Intelligent Design

Many Doctors Weigh in: Hydroxychloroquine (HCQ), Zinc and Azithromycin Should be Greenlighted for COVID-19

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From this article:

It’s important to note that HCQ, zinc, and azithromycin are very well understood drugs with clear safety profiles; they are widely available, generic, inexpensive, and can be scaled rapidly, including to the developing world…

Our primary strategic objective must be to prevent ICU overwhelm, which on our current course is imminent in most states. It is an axiom of infectious diseases that treatment in earlier stages is more effective than treating advanced stages. Early COVID-19 treatment is more likely to prevent disease progression to critical status, radically lowering hospitalizations and CFR than inaction.

Current clinical drug trials are mostly focused on treating late stages of disease, when immunologic damage is a dominant threat. We believe that trials should focus on earlier stage infection to prevent progression to advanced disease.

Some health authorities have given the typical caution against early treatment until large, peer-reviewed, randomized controlled trials (RCTs) provide conclusive data. We fully support the continued effort to investigate existing and novel pharmaceuticals to determine the best intervention through blinded and controlled trials. Weighing the urgency of this unprecedented situation combined with the effects of inaction, plus the relative safety of the drugs, and the preponderance of data showing effective early treatment significantly decreases the percentage of cases that progress to needing hospitalization, we believe that the proposed recommendation is not only adequately founded but ethically obligate[d]…

Early clinical reports suggest it’s best to treat within 5 days of symptom onset. Waiting until a patient is hospitalized or critically ill is unwarranted and unwise.

68 Replies to “Many Doctors Weigh in: Hydroxychloroquine (HCQ), Zinc and Azithromycin Should be Greenlighted for COVID-19

  1. 1
    polistra says:

    Overwhelm is NOT imminent in most states. Look at the facts.

  2. 2
    PaV says:

    There is a study from either 2003 or 2008, published in medical journal that concluded that hydroxychloroquine is an effective treatment and prophylactic for corona viruses. Why did Dr. Fauci not know this? Why is he talking about “anecdotal” evidence. As usual, government “servants” are, for the most part, incompetent.

  3. 3
    jerry says:

    There is a study just starting at McGill on quercetin and COVID19.

    The MedCtam videos have studies on Coronavirus and chloroquine and zinc from past years.

    From what I understand most hospitals are seeing much fewer patients and some are laying off medical personnel. The overwhelming is happening in certain areas.

  4. 4
    ET says:

    The facts say that sheltering in place is working. That sheltering in place has averted the overwhelming of hospitals.

  5. 5
    ET says:

    I am taking quercetin and zinc. Have always taken vitamin D- not so much in the summer, though. I make my own vitamin D during the summer. Just started taking liposomal vitamin C. Supposed to be more readily absorbed than regular C.

  6. 6
    rhampton7 says:

    Caution:

    A Brazilian study testing the antimalarial drug chloroquine for COVID-19 had to be stopped early in one group of patients taking a high dose of the drug, after some patients in this group developed dangerous heart rhythm problems.

  7. 7
    rhampton7 says:

    Caution

    From a preprint of a large multinational collaboration presenting data obtained from health care systems (claims data or electronic medical records) in Germany, Japan, Netherlands, Spain, UK, and the USA.

    T he paper concludes that short-term HCQ monotherapy does appear to be safe, but notes that long-term HCQ dosing is indeed tied to increased cardiovascular mortality.

    The trouble comes in with the azithromycin combination. Like many antibiotics (although not amoxicillin), AZM is in fact tied to QT prolongation in some patients, so what happens when it’s given along with HCQ, which has the same problem?

    Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment.

  8. 8
  9. 9
    Jim Thibodeau says:

    You know how the right wingers have said the media is overhyping the pandemic? Trump has a new campaign ad that attacks the media for minimizing the risk. How long before we’ve always been at war with Eastasia?

    https://www.motherjones.com/kevin-drum/2020/04/trump-blasts-fox-news-in-new-video-1/

  10. 10
    jerry says:

    Trump has a new campaign ad that attacks the media

    Did you look at or read the link you gave? It says the opposite of what your comment said. You are making the case for Trump with this link.

  11. 11
    ET says:

    In March CNN’s Anderson Cooper and their resident Dr. Gupta downplayed the virus. So yes, the media did downplay the risk. Now the media is in overhype.

  12. 12
    ET says:

    Did the Brazilians pair it with zinc? If not then they did it wrong.

  13. 13
    ET says:

    Why were they given a high dose? What is the dosage the rest of the world is using and why isn’t that good enough for Brazil?

  14. 14
    jerry says:

    A study from Brazil didn’t see the same success

    You failed to cite that it was. those receiving extremely high doses that died.

  15. 15
    ET says:

    The Brazilians need to watch medcram update #34

  16. 16
    rhampton7 says:

    Cardiovascular complications should be considered when hydroxychloroquine and azithromycin are used to treat patients with coronavirus disease 2019 (COVID-19), according to new guidance jointly published by the American Heart Association (AHA), the American College of Cardiology (ACC) and the Heart Rhythm Society (HRS).

    The full guidance, titled “Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment” can be found here. https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047521

  17. 17
    rhampton7 says:

    This is also now showing up in US hospital data reported to the CDC: Many of the sickest Covid-19 patients also have underlying medical conditions. Seventy-eight percent of all people put into intensive care for Covid-19 in the US have had an underlying condition like diabetes or heart disease: 32 percent had diabetes, 29 percent had heart disease, 21 percent had chronic lung disease, and 9 percent had compromised immune systems.

  18. 18
    Ed George says:

    Jerry,

    I didn’t cite anything other than the article.

  19. 19
    jerry says:

    Here is a Twitter link to a medical study at McGill university. There are about 20 references to the value of quercetin for virus protection and medication. There is also information on zinc. Hard to make out how valid this. thread is but there are lots of references to medical studies and medical sites. Open up the thread in case it is not fully opened.

    https://twitter.com/HighPeaks77/status/1249505664398954497

  20. 20
    jerry says:

    I didn’t cite anything other than the article.

    Yes, you did. You said it didn’t have the same success. You failed to cite relevant information on why it wasn’t successful.

  21. 21
    kairosfocus says:

    Folks, i/l/o the map by Raoult et al, kindly examine here. KF

  22. 22
    rhampton7 says:

    In Bridgeport Hospital, virtually every patient in the intensive care unit has been given hydroxychloroquine, which is normally used to treat lupus, an auto-immune disease, as well as arthritis and malaria, said Dr. Zane Saul, chief of infectious disease there.

    “We’re collecting data, so we don’t have any clear data,” Saul said. “I don’t think anyone does. We’ll know later in the year when all the data comes in. For the most part people are able to tolerate it. It does cause nausea and diarrhea.”

    Saul said that, sometimes, patients can remain on the drug for only limited amounts of time.

    “This is by no means a benign drug, but we felt good enough to give it to people who are a little sicker,” Saul said. “Everybody in the ICU is on it because they are the sickest of the sick.” Patients with histories of heart problems are kept away from it.

  23. 23
    rhampton7 says:

    UAB infectious disease doctor and recovering COVID-19 patient Dr. Michael Saag said Monday that the authors of the French study had to retract some of their initial conclusions, and only six patients took both drugs in the original study, making it hard to draw any conclusions about effectiveness. Worse, new concerns have emerged about potentially fatal side effects with the drug combination, side effects Saag said he did not know to watch for when taking the drugs.

    “In retrospect, now that I’ve survived and I’m doing better, I’m a little bit unhappy with myself only because we’ve now learned that that combination of hydroxychloroquine and azithromycin can lead to EKG abnormalities that can lead to fatal arrhythmia, and I wasn’t being monitored, so I was being a little cavalier and I think what we should do is do this under controlled studies.”

  24. 24
    Seversky says:

    Small chloroquine study stopped after irregular heart beats detected in subjects

    A small Brazilian study on the effects of the anti-malaria drug chloroquine, which is similar to the drug that President Trump has touted as a possible “game changer” in treating the coronavirus, was abruptly halted because some patients taking high doses developed irregular heart rates generating “safety hazards.”

    The findings were revealed in a study funded by the Brazilian state of Amazonas and published on Saturday in medRxiv, an online server for medical articles, The New York Times first reported.

    Chloroquine is similar to hydroxychloroquine, the drug Trump has repeatedly touted. Health experts have insisted that not enough is known about either drug to determine its efficacy in combating COVID-19.

    The Brazilian study included 81 hospitalized patients, with about half being given a 450 milligram dose of chloroquine twice on the first day of the study followed by one daily 450 milligram dose for four more days.

    The other participants were prescribed a dose of 600 milligrams twice daily for 10 days.

    Patients taking higher doses experienced heart arrhythmias, or improper beating of the heart, within three days, according to the study. Eleven patients died by the sixth day of treatment and caused the research on high-dosages to end.

    “Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards,” the study’s abstract said. “Such results forced us to prematurely halt patient recruitment to this arm.”

    We still need to be cautious and wait for stronger data.

  25. 25
    jerry says:

    By the way the dose of chloroquine in the Brazilian study was 1200 mg per day for 10 days for the high group. This is about 6 times as much of the Hydroxychloroquine Dr. Zelenko gave his patients. He gave 400 mg for 5 days. I assume the mg dosage is equivalent but do not know this. Maybe someone knows.

    The latest I have seen from Zelenko is two deaths, 6 hospitalizations, 4 intubations all extubated and no side effects except nausea and diarrhea.

  26. 26
    Seversky says:

    Jim Thibodeau @ 9

    You know how the right wingers have said the media is overhyping the pandemic? Trump has a new campaign ad that attacks the media for minimizing the risk. How long before we’ve always been at war with Eastasia?

    [Donald Trump, Titanic captain]

    1. There is no iceberg
    2. We won’t hit the iceberg
    3. We barely touched the iceberg
    4. Nobody could’ve seen the iceberg
    5. These deaths mean my plan worked
    6. I’m the best captain ever

  27. 27
    Jim Thibodeau says:

    7 I couldn’t possibly have dealt with the iceberg because I was being court-martialed for that other stuff I did.

  28. 28
    ET says:

    The President listened to his expert who said, on February 29, people should go on with their normal lives. And in March CNN’s doctor said the flu is more to worry about than covid 19. But the tarded left will blame the President, even though his actions have saved lives. The left would never have banned travel to China. The left never would have banned travel to Europe. With the left at the helm the USA would be in the midst of the worst case model predictions.

    So again, seversky is either high or extremely stupid

  29. 29
    ET says:

    Apparently the Brazilians are so dense they thought moar was betta.

  30. 30
    ET says:

    Anyone using any form of chloroquine without zinc, is a moron. Any doctor unaware of what zinc can do to viruses, is ignorant and shouldn’t be trying to help.

  31. 31
    Ed George says:

    Jerry

    Yes, you did. You said it didn’t have the same success. You failed to cite relevant information on why it wasn’t successful.

    Every study is different. All I did was provide a link to a study that had different results than some others. If you want to assign some nefarious motivation to my comment and link, that is your problem, not mine.

  32. 32
    rhampton7 says:

    “Chloroquine and hydroxychloroquine were both reviewed by the FAA Federal Air Surgeon when they entered the market and have long been considered generally incompatible for those performing safety related aviation duties,” the agency said in an emailed statement.

    Hydroxychloroquine can be taken by pilots in low doses for treatment of arthritis, according to the FAA. Generally, though, pilots who have taken the drugs aren’t permitted to fly within 48 hours.

    Because it’s currently impossible to know the doses needed to prevent infection — a use of the drugs that’s not approved — the FAA can’t perform a risk assessment. The known risks include heart disturbances and hypoglycemia, according to the agency.

  33. 33
    ET says:

    I wonder if the FAA assessed pilots ability to fly while in the grip of covid-19? I would think the FAA would want the pilots to be A) alive and B) healthy, regardless of how that came to be. Heart disturbances at doses no one is recommending shouldn’t even be discussed.

  34. 34
    rhampton7 says:

    After scrutinizing all of the evidence, the Infectious Diseases Society of America could not recommend hydroxychloroquine with or without azithromycin or any other experimental therapy for COVID-19 outside of a clinical trial.

    The reason: The data are just not there that the drugs are safe and effective alternatives to supportive care.

    In the case of hydroxychloroquine and azithromycin, the panel was concerned about the potential effects on the heart. The combination can cause QT prolongation, and patients must be monitored, which can be difficult especially in an outpatient setting, Dr. Bhimraj explained.

    The panel made seven recommendations for consideration among hospitalized patients with COVID-19:

    1. Recommends hydroxychloroquine/chloroquine in the context of a clinical trial.
    2. Recommends hydroxychloroquine/chloroquine plus azithromycin in the context of a clinical trial.
    3. Recommends the HIV combination lopinavir-ritonavir in the context of a clinical trial.
    4. Suggests against the use of corticosteroids for people with COVID-19 pneumonia (low body of evidence).
    5. Recommends using corticosteroids for people with acute respiratory distress syndrome due to COVID-19.
    6. Recommends the rheumatology drug tocilizumab (Actemra, Genentech), only in the context of a clinical trial.
    7. Recommends convalescent plasma in the context of a clinical trial.

  35. 35
    jerry says:

    All I did was provide a link to a study that had different results than some others

    You failed to point out that the study was not similar to other studies and not comparable. It is something you should have done so that people would know it didn’t represent what else was being done. RHampton did the same thing.

    If you want to assign some nefarious motivation to my comment and link, that is your problem, not mine.

    I didn’t assign any motivation to what you did. I just pointed out you misrepresented what you said. I have no idea why you posted the original link and why then misrepresented what you had posted.

  36. 36
    jerry says:

    the Infectious Diseases Society of America could not recommend hydroxychloroquine with or without azithromycin or any other experimental therapy for COVID-19 outside of a clinical trial.

    What treatment did they recommend? Was this treatment they recommended deemed effective? If there is no other treatment is this tantamount to sentencing some people to death? If not, why not?

  37. 37
    Ed George says:

    Jerry

    You failed to point out that the study was not similar to other studies and not comparable.

    None of the studies is comparable. That is the problem.

  38. 38
    ET says:

    No mention of zinc by the IDS. They can’t be that dense.

  39. 39
    ET says:

    None of the studies is comparable.

    Ed doesn’t know that.

  40. 40
    kairosfocus says:

    Folks, again, look here; where of course the map in my OP here from Prof Raoult speaks for itself on what the verdict on HCQ is in many significant countries, including Brazil, the US. Russia, India, China, Italy and South Korea. Instapundit is interesting, in:cluding this comment:

    Narniaman • 3 days ago

    As most know, the media/Democrat politicians/FDA want the use of the hydroxychloroquine/azithromycin/zinc combination to be restricted until late in the course of the infection, when the patient’s infection is well-advanced.

    As a physician, this baffles me.

    I can’t think of a single infectious condition — bacterial, fungal, or viral — where the best medical treatment is to delay the use of a anti-bacterial, anti-fungal, or anti-viral until the infection is far advanced.

    It would be interesting to see a cogent answer. KF

  41. 41
    kairosfocus says:

    PS: My first linked begins:

    Immediate Treatment for Early Stage SARS-CoV-2 Infections Recommended To Be Supported Nationally Starting Now
    A strategic principle and practical approach to rapid response to novel pandemics

    Authored by Ben Kaplan Singer, M.D.; Daniel Stickler, M.D.; Avery J. Knapp Jr., M.D.; with many contributing doctors.

    BOTTOM LINE: Our primary strategic objective must be to prevent ICU overwhelm, which on our current course is imminent in most states. It is an axiom of infectious diseases that treatment in earlier stages is more effective than treating advanced stages. Early COVID-19 treatment is more likely to prevent disease progression to critical status, radically lowering hospitalizations and CFR than inaction. Current clinical drug trials are mostly focused on treating late stages of disease, when immunologic damage is a dominant threat. We believe that trials should focus on earlier stage infection to prevent progression to advanced disease. Given the suggestion of efficacy of hydroxychloroquine (HCQ), and the imperative to treat disease before it progresses to cytokine storm, we believe that the current data are sufficient to recommend FDA provisional approval for early outpatient treatment of COVID-19 with HCQ plus zinc and azithromycin. This triple combination treatment can be modified where needed in patients with prolonged QTc or other contraindications at the physicians’ discretion Following this same rationale, we recommend that other clinical trials involving drugs that have already been approved for non-COVID-19 diseases, and for which the safety profile is well understood and reasonably acceptable, should begin clinical trials on patients in early stages of COVID-19 disease, alongside patients with more advanced disease.

  42. 42
    kairosfocus says:

    F/N: A reminder for those who need to clarify the timeline on crisis management: https://uncommondescent.com/medicine/tracking-covid-19-apr-3-are-we-peaking-for-this-wave/#comment-697652 KF

  43. 43
    jerry says:

    None of the studies is comparable. That is the problem.

    Probably could be said about anything in life.

    But three times the daily dosage as Zelenko, who claims near 100% success, seems like it should be pointed out. And also for twice as long. It leaves a false impression which was not warranted. Especially when some of the doctors using see a distinct change for the better within 12 hours.

  44. 44
    Seversky says:

    What verification do we have for Zelenko’s claims at this time?

  45. 45
    jerry says:

    What verification do we have for Zelenko’s claims at this time?

    The New York Times verified his results. By the “dog barking in the night” verification process. They did a hit piece on him but said nothing about his results being invalid. Can you imagine if his results were misrepresented that the Times would not have reported it.

  46. 46
    jerry says:

    BA77 sent several links to articles on the virus in a science journal. I read the first one on the history of CQ and HCQ and it is also a brief history of malaria and how these drugs might work. Gets very technical at end but first part is fascinating history.

    https://inference-review.com/report/antimalarial-drugs-as-covid-19-therapy

  47. 47
    kairosfocus says:

    Jerry, the key person is Didier Raoult. KF

  48. 48
    jerry says:

    Jerry, the key person is Didier Raoult

    He certainly is getting the most press. What is interesting is that the polarization going on for treating this disease mirrors the debate on politics. It also seems to mirror the debate on evolution. I have always emphasized the most fascinating thing about the evolution debate is human behavior towards it. It has nothing to do with science or reason or logic. It is all emotional.

    It seems this same human behavior shows up in lots of areas and the debate over HCQ and CQ is just another canary in the mine to the inner soul of individuals.

    I come here not to debate evolution anymore since it is so obvious what is known and not known. But I find that the pro ID people provide the best insights into science in general and I have learned more about the virus through links here than anywhere else. Which I said, I find interesting as a general assessment of human behavior. All this means is that there seems to be some broad underlying world view which determines how one reacts to facts. Which I said is the most fascinating part of these debates.

    I prefer Zelenko since his protocol is simple, logical, backed by science and extremely inexpensive. But the knives are out for Raoult by the obvious people which says to me he must be onto something.

    PS – most of the objectors come from the left of the political spectrum. They fail to recognize that the Jacobins turned on Robespierre and sent him to the guilotine. They should look up the Montagnards and Girondins. Eventually the left always turns on its own and destroys them.

  49. 49
    Bob O'H says:

    I prefer Zelenko since his protocol is simple, logical, backed by science and extremely inexpensive.

    What science? Does he have scientific trials to back up his claims?

  50. 50
    Truthfreedom says:

    @49 Bob O’H

    Does he have scientific trials to back up his claims?

    Did Darwin have any scientific trial to back up his claim that ‘natural’ selection has designing capabilities? How can you scientifically test such an abstract concept? Because fairy-tales (I can imagine this process went this way blah blah blah add some fairy dust…) ARE NOT science.

  51. 51
    ET says:

    It’s funny seeing evos, who obviously don’t care about science, talk of scientific trials.

  52. 52
    jerry says:

    What science? Does he have scientific trials to back up his claims

    You are making a fundamental mistake. Science and scientific trials are not the same thing.

    As someone just pointed out Darwinian processes are not science. There can never be a scientific trial to prove Darwin’s ideas. And you know it!!!!!

  53. 53
    jerry says:

    It’s funny seeing evos, who obviously don’t care about science, talk of scientific trials.

    Bob O’H believes in ID. Have you ever seen him present an argument that undermines it?

  54. 54
    kairosfocus says:

    Jerry & BO’H:

    trials, in both science [including med] and statistics are subject to ethical controls; that automatically means, there’s more than one way to skin a catfish. In this context, I already put up the control on Raoult’s work, per Google Translate: “Research protocol approved by the ANSM and the Île-de-France CPP in progress at the IHU Méditerranée Infection: Treatment of respiratory infections with Coronavirus SARS-Cov2 by hydroxychloroquine Acronym: SARS-CoV2quine”.

    As BO’H knows or knows he should know, there are other results on the ground.

    Ideologically loaded selective hyperskepticism and no true Sassenach in the face of a fast moving pandemic where 1 1/2 weeks can be time from onset to demise, with demise effectively irreversible in too many cases once cytokine storm fully sets in, cannot be justified ethically.

    Not when such trials are announced in terms like: “NIH scientists said urgent clinical evidence is needed. Even so, the study is not estimated to be completed until July 2021. ” In vitro studies showed broad chemical effectiveness since 2005, as published. Case investigations and other studies have shown a growing pattern of evidence of effectiveness.

    We are dealing with known quantity drugs, and as BA77 linked earlier today,

    “the FDA has recently given emergency approval to what had long been a common off-use application for treatment of viral infections. This approval was granted in light of a long history of using CQ and HCQ as antiviral drugs, including during past coronavirus epidemics. Furthermore, informal reports coming from emergency and critical care clinics indicate they are effective against COVID-19, particularly when combined with antiviral agents and antibiotics.”

    In short, there is evidently a track record here, reflected in clinical results. Which, is what Prof Raoult and Dr Zelenko have further put on the table.

    Where, the case study method is a longstanding, recognised method of investigation AND per phil of sci, despite the school “method,” there is no one size fits all and only conventionally labelled sciences.

    Moreover, logic and epistemology are actually aspects of core philosophy, so, yes, worldviews issues and ideology are pivotal. This point is of course directly relevant to longstanding major issues at UD and to the ongoing civilisational, cultural civil war. Which, in the USA, is at low end 4th gen civil war level.

    KF

  55. 55
    rhampton7 says:

    Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base

    https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30172-7/fulltext

    Fourth, the search for effective new drugs requires appropriate and valid trials—ie, prospective, randomised, placebo-controlled clinical studies. Although many drugs have in-vitro activity against the virus, the proposal that such drugs might provide more benefit than harm is inappropriate in the face of no clinical evidence supporting efficacy and safety in patients with COVID-19. International multicentre studies, such as the Discovery study (NCT04315948) and the Solidarity study (EudraCT Number 2020-000982-18), will randomise patients with COVID-19 to receive different antiviral drugs, including hydroxychloroquine, in an adaptive study design. These initiatives will provide important data to guide the management of patients with COVID-19 and help to improve understanding of the effects of antiviral therapies in critically ill patients.

  56. 56
    Bob O'H says:

    OK, so no trial results yet. In vitro results don’t support treatment straight away – humans are not Petri dishes, and it’s axiomatic in drug development that most drugs that show promise in vitro or even in animals won’t be clinically effective – there are just too may other variables involved. That’s why we have clinical trials – to test that they are effective, and to work out what dose to use (the Brazilian study that had to stop showed that their high dose was too high, for example).

    By not doing proper trials, Raoult is helping to delay the possible deployment of HCQ. And if it’s ineffective, he’s helping to extend the use of an ineffective and possibly dangerous treatment.

  57. 57
    kairosfocus says:

    BO’H:

    OK, so no trial results yet

    Why are you still in denial of the fact of multiple, global in vivo trials? And notice, again, this regarding Professor Raoult’s work, per Google Translate . . . and as again appears at 54 above:

    Research protocol approved by the ANSM and the Île-de-France CPP in progress at the IHU Méditerranée Infection: Treatment of respiratory infections with Coronavirus SARS-Cov2 by hydroxychloroquine Acronym: SARS-CoV2quine.”

    I suggest to you that it is thus manifestly improper for you to dismiss Professor Raoult’s work as not being “proper trials.”

    You are in the position of demanding a type of study that as the NIH reports, at best will deliver results a year from now (similar to the likely outcome on vaccines, though local news just had Cuba claiming to have an oral/nasal delivery vaccine in trials).

    The real-world, non Ivory Tower strategic and ethical decision problem here is, we have a disease capable of killing 100’s of thousands to tens of millions over the next several months. And, double-blind, placebo control studies will necessarily expose a significant fraction of patients to a disease capable of killing and/or of — emerging — major organ damage — within 2 weeks or less [much less] of onset. Such poses double ethical dilemmas in the face of the equivalent of a world war.

    In that context, we have a natural contrast of types of treatments and outcomes, with literally thousands of professionally recorded cases showing a strong pattern of clearing viruses in about 5 – 7 days, with some cases taking more than that. Significant numbers of patients report impact within 24 hours, consistent with the 4th power law on fluid flow with constrictions, i.e. relatively small changes in cross section have significant impact.

    In this context, it is unsurprising that, as Raoult further reports, there is a global wave of [emergency use] approvals, including that India has specifically approved for prophylaxis.

    All of this has been headlined here at UD with source-links, so there is no good reason for you to have written as above, in a way that is all too reminiscent of the “there’s no evidence . . .” claim we have seen so often over the years here. A claim, that exposes selective hyperskepticism, a fallacy that ill-advisedly tries to promote targetted skepticism as a virtue in place of prudence.

    Where, too, I again point out the Inference Review article BA77 brought to our attention yesterday:

    Antimalarial Drugs as COVID-19 Therapy

    J. Scott Turner

    J. Scott Turner is Professor of Biology at the State University of New York College of Environmental Science and Forestry, and a Fellow of the Stellenbosch Institute for Advanced Study.

    Section
    Special Reports

    Published
    April 10, 2020

    Chloroquine (CQ) and hydroxychloroquine (HCQ) are showing promise as therapeutic treatments for COVID-19 infections. These drugs are widely used for the treatment of malaria, and their use against COVID-19 was a source of some controversy in the early stages of the current pandemic. Nevertheless, the FDA has recently given emergency approval to what had long been a common off-[label] use application for treatment of viral infections. This approval was granted in light of a long history of using CQ and HCQ as antiviral drugs, including during past coronavirus epidemics. Furthermore, informal reports [–> in fact, see Raoult et al, as well as studies across the world, it is not just Zelenko et al] coming from emergency and critical care clinics indicate they are effective against COVID-19, particularly when combined with antiviral agents and antibiotics.”

    Those informal reports are increasingly backed by Raoult’s work and other studies.

    The fundamental challenge is to strike the balance of adequate warrant to base responsible action in the face of a global pandemic with life and health on the line. That forces us to balance accessible degree of empirical warrant with urgency, given the quasi infinite value of life on the line.

    In that context, fair comment: it is ill-advised or worse to suggest in the teeth of evidence on the table that “OK, so no trial results yet . . . ”

    KF

  58. 58
    Bob O'H says:

    kf @ 57 –

    Why are you still in denial of the fact of multiple, global in vivo trials?

    Huh? When have I denied that trials are taking place?

    I suggest to you that it is thus manifestly improper for you to dismiss Professor Raoult’s work as not being “proper trials.”

    I can dismiss it because I have the expertise to understand the problems with his work – no control groups, no randomisation (for example).

    And, double-blind, placebo control studies will necessarily expose a significant fraction of patients to a disease capable of killing and/or of — emerging — major organ damage — within 2 weeks or less [much less] of onset. Such poses double ethical dilemmas in the face of the equivalent of a world war.

    I agree. So everyone should be trying to reduce the time to get enough results. This means doing the studies rigorously, so we can be confident we are not going to kill patients by giving them ineffective treatments.

    Those informal reports are increasingly backed by Raoult’s work and other studies.

    What other studies? I know there’s a small one from China from a few weeks ago that suggested an effect in mild cases, but even the document in the OP says “According to ClinicalTrials.gov, there are 47 CQ/HCQ & COVID-19 trials with only 1 complete and results not yet published. There are two small RCTs from China available in pre-publication.”

  59. 59
    kairosfocus says:

    BO’H: you know just what you wrote and just who it was meant to dismiss directly [Zelenko et al] and indirectly [Raoult et al]. I quote you from 56 above, again: “OK, so no trial results yet.” KF

    PS: You also know that informed opinion is studies on the grand scale you envision would come in at best a year from now. Too late for the pandemic we deal with. You also continue to duck the summary certificate on Raoult’s study, now at the 2500 level. And more.

  60. 60
    Truthfreedom says:

    @58 BobO’H

    so we can be confident we are not going to kill patients by giving them ineffective treatments.

    Where in ‘nature’ is it written that we shall not kill? Is killing objectively wrong?

  61. 61
    kairosfocus says:

    BO’H, and in the face of a fast acting killer plague, what is a sugar pill, again? As in “an i ____ t___. ” See what dismissing evidence in hand leads to? KF

  62. 62
    jerry says:

    Because no sick patients were refused treatment as a control, an inhuman action by any standard, critics argue that the results were worthless. Those critics are in fact people who do not have the coronavirus. The truth is that the entire infected world of people who were not given this drug were the control. Their lengthy recovery times are the data.

    Hydroxychloroquine is a pleiotropic drug, a fancy way of saying it works in many mysterious ways. One primary action is that it increases the pH of lysosomes inside cells from around 4 to 6. This inhibits acidic proteases and decreases intracellular processing, glycosylation, and protein secretions. In antigen-presenting cells, this leads to a decrease in inflammatory activities. Perhaps more importantly, in other cells infected with the coronavirus, this leads to a decrease in viral loads.

    Hydroxychloroquine also binds to specific zinc transporters, or zinc ionophores, and keeps them open. If excess zinc is available, this presumably lets more zinc enter the cell. Zinc appears to alter the membrane permeability of lysosomes,7 but it has another important function. It can block the unique RNA-dependent RNA polymerase (RdRP) of the coronavirus.8 Although the literature calls hydroxychloroquine itself an ionophore, it only binds to the real zinc ionophores in the cell. This term is at best awkward and at worst misapplied.

    There is a lot more.

    From one of the inference references posted: https://inference-review.com/report/therapeutic-options-for-covid-19

  63. 63
    bornagain77 says:

    I wonder if Bob O’H will volunteer for the following randomised controlled trial?

    Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials
    Excerpt: We were unable to identify any randomised controlled trials of parachute intervention.
    Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
    https://www.bmj.com/content/327/7429/1459

  64. 64
    jerry says:

    Hey, there has be a controlled double blind test done in China.

    Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial

    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 31) compared with the control group (54.8%, 17 of 31). 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.

    Reactions to HCQ – one patient developed a rash and one patient experienced a headache when they compared CT changes seen on day six as compared to day zero

    https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3

    Let’s here if from the nitpickers. They are in the comments section which I am sure our nitpickers will reinforce.

  65. 65
    kairosfocus says:

    Jerry, they object to size. It seems a 100,000 trial is now starting up. Wec await the new objections. KF

  66. 66
    Bob O'H says:

    kf @ 59 –

    You also know that informed opinion is studies on the grand scale you envision would come in at best a year from now.

    Err, no, the UK’s trial, which is just starting, is saying they expect results by June.

    You also continue to duck the summary certificate on Raoult’s study, now at the 2500 level.

    The summary certificate doesn’t mitigate the glaringly obvious methodological problems with the “study”.

  67. 67
    Bob O'H says:

    Jerry @ 64 – as kf notes, the problem is size. We’d need larger sample sizes to be sure the patterns aren’t just noise. They also only accepted patients who had a mild case, i.e. the patients who are less likely to die. What I take from this study is that it’s worth doing larger studies.

  68. 68
    Ernst Reim says:

    To break a lance for Bob O’H and in reply to the “parachute” trial:

    bornagain77 wrote:
    “I wonder if Bob O’H will volunteer for the following randomised controlled trial?
    Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials”

    Non randomized/blinded trial **can** have conclusions, if the effect size is big enough:
    We know from a long history of clinical trials that
    – The placebo effect: It is real and can effect the outcome with up to 30%. I. e., some patients in a trial **always** get better, just because they believe on being treated. Thus a non-blinded trial on the patient side **always** yields slightly better results than standard of care.
    – Evaluation bias: Humans **want** to see a positive effect. Thus if the evaluator is not blinded towards whether the patient was dosed, the results are always slightly better.
    – Selection bias: If the researcher decides which patients to include and which to exclude in his results (as Raoul did) we **know** that he will unconsciously bias the results, even if he tries to be objective.

    All these three points are unimportant in a “parachute study” with a large effect size. If we chuck two people out of an airplane and both of them survive, we can conclude that parachutes are effective, because there is a really big difference between 100% survival and the 0% survival which is reported from standard care (= no parachute). In such a trial, a control group without parachute would be unethical, since we know that these patients would die.

    However if two people wearing parachutes cross a street and survive, we cannot conclude that parachute are effective against traffic accidents, since 9999 out of 10 000 people survive crossing streets. To see such small effects, we need blinded, randomized trials of big groups. It is not unethical to not provide a parachute, since we do not know if a parachute actually helps. It might even increase the risk (begin bulky and such).

    Clincal trials on terminal cancer patients are airplane-parachute studies and done without any control group. COVID-19 is a street-crossing parachute study.

    Look at Raoult’s reported results: only 10 out of 2500 people treated died. That’s 0.4% and looks good compared to the 3% we see floating around. However, the real mortality rate is **not** known. It is likely to be around 1%, but might be 0.1%. Or 5%. Add to this, that his 0.4% where affected by the placebo effect. And add to this that Raoult selected which patients to include in the study. I cannot stress enough how **useless** this makes this study. We know, for example, that mortality rate is higher in social classes with less income (for a variety of reasons). Thus simply the effect that you might have to pay to receive the treatment, that patients drove from outside the area to participate or other factors would induce a selection bias which would be easily large enough to explain his results.

    Even statistical error makes this difficult to distinguish from the 1%.

    All this does not mean that HCQ does not work. And do not forget: doctors **are** authorized to use it. We just do not **know** right now if it works. And we know that Dr. Raoult knows all this and decided to do it anyway. And for that reason I call him a quack.

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