back to article Remember that clinical trial, promoted by President Trump, of a possible COVID-19 cure? So, so, so many questions...

A research paper, championed by President Donald Trump, that suggested hydroxychloroquine and azithromycin could effectively treat COVID-19 coronavirus victims is flawed, scientists fear. As world leaders face mounting pressure to contain the novel coronavirus, and hospitals are overwhelmed with patients needing beds and …

  1. Still Water

    44 is way too small to have any power in a clinical trial - exactly the reason why large scale trials are needed. In this case - the RECOVERY trial at Oxford University is a prime example of how to do scientific research like this properly.

    1. Anonymous Coward
      Unhappy

      Donald Jenius Trump

      44 is way too small to have any power in a clinical trial - exactly the reason why large scale trials are needed. In this case - the RECOVERY trial at Oxford University is a prime example of how to do scientific research like this properly.

      Small trials are essential precursors to large trials. Large scale clinical trials are very expensive and time consuming - the trial you mention has initial funding of nearly £11 million. But there are thousands of potential treatments, some possibly effective, some not.

      You need to screen these first with much smaller, limited trials to separate the potential wheat from the obvious chaff. You must also supply ample evidence of the safety and likely efficacy in the trial approvals process before you start injecting hundreds of patients with the stuff as part of the large trial, and you don't get that without doing smaller trials.

      The real problem starts when the idiot President announces that a drug combination has "a real chance to be one of the biggest game changers in the history of medicine" and suggests they should be immediately put into large scale use based on very flimsy evidence.

      1. Anonymous Coward
        Anonymous Coward

        Re: Donald Jenius Trump

        You miss the point. 44 is still too small for a small scale trial. I am at the point where whenever I see a media report of a study I stop reading or listening once the sample size is smaller than a few hundred. In this case it is even more deficient given the number of patients that recover with little no treatment. 44 patients, ok divide it by 2 and get two control groups of 22. Two samples of less than 30 no useful statistical inference can be drawn from each or between each. Useless study and even more useless reporting.

        The fact is no useful statistical inference can be drawn from a sample size that small.

        It is at best dangerous to report otherwise as we see with that couple from Arizona.

        There is not even a need to look at he design of the study or the other points made in this article. Once the sample size is that small just dismiss it all as garbage.

        1. doublelayer Silver badge

          Re: Donald Jenius Trump

          I mostly agree with you, but the couple in Arizona don't prove anything one way or another. They read a short thing online and found something that had a similar name before ingesting it. That is almost certain to end badly. If I write a message that says "I've found that potassium-rich foods are nutritious and generally taste nice", and someone goes out and puts potassium cyanide on their food, that's not my fault nor does it make what I said incorrect. Even if what I said was incorrect, it doesn't make me responsible for their doing something extremely dangerous.

          1. asdf

            Re: Donald Jenius Trump

            >Even if what I said was incorrect, it doesn't make me responsible for their doing something extremely dangerous.

            As Joe Shmoe poster a few dozen people see mayble. When you are the POTUS and your words are potentially seen by billions (translated anyway) there is a very high bar for using words carefully. He never should have said anything about those drugs period unless he was dead sure they are a game changer. His political fortunes should be pretty far down the list of his priorities at the moment, much as he wants this to disappear tomorrow like us all.

            1. Anonymous Coward
              Anonymous Coward

              Re: Donald Jenius Trump

              Ah the concept of balance between power and responsibility, in the western world I think only Spiderman commits to it.

          2. Charlie Clark Silver badge

            Re: Donald Jenius Trump

            The FDA expressly forbids the kind of remark that Trump made for precisely the reason that some idiot might follow it: remember in the USA unlimited liability. If he was anyone else he'd be looking at a massive fine and possibly even jail time + potential class action cases.

            1. Pete!

              Re: Donald Jenius Trump

              Is he immune ?

              (from FDA action i mean, not from CV19)

              1. Vincent Ballard

                Re: Donald Jenius Trump

                If you look at statements made and actions taken or not taken around last year's impeachment proceedings, he believes that he's immune, and since he's the boss of the Justice Department it does too. He's also the boss of the FDA. Once he leaves office, on the other hand, who knows?

              2. Anonymous Coward
                Anonymous Coward

                Re: Is he immune ?

                "It's not illegal when the President does it ...."

            2. Michael Wojcik Silver badge

              Re: Donald Jenius Trump

              The FDA expressly forbids the kind of remark that Trump made

              "forbids" how? The FDA are not the speech police. Perhaps within the scope of their regulatory authority they can prohibit or penalize certain types of statements - for example, claims by companies regarding their products. But the FDA couldn't prohibit me from making public statements about medications, regardless of how stupid or dangerous. They can't shut down the antivaxxer idiots.

              If he was anyone else he'd be looking at a massive fine and possibly even jail time + potential class action cases.

              Complete nonsense. Let's see you cite a single case in which an individual in the US received a "massive fine" or "jail time" solely for making misleading statements regarding medical treatment. As for class action - good luck with that, particularly after Bristol-Meyer Squibb Co. v. Superior Court of California, and considering that there's little incentive for lawyers to go through the expense of organizing a class action when the defendant is an individual, unless that individual has very deep pockets indeed and the case is strong.

              1. Anonymous Coward
                Anonymous Coward

                Re: Donald Jenius Trump

                I would suggest folks type "SARS-Cov chloroquine 2009" or similar into the search engine of choice and read the literature on the subject. Surf around and discover how totally fucking ignorant you are.

                Ignorance is curable

          3. gzuckier

            Re: Donald Jenius Trump

            Except that potassium rich foods are nutritious and do generally taste nice, so there's an upside to the statement.

            Chloroquine being toxic and there being no real evidence for its efficacy in this case, Trump's statement was more like stating that cyanide rich foods are nutritious and generally taste nice, and somebody reading that going out and putting potassium cyanide on their food. Most people would at least consider there being some responsibility (or irresponsibility) on the part of the poster.

        2. Ian Johnston Silver badge

          Re: Donald Jenius Trump

          The fact is no useful statistical inference can be drawn from a sample size that small.

          It is at best dangerous to report otherwise as we see with that couple from Arizona.

          You're happy to draw a statistical inference from a sample size of two?

          1. John Brown (no body) Silver badge

            Re: Donald Jenius Trump

            To be fair, the sample size in that case was not relevant. They ingested a non-medical of unknown dose substance because it had a name that sounded a bit like what the President had suggested might be a cure.

            1. Pete!

              Re: Donald Jenius Trump

              possibly you are posting from US? I think the sample size of two thing was irony.

          2. Clunking Fist

            Re: Donald Jenius Trump

            "You're happy to draw a statistical inference from a sample size of two?"

            Actually, it could be argued to be a population size of 330M Americans,only 2 ingested (that we know of).

            Or perhaps 142,000 confirmed US positives, only 2 ingested?

        3. This post has been deleted by its author

        4. Anonymous Coward
          Happy

          Re: Donald Jenius Trump

          There is not even a need to look at he design of the study or the other points made in this article. Once the sample size is that small just dismiss it all as garbage.

          Doesn't the meaningful sample size depend on the effect size? The bigger the effect, the smaller the sample needed to see it.

          e.g. Imagine there was a condition with no effective treatment but 0.1% of people with it recovered naturally within a week. If 12 people with it were split between 6 receiving a newly invented treatment and the other six no treatment, and the study reported that all the people who had the treatment got better in a week (and that none of the others did), then the probability that the treatment did nothing and the result was obtained solely by chance would be 0.001^6 = 0.000000000000000001.

          Even with a smaller effect, the results can be meaningful. If there was a 20% chance that people got better in a week without doing anything, the probability of the treatment group all recovering with the week would be 0.2^6 = 0.000064. i.e. if you repeated the study 15,600 times you would expect see this good a result just once if it was just by chance.

          Unless there was something fishy about how the study was done, or the participants selected, then both results would demand further investigation.

          A large clinical study for the treatment of a common illness is not about getting gross statistics, it is about getting fine detail. A small study cannot be representative of the demographics of the people with the illness if it is common - perhaps the treatment doesn't work on some group - maybe it isn't effective on females under 30 for example. That could be many thousands of people, who might not even be represented in a small study. Perhaps it is only really effective on females under 30. You would want to know that too. Small studies also have a low probability of finding out about even quite common side effects. e.g. even if as many as one person in thirty suffers serious side effects from the treatment, then there would be an 82% chance that the experimental group of 6 didn't contain one of those people.

          1. Glenturret Single Malt

            Re: Donald Jenius Trump

            Your probability calculations are correct but only if the individuals in the samples are all identical. Any such sample has to take account of other human variables such as age, sex, height and weight, general state of health etc. etc, which means that the sample has to be significantly larger in order to be meaningful.

          2. CAPS LOCK

            It's no good trying to explain medical statistics to muggles...

            ...it's a dark art...

          3. Anonymous Coward
            Anonymous Coward

            Re: Donald Jenius Trump

            Correct and yet so wrong.

            The sample size depends on a lot of things. And a sample size that is appropriate for one study may not be appropriate for another. Yeah, you are correct on this

            But the rest of your analysis is so wrong and highlights the difference between a anecdotal analysis and a true scientific statistical analysis. Scientific analysis is based on and employs statistical methods that ascribe Statistical Significance to various outcomes.

            The point I was trying to make in my original post and which was lost is that a sample size of 22 is useless. This is where you are wrong. There is not useful statistics from sample size less than 30. n must be greater then or equal to 30.

            This does not mean a sample of 30 is appropriate. It just means that the statistics derived from a sample of less than 30 is useless. They cant be used to perform any type of variance analysis or to measure statistical significance.

            This is where you are wrong. You could perform a study with 12 people in two control groups but the finding would be ANECDOTAL because there is no statistics on which you can base the conclusions.

            The key term is STATISTICAL SIGNIFICANCE.

            1. Anonymous Coward
              Happy

              Re: Donald Jenius Trump

              This is where you are wrong. You could perform a study with 12 people in two control groups but the finding would be ANECDOTAL because there is no statistics on which you can base the conclusions.

              The key term is STATISTICAL SIGNIFICANCE.

              A statistically significant result is conventionally one in which the probability of obtaining it by pure chance is less than 0.05, i.e. less than one in 20. Sometimes people use other values, like 0.01 or 0.001, particularly as 0.05 is popular mostly because of history. By now you will have noticed how I sneakily rigged my examples so that both probabilities were << 0.0001, and so statistically highly significant.

              In statistics-speak this probability is called the p-value, formally something like "the probability, if the null hypothesis was true, of obtaining a result at least as extreme as that actually observed". I avoided trying to explain p-values, null hypotheses, type I (and II) errors and all the other tedious jargon in my little example. I also invented a study so simple that it produced solely categorical data as pulling something that you might use to see if the means of two samples were from the same statistical population, like an unpaired t-test, out of my arse would only confuse, and possibly open up arguments with some smart aleck about e.g. data normality and whether a Mann-Whitney test should have been used instead. Statistical results from categorical data are just as valid as from numerical data.

              I appreciate that you intuitively feel that a small sample size can never produce a meaningful result, but the mathematics says that it most definitely can if the effect is large enough.

              1. Anonymous Coward
                Anonymous Coward

                Re: Donald Jenius Trump

                And the question you must answer is.

                "What is the minimum sample size on which a P-Value can be calculated." Do the same for all the other statistics and statistical methods you mentioned. Thats the point you are missing. It is 30. Not that a 30 point sample would be useful for a medical trial but all these statistics have a minimum number of observation against which they can be used. That is the point I am making and that was my original point.

                Again a 44 observation sample is useless when you divide it by two to get a control group none of the nice sexy statistics you mention can be used with the study because the sample size is too small for the statistics to be calculated.

                1. Anonymous Coward
                  Megaphone

                  Re: Donald Jenius Trump

                  And the question you must answer is.

                  "What is the minimum sample size on which a P-Value can be calculated." Do the same for all the other statistics and statistical methods you mentioned....

                  Again a 44 observation sample is useless when you divide it by two to get a control group none of the nice sexy statistics you mention can be used with the study because the sample size is too small for the statistics to be calculated.

                  A p-value relates to a particular result, so you don't have a "minimum sample size" that it can be calculated for. It can be calculated for any sample size, and you need an actual result to calculate it from, so your question is meaningless.

                  Also, I am not your slave, so I am not going to run around like a headless chicken at your bidding. If you want to examine how sample sizes affect alpha, the threshold probability for null hypothesis rejection, in trials involving these "nice sexy statistics", which are of course completely bog standard and taught in most experimental science undergraduate courses, then I suggest you visit e.g. https://www.sample-size.net/ and do it yourself.

        5. Anonymous Coward
          Anonymous Coward

          "44 is still too small for a small scale trial"

          There is no absolute minimum to the size of a trial, the required N depends on a lot of things and is usually calculated before the trial. In some settings N = 10 could be enough. In other settings N = 10000 is not enough.

      2. Marshalltown

        Re: Donald Jenius Trump

        It isn't just the sample size. The idea that they would try a combination of antimalarial and an antibacterial is bizarre. Malaria is essentially a blood born parasite that essentially destroys your red blood cells. Sickle cell anemia is an evolutionary adaptation that protects the (heterozygous) carrier by shortening the life of thier red blood cells, interrupting the reproductive cycle of the parasite. And antibacterials help against bacteria. COVID is a virus. It is not a bacterium or a plasmodium. There was essentially not a snow ball's chance in Hades that such a cocktail would do anything useful, though it might help protect you from a bacterial secondary infection - and malaria. It would do nothing to a virus.

        1. Anonymous Coward
          Anonymous Coward

          Re: Donald Jenius Trump

          You need to read a few medical journals to increase you knowledge. The treatment was a blind stab in the dark, it was designed for very specific known reasons.

          Your general statements about antibacterials and anti-malaria is correct. But understanding why they work for their original purpose PLUS the attack vectors of the covid19 virus affords the opportunity for novel use protocols of the drugs for a wholly different purpose than the original.

          This is not even remotely contentious or even slightly unusual.

          Your conclusion is wrong because you are wholly ignorant of but a few of the factors involved.

          Not stupid, just ignorant (in the classic sense, unknowing)

        2. Anonymous Coward
          Alien

          Re: Donald Jenius Trump

          There was essentially not a snow ball's chance in Hades that such a cocktail would do anything useful, though it might help protect you from a bacterial secondary infection - and malaria. It would do nothing to a virus.

          The paper explains why the study used these drugs:

          "Hydroxychloroquine (an analogue of chloroquine) has been demonstrated to have an anti-SARS-CoV activity in vitro [12]."1

          "Azithromycin has been shown to be active in vitro against Zika and Ebola viruses [20], [21], [22] and to prevent severe respiratory tract infections when administrated to patients suffering viral infection"1

          Whether or not these, or other drugs, are actually worthwhile treatments in practice is of course an open question. The RECOVERY trial is itself evaluating hydroxychloroquine, amongst others, as a potential treatment.2

          1https://www.sciencedirect.com/science/article/pii/S0924857920300996

          2 https://www.recoverytrial.net/

        3. sniperpaddy

          Re: Donald Jenius Trump

          That's a hell of a limited statement. A little knowledge is a dangerous thing !

          The logic of the cocktail was to reduce the inflammatory immune response.

          Chloroquines:

          The most likely reason is that because chloroquines can be used to treat rheumathoid arthritis and lupus (autoimmune diseases). It is possible that it reduces the inflammation response to cov-2 that causes the acute respiratory distress (fluid in alveol;i)

          Azithromycin:

          Azithromycin appears to be effective in the treatment of COPD through its suppression of inflammatory processes and potentially useful in asthma and sinusitis via this mechanism. It is believed to produce its effects through suppressing certain immune responses that may contribute to inflammation of the airways.

        4. Richard Parkin

          Antibiotics can treat malaria

          Not entirely true that antibiotics don’t kill trypanosomes. Doxycycline is used to treat malaria because it kills a bacterium that the trypanosome foolishly rely on for their digestion ;-).

        5. gzuckier

          Re: Donald Jenius Trump

          There is in vitro evidence that quinine derivatives interfere with viral reproduction, and a suggested mechanism involving pH of lysosomes and post-translation protein modification or some such.

          But that's not terribly specific, it's pretty much the old anti-cancer trick of finding some poison that hopefully kills off the bad cells before killing off the patient.

      3. gzuckier

        Re: Donald Jenius Trump

        Not a "trial", just anecdotal evidence that provides a promising hint.

        But this doesn't even meet that hurdle. Some folks got chloroquine, some didn't, there wasn't any difference in the folks who were severely sick, the folks who weren't too sick and got chloroquine got better, but nobody who wasn't too sick didn't get chloroquine so there's no reason to think that they would have done worse without the drug. They were, after all, not too sick

      4. bombastic bob Silver badge
        Thumb Down

        Re: Donald Jenius Trump

        I bet your opinion would be OPPOSITE if someone like OBAKA had said it was a cure...

        this certainly would NOT pass the "shoe on the other foot" test.

        1. Intractable Potsherd

          Re: Donald Jenius Trump

          Obama (correct spelling, for future reference) wouldn't have said anything so fucking stupid.

      5. Jaybus

        Re: Donald Jenius Trump

        "The real problem starts when the idiot President announces....."

        No. The real problem starts when researchers conspire with publishers for their own gain.

    2. StargateSg7

      The Clinical trial being talked about here is taking place in North Vancouver, British Columbia, Canada at the Lynn Valley Care Facility where sick elderly patients are being put through controlled care regimens of the anti-Malaria drugs. This care centre is almost completely filled with active symptom Coronavirus patients.

      Right now, it's the ONLY place in the world where this small scale trial is being done on such drugs using appropriate medical controls to determine the safety and effectiveness of the drugs. The current regimens of using anti-Malarial and anti-Ebola drugs were ALL recently pioneered at UBC (University of British Columbia) and the results and latest pharmaceutical regimens are now being seeded across the world! The French doctors this was sent to pioneered other regimens based upon this research. Not bad for a bunch of rainy West Coast B.C. hicks! Canada saves the world yet again!

      China has already done HOSPITAL runs in another study within Wuhan and Weibei using direct injections of Vitamin-C into the bloodstream with SOME success at alleviating Coronavirus symptoms in ACUTE care patients. This study by Chinese and American researchers is more for reducing the bacterial lung-infection symptoms than for actively curing the virus itself. Evidently, direct injection of 1000 mg (or more!) of Vitamin-C and from 25-to-50 micrograms of Vitamin-D (studies using 60 micrograms to 150 micrograms of Vitamin-D were found to be getting a little too close to the toxic limits - aka hypercalemia / hypervitaminosis). This regimen seems to have a VERY REAL EFFECT on reducing bacterial lung infection symptoms!

      d

    3. bombastic bob Silver badge
      Meh

      I don't anyone doubts the need for proper trials. however, you also have to consider how many physicians are now trying this out on their own, and some (in New York City, specifically) have been indicating that they have promising results of having done so. Anecdotal evidence is NOT a clinical trial , but it IS evidence, and should be considered when making the choice between getting that particular medicine, or dying (so yeah only the sickets patients would be given something that is 'experimental').

      For most people, of course, they won't need it.

      Keep in mind that clinical trials can take YEARS and as such, won't be very helpful *RIGHT* *NOW*.

      1. StargateSg7

        The trial at the Lynn Valley Care Centre anti-malarial + ebola drugs + others is the FIRST CONTROLLED ENVIRONMENT TRIAL (i.e. with blind / control subjects!) because almost everyone in there has Corona. The French studies are more real-time in less controlled environments.

        The difference between the two approaches is that the French doctors WANT something for RIGHT NOW, while the Canadian trial is for anticipating a CURATIVE REGIMEN for a huge number of acute patients that are expected in a coming SECOND WAVE of Corona infections which is anticipated to come again in starting this November, December, January. There are multiple labs in Canada being ramped up for ACUTE CARE pharmaceutical production which will include the anti-malarials but the first batches won't be ready until September 2020.

        The Canadian study at Lynn Valley is NOT focused on a vaccine but rather a curative regimen, while the French doctors are focusing on everything else including BOTH immediate RIGHT NOW curative therapies AND vaccine-oriented preventative therapies in uncontrolled (i.e. in-the-city hospitals) environments.

        China's earlier research is helping on the BACTERIAL SIDE, and ALMOST EVERYONE SHOULD buy and orally intake 1000 milligrams of Vitamin-C and up to 50 micrograms of Vitamin-D per day in order to obtain a simple preventative benefit that allows your body to better resist or fight off a bacterial infection.

        It won't cure anything BUT it will give your body enough of a fighting chance that it could be the difference between YOU having a home-based recovery with relative mild-to-low-moderate symptoms OR ending up in emergency care on a respirator! For the $15 US for a 30 day box of 1000 milligrams of Emergen-C packets and Vitamin-D Tablets, I can live with that sort of investment if it gives my body even 20% better resistant against a bacterial infection. That 20% extra help MAY BE ENOUGH to keep me out of the hospital!

        With Coronavirus, it is the SECONDARY BACTERIAL lung infections that kill you! If you can keep it to a mild upper-throat-like infection, you will likely make it through! AND that extra Vitamin-C and Vitamin-D just might be enough to KEEP ANY INFECTION to just your upper throat area and OUT OF the bronchia and/or lungs!

        d

        1. quxinot

          Bob, is that you?

          1. Alistair

            No, its his nephew or perhaps the result of a long alcohol soaked meeting between Bob and aMfM.

            1. Intractable Potsherd

              Re: Bob and AMfM: Mind-bleach NOW!!

      2. gzuckier

        ethics

        There is a real huge ethical problem here, obviously; if a doctor really believes a drug is effective, it is unethical to withhold it from the control population. If a doctor doesn't believe a drug is good for what ails a patient, it is unethical to give it to a patient just as a test (Dr. Mengele anyone?) particularly when it is toxic as chloroquine is, and also if it means the patient is not given other treatments which may be effective.

        That's why clinical trials are a Big Deal not tossed together by every doctor who thinks he's got a Miracle Cure.

  2. Anonymous Coward
    Boffin

    I know a couple things about clinical trials.

    And if chloroquine was REALLY the cure-all that people keep hoping it is, the current trials would have been ended early with a declaration of victory and a clearance for medical personnel around the world to start using it widely against the coronavirus. Considering that this hasn't happened, it is much more likely that chloroquine is useful for patients at some stages of the disease, but not others, or that it is somewhat useful against coronavirus infection, or it is not that useful at all.

    I certainly hope for positive news from the various chloroquine trials going on, but for now, I would not encourage people to go out of their way to get or use the drug.

    1. adam 40
      Big Brother

      Re: I know a couple things about clinical trials.

      The Chinese (small scale) trials have not yet been published and we won't see the results for 4 months now.

      Follow the links through https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.01047/_article

      I suspect and have heard anecdotally that the trials we curtailed on ethical grounds for not withholding treatment from the control group. But maybe not - this is China after all.

      See the death rate in China now compared with the number of people in ICU - it's tiny, and has been for many weeks now.

      Belgium started using chloroquine 5-ish days ago, and Netherlands doesn't. Two neighbouring countries, similar demographics and ethnicities.

      Compare "Outcome of Cases (Recovery or Death) in Belgium" graph here:

      https://www.worldometers.info/coronavirus/country/belgium/

      with the same graph for NL:

      https://www.worldometers.info/coronavirus/country/netherlands/

      Stark, isn't it?

      UK still doesn't use it (in ICU anyway) - look at our graph.

      The time for clinical trials is over. And we should have the stock somewhere in the UK because:

      https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/868061/medicines_that_cannot_be_parallel_exported_from_the_UK_26_feb_2020.csv/preview

      List of medicines that cannot be parallel exported from the UK. Updated 25 February 2020 ... Chloroquine phosphate.

      1. Anonymous Coward
        Anonymous Coward

        Re: I know a couple things about clinical trials.

        You were doing so well up to "chloroquine phosphate". Now read the last sentences of the article.

        1. adam 40

          Re: I know a couple things about clinical trials.

          The couple took one teaspoon each of fish tank Chloroquine phosphate, I calculated around 6000mg each if it was pure, not counting other contaminants. As a comparison, standard antimalarial dose is 250mg once every 3 days.

          Just because someone takes an overdose of something does not negate any beneficial effects at a "Normal" dose.

          Oh and the words "Chloroquine phosphate" come from quoting the UK government website, look at the site address, .gov.uk.

        2. Ian Johnston Silver badge

          Re: I know a couple things about clinical trials.

          You were doing so well up to "chloroquine phosphate". Now read the last sentences of the article.

          Are you aware the chloroquine phosphate is the normal anti-malarial drug (it's the active ingredient in Boots' own-brand anti-malarial) although the hydrochloride and sulfate are also used? You didn't fall into the trap of thinking that chloroquine phosphate is a different drug, did you?

      2. Anonymous Coward
        Anonymous Coward

        hydroxychloroquine vs Chloroquine

        The Chinese paper, is NCT04261517 no? Which suggests using Hydroxychloroquine in place of chloroquine and concludes it has a more 'tolerable safer profile'.

        i.e. this one:

        https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa237/5801998

        "Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients."

        ************

        Chloroquine use against Coronavirus is not new:

        https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa237/5801998

        This is its use against MERS Corona virus from 2018:

        "Chloroquine inhibited MERS-CoV replication and blocked infection at an early step with an EC50 of 3 µM and a CC50 of 58 µM (Table 2; Figure 5(4)) [34]. "

        ***********

        So, I did the Googling thing, and I admit I had my doubts already about your comment because your claim of Belgium vs Netherlands would have required a magic cure. i.e. Belgium people given Chloroquine 5 days ago, hoping out of bed and declared healthy! Which made no sense.

        Sure enough that does not fit:

        Netherlands lists chloroquine and hydroxychloroquine in their 20th March document. Belgium lists it in the March 19th Version 4 of their document.

        The reason Holland has 100% death rate is because they're not declaring patients recovered till a longer recovery period. And the trough/peak in Belgiums recovery rate stems from the low initial death numbers, 1 death, nothing, nothing, 3 deaths,

        **************

        Netherlands:

        https://swab.nl/nl/covid-19

        "** Duration of treatment: 5 days chloroquine and 5 days hydroxychloroquine. Remdesivir treatment time is 10 days. Optimal duration is unknown and can be prolonged based on clinical condition, occurrence of side effects, and / or virus clearance. It is currently unclear whether a dose reduction should be performed in severe renal impairment. In NL there are now two flows, versus versus halving the dose after charging."

        Belgium:

        https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf

        *********

        China death rate is flattening out at 4.21%. I was hoping for 3.4% or less. Shit.

        https://www.worldometers.info/coronavirus/country/china/

        1. adam 40

          Re: hydroxychloroquine vs Chloroquine

          Thanks for the link to the nl site although it seems quite old article:published_time" content="2020-03-03T15:51:00+01:00 I hadn't actually seen any announcement that NL had started using it in ICU, but if they are so much the better. If you can post up more timely references that would be of great interest.

          I know the posted data is very sparse and unreliable - for example the UK was posting only 20 patients in ICU for days on end, then updated to a new (but still too low) figure of 163, which is also static. How can we have 260 dead and only 163 in serious condition? The stats are obviously wrong somewhere.

          There are several Chinese papers evaluating different treatment regimes with various combinations, accessible from that link.

          Yes the Chinese figures are almost fully resolved at near 4.2%, at least until the next wave of outbreak starts when they relax controls a little too much..... But that does include a big wodge of deaths upfront before they worked out the best treatments.

          My reason for posting isn't really about Chloroquine per se, I'm more concerned that the UK is not promoting such treatments - at least for the general populace. So - let's go back to the In Vivo study that is the passage of Covid-19 through the UK population, and publish the results in a year or two.

        2. gzuckier

          Re: hydroxychloroquine vs Chloroquine

          Yes, but... given that the proposed mechanism of action of these drugs against malaria has little or nothing to do with the mechanism against the virus, which in vitro is proposed as a general disruption of cellular protein processing, the stated assumption that "Hydroxychloroquine shares the same mechanism of action as chloroquine" is inappropriate. In fact, the better safety profile of hydroxychloroquine may well be due to lesser disruption of protein processing which would also mean lower efficacy versus the virus.

    2. MarkSitkowski

      Re: I know a couple things about clinical trials.

      Researchers here, in Australia, have conducted in vitro tests of chloroquine , and found that it kills the virus dead. Perhaps it's the in vivo delivery method that returns the unpredictable results?

      Also, researchers in Poland (Warsaw University?) have isolated the enzyme the virus generates to activate itself, and are pursuing ways to stop it creating this enzyme.

      The truth is out there...

      1. ibchristian
        Boffin

        Re: I know a couple things about clinical trials.

        ... ffs, have a gin and tonic (not that diet crap) and relax... just sayin'... I just returned from a visit to Thailand to celebrate our 5th anniversary and am now required by my employer (municipality) to "quarantine in place" for 14 days... lovely! I get to have lunch at home and oh by the way, I have no symptoms, feel fine in spite of all of the opportunities for exposure but have to say that my wife and I stayed only at the resort and took all PRACTICAL precautions... as I live in Arizona this is our pollen and flu season... people freaking out about "sniffles" and such need to stop watching "panic television" and assess their symptoms compared to normal seasonal symptoms... but there's no profit in that is there...?

        Saying this because I can, and other local business owners (including a local grocery store owner) agree with this take on things...

  3. IGotOut Silver badge

    There was the other bit in the statement....

    "The FDA has moved mountains - Thank You!"

    The FDA response?

    WTF? We haven't approved the drugs for use against Covid19

    1. Anonymous Coward
      Anonymous Coward

      Re: There was the other bit in the statement....

      It's difficult to comprehend if you're the smartest person around (according to personal disclaimer) and you and you have no clue what you're talking about...

      IRL FDA does not do any research. Never did. The only thing FDA does is review applications compiled by others and green light it if they think it's OK. And for an indication extension on an existing, already approved NDA the work is minimal. But then again, I'm sure some added stable genius effort here has helped...

      1. fishman

        Re: There was the other bit in the statement....

        "IRL FDA does not do any research."

        My wife is a biologist for the FDA. She and her coworkers do research - and have written quite a few papers on their work.

        1. This post has been deleted by its author

        2. Anonymous Coward
          Anonymous Coward

          Re: There was the other bit in the statement....

          Define research... I'm not in any way implying the research she has done is not valuable, but I doubt she came up with and developed any kind of therapy (come up with a molecule, go from IND to NDA). Don't get me wrong, the people at FDA do a very valuable and important job, but their JD does not include coming up with and developing new therapies, whether classed as NDAs, 510k, PMA, DeNovo or what ever. Their job is to review, regulate, and control. And my remark was meant in that context.

  4. Sorry that handle is already taken. Silver badge

    That's a very diplomatic way of saying "scam"

  5. Anonymous Coward
    Anonymous Coward

    The most important statement in the whole article.

    "Don’t believe anything that the President says..."

    1. Mark 85

      Re: The most important statement in the whole article.

      Well, he keeps reminding everyone that he is the world's smartest person.... which leads me to reference allegedly by P.T. Barnum about a sucker being born every minute for those following medical advice from Trump.

      1. BebopWeBop

        Re: The most important statement in the whole article.

        It reminds me of a joke I was told the other day

        Plane with 5 passengers on board, Donald Trump, Boris Johnson, Angela Merkel, The Pope and a ten year old school boy. The plane is about to crash and there are only 4 parachutes.

        Trump said “I need one. I’m the smartest man in the USA and am needed to sort out the problems of the World!’, takes one and jumps.

        Boris said ‘I’m needed to sort out Britain’. He takes one and jumps.

        The Pope said ‘I need one as the world needs the Catholic Church.’ He takes one and jumps.

        Angela said to the ten year old: "You can have the last parachute. I've lived my life, yours is only just starting."

        The 10 year old replied: "Don’t worry, there are 2 parachutes left, the smartest man in the USA took my school bag."

        1. Martin an gof Silver badge

          Re: The most important statement in the whole article.

          It reminds me of a joke I was told the other day

          I'm sure variants of that joke have been around for years, but I heard it most recently on the Today programme's Thought for the Day, given on the 17th of March by Anne Atkins.

          Her variant had a Nobel-winning professor, an old clergyman and a boy scout. It was otherwise similar, with the professor taking the "Trump" role, the clergyman taking the Merkel role and a boy scout with a rucksack taking the role of the schoolboy with schoolbag. Some TftDs are better than others, and Anne Atkins is not one of my favourites (to say the least) but this time she was particularly moving - if you have the time, listen to the end.

          M.

        2. JPeasmould

          Re: The most important statement in the whole article.

          I seem to remember a variation of that joke from school, and I'm 59. Then it was a "Scotsman, Englishman and Irishman" joke.

          1. M. Poolman

            Re: The most important statement in the whole article.

            The version I remember (from the early '90s?) had a backpacker, the Dali Lama and Bull Gates in the plane.

      2. Alan Brown Silver badge

        Re: The most important statement in the whole article.

        "reference allegedly by P.T. Barnum "

        Don't take medical advice from someone who looked directly at a solar eclipse.

    2. Dan 55 Silver badge

      Re: The most important statement in the whole article.

      Shame they have to find out the hard way that Emperor Trump is stark bollock naked. If only critical thinking was as contagious as the virus.

      1. Alan Brown Silver badge

        Re: The most important statement in the whole article.

        "Shame they have to find out the hard way that Emperor Trump is stark bollock naked."

        Oh, they already knew. The REAL ending of that story is that the kid was killed on the spot by the palace guard and the crowd.

        1. Richard 12 Silver badge

          Re: The most important statement in the whole article.

          I thought it ended with the entire kingdom discovering the joys of naturism?

        2. Andy Tunnah

          Re: The most important statement in the whole article.

          Not only do they not care that he's naked, they're envious of it, as they wish they got to be naked too.

          Trump supporters don't care what he says or does. They're on his "side" because they view this as a very simple thing - a culture war. And he's their guy. Doesn't matter what else happens, at the end of the day he's attacking "them", and as long as he keeps on their side, he can't do no wrong.

      2. the Jim bloke
        Facepalm

        Re: The most important statement in the whole article.

        I did not need that image.

        The important thing to remember, is that the president is an arsehole and he tells lies.

        Its tragic, but thats where the USA is today.

      3. fajensen
        Flame

        Re: The most important statement in the whole article.

        Trump is all what America has allowed itself to become, purified and distilled into one person, so - they are basically fucked!

    3. Robert Carnegie Silver badge

      Re: The most important statement in the whole article.

      I do not believe that President Trump knows how to "cite" a scientific paper. Putting an exclamation mark after the word "Fact" does not constitute citation.

      1. paulll

        Re: The most important statement in the whole article.

        Maybe it's the waving of the (very small) finger that makes it factual? (Swear to gawd I'd tear that thing right off and shove it etc, etc.)

  6. Dyspeptic Curmudgeon

    The most important statement in the whole article.

    -And because of that, whatever happened in France *must* be wrong and discarded.

    Right after those comments by President Trump, Dr. Fauci mentioned that the reports were "anecdotal". To a prissy statistician bureaucrat , everything is 'anecdotal' if it is not a perfectly designed test structure and report with a control group.

    To him, if 10,000 doctors treated 100 patients each, and 96% of them recovered, it would still be 'anecdotal' reports. Unless of course, there were another million patients, who were given nothing, (and of which maybe 50% would have died).

    Typical of the LameStreamMedia to latch onto President Trump's reference to the drugs being FDA approved and call that a lie (since the FDA has not approved *anything* to treat the coronavirus). But this is not what the President said, nor meant to imply.

    There are two things going on here: alleviating patients and doing research. Doing the first can often, and should often conflict with the second.In a more rational world the power of the FDA to obstruct the first would be much more restricted.

    1. Anonymous Coward
      Anonymous Coward

      Trump, the *real* Covid 19 victim?

      Even doing some reading suggests it suppresses the immune systems response. The sort of thing you'd use only on patients whose immune system is doing more damage than the virus. Other cases it would weaken the patient at a time they need their immune system. FDA does that research, and specifies those cases. Not Trump, not Fox News.

      I get it: you think Trump is the real victim here.

      You backed him, you cannot face the error of your choice. To admit he's a lying moron, would be to admit you're an idiot who fell for his lies. The more of his lies you've ignored, the more invested in the fictional version of Trump you've become.

      To you, Corona Virus is an attack from China on Trump...

      ...And all the people Trump's incompetence and maliciousness kills, well they are 'soldiers' in the fight against China! People to be lauded for their sacrifice in saving the economy! Fox News telling old Republicans, that their death is necessary, because 'China'! They're supposed to be so stupid they volunteer their own lives, rather than let people stay at home for 2 weeks.

      None of that is real. You need mental help.

      USA has not done lockdown, you are not wearing face masks, you are not self isolating, you are pretending deaths are 'Flu' deaths, you are not testing, and pretending the reported cases is lower.

      Republican governors are blocking quaranteen orders, "this State is not China" they say. Simple quarantine methods are blocked and the disease is spreading in their state among their people. So you may as-well plan for 100% infection rate in months, an overwhelmed healthcare system, millions of deaths.

      Failure.

      You think you don't need 40k ventilators? You need millions of them, tens of millions, if you don't flatten that curve.

      You think you lose only unproductive older people? That the people sacrificed are unneeded overhead? People you won't miss?

      Trump isn't the victim, they are.

      1. Palpy

        Re: Ventilators: "You need millions of them, tens of millions..."

        Mmmm, I'm in sympathy with the content of your post. Numbers, though.

        Epidemiology suggests that this epidemic will die out when a population achieves somewhere between 30% and 60% immunity. Between about one third and two thirds of the population have to catch COVID-19 and recover before the spread will peter out.

        Assume the US population is 330,000,000.

        Best case scenario, 30% infection: 99,000,000 cumulative cases. If that number of people become infected over the course of 6 months, then there will be an average of 550,000 new infections per day. If 20% of these need hospital beds for four days during their illness, then the need for hospital beds would be 440,000.

        Worst case scenario, 60% infection: 198,000,000 cumulative cases. If that number of people become infected over the course of 3 months, then there will be an average of 2,200,000 new infections per day. If 20% of these need hospital beds for six days during their illness, then the need for hospital beds would be 2,640,000 beds.

        That last is 2.66 million beds, not ventilators. And these scenarios assume a linear infection rate, which we know. is wrong -- it's a curve. But even so, I don't see the need for ventilators reaching into the tens of millions.

        For me, the more important part of this exercise is the realization that in order to reach the lower possible bound of herd immunity (30% immune) in six months, the US will need to endure an infection rate averaging 35 times higher than the infection rate today, 3/28/2020. And obviously the US will have to sustain this onslaught until the end of September, 2020.

        Most of us are techies, here, so: numbers.

        1. Anonymous Coward
          Anonymous Coward

          Re: Ventilators: "You need millions of them, tens of millions..."

          In Italy, Covid-19 patients have been spending on average over two weeks in intensive care units.

          1. Palpy

            Re: Italian COVID-19 patients in ICU 14 days...

            Thanks for that statistic.

            Taking that at face value puts the worst-case hospital bed need at pretty near 6 million.

            But 'cos it's a curve, the peak infection rate will be far above the "average" rate. So maybe the original "tens of millions" would look sensible when the curve is hitting the highest rates of disease.

            I'd like to know what percentage of Italian patients require ICU versus how many make it with standard hospital support. And how many in ICU require a ventilator versus making it with supplemental oxygen.

            But all the numbers I put out ignore granularity -- some communities will be devastated first, some will hardly be hit until later, some may escape with only "drastic" and not "catastrophic" rates of infection. Some will be OK initially, only to be hit with a wave after other parts of the country have reached herd immunity levels. Treating the US population as a block, as I did (for lack of expertise) makes for a very cloudy crystal ball.

            YMMV.

            1. John Brown (no body) Silver badge

              Re: Italian COVID-19 patients in ICU 14 days...

              "I'd like to know what percentage of Italian patients require ICU versus how many make it with standard hospital support. And how many in ICU require a ventilator versus making it with supplemental oxygen."

              And even that doesn't really inform us on survival or death rates. No one has a clue as to how many are infected and never get ill enough to go to hospital, let alone those who get infected and don't even realise they got it. I suspect we won't get any statistical data that is even close to reality for at least another year, probably longer. Death rates in the media of 1-4% are based on deaths as a function of diagnosed, known case and estimates. Maybe if the Chinese start giving out some real numbers, the rest of the world can get some better estimates.

              1. Palpy

                Re: Survival and death rates

                John Brown (no body): "And even that doesn't really inform us on survival or death rates. No one has a clue as to how many are infected and never get ill enough to go to hospital, let alone those who get infected and don't even realise they got it."

                Strewth! We can't even assume that tested-and-confirmed cases keep a constant ratio to real infections. With little testing, one may estimate that each positive case implies 17 undetected cases (1:17); if testing is increased, the ratio may decline to 1:8 or less. One can try to estimate the magnitude of the infection in one region from known COVID-19 deaths -- 50 deaths divided by the death rate -- but one needs to put a number on the death rate. 3.4%, 5%, 1%, 0.6%? Assumptions must be made at every step of the way, and the pandemic is moving faster than we can quantify it.

          2. Anonymous Coward
            Anonymous Coward

            Re: Ventilators: "You need millions of them, tens of millions..."

            https://www.globalresearch.ca/swiss-doctor-covid-19/5707642

            N. Italy is an outlier case for several reasons which combined to give a perfect storm.

            1: Very old and infirm population

            2: Uncontrolled massive influx of Chinese from Wuhan which was unchecked for far too long

            3: Fear of not being "woke" and being branded racist delayed dissemination of actual information

            3a: The medical profession gagged itself

            3b: Politicians, being "woke" were admonishing their constituents to "hug a Chinese"

            If you wanted to kill off the aged and infirm segment of the population in N. Italy without resort to weaponry, this is how you'd do it!

            1. Anonymous Coward
              Anonymous Coward

              Re: Ventilators: "You need millions of them, tens of millions..."

              As every part of this post was objectively true and demonstrably so, it is thus a sad indictment on the intellect of some posters here.

              -7

              +2

              I get it, you're woke. But it doesn't change the facts on the ground. That's always a problem for the woke crowd, the fact that they are wrong so often.

              Now, I know I am mind reading here as to attributes of the down voters, but I'm willing to punt.

              "Hug a Chinese" is a quote from a figure of authority. Christ in NYC the fucking commissioner of Health said the same thing at the same time (NYC is the new Italy in this affair). There are published Op-Eds from Italian physicians decrying the wokeness, the fear of being called racists, that disabled their ability to react effectively.

              Is there a virus that can take out the woke generation and their rampant stupidity?

              1. Irongut Silver badge

                Re: Ventilators: "You need millions of them, tens of millions..."

                No, you're just an anonymous arsehole.

        2. Paul Shirley

          Re: Ventilators: "You need millions of them, tens of millions..."

          Between about one third and two thirds of the population have to become immune to COVID-19 and before the spread will peter out. Too many leaders (I'm looking at you Johnson) initially chose infection and recovery over maximizing the chance of vaccination as the route to that, economy over lives.

        3. Someone Else Silver badge

          Re: Ventilators: "You need millions of them, tens of millions..."

          You like numbers, but got some of them wrong, and missed others.

          As stated earlier, folks in ICUs are requiring on the order of 14 days, not 6 (or 4). So for the sake of thumbnailing, your worst-case scenario would require twice the number of beds, or roughly 5.2 million beds (and about 2.2 million for your best case estimate).

          Now a large percentage of those patients need ventilators to stay alive. I do not have those numbers (maybe you do?), but if 80% of them did, that would be up to roughly 4 million ventilators needed in your worst-case scenario. Not the "tens of millions" that the original poster hyperbolically stated, but millions (plural) nonetheless.

          Not sure I get the point of your post. Was it to shoot down the "tens of millions" point? OK, point taken; "tens of millions" is likely overstating the point. But your own numbers seem to indicate that millions is not overstating the point, and when our Douchebag-in Chief is squabbling over "40,000 or 30,000 ventilators", it is clear from your numbers that His Royal Hinie's concern is off by several orders of magnitude.

          1. Palpy

            Re: "Not sure I get the point of your post..."

            Fair enough. On the ventilators, I agree that millions of ventilators for the US is not overstating, and it may well go upwards of 10 million.

            The point of writing the post was, for me, to demonstrate to myself if not to others, that while there are a lot of unknowns, there are some reasonable checks you can make. Compare those to some of the statements being floated, and you can see how wildly off-target some officials are. Trump, obviously, but he's neither knowledgeable nor educable.

            But, an example that's all over the news today: Fauci recently estimated 100,000 to 200,000 deaths in the US.

            Right, then. If 30% of the population is the lower bound for herd immunity in this epidemic, and we assign a very conservative fatality rate -- 0.6% of total infections -- then US deaths will probably total 576,000, not Fauci's 200,000. And we calculate that 576,000 number using very, very optimistic assumptions.

            That's the real point of the post: Check the statements being made about the pandemic. My guess is that Fauci put out unrealistically optimistic numbers to avoid alarming the citizenry. But if you want to have more realistic ideas about what is probably coming, check the numbers.

      2. Anonymous Coward
        Anonymous Coward

        Re: Trump, the *real* Covid 19 victim?

        The sort of thing you'd use only on patients whose immune system is doing more damage than the virus.

        Which is the cytokine storm referred to further up the page that actually kills people and kills them fast. So a last ditch response that needs good timing even if it works and no help at all in ensuring everyone that needs treatment will have a hospital place.

    2. knelmes

      Re: The most important statement in the whole article.

      "Typical of the LameStreamMedia to latch onto President Trump's reference to the drugs being FDA approved and call that a lie (since the FDA has not approved *anything* to treat the coronavirus). But this is not what the President said, nor meant to imply."

      Did he not say this?:

      "Normally the FDA would take a long time to approve something like that, and it's -- it was approved very, very quickly and it's now approved, by prescription."

      If not, those damn dems have got really good with deepfakes because there's video of him saying it.

      1. Jamie Jones Silver badge
        Facepalm

        Re: The most important statement in the whole article.

        The number of times I've seen Trumpets flat out deny something even when theres video proof is incredible...

        1. IGotOut Silver badge

          Re: The most important statement in the whole article.

          Well when the arsehole himself calls it fake news when someone points out a recording of something he said, what do you expect.

      2. John Brown (no body) Silver badge

        Re: The most important statement in the whole article.

        The thing is, what he said was almost true. The drugs are approved, are available on prescription. Just not for this particular disease. I'm never sure if he's clever enough to make these sort of statements with embedded plausible deniability or if that's just a "happy circumstance" (from his point of view). And as others have said, he can always back track and scream "Fake News" or call the questioner a "cutie pie" while deflecting the question.

        1. Someone Else Silver badge

          Re: The most important statement in the whole article.

          I'm never sure if he's clever enough to make these sort of statements with embedded plausible deniability or if that's just a "happy circumstance" (from his point of view).

          He's not (clever enough), in spite of his claims to the contrary. How to be sure? Just remember that everything he says is a lie, so when he claims to be the "smartest" or "a genius" or "stable", or ..., it's a lie. Simples.

        2. DiViDeD

          Re: statements with embedded plausible deniability

          I don't think the Orange Buffoon(tm) thinks deeply enough for that. Remember, he said a few months ago that COVID-19 was no big deal and would be eradicated in the US within a couple of weeks.

          He followed this up a few days ago with that "It's a pandemic. It's serious. I always knew it was serious. I was calling it a pandemic before the medical experts did. I'm so clever, people are amazed how I know so much about everything. Yadda Yadda" speech.

          He's one of those politicians who realises that his supoorters have no memory and simply believe what he says right now. He doesn't need plausible deniability because he can change history at will.

    3. paulll

      Re: The most important statement in the whole article.

      Right after those comments by President Trump, Dr. Fauci mentioned that the reports were "anecdotal". To a medical practitioner , everything is 'anecdotal' if it is not a perfectly designed test structure and report with a control group.

      FTFY

  7. Anonymous Coward
    Anonymous Coward

    Echo chamber aside

    You know, you can simply google stuff! You don't need to echo The Registers endless sarcasm, or Fox News' "Trump is the real victim of Covid19" drivel.

    ---------

    The studies relating to Covid 19:

    https://en.wikipedia.org/wiki/Hydroxychloroquine

    "Hydroxychloroquine is also studied as an experimental treatment for coronavirus disease 2019 (COVID-19).[3] Some are also using it off label for the disease.[32]"

    "A randomized controlled trial on 30 patients by Chinese researchers showed that hydroxychloroquine "didn’t shorten the time to SARS-CoV-2 clearance".[33][34] Also, in the study patients were being treated with several other treatments (such as lopinavir/ritonavir or umifenovir) at the same time as the hydroxychloroquine treatment, making it difficult interpret the results.[33]"

    "A study of 36 patients in Marseille, France, showed a reduction in viral load, but its methodology was criticized.[35] The patients were not randomized, the analysis excluded three patients in the treatment group who were transferred to an intensive care unit and one who died,[36] and the study was published in a journal whose editor-in-chief is one of the article's authors.[37]"

    "In vitro studies in cell cultures demonstrated that hydroxychloroquine was more potent than chloroquine against SARS-CoV-2.[38][39] On 17 March 2020, the AIFA Scientific Technical Commission of the Italian Medicines Agency expressed a favorable opinion on including the off-label use of chloroquine and hydroxychloroquine for the treatment of COVID-19.[40] "

    -------------

    My Takeaway on the mechanism of action:

    Looking at the mechanism of action, it seems to dampen the immune system. I read Covid 19 in the lower lung is so aggressive that the immune system cannot distinguish infected cells from nearby cells and kills everything. I assume, from this mechanism, that its use is to lessen the immune response in that case? Which would be hit or miss, you'd presumably only administer it when the immune response is killing the patient? Otherwise it would make things worse!?

    Is there a clinician here who can spell the assume mechanism?

    1. randomengineer

      Re: Echo chamber aside

      I thought the basic problem was cytokine storm hence an autoimmune problem like lupus

    2. MrMerrymaker

      Re: Echo chamber aside

      What are you, some kind of idiot?

    3. Anonymous Coward
      Anonymous Coward

      Re: Echo chamber aside

      Yes. First of all this, for which you don't have to be a clinician. We all here know that the "source of all knowledge", Wikipedia, might be a nice to get a general impression on a topic. But we also know that every stable genius can input something there. Any kind of rubbish. And that's assuming that Wiki's (in)famous moderators also are part of the worlds KOL on that specific topic. So please, don't forget the info that Wikipedia holds is NOT the always correct, undisputed, absolute truthful source of all knowledge.

      As for the MOA and the specific study here itself: if you really want some meaningful substance, get on PubMed and you'll find that COVID caused a surge of publications that already started December last year. After all, clinicians/ scientists are also just people and publication and quotation indexes are vital. Having said that, here you find (at least abstracts if you don't have journal access) many case studies describing many observations, clinical (therapeutic drug) approaches and results. In good (like El Reg points out as criticism here very correctly) journals like NEJM, Lancet, JAMA and such. But...

      Let's go back to basics and state some things for which you don't have to be a matter expert:

      + Diseases do not care about nationalities.

      + Diseases do not care about borders.

      + Diseases do not care about political ideologies.

      + Really smart people are the ones who (dare to) say that they don't know (right now).

      + (Most) people who know what they are talking about don't spout generalised BS to a as big as possible audience to enhance their own personal situation (and give fuck all about others who have to clear up their shit. Bog roll anybody?)

      + You might (think you) impress people standing on a dais, using big words. It's more impressive if you come hold a hand of a current COVID patient. Or come and have a cuppa with those who are pulling the double/ triple shifts right now.

      + Sure, people are smart enough nowadays to treat patients and maybe find a cure eventually.

      + Some stuff takes time. Magic does not exist. How ever much you want it.

      + Whining like a small child that you want something really really bad, or acting like a school yard bully to push your (unrealistic) opinion through is NOT helpful.

      + Whining like a small child that you want something really bad, or acting like a school yard bully does NOT speed up things.

      + Stuff like this only works with cooperation, info exchange, working together. You might think this too academic, naive, or not "realistic". Then again, ask yourself if, when you're short of breath, you really give a toss whether your air comes from a vacuum-cleaner-turrned-ventilator-because-we-are-not-a-part-of-EU-let's-fight-them-on-the-beaches or something else.

      + Although humans regard themselves as really smart, we as a species do not behave any different as we did when we encountered the Plague a couple of centuries ago (Got bog roll? Got pasta? Wearing your mask which your rubbed with onion?)

      + And on a personal note consider this every day life experience: if you come in for treatment, a big mouth, threatening staff does NOT enhance your situation, nor does give you any advantages in any way. Although we do notice nowadays that it might help if you're not an NHS employee, but a prince or PM.

      1. Anonymous Coward
        Anonymous Coward

        Re: Echo chamber aside

        PS on my remark;

        + Whining like a small child that you want something really really bad, or acting like a school yard bully to push your (unrealistic) opinion through is NOT helpful.

        Just take a look how helpful this kind of behaviour is...

        I assume Science is OK as a scientific journal?

        https://science.sciencemag.org/content/367/6483/1169

      2. Anonymous Coward
        Anonymous Coward

        Re: Echo chamber aside

        "Diseases do not care about nationalities"

        Errr. No.

        While that may be the case for for CV19 (it's perhaps a little early to tell), it is not universally true.

        There are many diseases which disproportionately affect (or fail to affect) specific ethnic/racial groups. The risk can be a factor or orders of magnitude different.

        The fear of being called "racist" is directly implicated in Italy's and also NYC's disastrous early response where public health officials openly took the politically correct line and disseminated false information and admonitions that ended up shortening the lives of a lot of old and sick people. This fact is not in dispute.

        1. Anonymous Coward
          Anonymous Coward

          Re: Echo chamber aside

          Sure, be a smart arse. We are not talking about sickle cell or alcoholdehydrogense levels (of course you know what I'm talking about now and am implying, right?). Perhaps there is even another reason why these kind of flu viruses jump so easily between e.g. pigs and some kind of humans?

          So don't be more stupid than you probably are. The remark was meant in the context of how this pandemic is handled right now, and you know it. But if you are trolling, at least use the right icon...

        2. Malcolm Weir

          Re: Echo chamber aside

          OK, so given the third part of your comment is true, let's go back to the claim you're trying to substantiate with that comment: do diseases care about nationalities?

          And the answer is, still, that they don't.

          You lose.

          Turns out that "nationality" and "ethnic/racial groups" are different things... many people spot that fact based on the words being different and all! So Luxembourgers are not French/German/Belgian in nationality, but have pretty much identical "racial/ethnic" makeup with their neighbours.

          Oh, and while you're trying to be a smartarse, you missed the fact that many _cultures_ behave in ways that help or hinder propagation of illnesses. So in this particular situation, China's more authoritarian society and more communal housing policies facilitated some of the tactics they used to help control the spread of the virus, which tactics have little applicability to, say, rural America, but might have some relevance to housing in NYC.

          1. Anonymous Coward
            Anonymous Coward

            Re: Echo chamber aside

            "Hug a Chinese" - Italy ... NYC and Spain admonished their citizens to congregate massively in public to support irrelevant woke causes in early March ... that was moronic when it happened and was the direct result of wokeness and/or stupidity - hard to tell the difference at a distance.

            Yes, "nationality" <> "ethnic/racial groups", though it just happens that they are highly correlated. Exceptions are the diversity capitals of the world, of which NYC must surely be a leader.

            The Corona virus seems to have little effect on the young and healthy. It is less fatal to women in the current data, which is admittedly massively incomplete and sparse.

            It also seems that pretty much all the data for infection rate has been polluted by massive false raselts from faulty tests across different countries.

            The data for recovery is totally useless as it by definition excludes the massive majority of instances which were untested and recovered with mild symptoms. Worse, many countries do not even register recoveries. https://www.worldometers.info/coronavirus/country/denmark/ for example shows exactly 1 recovery. I can tell you exactly why that value is there - he was a journalist for a national TV station. No one else has been counted. So the recovery AND active cases values are totally broken. Denmark also has had a limited testing regimen, testing only the sick. This is one of the wealthiest and advanced countries on the planet with a very well run and integrated national healthcare system.

            Without data, you're just another person with an opinion.

            The is an almost perfect inverse correlation between Malaria and Corona virus incidence apparently. Who knew?

            1. Spacedinvader
              Unhappy

              Re: Echo chamber aside

              https://www.washingtonexaminer.com/news/family-says-21-year-old-british-woman-with-no-underlying-health-issues-died-from-coronavirus

              Young, female and healthy...

              1. dieseltaylor

                Re: Echo chamber aside

                The coroner said it, the family repeated it, and the hospital says it never gave Covid as the cause. More news to follow ...... But it looks a little dubious. Coroner's office response still awaited.

              2. Anonymous Coward
                Anonymous Coward

                Re: Echo chamber aside

                Delingpole tweeted recently about the press searching relentlessly for an apparently healthy young female who died so as to further their PANIC narrative.

                The press are truly appalling

              3. Irongut Silver badge

                Re: Echo chamber aside

                Because the family of a patient have the most medical knowledge.

              4. julian.smith

                Re: Echo chamber aside

                You get your science news from the Washington Examiner?

            2. First Light

              Re: Echo chamber aside

              The Graun is reporting an Atalanta vs Valenica soccer match may have been a significant factor in the spread in Bergamo. Unlikely to be attended en masse by" woke" types.

            3. Doctor Syntax Silver badge

              Re: Echo chamber aside

              "The is an almost perfect inverse correlation between Malaria and Corona virus incidence apparently."

              On your own criteria - data?

              1. Anonymous Coward
                Anonymous Coward

                Re: Echo chamber aside

                http://www.drroyspencer.com/2020/03/some-covid-19-vs-malaria-numbers-countries-with-malaria-have-virtually-no-coronavirus-cases-reported/

                There is a link to the data he used somewhere else, I don't have it at hand, but I am sure you'll find it because you're a concerned and interested citizen, not a troll, right?

                1. Doctor Syntax Silver badge

                  Re: Echo chamber aside

                  Thanks for that.

                  Scrolling down the comments I find "An obvious confounding factor is the fact malaria is mostly in poor countries, and they probably have little testing and reporting of these cases." apparently from the blog owner. And this is the trouble with statistics. The factor which gives rise to the source of the correlation isn't necessarily the one that you're looking as but one which influences what you're taking as the independent variable.

                  I was brought up short on this a few days ago. Because my area (part of the old West Riding) is known to have escaped fairly lightly in the '18/'19 epidemic, probably because of a widely scattered rural population I looked at the recent confirmed cases as a percentage of population, as given on the Beeb's site, for different local govt. areas. The rates were very close between us and a similar area to the north. A ordering area which I think has a proportionally greater urban element (none of these areas are purely rural) had about twice as many cases as we have. Looking good. Then I tried another adjacent area which I thought comparable with the last and it fell in between. So did a more urban area. Then I tried another urban area and it had a significantly lower number of cases per head than mine. So am I looking at genuine incidences of disease or at health authorities with different testing policies (the almost identical area to ours is under the same health authority)?

      3. Doctor Syntax Silver badge

        Re: Echo chamber aside

        "It's more impressive if you come hold a hand of a current COVID patient. Or come and have a cuppa with those who are pulling the double/ triple shifts right now."

        I always found the visits from the big cheeses were simply obstructions to BAU and hence couner-productive.

  8. herman Silver badge

    Small trial evidence suggests that Quinone helps if administered early enough. That kind of result is similar to other anti-viral treatments like Tamiflu. If you take it too late, the damage is done already and once you are dead, nothing helps, unless your name is Lazarus.

    However, the Quinone works in conjunction with other things, notably Zinc and an antibiotic. Without those two, it does almost nothing. That is why there are all these attention seeking allegations of It Works! It Doesn't Work! The Sky Is Falling! We are All Going to Die! flying around. People are cherry picking results to criticize Trump or whoever else they want to criticize, but in the end they just make themselves look stupid.

    In the mean time, the large pharmaceutical companies are ramping up production of Quinone and they probably know what they are doing better than a political journalist with a preconceived agenda.

    1. Anonymous Coward
      Anonymous Coward

      Citation Needed

      None of that is true.

    2. Sorry that handle is already taken. Silver badge

      What the actual fuck are you talking about?

    3. Spacedinvader
      Pint

      Quinone

      So we all just get shit faced on G&Ts while this goes down? Sounds like a plan!

      Mine's a pint of the stuff -->

      1. Spasticus Autisticus

        Re: Quinone

        So that's why there are no lemons in the supermarkets! I wanted to use some in cakes and scones I plan to bake.

        1. John Brown (no body) Silver badge

          Re: Quinone

          I'm starting to get worried that my Brexit hoard of yeast might run out before the shops start stocking it again. I have enough cocoa that I can make chocolate cakes instead of lemon cakes. And anyway, if you really get desperate for a lemon cake, you should just open your stash of lemon scented napkins.

      2. Sorry that handle is already taken. Silver badge

        Re: Quinone

        I would hope (for your sake) there's no quinone in your G&T!

        OP was so confused that not only did they mix up two different anti-malarials, they then confused that with a different class of organic compounds.

        1. Strahd Ivarius Silver badge
          Joke

          Re: Quinone

          The use of quinone instead of quinine is quite revealing..

        2. DiViDeD

          Re: Quinone

          OP could have actually meant Quinone. After all, there are woo peddlers out there telling people they can cure cancer with borax, arsenic and cyanide, so Quinones are relatively benign in comparison.

  9. randomengineer

    I'm not sure I even understand the point of this article other than some random writer taking yet another poorly considered shot at Trump. It makes little sense. If whatever the doctors are doing now isn't working then trying the treatment of quinine and z-pack and zinc possibly changing a certain negative outcome is worth the attempt. The notion that something isn't peer reviewed enough to be certain therefore it's unproven crap is nonsense in a world where people are dying NOW regardless and there isn't the luxury of time. For heaven's sake, try the treatment; if I (old enough to be at risk) am in the hospital dying on a ventilator and otherwise out of options, I'm not going to reject the attempt because some writer at El Reg doesn't reckon the attempt to be peer reviewed enough. Moreover, the very notion of freedom requires that we have agency, as in the right to request the treatment. It is not up to governors nor well intended officials nor all knowing superior writers with nothing at stake in my recovery. OK go ahead and downvote.

    1. Anonymous Coward
      Anonymous Coward

      Trump the victim

      So this is an attack from El Reg on Trump? MAGA'd too much?

      So this:

      "the analysis excluded three patients in the treatment group who were transferred to an intensive care unit and one who died,[36] and the study was published in a journal whose editor-in-chief is one of the article's authors"

      So as long as you take out the potential negative effects it has a positive effect!

      Nobody dies if you don't count the dead in a study.

    2. Dinanziame Silver badge
      Stop

      'In a clinical trial, absolutely none of the people treated with cyanide died of the Coronavirus! Feel like giving it a try? Or maybe we should try homeopathy? There are no side-effects!"

      There is no situation so desperate that you should try any random crap just because there are stupid people who think it works.

      1. Anonymous Coward
        Anonymous Coward

        Random

        There are many instances where one should try. Life and death choices. I have a dying friend trying a drug for which only one clinical study exists for his ailment, and that study had 8 patients (it's pretty rare ailment, so big studies are impossible). Grow up.

        Also, it's not random. There are fundamental scientifically well understood reasons for trying the treatments that are being tried. If you think it is random, you are both ignorant and an idiot.

        You're welcome.

    3. Dan 55 Silver badge

      I'm not going to reject the attempt because some writer at El Reg doesn't reckon the attempt to be peer reviewed enough

      It's not that it wasn't peer reviewed enough, it's that it wasn't peer reviewed. Thousands of doctors treating severely ill patients don't need to waste time and money going down dead ends like this one at this time, that's why peer review is done in normal times, and it's even more important now.

    4. Dave K

      You have a shocking lack of understanding of science and clinical trials in general. Yes, Covid-19 is a serious issue and people are dying, but pumping poorly-tested drugs into people in the "hope" that it fixes things is not the answer. Many drugs have serious side-effects that need to be carefully understood, and they can cause other issues and conditions as well. Using drugs like this widely when we don't understand the ramifications is unbelievably risky and stupid and has the potential to kill more people than Covid-19 is doing.

      So why is Trump saying these things? Two reasons actually:

      1) To boost his own standing. He wants the average dumb American to look at him in admiration for having fixed the issue so quickly.

      2) To cover up for the fact that he sat on his fat arse for far too long initially. He wasted far too much time blaming everything on China and the Democrats instead of putting plans and resources in place to minimise the impact. Now America is paying the price for this.

      So what should happen? Isolation where necessary, social distancing, lots of testing to implement the correct controls in areas that need it, urgently boosting supplies of ventilators and equipment to treat people. This flattens the curve, allows hospitals to treat people effectively, minimises deaths and buys time. Meanwhile, fund science and allow proper clinical trials to be run to eliminate ineffective "cures", find ones that do work, understand the limitations and impact of such drugs so that they can be safely and widely deployed, then ensure sufficient manufacturing capability exists so these can be handed out once they are proven to be beneficial.

      You don't just open your fat gob on Twitter having read one deeply flawed "paper".

    5. Anonymous Coward
      Anonymous Coward

      Precisely

      " The notion that something isn't peer reviewed enough to be certain therefore it's unproven crap is nonsense in a world where people are dying NOW regardless and there isn't the luxury of time. "

      Denying treatment to the control group while the treated group shows positive recovery signs is directly and abominably unethical. Armchair quarterbacks calling for prefect tests in the current situation and peer review should be ignored - you can't fix stupid.

      Factoid. Many massive trials have been abandoned when one or other of the groups showed increased mortality! Cancelling trials on ethical grounds is a thing. Suggesting otherwise and demanding perfect case studies whereby people might need to die to fulfil the test design is, to put it mildly, retarded.

      Curiously, it is the same argument that the AGW crowd use to beat up on those with more nuanced views. Same people methinks.

      1. Dave K

        Re: Precisely

        There is a major issue here, which is that until you've completed proper clinical trials, you don't know if it is a treatment or not. Until there is clear and proper evidence to suggest a treatment works, it is just an "experimental drug". Plus, proper clinical trials involve double-blinds where neither the patients, nor the researchers know whether a particular person is on the treatment or the placebo. It's necessary to eliminate any placebo effect from the results.

        Covid-19 isn't the only serious disease in the world you know. Cancer killed nearly 9m people in 2015, diabetes is estimated to cause up to 5m deaths a year. We're constantly working hard on new treatments for these diseases, yet you cannot just pump everyone full of an experimental drug each time one is developed because you cannot then gauge clearly whether a drug works or not, what effect different doses of the drug may have, etc. etc.

        Yes, it's tough to say this, but if you want an effective treatment for Covid-19 as quickly as possible, you MUST follow the proper scientific processes to test the drugs first. Otherwise, you'll end up wasting time down blind alleys, approving flawed drugs that may not help much (or which may unexpectedly make things worse), plus all manner of other issues.

        You're correct when you say that many large trials have been abandoned when a group shows increased mortality - this is because the trial is being performed in a proper and controlled way and it can therefore accurately show that the drug isn't working properly. In these cases, the trial is halted. Pump everyone with the drug however and where is the baseline? How do you know mortality has increased? Simple, you can't tell without a proper, blind control group to compare the results to.

        Believe me, I want an effective treatment for Covid-19 to be developed quickly just as much as you do, but if you piss away hundreds of years of scientific process in a blind state of panic, you won't end up with an effective treatment. All you'll do is cause more problems than you will solve.

        1. John Brown (no body) Silver badge
          Thumb Up

          Re: Precisely

          "Otherwise, you'll end up wasting time down blind alleys, approving flawed drugs that may not help much (or which may unexpectedly make things worse), plus all manner of other issues."

          eg Thalidomide.

          1. Dave K

            Re: Precisely

            Excellent point. In fact the Thalidomide scandal helped to introduce a lot of the current testing and regulation of drugs and is an excellent case in point of what can happen if poorly tested and understood drugs are taken en-mass.

            Thalidomide is still a widely used drug today, but now that the side effects and risks are properly understood, we know where we can prescribe it safely and when we can't.

            1. Anonymous Coward
              Anonymous Coward

              Re: Precisely

              In this case it is the strawman fallacy.

              1. Someone Else Silver badge

                Re: Precisely

                Maybe, instead of spewing horse exhaust, you should perhaps look up and see exactly what a strawman argument is, exactly. Then perhaps you might measure your remarks so as not to come of like a complete ass/arse. Or not.

        2. Anonymous Coward
          Anonymous Coward

          Re: Precisely

          " ...you MUST follow the proper scientific processes to test the drugs first."

          This makes you a fucking moron, I am sorry to say, like the five thumbs down who also think people dying for the sake of clinical trials is OK.

          In this specific case, we are talking about novel applications of very old and previously approved drugs for which there are known human tolerances and side effects. We are not talking about something cobbled up in the lab yesterday!!

          Y'all are retarded if you think that the medics are running clinical trials in panic and wildly guessing. This is provably not the case, as a simple review of the medical literature would show.

          Testing new protocols for known drugs to treat a novel and sometimes fatal condition is not a new thing. People here are becoming dumber on average judging by the negative responses which include the position that people dying is OK for the integrity of the test.

          1. Intractable Potsherd

            Re: Precisely

            Research Ethics Committee member here: it would be unethical to deny an existing, approved, treatment to a control group whilst another group got an experimental treatment. It is NOT - repeat NOT - unethical to refuse an experimental treatment where no existing, approved, treatment exists. In fact, it is unethical in the extreme to do otherwise. So far, the evidence for H+A treatment is interesting but equivocal - only one step above opinion.

    6. John Brown (no body) Silver badge
      Pint

      So, some world leaders claims that ingesting large amounts of alcohol could be a cure and we should all get shit-faced on the off-chance that it might be true?

      1. Anonymous Coward
  10. Anonymous Coward
    Anonymous Coward

    Follow

    The Money.

    1. Frumious Bandersnatch
      Joke

      Re: Follow

      No! Follow the Monkey! MAGA!

      1. nxnwest

        Re: Follow

        Shock the Monkey!

        (Sh*tgibbon in this case.)

        1. Someone Else Silver badge

          Re: Follow

          +1 for the ob Peter Gabriel reference.

  11. sanmigueelbeer
    FAIL

    Smart man or smart a$$?

    Trump kept saying it was basically pretty much a cure

    IF she can find multiple video/audio recordings of his statement, she is going to be one very, very, very rich woman.

  12. Anonymous Coward
    Anonymous Coward

    Whilst We’re On the Topic...

    So how come a simple corona virus has caught us out? Why is there little basic science being done into infections viruses? Why hasn’t the forecasts of people like Bill Gates (who basically predicted this entire situation 5 years ago) not turned into academic research into what to do about it?

    Some Bits of the Scientific Community are Badly Dysfunctional

    Basically the entire biomedical immunological research academic community is rife with internal politics, the pursuit of money, selfish behaviours. Academics have to make a living, usually by getting research grants. Funding bodies (often charities these days) measure success by counting papers published in magazines like Nature. Nature and it’s peers won’t publish “boring” papers, they have to sell copies. The audience for such journals is, by and large, academics... And what a lot of academics are interested in is topics that might attract fame or fortune. Topics like cancer. There’s a lot of money and fame at stake for whoever solves that one.

    And as for the peer review system; don’t count on that being the pure, objective process it’s supposed to be. Basically the point of this article being that a “peer reviewed” article has run round the world on the back of this pandemic, and now the genie is having to be stuffed back into the bottle. There are plenty of examples of papers which are hugely questionable. Some really quite prestigious journals give some highly regarded labs some “free passes“ skipping peer review, leading to some carefully disguised rubbish with eminent corresponding authors names attached getting splashed all over the press.

    This Branch if Science is Too Important to be Run by Scientists

    Whilst cancer is a worthy topic, it’s not the only topic out there. The trouble is that the way a large part of the scientific research effort is directed is useless. It allows everyone in that community to all work on the same popular and fashionable topics (eg cancer) and there is no one making sure that scientific effort is put into other topics (eg basic research into viruses).

    Bill Gates, who funds a lot of research these days, has even publicly complained that he can’t persuade scientists to work on “boring” topics (like dysentery) no matter how lavish his funding is, because they see it as “bad for their careers”.

    So here we are. The entire funding structure is wrong, and the scientific community clearly hasn’t got the internal discipline to govern itself properly with regard to what work gets done.

    The Role of Governments

    There used to be government funded labs to address this kind of thing, but that’s largely long gone due to the disinterestedness of politicians and the occasionally prima donna nature of elite academic science (scientists working for government labs are often sneered at by their pure academic colleagues).

    That has got to change or this will simply happen all over again. Modern travel capabilities will make this happen more often if we don’t.

    Other Fields

    Climate Science. There’s no need for more science saying how we’re damaging the planet. We already know. What we do need is a lot more science saying “this is a cheaper way to generate and use energy”. A lot of the bad politics around climate change / denial comes from the way in which Science has engaged with politicians and the public, and yet basically all that the bulk of the scientific community can contribute is “this is what you’re doing and it’s all your fault”. The reaction of climate change deniers is disappointing of course, but in the circumstances it was inevitable.

    And again, the discipline command control thing: what if all the academic funding put into measuring the atmosphere yet again was put into fusion research instead? Continued funding of climate research does smack rather of preserving jobs for the boys and gals. Climate scientists can’t design fusion reactors or better wind turbines or solar panels, but what we actually need is fusion reactors and wind turbines and solar panels. We don’t need carbon neutral yachts either.

    I suppose if Nature were printed on sustainable paper I could burn it to keep warm...

    1. Anonymous Coward
      Boffin

      Re: Whilst We’re On the Topic...

      Your comment is, I think, well-meant but unfortunately deeply confused and in various places plain wrong.

      I don't know how much funding there is into viral diseases an epidemics, but there's pretty clearly a lot: there have been well over 1,000 papers published on COVID-19 this year. And there has been plenty of research into what to do about it: the answer is 'what we're doing': It turns out there is no magic silver bullet you can invent for a virus which does not exist yet. Indeed there's no magic silver bullet for some viruses which do exist: HIV is still a problem, for instance, as is influenza, which happens every year and for which people try and find a vaccine every year.

      People have predicted that pandemics will happen because they will happen: this does not mean that there is some magic solution to the problem which you can find by throwing money at it. Of course, there are things you can do by throwing money at the problem: for instance you could make it really quick to sequence the genome of a novel virus ... oh, look, we did that.

      Perhaps someone who actually works in the field could comment on how much research gets done into viral diseases and pandemics.

      Your comment about Bill Gates and dysentery doesn't make the point you think it makes: dysentery (and malaria) is a disease which kills poor people: dysentery kills children in Africa in large numbers for instance. Bill & Melinda Gates are doing a good thing here: they want to save people even if they are poor, brown and live far away. Do you think governments in rich countries are going to start funding research into dysentery, which doesn't kill people in rich-world countries? What do you think Trump would say if you asked him to do that? No, they're going to fund research into cancer, which does kill people in rich-world countries, and into things like viral pandemics and so on.

      dysentery research is not underfunded because of a problem within the scientific community: it's underfunded because voters in rich countries don't care about people in poor countries.

      Your comments about climate research are equally confused, and this is something I do know about. We do understand what goes on in the atmosphere relatively well. It might even be that different atmosphere-only simulations make numerically-similar predictions about how surface temperature behaves: I'm not sure. It may well be that they don't, because while we understand the underlying physics in the same way we understand the physics of an atomic weapon, we also know that fluid dynamics is really hairy and without very extensive numerical simulation we can't actually predict what happens very well. Simulating atomic weapons is most of the reason supercomputers exist, after all.

      But we don't live on a billiard ball of unchanging rock surrounded by an atmosphere into which we inject CO2: we live on a planet with mountains, oceans, continents, vegetation, animals, land & sea ice. And we really don't know very well how that system behaves, because it's a crap load more complicated than a billiard-ball planet with an atmosphere if we could even make really good predictions about that.

      And we need to know how the real planet will behave, because we can do only one experiment and if we get it wrong it will have consequences which will kill most of us. We need to know if the wheat and rice which feeds us will die or get eaten by insects which suddenly find the environment a lot better for them. We need to know if wind speeds will get high enough to blow forests down. We need to know the places which will flood and about how often they will flood. We need to know how soon we need to be moving out of London and New York: now, or in a century, or several centuries. We need to know what solar geoengineering might do. We need to know if the planet will become more or less hospitable to things we don't want there, like viruses, say. We need to know all sorts of things about timescales, because that tells us how long we have to address the problem. So, as well as improving atmosphere and ocean models, we have to construct earth-system models which involve components for all these things, and then explore how they behave. And that is what people are doing, and doing that is extremely important: trillions of dollars worth of important.

      In fact it should be obvious, right now, why this is so important. Everyone numerate knows what a pandemic looks like in terms of infection numbers: there's an initial exponential phase followed by a peak and then some tail which either declines to close to zero if there's long-lived immunity or turns into some complicated long-term behaviour if the immune behaviour is more complicated. I could sketch a graph of this: anyone who can think about the maths could sketch a graph. I could even write a program to simulate it naively (and I've done so in fact).

      But sketching a graph is nowhere near good enough: it is absolutely critical to know the time-constant of the initial exponential bit, how long and how high the peak is, what happens after the peak, and what you can do to change these things. To do this you need to run a hairy numerical simulation which makes a serious attempt to incorporate the parameters which actually control what happens. Then you can look at what happens when you adjust parameters of that model: can you afford to let the thing play out? (no) can you smear and lower the peak (yes) and afford to let it play out that way? (no, it turns out) can you suppress it altogether (yes, probably) and what do you need to do that? What happens when you stop suppressing it? And so on.

      Well, the people at Imperial ran a model like that a couple of weeks ago, and it completely changed how the UK was planning to deal with CV19. It turns out that what I, or anyone numerate, could have told you about how pandemics pan out based on the basic science and naive simulations was not anywhere near good enough to use for planning what we should do about it.

      1. Anonymous Coward
        Anonymous Coward

        Re: Whilst We’re On the Topic...

        Your comment is, I think, well-meant but unfortunately deeply confused and in various places plain wrong.

        Deeply confused? Well, let me clear that up then.

        My comment should be taken as a scathing attack on those elements of the scientific community that more or less refuse to consider the social value of what they do nor seeking out topics that deliver more social value, or act largely out of self interest and self promotion, or have no interest in coordinating and organising their efforts for the greater good, and consume vast resources whilst doing so that might otherwise be put to better use. Every climate scientist should really be asking themselves, does one more paper telling us what we basically already know really help more than a paper on better wind turbine designs? Every immunilogical researcher will tell you "getting a basic common understanding of viruses is hard" (which I don't doubt), but they're not exactly banding together to divide up the problem amongst themselves. Immunology is perhaps the worst; there's people in that field who will deliberately sow ideas that they know don't work, simply to divert others onto that topic leaving the field clear for their own research.

        For further clarity, there are elements of the scientific community that do consider the social value of what they do very carefully, selflessly cooperate for the greater good, are delivering social benefits and should be applauded every moment of the day. For example, someone working on making the photovoltaic effect work better is leading towards better solar panels. Aerodynamicists looking to further reduce drag will make wind turbines better. And the granddaddy of them all is the international project looking at fusion power which has been a commendable, well planned out cooperation between science, engineering and many governments for multiple decades now, and is bang on published schedule (if you go back to the original blueprint from decades ago). If that actually delivers (and it probably will), that'll save our necks. These are all good things for society. There is also the noble and mature science of epidemiology which, when fed with correct data (which it's not at the moment), is also extremely socially valuable. I suspect most epidemiological research these days comes down to, "how badly do we get lied to?", which would be a sorry but accurate commentary on the state of politics...

        And we need to know how the real planet will behave, because we can do only one experiment and if we get it wrong it will have consequences which will kill most of us. We need to know if the wheat and rice which feeds us will die or get eaten by insects which suddenly find the environment a lot better for them. We need to know if wind speeds will get high enough to blow forests down. We need to know the places which will flood and about how often they will flood. We need to know how soon we need to be moving out of London and New York: now, or in a century, or several centuries. We need to know what solar geoengineering might do. We need to know if the planet will become more or less hospitable to things we don't want there, like viruses, say. We need to know all sorts of things about timescales, because that tells us how long we have to address the problem. So, as well as improving atmosphere and ocean models, we have to construct earth-system models which involve components for all these things, and then explore how they behave. And that is what people are doing, and doing that is extremely important: trillions of dollars worth of important.

        You're missing the point. There is zero value knowing those things if we're not equipping ourselves with the tools to do something about it. We already know roughly what the planet used to look like with less CO2 in the atmostphere, when we were still cavemen - the ice / mud cores have been exhaustively examined, tree rings counted, and it was a pretty nice place to be (apart from the occassional ice age). Talent spent on modelling it means there's less talent dedicated to doing something about it.

        There is only one experiement we can do anyway - emit no CO2, see what happens. You sound like you're suggesting we should do something else. Deep space travel, go somewhere else instead? Or are you suggesting there may be modelling results that advise against cutting CO2 emissions? I think you'd be in a minority there.

        1. Anonymous Coward
          Anonymous Coward

          Re: Whilst We’re On the Topic...

          "We already know roughly what the planet used to look like with less CO2 in the atmostphere"

          Was it ever below the "concensus" 285ppm pre-industrial level? It can't have even been that much lower or life would have disappeared due to lack of photosynthesis.

          1. Aquatyger

            Re: Whilst We’re On the Topic...

            I believe it used to be in the 6000ppm - 8000ppm range until shellfish started to sequester it down to the dangerously low levels we have today.

        2. Anonymous Coward
          Anonymous Coward

          Re: Whilst We’re On the Topic...

          "Talent spent on modelling it means there's less talent dedicated to doing something about it."

          After you see the code and the way those models work, you might like to remove the word "talent"

        3. Anonymous Coward
          Anonymous Coward

          Re: Whilst We’re On the Topic...

          Both of you are correct, but both of you are pulling in different directions:

          Knowing the problem:

          We need to know if the wheat and rice which feeds us will die or get eaten by insects which suddenly find the environment a lot better for them.

          and

          Coming up with a solution:

          There is zero value knowing those things if we're not equipping ourselves with the tools to do something about it.

          Basically, we can't do anything about a problem if we don't know how large it is ... and if we know how large the problem is, then we are bound to find a solution.

          There are exceptions, but that's what they are, exceptions. AC tends to be a little unrealistic in their demands, because researchers are still people ... some really want to change the world, while others want to change how much (in a financial sense) the world owes them, unfortunately.

        4. paulll

          Re: Whilst We’re On the Topic...

          "elements of the scientific community that more or less refuse to consider the social value of what they do"

          I'm not sure how you think the world works (like, is,"Iron Man," real in your universe?) but scientists don't generally get to pick and choose their research projects and automatically get funding (let alone pay).

          The people who control the money set the direction, and that is largely not scientists.

    2. doublelayer Silver badge

      Re: Whilst We’re On the Topic...

      "Why hasn’t the forecasts of people like Bill Gates (who basically predicted this entire situation 5 years ago) not turned into academic research into what to do about it?"

      Are you serious? What Bill Gates said boils down to "There will come a pandemic at some point relatively soon, and when it does, we won't be able to handle it". Well, of course. That's a relatively obvious thing to everyone. And that's fine, because he was not called on to be a predictive epidemiologist. He was stating a generality because his point was a general one. However, he did not "predict this entire situation". If this counts as a complete prediction, I'd like to get my own in here. How's this:

      There will come a time, probably sooner than we'd like, when a war happens. The war may be a world war or it may be a localized one that many nations wisely stay away from, but it will involve at least two modern economies with large militaries. When this war happens, we are not prepared for the pain that will be created by unexpected weapon technologies and tactics as well as disruption to globalized processes. It will be very unpleasant when that happens. We should do something about this.

      When I'm proven correct, I want to be similarly lauded as a visionary who accurately predicted the Chinese-American war, or the Russo-Euro war, or the Persian-Australian-Indian war or the Eurasian war of 2028 or the Transpacific war or the war of the missiles or whatever it's called. I predicted it back near the end of March 2020; all of you are witnesses.

      Now, to answer your question. Why didn't a generality by Gates turn into academic research? Do you mean more academic research? Because there was already a lot of academic research on epidemiology and microbiology. Thousands of papers are printed every year from diligent researchers. If you're only referring to new research, there are two primary ways of increasing the quantity of research being done: 1) increase the number of researchers and 2) increase the funding for existing researchers so they're never lacking for resources. If we were supposed to do the former, we haven't had enough time to increase the entry rate of properly-educated researchers, which takes years. If the latter, you have a better point, but you would need to ask the various places that fund such research. Many of those places have been increasing funding. Many that haven't simply cannot--they're already donating what they can. Plenty have decreased funding, and you can be angry with them if you like, but that is the nature of academic funding and your complaints will not help to change it. Since it's such a large field, their efforts are spread out across it, which isn't helpful right now when we wished they spent all their time looking at respiratory viruses, but would have been great in the possible alternate timeline where we were dealing with persistent antibiotic-resistant bacteria that cause neurological damage. So you name the thing that should have happened, and who should have done it, and we can argue about why it didn't happen.

      1. Anonymous Coward
        Anonymous Coward

        Re: Whilst We’re On the Topic...

        If you're only referring to new research, there are two primary ways of increasing the quantity of research being done: 1) increase the number of researchers and 2) increase the funding for existing researchers so they're never lacking for resources

        You're focusing on the wrong things. What matters to society is the quality of research being done, and the efficiency with which it is carried out.

        Putting more money into the current academic system won't lead to the right research producing the necessary results in the shortest timescales: it leads to more scientist duplicating effort in topics scientists like to study, which probably (it is pretty random how ideas get taken up for investigation) don't overlap with what is actually important. That is not helpful to society.

        1. Francis Boyle

          I think I get it

          You're an old-fashioned moralist. You desperately want people to be better You think that only when people become better will they deserve a better world. But it's you who have got it backwards. We make people better by making a better world. And to do that we need concrete suggestions. So if you're worried about inefficiencies in the way scientific research is directed (which may or may not be a problem – you haven't exactly proved your case) you need to look at the mechanisms of reward rather than complaining that scientists are being selfish. (That science is a general public good doesn't actually require individual scientists to be be any less selfish than the general public. That's the thing about science – it's a mechanism for overcoming individual human limitations.)

        2. John Brown (no body) Silver badge

          Re: Whilst We’re On the Topic...

          It might be worth noting that the US model of "publish or perish" isn't something that happens in all countrys and may have an effect on the quality of published papers. I'm sure there have been papers published on this very subject.

        3. doublelayer Silver badge

          Re: Whilst We’re On the Topic...

          "What matters to society is the quality of research being done, and the efficiency with which it is carried out."

          Agree entirely. And so:

          "Putting more money into the current academic system won't lead to the right research producing the necessary results in the shortest timescales: it leads to more scientist duplicating effort in topics scientists like to study, which probably [...] don't overlap with what is actually important."

          Fine. Then you tell us what we're supposed to have done. Evidently, scientists can't be trusted to find useful things to study, someone needs to tell them. But you have so far failed to identify who does tell them what is important, and how that person gets that information, and how we get that research done if the current academic structure won't do it voluntarily. You've* made some statements about what isn't important to you, which have been ably dispelled by existing replies so I won't reproduce their work.

          Consider this particular issue. We have a virus that causes respiratory disease and spreads easily through the air. So, since you haven't said what particularly we need to be researching, I'm guessing the subjects of most importance include virology, epidemiology, and study of respiratory disease? You have stated that cancer isn't such an important topic, so I'm assuming that's where we get extra capacity for those things? Assuming you agree with all of this, imagine how we would feel if we forced most cancer research to stop three years ago to focus on those topics instead and, instead of this particular virus, we had a pandemic of another one that caused little damage in and of itself, but led to high rates of carcinogenic behavior among previously healthy cells--such viruses exist. I believe your problem is that you think you know what is and always will be important and you don't acknowledge that basically every type of scientific research is important. There are many failings of the system that could get repaired, but in reality, many deficiencies are the result of a lack of resources, whether that is staff, money, equipment, or data. All you are suggesting is robbing one discipline to pay another.

          *Actually, the opinions I'm replying to are across the original post and the one I've replied to. Both have been posted anonymously, so I don't know for sure that it was the same person.

        4. Someone Else Silver badge
          Alert

          Re: Whilst We’re On the Topic...

          Putting more money into the current academic system won't lead to the right research producing the necessary results in the shortest timescales:[...]

          I wanna know:

          * What is the "right" research?

          * Who determines what is the "right"research? (You? Me? If the answer to either of these questions is "yes", we're fucking doomed!)

          * What are the "necessary" results?

          * Does your world view account for the possibility that "unnecessary" results might prove interesting, useful, or even necessary. (Ooooh, a conundrum. Your brain might hurt....)

        5. Doctor Syntax Silver badge

          Re: Whilst We’re On the Topic...

          " What matters to society is the quality of research being done, and the efficiency with which it is carried out.....it leads to more scientist duplicating effort in topics scientists like to study"

          One of the things that drives quality of research is time spent trying to duplicate - actually replicate - others' results. If you don't do that you find that some dodgy stuff gets published. Read Feynman's comments, especially on psychological research.

    3. Doctor Syntax Silver badge

      Re: Whilst We’re On the Topic...

      "And what a lot of academics are interested in is topics that might attract fame or fortune. Topics like cancer. There’s a lot of money and fame at stake for whoever solves that one."

      Let's try to unpack that a bit. What a scientist researches is the consequence of two things.

      One is the particular field in which they find themselves. A virologist, cancer specialist or whatever is likely to have started down that line early in their career because something they encountered grabbed their attention and/or because the subject suits the way they think. Just think of your own situation here: why is it you do whatever it is you do and not something else?

      The other is the financing for that field. It's society as a whole that determines what that is. If society were prepared to put a lot of money into cancer research and none at all into virology than the only work the virologist could do would be on those cancers caused by viruses such as HPV.

      Of course some research institute could take the money it's been given for cancer research and, on the basis of its own unilateral decision that not enough money for virology, divert wome of it in that direction. A few moment's thought should be enough to realise the likely outcomes of that are going to range somewhere between loss of future funding and prosecution for fraudulent diversion. It wouldn't lead to more virology.

      If you think some aspect of science doesn't get the attention it should don't blame the people working in some other field, blame the way society chooses to allocate its money.

      1. NATTtrash

        Re: Whilst We’re On the Topic...

        Hello Doc,

        Sorry for the late reply, but wanted to add to the comment you wrote. Yes, you're right, but every day clinical (R&D) practice in our societies works a bit different than what you describe. Please don't get me wrong, I agree with what you conclude, but if you look at the reality of every day, the drivers are a bit different.

        "One is the particular field in which they find themselves. A virologist, cancer specialist or whatever is likely to have started down that line early in their career because something they encountered grabbed their attention and/or because the subject suits the way they think."

        You got a point there, but practice (personal and if I look at my colleagues) shows that the "because something they encountered grabbed their attention..." piece is a bit too optimistic. For clinicians most of the time the subject you're on is where there is an education/ training vacancy. Every year, submissions show that paediatrics, ophthalmology, and CV are top favourites. Gastro intestinal stuff (e.g. proctology, urology, endocrinology) are not. But in the end you take what you (can) get, and that becomes your field. For R&D it's perhaps somewhat more in the direction of what holds the candidates fancy, but in the end every PhDs interest is formed mainly by the project her/ his mentor initiated.

        As for your second one, "The other is the financing for that field. It's society as a whole that determines what that is", this is, at least for the clinical sector, true for a very limited extend. Here, I have to admit that the bulk of the R&D, especially pharmacological, is determined by (maximised) profit margin thought. And yes, you're right if you say that unis and institutes do R&D. But the stuff that will land on patients coffee tables comes from industry. And, if industry doesn't see a profit, it doesn't invest in development, and it will never reach patients/ the market. That's why many governments and the EU do have initiatives (e.g. orphan drug development, paediatric dosing stimulation projects) to coax industry to develop in other indications/ look at other approaches. But in the end, the main force is always a simple equation: how many patients are there (prevalence = market size), how does the disease develop over time (incidence = market growth = volume), and what can we charge for such a product (= ROI).

        So yes, you're right if you say: "blame the way society chooses to allocate its money", but I think it's good to also realise which part of society that is, and how "steerable" it is nowadays with the (healthcare) system we decided to run with...

  13. mark l 2 Silver badge

    Because Trump is the smartest man in the world, one of his devout followers died and his wife because very ill after taking chloroquine phosphate in an attempt to ward off corona virus

    https://news.sky.com/story/coronavirus-man-dies-after-ingesting-chloroquine-in-attempt-to-ward-off-covid-19-11962685

    Now in this case it wasn't chloroquine malaria drug they took but a similar sounding compound used to kill parasites in fish, but it goes to show that Trump spouting off on the news how untested drugs can cure corona virus could cause people to go out an take things without consulting medical experts first.

    Even if they had taken the anti malaria drug chloroquine without speaking to a doctor/pharmacist, who is to say that they aren't taking other medication which could cause side effects just as bad getting the corona virus in the first place.

    He needs to learn to start engaging brain before his mouth starts talking

    1. Phil O'Sophical Silver badge

      He needs to learn to start engaging brain before his mouth starts talking

      There's an underlying assumption in that statement which could be problematic.

    2. Shooter

      Two additional points to your comment:

      1) The *quine drugs are not just used as anti-malarials, they are also used to treat other serious diseases such as lupus. And apparently the dosage has to be pretty closely controlled as they can become toxic in pretty short order. Also, I understand that they can cause heart arhythmia in some patients.

      2) Due to the wild speculation over these drugs, I have seen reports that some doctors and pharmacists are already hoarding them for use by themselves and their families. This is causing shortages for patients who in some cases are already having a difficult time filling their prescriptions do to problems associated with being in lock-down.

      1. jukejoint

        Prescription shortage

        I came here to rant and your post is the perfect intro.

        My daughter, who has a *variant* of a rare autoimmune disease, yesterday was sent a message from her healthcare provider stating that her provider 'temporarily cannot provide a future refill' for her medication - Plaquenil.

        I don't know if it's the fault of doctors hoarding or the Dumpster in Chief or the fuqqin' mobsterati.

        The message went on to say that basically, she should try to make it last by expanding time between doses - simple!

        I surely wish this was a world in which patients were actually cared for, in which providers and others were thinking on their feet and reserving a script or two for pre-existing patients already at high risk between this virus and their chronic condition.

        So the shortage is here, it was fuqqin' instantaneous after the Slime oozed over the airwaves.

        [Pssst know where I can score?]

        OK the bracketed part is a sad joke.

    3. MacroRodent

      The other way...

      As a kid I once did the reverse, treating white spot disease in my aquarium with ground-up malaria pills, left over from a journey in Africa (this was in the early 1970's when chloroquine was still effective in Africa). I reasoned it should work because both diseases are caused by protozoans. It was a success.

  14. Anonymous Coward
    Anonymous Coward

    The Trumpists are out in force here today.

    1. Anonymous Coward
      Anonymous Coward

      'Trumpers' would be a more appropriate moniker, as they do seem to be coming out with rather a lot of guff...

    2. Anonymous Coward
      Anonymous Coward

      We prefer being called Trumpeteers, thankyouverymuch!

      1. mevets

        I call fake.

        Too many syllables.

        1. Doctor Syntax Silver badge

          Re: I call fake.

          Possibly but then if they lose count they wouldn't know when to stop adding a few more.

    3. Anonymous Coward
      Anonymous Coward

      Obviously you can't count the votes, then. Every hate Trump statement is voted up, every statement that would indicate otherwise is heavily downvoted - even if likely correct.

      The bias is really obvious, and playing word games to try and deflect from it doesn't work for people who can think.

      According to some, we should wait for peer reviewed well designed studies - in other words, until after it's too late - to try anything. Not realizing how progress is made in such things, or the urgency of casting a wide enough net to maybe catch something at all. You have to begin somewhere, if there's a mistake, it's not then doing further testing as quickly as possible - oh, wait, that's being done. This is just an excuse to hate that I suspect is largely sour grapes.

      As a poster above mentioned, nothing helps after you're dead. Go ahead and wait - it won't hurt for long.

      1. Anonymous Coward
        Boffin

        we should wait for peer reviewed well designed studies

        We may not have time for really formal peer-review (although there's no reason why peer-review shouldn't happen very fast indeed if it needs to: there's this internet thingy now I'm told). But we should at least wait for studies that don't reek of incompetence or worse than that as this one so clearly does.

      2. Anonymous Coward
        Anonymous Coward

        You're right. There's some pretty virulent anti-DJT here.

        E.g. The idea that DJT is somehow responsible for some idiot ingesting poison (it will have been clearly labelled POISON on the packaging, as law proscribes) because the two chemical names sound similar is facile. Stupid people do stupid things and some people terminate their own existence while at it.

        That said. Someone should find out whether he had progeny, because if not, he is a top candidate for a Darwin award this year!

      3. Doctor Syntax Silver badge

        "According to some, we should wait for peer reviewed well designed studies - in other words, until after it's too late - to try anything."

        It's the peer reviewed well designed studies that tell you what to use in clinical practice. The substances tried in those studies aren't "anything", they're those that existing knowledge suggests might be useful and not likely to be harmful. Your "anything" ranges from water diluted with water diluted with more water to cyanide.

    4. Anonymous Coward
      Anonymous Coward

      Maybe they are all here to here the fat guy sing...

    5. Someone Else Silver badge

      I prefer MAGATs, the homophone is just exactly right...

  15. Curly4

    As you should know Trump stated that these drugs should be tested to see if they DID aid the recovery. At the same time he also said that those who wanted to use drugs should be allowed to do so under a doctor's supervision. These results if added to the other results could also show if these drugs should or could be use as a treatment or not. This is true even if the patients are approaching death if the results with the proper footnotes are included in the study would help refine the conditions that these drugs may be usable. But until the effectiveness drug is established no body would be forced to take the drugs, only volunteers. But this will have to have a waver from the CDC here in the US.

    1. Malcolm Weir

      This is really accurate. Trump didn't state they should be tested, he stated they had been and were looking good, and invoked the FDA's name to added credibility.

      I completely agree that there is a very reasonable comment that a leader could have made along the lines of "There has been some indications that an existing drug therapy for another disease could be beneficial to COVID-19 patients, and the FDA is doing great things to help investigate that"..

      The trouble is that Trump is apparently congenitally incapable of saying "good" when he could say "best", or "unhelpful" when he could use "bad". The man doesn't do nuance, and that's a problem in a world where nuance directly translates to (perhaps fractions) of a death rate; if a remark from a leader reduces / increases the fatality rate between (say) 4.21% and 4.20%, that's a difference of 32,000 bodies, i.e. the population of a small city...

      1. First Light

        There is video of Trump Sr speaking and it is the EXACT same kind of language, full of superlatives. Still playing out old family dramas in his head, that one.

  16. Richard Boyce

    Reader beware

    Some publications are reputable, but many are just designed to professionally masquerade as such to the unwary. There's no shortage of people willing to pay to promote their quackery in a "prestigous" journal, so the market meets that demand.

  17. a_yank_lurker

    The Problem

    Many have confused Trump comments on a preliminary report that indicates there might be a cure using existing drugs as opposed to someone who is saying use it now. This is forgetting, Trump and other leaders are focused on many other issues besides reading the details in a preliminary clinical report. What Trump was actually doing was telling people there a clinicians and scientists who are working on cures and vaccines and with some luck we might get a cure out of left field. So keep your hopes up because there is much more activity unreported in the media that might bear fruit, a point that is overlooked. Keeping morale up is an important part of a leader's job in any crisis.

    As someone who works in the pharmaceutical industry I am aware many organizations and companies are heavily focused on finding both a cure and a vaccine and getting both to market fast. But the public is largely unaware of these activities. So telling people while we do not either yet others are diligently working on both and anything promising will get to a larger scale trial as soon as we can gives hope that if you can hang on you there is light at the end of the tunnel.

    Whether the quinine/antibiotic regime works is apparently murky but it some are trying in trials to see what it does. If it does work, it might give us a better clue on how to handle similar viruses with existing drugs that nobody thought trying before.

    1. Francis Boyle

      I agree

      It's completely unreasonable to expect Trump to express an idea as complex as "people are working hard on treatments but results will take time" so, when he said something completely different, people should have understood that that was what he really meant.

    2. Stoneshop

      Re: The Problem

      This is forgetting, Trump and other leaders are focused on many other issues besides reading the details in a preliminary clinical report.

      In which case the smart thing to do is to let a specialist do the reporting.

      And like so often, someone needing to claim they're smart tends not to be. As evidenced here. Again.

    3. John Hana

      Re: The Problem

      Spot on. I completely agree with you.

  18. Anonymous Coward
    Anonymous Coward

    New French study confirms results

    https://techstartups.com/2020/03/27/coronavirus-cure-new-results-french-study-shows-combination-hydroxychloroquine-plaquenil-azithromycin-successfully-treated-80-coronavirus-patients-significant-dr/

    New study in France with a new cohort of 80 patients shows the drug combo works in all but the worst cases.

    Good news!

    1. Malcolm Weir

      Re: New French study confirms results

      Not really: there was no control group, so we have no idea what the prognosis would have been without the treatment (and I acknowledge that this is a horribly tricky issue for clinicians: if you believe a treatment will work, how can you ethically withhold it from the control group?).

      The potential issue is the same as that which homeopaths have been using to scam people for ages: was the improved outcome a function of the treatment, or of other factors incidental to the treatment? (With homeopathy, the source of the improved results wasn't the magic of the treatment, but the fact that the "treatment" was clean water, while other patients got untreated water!)

      1. Scott 1

        Re: New French study confirms results

        I fear that you are correct. However, it is so hard to not hope.

    2. Anonymous Coward
      Anonymous Coward

      Re: New French study confirms results

      That's a terrible study because there was no control group.

      1. Anonymous Coward
        Anonymous Coward

        Re: New French study confirms results

        ... and one assumes you'd have been fine with a control group of 80 of which some value greater than zero died.

        It's for the good of medical science, right?

        Turd.

        1. Phil O'Sophical Silver badge

          Re: New French study confirms results

          If, say, 5 people die in the trial, and you have no control group, you have no idea if the death rate wthout the treatment would have been 0 or 10, so for all you know the treatment might make things worse. You have to have a control group, it has nothing to do with " the good of medical science".

        2. Anonymous Coward
          Anonymous Coward

          Re: New French study confirms results

          Since this study treated fewer than 100% of potential candidates, there was a "control group", they just didn't bother pairing them to the ones they tested on or measuring their outcomes.

          The idea that you can't test a potential treatment unless you give it to everyone because more of the untreated ones might die is pretty stupid. What if the treatment was found to reduce symptoms in those who were treated but ALSO increase the percentage who die? Congratulations, you just killed people unnecessarily.

          These medications are known to have some fairly nasty side effects so it wouldn't be something you'd be offering to healthy people even if it was found to be beneficial in reducing the severity of symptoms and risk of death. It would only be given to those who have taken a turn for the worse so their symptoms have become worse than the side effects.

  19. Grogan Silver badge

    It's not so much about "virus levels", it's about surviving the infection. Much of the damage to tissue in a viral infection is the body's own immune system attacking cells. Necessary, to some extent, because virus infected cells need to be destroyed but if it goes too far it can kill the victim (lung tissue is pretty important obviously). That is how the hydroxychloroquine cocktail may help. It's an extension of "well, it helps with autoimmune diseases, so..." but its not been tested well enough for viral infections to make those claims. It is not anti-viral.

    1. Duncan Macdonald

      From the in-vitro tests carried out back in December, chloroquine inhibits viral reproduction. If these tests were correct and the same effect is observed in-vivo then a dose of chloroquine could give the immune system a few extra days to combat the infection. As chloroquine is a somewhat toxic drug, it is probably best only given to patients that need supplementary oxygen (people that are recovering without medical treatment should be left alone). It probably needs to be given before the patient reaches the stage of needing a respirator for best effect. (Once a patient needs a respirator, lung and possibly other organ damage has already started.)

  20. usariocalve

    It's amusing to me that people are fiddling while Rome burns. In an emergency all kinds of standards are thrown out the window.

    Or we can wait and die, which seems to be what "reasonable" people want us to do.

  21. Anonymous Coward
    Anonymous Coward

    Research on Coronaviruses has been ongoing since the 1960s, and as modern genetic methods have emerged so has understanding of Corona and other viruses in general including characterisation. Similarly, post the SARS and MERS outbreaks, research was and has been done on potential treatments some of which was cross-fertilised with work from HIV and Ebola. However, even with all this background work, the problem is that COVID-19 is a new, previously unknown, variation. We knew nothing about it really until January. Even in December all China knew was that it had an outbreak (these things are monitored globally because of the risk of the emergence of new diseases). Identifying the cause, the modes of transmission and then serious attempts at treatments all really started in earnest end of December/January under battle conditions - a total of 13-14 weeks to now, in total.

    The basic response was to throw anything credible at the disease, and that's what the Chinese did. Discarding treatments which seemed to make no difference and repeating with those which had some apparent benefits. This is straight Bayesian learning. It is different from inferential statistics that is normally associated with clinical trials. At the moment a number of candidate drugs have been identified. Hydroxychloroquine is one. Others have come out of the previous anti-viral research work, including 'designed' anti-virals that were previously aimed at HIV, Ebola or SARS. There are around 150-200 papers a day looking at this stuff - an absolute massive clinical and lab research effort.

    Hydroxychloroquine/chloroquine has been identified as a possible treatment. It has been shown to be effective in-vitro against SARS and it has some apparent effect in the 'throw everything at the wall' done so far. Plonkers drinking fishtank cleaner are irrelevant (equivalent to discarding warfarin because its also used for rat poison, or banning beer because pure alcohol kills - in drugs, dose is the difference between a poison and a cure). HCQ is a common, cheap anti-malarial with a known and relative safe risk profile for normal use (it's safe enough to be available without prescription in the UK) - if you've travelled to the tropics, there's a reasonable chance you've taken it.

    However, before going too far, although HCQ had an in-vitro (ie in a test tube) effect for SARS and other viruses, previous research found this didn't necessarily translate to an in-vivo effect. And some doctors have concerns that chloroquine might inhibit the natural immunity responses and so might make symptoms worse in some patients. The first part of the clinical trial process is therefore to test safety, not efficacy - small scale. If the treatment is safe, then it can be moved to larger efficacy trials (ie does it work). However, this takes time. If the treatment is determined to be safe, then there is an argument that doctors should have it available as a treatment option as the worst then that could happen is it doesn't work - no effect. As we know some frontline doctors have already identified that they have experience for the treatment being useful. Clinical tests in other countries also suggest some potentially positive results.

    If it is effective, that then runs into the next problem, which is production and manufacture. Chloroquine isn't a cure. If it works, then it limits the virus's symptoms and helps protect the lungs and prevent the pneumonia stage, and it is possibly best used as a prophylactic - ie to prevent the worst symptoms from happening early on after infection. Again, it isn't a cure, and it isn't a vaccine. Coronavirus would still continue to spread, and any vulnerable populations without access to or not using these treatment drugs would remain at risk.

    Manufacturers would have to ramp up production (which they are doing), and distribute to front line medical services in the first instance. Assuming it works, this would then cut the death rate. However, the rest of the population would still have to take social distancing measures until availability becomes widespread - HCQ might not work for everyone for instance. The risk of crowing too early is that it doesn't work, or doesn't work that well, but it encourages people to stop social distancing because they think there is 'a cure', or leads to panic buying - clearing out stocks for those who currently actually need it.

    While we would like hope - the information coming out is unbalanced. Newspapers deliberately mixing self-poisoning with the drug is terrible reporting. However Presidents over-promising is also pretty bad news. A little bit of cautious optimism while still self-isolating wouldn't go amiss though.

    1. John Brown (no body) Silver badge

      "However Presidents over-promising is also pretty bad news."

      The difference between Trumps announcements to his people and other world leaders announcements to their people is generally quite stark. Most world leaders seem to be being fairly frank about what is happening and what is likely to happen. Trump still seems to be in denial, or at least spinning the small amounts of good and simply not talking about the bad. Putin seems to be doing the same.

      1. John Brown (no body) Silver badge
        Trollface

        A downvote? I didn't realise there where Putin supports reading here too!

    2. Anonymous Coward
      Anonymous Coward

      Oh dear

      Couldn't have said it better myself.

      Buuuuut .... I am sure there will be quite a few people here who disagree and are eager to see people die in the name of clinical double blind tests and peer review. (see previous posts)

      1. Anonymous Coward
        Anonymous Coward

        Re: Oh dear

        eager to see people die in the name of clinical double blind tests and peer review

        Take 1000 people, and give them drug "X". 15 of them die from COVID-19.

        What have you learned about the effectiveness of drug "X" against COVID-19? Absolutely Nothing.

        Maybe those 15 would have died anyway, and you've wasted time & money that could have helped elsewhere.

        Maybe 25 would have died without the drug and you've saved 10 lives, or maybe only 5 would have died, and you've killed 10 people.

        Without clinical trials, double-blind tests and control groups you simply cannot know if drug "X" is helpful, harmless, or harmfull.

  22. Anonymous Coward
    Anonymous Coward

    "Low and behold". Dropped 20 scientist credibility points right there.

    1. ChrisBedford

      One hopes it wasn't the scientist who wrote that, but the reporter quoting a verbal statement.

      Oh but wait, reporters are supposed to be good at words. Ummm.

      1. jukejoint

        Low, wut lite thru yonder winder brakes?

        --- Billybob Shakespeare, probably

  23. Aquatyger

    Proof of concept

    There seems to be an awful lot of Trump Derangement Syndrome in this thread. Anyways, back to the chase.

    The suspicion that something was biased in this article was "a well-known French doctor and microbiologist who is skeptical of human-caused climate change".

    What has "skeptical of human-caused climate change" got to do with anything in the COVID-19 world. It just proves he is properly skeptical of any current paradigm. Also the trial was really just a "proof of concept" And it looked pretty good to me if the combination of hydroxychloroquine and azithromycin cleared 6 patients of virus in 5 days compared to a control group. A lot of "proof of concept" studies only have about 6 or so rabbits in each group and they are designed to pave the way to more rigorous studies. Rabbits are expensive but there appears to be plenty of sick people cheaply available for larger trials and happy to sign up for what appears to be a promising result.

    The final conclusion that some stupid people took an overdose of chloroquine phosphate is also irrelevant. I guess that was just to trigger the Trump Derangement Syndrome and increase the negative bias this article displayed. Sucked in.

  24. Anonymous Coward
    Anonymous Coward

    Antibiotic for a virus?

    I am not a medical researcher or doctor, but in what way is an antibiotic such as azithromycin useful against a virus? Does it help contain secondary bacterial infections or is it just wishful thinking?

    1. Aquatyger

      Re: Antibiotic for a virus?

      "Does it help contain secondary bacterial infections"

      That.

    2. Aquatyger

      Re: Antibiotic for a virus?

      This provides a nice explanation of the process of the disease. https://youtu.be/BtN-goy9VOY

  25. Ubermik

    What utter fake news nonsense, you need to do MUCH better.....

    The wife of the man who died from eating fish tank cleaner said EXACTLY who gave them the idea to eat it and it was NOT trump

    He also didnt initiate the trials for the drug regime, it wasnt HIS paper, he merely pointed out that there was "something" that "might" work for covid, which absolutely ANYONE in power would have mentioned to try and avoid panic

    The fact it didnt work out wasnt HIS fault, and its probably not going to be anything like the last drug treatment regime that is both tried AND fails miserably, thats kind of how science works, often you go through a 1000 failures before you get success

    I am very disappointed with this DELIBERATELY misleading sack of utter journalistic gutter trash and lies, you should be ashamed of yourselves publishing this tripe

    1. ChrisBedford

      Re: What utter fake news nonsense, you need to do MUCH better.....

      Naah. What you are disappointed about is that Trump's characteristic stupidity and style of rhetoric were even quoted at all.

    2. Anonymous Coward
      Anonymous Coward

      Re: What utter fake news nonsense, you need to do MUCH better.....

      Why would you mention something that is unproven and untested, thus causing panic buying by people who don't need it and leaving those you use it as a life saving medicine without any supply? Can't you see how fucking irresponsible and stupid that is?

    3. John Brown (no body) Silver badge

      Re: What utter fake news nonsense, you need to do MUCH better.....

      "which absolutely ANYONE in power would have mentioned to try and avoid panic"

      Most world leaders are NOT sugar coating things and are NOT spouting off about outside chances as beacons of hope to "avoid panic". Not surprisingly, in those countries, other than some initial panic buying in the shops, there has been a dearth of reports of panic in the streets. Maybe those in charge in the US actually think this is going to lead to riots and looting? I suppose with so many armed citizens and a constant diet of zombie apocalypse TV and Movies, the odds may be a bit higher there.

    4. Anonymous Coward
      Anonymous Coward

      Re: What utter fake news nonsense, you need to do MUCH better.....

      Husband 88 yo - victim.

      Wife 61 yo - fanatical DNC supporter and donor with history of psychological issues

      Husband ingests fatal dose of poison and wife ingests non-fatal dose and calls 911. Later blames POTUS (whom she hates viscerally).

      Murder she wrote!

  26. tjb

    SoonNursePreviousSoftwareDev

    I agree with many comment here. I try to look for successful interventions around the world, before forming opinions about problems/solutions (with coronavirus I have looked at Taiwan's response, along with China, South Korea and Vo, Italy) contrasted to yet unsuccessful ones(so far I judge US and many others as not successful yet). Ultimately hindsight will be the measure. Unfortunately, hindsight is not a process to solve/decide actions in future problems (but reflective/planning is, before the problem arises). Motivations are different for different players, politicians want re-election(decisive action, right or wrong gets votes, better than review/reflection on history/alternatives), business people ($$$ mostly, survival?), or effected people (situational basis/selfish, ~altruistic, treat other how you would like to be treated, treat other how they want to be treated).

    There is a large part of the general population (if not all) that do not possess sufficient critical thinking processes or reflective thinking processes to form relatively unbiased/unemotional viewpoints. They continue to form opinions based more on their emotional responses and snap judgments than scientific information (maybe because of their perceived level of stress and relative lack of time/interest in investigating). I also have feeling and 'intuit' hypothesis, but then try to research the facts (sometimes I "forget"/ignore critical contradictory information and need to be reminded of them). People have opinions that seem contradictory to others (climate science for example) holding on to facts supporting their beliefs, but ignoring/discrediting contradictory facts (a natural human response to the emotional feeling of being attacked overcoming rational thought process). The challenges of everyone is to have clear values/motivations (altruistic/selfish scale) and a sufficient measure of critical and reflective thinking processes to carry on a respectful discourse that contributes to advancing each others understanding and progress discourse and problem solving.

    That is why I tend to try to look for examples of successful instances of such discourse taking place for various problems, which have more to do with educating/showing people how valuing each other helps promote the growth of success and realize that some places are not yet capable of seeing the benefit of changing their behaviors. The United States is a fine example of where there is not enough of this respect, care and effort put into processes that solve problems very effectively. It may be better to put effort in to education, rather than discourse on a particular current problem, in the US.

  27. ChrisBedford

    It's not LOW and behold, people

    Lo, an archaic form of "look". Behold, ditto of "see".

    Look and see. "Low" means something else, doesn't it?

    1. Glenturret Single Malt

      Re: It's not LOW and behold, people

      Moo!

  28. FromTheRoot

    Don't believe your government she says

    I don't, but I also don't trust the doctors or the news, or the scientists, or even the register!

  29. Anonymous Coward
    Anonymous Coward

    Thanks to these fuckwits, my partner who has lupus is having trouble getting her essential hydroxychloroquine because the pharmacies are out of stock (in Australia) - either hoarding or anecdotally being taken by doctors who are writing scripts for themselves and their families based on zero evidence. Nice one, Trump!

    1. John Brown (no body) Silver badge

      "doctors who are writing scripts for themselves and their families"

      Are they all planning an acting career for the aftermath? Traveling players in the era of Mad Max?

    2. TomG

      I find it interesting that you think Trump has that much power in Australia. Sorry to hear about your partner. Hopefully the situation will ease up a little and she can get the medication soon.

      1. Anonymous Coward
        Anonymous Coward

        TDS respects no international border.

      2. Anonymous Coward
        Anonymous Coward

        I wouldn't have thought that either but there you go. One of her specialists actually rang her to tell her to get some immediately before everyone ran out of stock. Luckily she managed to find a couple of pharmacies with some but it was literally "that's the last of it". What about the people not so lucky?

  30. WeaselBreath

    Big Pharma News Story

    More Fake News!! Big pharma certainly does not want a 50 year old drug that no longer has a patent to be the cure. They would only make 100's of millions in profit. They need a "New" patented cure that will provide them with tens of billions in profit.

    1. Anonymous Coward
      Anonymous Coward

      Re: Big Pharma News Story

      I once addressed this issue over a few beers with a good friend, who just happens to be a PhD in microbiology working as a senior research scientist at a globally known pharma company.

      It was indeed disappointing to hear him confirm that "curative" is rarely the goal and that "palliative" is the principal focus of his organisation, and that this was overtly a financial consideration for the company. Drugs are expensive to develop and there needs to be a return of significant amount to make the R&D worthwhile.

      It's all very well thinking it's true as some sort of evil Big Pharma conspiracy, but having a significant player on the field say it aloud is a depressing jolt.

  31. derrybeg

    FDA issues emergency authorization of anti-malaria drug for coronavirus care

    FDA issues emergency authorization of anti-malaria drug for coronavirus care

    The drugs have been championed by President Donald Trump for treatment despite scant evidence.

    https://www.politico.com/news/2020/03/29/fda-emergency-authorization-anti-malaria-drug-155095

  32. MarkG.

    *Emergency Exception.

    Should make it available under medical supervision to everyone who wants it, Then compare data from this group with the ones who choose not to take the drugs. (This approach may save lives!)

    1. Anonymous Coward
      Anonymous Coward

      Re: *Emergency Exception.

      "under medical supervision to everyone who wants it"

      How else would one obtain a prescription drug?

      (Asking for a friend)

  33. Wzrd1 Silver badge

    Odd bootnote that's inaccurate and helpfully misleading

    A husband and wife in Arizona took chloroquine phosphate, an ingredient of fish parasite killers rather than the anti-malaria medication, following the President's recommendation. The man died soon after ingesting the toxic chemical. His spouse was left in a critical condition. "Trump kept saying it was basically pretty much a cure," she later told NBC. “Don’t take anything. Don’t believe anything. Don’t believe anything that the President says and his people ... call your doctor.”

    I'm fairly certain that none will disagree that chloroquine phosphate is chloroquine phosphate, regardless of its source. Chemistry 101 and all.

    Helpfully misleading in, most laypersons have no bloody clue how to create a proper dose of a drug from what is used for an aquarium for fish, due to concentration of chloroquine phosphate vs what is in a capsule/tablet and heaven knows what ingredients are considered acceptable for an aquarium, but likely wouldn't do a human very well. This debacle will hopefully discourage repetition, even if in the same time frame, someone in Africa also died of the same cause.

    When I need a medicine, I consult a physician, not a doctor with a bone through his nose and not some failed real estate typhoon (sorry, but he blew away more of his properties investments than a typhoon could even manage, but he's as disastrous for investors).

    But, feel free to ask my medical advise. It's always the same.

    See a physician, don't ask random strangers on the internet to medically help you and never, ever, *ever* accept a politician or failed unreality TV star for medical advice.

  34. goldcd

    Quite a fun analysis of his paper (and his previous questionable stuff)

    https://forbetterscience.com/2020/03/26/chloroquine-genius-didier-raoult-to-save-the-world-from-covid-19/

  35. dncnvncd

    Naysayers-Again!

    Curiosity and doubt are the two essential traits of any scientist whether they have more degrees than a thermometer or a backyard tinkerer. A degree of knowledge is required. Ingesting something clearly labeled as toxic with no recommended levels for human treatment, doesn't register high on the knowledge meter. In the case of COVID-19, China refused to share the knowledge they gained in testing and treatment as well as withholding a chemical they have a license to manufacture, probably given to them by a U.S. manufacturer, from the world. That said, the virus SARS-CoV-2, which causes COVID-19 is known allowing it's communicability to be studies as well as the stages of the illness it causes. It is caused a novel virus because it jumped from animals to humans. Therefore, there must be a novel approach which may not fit stale and staid scientific protocol. Including using anecdotal evidence to start clinical trials. Scientific trials begin in the lab in vitro before advancing in vivo in stages of ever larger sizes and differentiation. The anti-malaria drug is harsh and must be used under a doctors supervision. The HIV drugs prevent the pneumonia associated with COVID-19. Using drugs that treat similar symptoms in other diseases just makes sense in a pandemic. Why zoonotic diseases are on the rise is matter for deeper research and not urgent at this time. Simians are immune to SARS-CoV-19 so this virus is not new to them since they have developed a natural immunity. Most likely by natural selection. That isn't a valid option for humans and thus grasping at straws is wise when knowledge gained is applied.

    1. crayon

      Re: Naysayers-Again!

      "as well as withholding a chemical they have a license to manufacture, probably given to them by a U.S. manufacturer, from the world."

      Is there a problem with that? Given that they had to ensure enough supplies were available for domestic use? Now that the pandemic in China is somewhat under control, they are sending medical staff and supplies to various hard-hit places around the world - and then they're accused (by certain Western critics) of "facemask diplomacy".

  36. CAPS LOCK

    All this talk of hydroxychloroquine is making me want...

    ... a G&T. Cheers.

    1. gzuckier

      Re: All this talk of hydroxychloroquine is making me want...

      Note that tonic water has been limited to 83 ppm of quinine for quite a while now, due to quinine's toxicity. Which is cumulative over long periods, BTW.

      1. Anonymous Coward
        Anonymous Coward

        Re: All this talk of hydroxychloroquine is making me want...

        cumulatively good, if we take the Royal Family as examples ;)

  37. Someone Else Silver badge

    Start here...

    “Don’t take anything. Don’t believe anything. Don’t believe anything that the President says and his people ... call your doctor.”

  38. TomG

    Never take medical advice from non-medical personnel. Especially politicians such as the President of the United State of the Prime Minister of Australia.

  39. gzuckier

    "still too thin"

    That overstates the case, The evidence for efficacy of chloroquine, hydroxychloroquine, or just plain quinine is absolutely zero. The fact that a researcher says it's effective on the basis of data that shows zero efficacy does not constitute thin evidence.

    1. Anonymous Coward
      Anonymous Coward

      Re: "still too thin"

      There are in fact 10-15 years of research (probably more) into the efficacy of these compounds as treatments for corona vira. This is not even a remotely new line of research!

  40. Torchy

    Trump !

    I would not trust him if he told me that tomorrow is the day after today.

  41. Anonymous Coward 99

    Thanks to the possibility this might work, there is now a worldwide shortage of the drug, which is currently used to treat patients with things like Lupus. India has slapped on an export ban, so no more is coming. Net result - people are going to get worse and die from not having it.

    All I can say is it better help Covid patients, or Trump has harmed people (again) by ill-advised comments.

  42. Aquatyger

    Fake news?

    Apparently the involvement of Donald Trump with the fish tank cleaner lady is fake news. https://www.youtube.com/watch?v=-n4Ed9SD4Q0

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