that essentially started the modern anti-vaxxer movement.

The data in the paper that Andrew Wakefield published was falsified, and the Lancet retracted the article from print as soon as they learned. For the reasons I stated previously, this is not relevant to the quality of the HCQ article in question.

The issue there is not the collection of data but the conclusions drawn by people who didn't author the study and the way it's being presented. The study only involved people that were hospitalized and treated within 48 hours. This of courses predisposes towards more severe cases and cases where a medicine that interferes with viral replication is already fighting a losing battle. The case fatality rate of the patients in the study was 11.1%. This is far higher than even the most liberal estimates of the CFR of COVID. This is a study of people predisposed to dying of this. Those people are also predisposed to HcQ complications. That was known and understood before the pandemic.

Your point here is a little hard for me to follow - this study did not seek to define COVID-19 CFR -, but it sounds like you are suggesting that HCQ would provide a protective effect if given to patients with milder symptoms. That's not an unreasonable hypothesis.

However, I would also ask the question: why are you concerned about patients with mild to moderate symptoms? If they are are healthy enough to not require inpatient care and can recover at home, why are you treating them? (Hint: we don't make a habit of treating people who don't need treatment).

I will also repeat the fact that all things held equal (e.g. after controlling for variables such as patient comorbidity, age, disease severity, etc), patients who are taking HCQ are more than twice as likely to have a ventricular arrhythmia than patients not taking HCQ (hazard ratio). This is demonstrable, measurable iatrogenic harm, and needs to be taken very, very seriously. Remember : First, do no harm...

All the evidence against it's usage as a prophylactic/early treatment is based on its use as a last ditch effort in severe/hospitalized cases. The only evidence that it would ever work in that setting was it killing SARS in vitro in 2005.

I'm only able to find one, old paper that mentions HCQ and SARS-Cov-1. Everything else discusses SARS CoV2. My understanding is this argument was advanced by a French scientist in the early pandemic based on early in vitro work with SARS CoV2. If you have papers re: HCQ and SARS CoV 1 I would be curious to see them.

Our study has several limitations. The association of decreased survival with hydroxychloroquine or chloroquine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured confounding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred.

Of course their findings should be interpreted cautiously. This verbiage is appropriate boilerplate disclaimer for any large retrospective case cohort series. All studies of this kind should be interpreted cautiously due to their inherent limitations. This question is better answered with prospective randomized controlled trials, which are ongoing (our hospital is a site for ORCHID, a HCQ/COVID-19 trial).

A strong amount of anecdotal studies and trials suggest it is useful in that setting.

The plural of anecdote != data. As I stated before, we have learned a lot very quickly. There were early, poor quality studies that suggested a potential benefit which were followed by larger, higher quality studies (e.g. the one I linked) that have shown no benefit and the potential for harm.

If you want to argue this point, please provide me with appropriate references.

Additionally, Plaquenil is a safe and well understood medicine that is cheap and easily mass produced. The side effects and contra indications are well understood. It's an over the counter medication in many countries.

I keep addressing this argument and you continue to ignore my point. Drugs are not generically "safe" or "unsafe."

Tylenol is an over the counter medication that every one of us has taken and is perfectly safe when limited to <4g/day. However, if you give 50g/day to a patient with underlying alcoholic cirrhosis , you will quickly destroy what is left of their liver.

This is why it simply is not relevant that HCQ is an old drug or that it is safe in patients with RA. We aren't talking about treating RA - we are talking about COVID 19.

Per UpToDate, max daily dose of HCQ for rheumatoid disease is 400mg/day. Previously, we were giving all intubated patients loading doses of 800mg/day and 400mg qD after that.

The dose makes the poison.

I trust and respect individual doctors. Medicine as a whole is incredibly untrustworthy. It kills more people than Covid every year and it's held to a lower standard of diagnosis than certified auto mechanics.

There are lots of reasons to be skeptical of the medical-industrial complex and it is unfortunate that this is the attitude of the era. However, it is not true that it kills more people than COVID per year (the study that famously propogated this idea has been thoroughly disproven), and the vast majority of practicing physicians work really hard because they care about people.

It is also simply not true that we are held to lower standards then auto mechanics.

Auto mechanics do not go to school for 8 years and then complete another 3-8 years of supervised clinical training after that. Auto mechanics do not have their license to practice suspended and revoked for seeking treatment for depression or substance abuse - let alone for making a mistake of judgment on the job. Auto mechanics do not endure higher rates of substance abuse, suicide, depression and anxiety than their peers precisely because, in fact, they are held to higher standards than frankly any human could possibly meet.

I don't know if HcQ will work and I'm not the person to ask. However, I can recognize when there's a narrative being pushed and I'm capable of looking at the data and seeing if it's horseshit. If someone who went to medical school tells me that it's actually Equine Fecal Matter for Fertilization I don't just step in it, because the experts have been dragging us through horseshit the entire pandemic.

This is wrong. You are not capable of "looking at the data and seeing if it's horseshit." In fact this is something you have repeatedly proven in this post. The fact of the matter is, you have not advanced a coherent rebuttal to this paper nor persuasively demonstrated any flaws in its argument. I have spent a really absurd amount of my professional life reading, digesting, and debating biomedical literature. It is painfully obvious that this is not something you have much experience with.

You should not feel bad about this - this material is hard and, funny enough, it takes a lot of formal education to be able to really engage with it. In fact, this is the reason I am doing a PhD on top of my medical degree. Research is hard and you do not gain enough experience with it in medical school to make it a career of it.

Like I said, that's fine. I'm a pretty shitty engineer and a worse musician. We all have our strengths and weaknesses. I encourage you to reflect on this fact at length, and to accordingly temper the strength of your convictions in this arena with an appropriate degree of humility.

Maybe it's helpful and maybe it isn't. Doing proper trials is going to be challenging because the disease is so mild in so many people. I don't see any reason not to continue those trials and I'm suspicious of the efforts to stop them.

As a final point, this paper does not represent an effort "to stop [HCQ clinical trials." You are terribly mistaken to interpret it as such. It is one paper, of many papers, that will help us get a picture of the truth.

HCQ clinical trials are still actively ongoing - but again, as mentioned, we are not enrolling people with mild symptoms... because you don't treat people who don't need treatment (duh).

[Nephrology]

Also, just so we're clear, I have no blind allegiance to this paper, its authors or its conclusions. All studies have limitations, which is why we keep doing them. In fact, I'm in favor of the ongoing HCQ clinical trials. As mentioned, retrospective studies - where you answer a question based on historical observation - have inherent limitations.

The gold standard is a prospective, randomized clinical trial, in which you carefully define in advance the treatment, the changes expect to see and how they will be measured, the number and health status of patients in each treatment arm, etc. You examine the results while deliberately blinded to whether the data in front of you represents treatment or placebo and see what happens. This is what is ongoing on our campus and I am in support of it, given the degree of monitoring study patients tend to receive.

To demonstrate the limitations of retrospective trials, here is a big caveat underlined in the figure I posted a page or two back:



The red underlining is mine. To make a very long story short, this is significant because if you were to adjust for multiple testing, the degree of uncertainty for each hazard ratio would be much wider. This is because each time you ask a question statistically, there is a quantifiable chance that you will be right by mistake (e.g. You predict A will cause B because of C. You observe that A causes B and infer it is because of C, but it is actually because of X, which you have no knowledge of).

Because of this phenomenon, each time you ask a different question of a big population (does obesity make you more likely to die of COVID19? Hypertension? Sex? HCQ? etc), you contribute exponentially to the noise induced by random chance. This means that graph overstates the degree of uncertainty represented by the hazard ratios calculated for each variable.

This is a valid criticism of this article and a limitation that should be kept in mind when drawing conclusions from it. The authors openly acknowledge this in the figure legend. As has always been the case, despite its weaknesses, this study will inform and inspire further research of greater scope and quality in the months and years to follow, and together the medical community will get its arms around this disease. To do so will require circumspection, diligence, and the cooperation of experts from diverse places and fields. It will require the strength to say, "We don't know" and "We were wrong."

[Paul D]

I'm getting worried. Ever since the governor lifted stay at home and business restrictions on 5/16/20, the number of COVID positive patients in the hospital has doubled the max number in April. My wife's internal medicine office (which has a residency program) had 100 positive COVID nasal swabs today. The max was about 20. A colleague who I work with regularly in the hospital is now a patient in the hospital due to COVID-19 infection. He is a critical care doctor so he has the highest exposure risk. I'm probably getting paranoid because the number of daily positive tests in AZ is about 375 per 5000 tests. It was about 200 per 2000 tests last month. To me the future couple of months in AZ looks a dude standing next to the ATM compulsively grooming himself and nervously looking around.

[MickAK]

Your point here is a little hard for me to follow - this study did not seek to define COVID-19 CFR -, but it sounds like you are suggesting that HCQ would provide a protective effect if given to patients with milder symptoms. That's not an unreasonable hypothesis.

The CFR of the patients in the study shows that it's a sample of severe cases and the fact that they were hospitalized shows that the disease was advanced enough to require hospitalization at a time when hospital space is limited. Treatment began after hospitalization. I suppose that's useful for the long shot that HcQ could be helpful at that stage but that's not where the hope comes from.

However, I would also ask the question: why are you concerned about patients with mild to moderate symptoms? If they are are healthy enough to not require inpatient care and can recover at home, why are you treating them? (Hint: we don't make a habit of treating people who don't need treatment).

Yeah, you do, and with the exact same drug for malaria. There's a bunch of drugs used as prophylactics and when early symptoms manifest to stop them from becoming severe but you know that. I guess you just think I don't.

I will also repeat the fact that all things held equal (e.g. after controlling for variables such as patient comorbidity, age, disease severity, etc), patients who are taking HCQ are more than twice as likely to have a ventricular arrhythmia than patients not taking HCQ (hazard ratio). This is demonstrable, measurable iatrogenic harm, and needs to be taken very, very seriously. Remember : First, do no harm...

Yeah, agreed, but the people in the study are predisposed to complications like that so that's not really surprising. If the study was represented as 'Giving HcQ+Azithromycin to patients at risk of arrhythmia still bad idea even if they have severe COVID' that would make sense. Using it to say that HcQ is dangerous doesn't.

I'm only able to find one, old paper that mentions HCQ and SARS-Cov-1. Everything else discusses SARS CoV2. My understanding is this argument was advanced by a French scientist in the early pandemic based on early in vitro work with SARS CoV2. If you have papers re: HCQ and SARS CoV 1 I would be curious to see them.

Here you go. Chloroquine instead of HcQ of course.
https://virologyj.biomedcentral.com/...1743-422X-2-69
https://aac.asm.org/content/53/8/3416

The plural of anecdote != data. As I stated before, we have learned a lot very quickly. There were early, poor quality studies that suggested a potential benefit which were followed by larger, higher quality studies (e.g. the one I linked) that have shown no benefit and the potential for harm.

https://www.sciencedirect.com/scienc...77893920302179
The studies that show no benefit or increased harm are being done on severely Ill patients after hospitalization. There is no scientific basis to even start to think that would work.

This is why it simply is not relevant that HCQ is an old drug or that it is safe in patients with RA. We aren't talking about treating RA - we are talking about COVID 19.

Ok. So you're suggesting that COVID 19 interacts with HcQ somehow in a way that makes it dangerous. That's possible, but so far you have a lot less and worse data to show that than there is data that shows it has a beneficial effect on virus replication.

and the vast majority of practicing physicians work really hard because they care about people.

Heartily agree. Not sure where you thought I suggested otherwise.

You are not capable of "looking at the data and seeing if it's horseshit."

I sure am. In fact, the first time you posted a study saying HcQ had no effect I went and read the study and found it was only 30 people. 13 were treated with HcQ and recovered quickly and 14 were treated with Remdesivir and recovered quickly. There were any number of problems with the study. I found it odd you drew a conclusion so fast and with such poor data.

The fact of the matter is, you have not advanced a coherent rebuttal to this paper nor persuasively demonstrated any flaws in its argument.

That's probably because I don't have any issues with the paper other than the data looking funny. I have issues with false conclusions being drawn from it and a narrative being pushed that it doesn't support.

You should not feel bad about this - this material is hard and, funny enough, it takes a lot of formal education to be able to really engage with it.

I don't.

As a final point, this paper does not represent an effort "to stop [HCQ clinical trials." You are terribly mistaken to interpret it as such.

https://amp.theguardian.com/world/20...96JpmK&ampcf=1
https://www.forbes.com/sites/alexled...-lancet-study/

because you don't treat people who don't need treatment (duh).

Ok. You are confusing me with someone that either thinks they are an internet doctor or a rah rah everything that Trump says is right idolator. That's an easy mistake to make these days but you're wrong.
There are ways to determine whether the narrative of the day is organic, attempting to look organic, or being pushed. I am highly suspicious of anything I see getting pushed. I want to know the reason it's getting pushed.
This is getting pushed. Hard.

[Wise_A]

Last week, I tried to drop off a background check packet to a county agency, so as to get a job that does not make people say, "I'm sorry" when I tell them what I do. I was not allowed inside, and nobody was allowed to come in contact with me, because my body temperature was 99.3 degrees, and because the county has decided to block anyone with a temp over 99 degrees. The reading was conducted with some type of blocky thermometer, in contact with my forehead.

Doctors, am I:

(A) righteous in my indignation at such nonsensical security theater, or
(B) a fucking retard

[Wingate's Hairbrush]

Last week, I tried to drop off a background check packet to a county agency, so as to get a job that does not make people say, "I'm sorry" when I tell them what I do. I was not allowed inside, and nobody was allowed to come in contact with me, because my body temperature was 99.3 degrees, and because the county has decided to block anyone with a temp over 99 degrees. The reading was conducted with some type of blocky thermometer, in contact with my forehead.

Doctors, am I:

(A) righteous in my indignation at such nonsensical security theater, or
(B) a fucking retard

Where's the "C" option?

(Sorry, had to. I say "A". Not a medical professional.)

[MickAK]

13 were treated with HcQ and recovered quickly and 14 were treated with Remdesivir.

Not Remdesivir, a different retroviral.

[TQP]

Last week, I tried to drop off a background check packet to a county agency, so as to get a job that does not make people say, "I'm sorry" when I tell them what I do. I was not allowed inside, and nobody was allowed to come in contact with me, because my body temperature was 99.3 degrees, and because the county has decided to block anyone with a temp over 99 degrees. The reading was conducted with some type of blocky thermometer, in contact with my forehead.

Doctors, am I:

(A) righteous in my indignation at such nonsensical security theater, or
(B) a fucking retard

(Not a doctor)

I choose 'A'. First, under the CDC definition, you're not considered febrile below 100.4.

We're doing temp screenings ( employee and patient) with a non-contact thermometer. Ours says not to use it outside, or on anyone who has recently come in from outside. One day, when it was cold outside, I came to work and got a reading of 95.3. It also gives inconstant readings if it is too close, or too far away. We are confirming any high readings with an oral thermometer.

[TiroFijo]

Any comments on AstraZeneca promise to deliver a large number of doses of Oxford's vaccines by the end of the year (if it works)?

https://www.astrazeneca.com/content/...w-vaccine.html

It seems there is still quite a long way to determine if this vaccine actually works...