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Medicine

Study Finds Hydroxychloroquine May Have Boosted Survival. Other Researchers Have Doubts (cnn.com) 173

"A surprising new study found the controversial antimalarial drug hydroxychloroquine helped patients better survive in the hospital," reports CNN. "But the findings, like the federal government's use of the drug itself, were disputed." A team at Henry Ford Health System in southeast Michigan said Thursday their study of 2,541 hospitalized patients found that those given hydroxychloroquine were much less likely to die. Dr. Marcus Zervos, division head of infectious disease for Henry Ford Health System, said 26% of those not given hydroxychloroquine died, compared to 13% of those who got the drug. The team looked back at everyone treated in the hospital system since the first patient in March. "Overall crude mortality rates were 18.1% in the entire cohort, 13.5% in the hydroxychloroquine alone group, 20.1% among those receiving hydroxychloroquine plus azithromycin, 22.4% among the azithromycin alone group, and 26.4% for neither drug," the team wrote in a report published in the International Journal of Infectious Diseases.

It's a surprising finding because several other studies have found no benefit from hydroxychloroquine, a drug originally developed to treat and prevent malaria...

"Our results do differ from some other studies," Zervos told a news conference. "What we think was important in ours ... is that patients were treated early. For hydroxychloroquine to have a benefit, it needs to begin before the patients begin to suffer some of the severe immune reactions that patients can have with Covid," he added. The Henry Ford team also monitored patients carefully for heart problems, he said...

Researchers not involved with the study were critical. They noted that the Henry Ford team did not randomly treat patients but selected them for various treatments based on certain criteria. "As the Henry Ford Health System became more experienced in treating patients with COVID-19, survival may have improved, regardless of the use of specific therapies," Dr. Todd Lee of the Royal Victoria Hospital in Montreal, Canada, and colleagues wrote in a commentary in the same journal. "Finally, concomitant steroid use in patients receiving hydroxychloroquine was more than double the non-treated group. This is relevant considering the recent RECOVERY trial that showed a mortality benefit with dexamethasone." The steroid dexamethasone can reduce inflammation in seriously ill patients...

Eli Rosenberg [lead author of a New York study of hydroxychloroquine], also pointed out that the Detroit paper excluded 267 patients — nearly 10% of the study population — who had not yet been discharged from the hospital. He said this might have skewed the results to make hydroxychloroquine look better than it really was.

"There's a little bit of loosey-goosiness here in all this," he told CNN.

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Study Finds Hydroxychloroquine May Have Boosted Survival. Other Researchers Have Doubts

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  • Simple ruling (Score:4, Insightful)

    by Opportunist ( 166417 ) on Sunday July 05, 2020 @04:13AM (#60263108)

    Was it double blind? No? Chuck it in the bin.

    Seriously, with a disease that has SO many variables, you can so easily fudge results that it's at best a honest mistake and at worst an attempt to mislead. At this stage I'm honestly surprised to homeopathetic idiots didn't try to push their snakeoil, claiming that they cured Covid successfully by carefully selecting the patients that get their sugar balls.

    • Re:Simple ruling (Score:4, Informative)

      by thegarbz ( 1787294 ) on Sunday July 05, 2020 @04:52AM (#60263134)

      At this stage I'm honestly surprised to homeopathetic idiots didn't try to push their snakeoil

      They did! The FDA maintains a list of warning letters they've sent out to companies for fradulant claims on COVID-19 be it cures, preventatives, or unapproved home test kits. There's actually oils in the list too, preventative "essential oils".
      https://www.fda.gov/consumers/... [fda.gov]

      • Yes, various (essential) snakeoils have been released, but so far (at least to my knowledge) their lobbying groups have been surprisingly silent. Probably because they know better.

        • Sure because it's one thing to sell high priced water to hypochondriacs, it's entirely different to be responsible for helping to spread a plague.

          A friend's gf has been "taking" expensive water for decades. She's dumb as rocks. He's a science genius but eventually gave up trying to explain to her why it's bullshit and all the real science that proves it.

    • Re:Simple ruling (Score:5, Insightful)

      by ilguido ( 1704434 ) on Sunday July 05, 2020 @05:03AM (#60263150)

      Was it double blind? No? Chuck it in the bin.

      That is utterly idiotic. When they say that Covid-19 is more dangerous to elders, did they perform a double-blind to judge that? When they say that Covid-19 is more dangerous to people with certain conditions, did they perform a double-blind to assess that? When they say that Covid-19 is more dangerous to men than women, did they perform a double blind to say that? When they say that the viral load is linked to the severity of symptoms, did they perform a double blind?

      Nope, they observed what happened. Like the NY medics who wrote: "Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality" [springer.com].

      • Re:Simple ruling (Score:5, Insightful)

        by Opportunist ( 166417 ) on Sunday July 05, 2020 @05:34AM (#60263178)

        How do you just observe what happens when you get to pick and choose the conditions under which you observe? If you get to choose the patients that get a certain medication, you obviously have the option to skew the outcome in the way you prefer. Unless you can show that your sample group and the control group are actually comparable, any kind of comparison is bollocks.

        • Re:Simple ruling (Score:5, Insightful)

          by ilguido ( 1704434 ) on Sunday July 05, 2020 @06:03AM (#60263200)

          Unless you can show that your sample group and the control group are actually comparable, any kind of comparison is bollocks.

          That is exactly what the Henry Ford Health System study and the NY study (and others by the way) tried to achieve: define comparable sample groups, so to get some sensible results.

          Furthermore, I'd like to point out the fact that the double-blind is not a method about picking good sample groups. It is about removing biases, but since the biggest bias is intentional fraud (e.g. being paid by some big pharma to get some given results, e.g. advancing someone's career at the expenses of someone else etc.), in the end double-blind gets trapped in the "Who watches the watchers" dilemma [wikipedia.org]. Double blind is like security through obscurity (am I on a nerdy site?) and we all know that security through obscurity does not work in practice even if it sounds good in theory.

          • The biggest bias at this point is making headlines. And you will make headlines by having a cure for Covid.

            • The biggest bias at this point is making headlines. And you will make headlines by having a cure for Covid.

              That is nothing compared to the amount of money you could make with a NEW cure. That is why, while there is a tremendous scientific crisis, because research with negative results is done, but rarely published (e.g. infamously for antidepressants [crossfit.com]), instead you read a lot of negative results published (and sometimes retracted) for Hydroxychloroquine.

            • Re:Simple ruling (Score:4, Insightful)

              by LynnwoodRooster ( 966895 ) on Sunday July 05, 2020 @10:14AM (#60263642) Journal

              This is not a cure for SARS-CoV2. This is a treatment to increase the survival rate of for those suffering from it. You're apparently criticizing the study and drugs used because you don't understand what they're trying to address and how they're being used.

              With a typical flu, lots of fluids are recommended as they increase your survivability - you don't dehydrate and die [cdc.gov]. Does that mean that fluids are a cure?

              • I'm the last person who'd say that only a perfect cure is worth using. The masks are a great idea because if only one infection can somehow be avoided by them, they already served their purpose because it's side-effect free. Hell, if we only think it might serve a purpose it beats doing nothing.

                Chloroquine is anything but side effect free. It is taxing on the coronary system and it can wreak havoc to your glucose levels, making it dangerous to diabetics. And to make matters worse, the chloroquine group of m

          • Double blind is like security through obscurity (am I on a nerdy site?) and we all know that security through obscurity does not work in practice even if it sounds good in theory.

            Security through obscurity does not work alone, but can be a fun (and perhaps useful) layer, assuming one does not invest too much time into it. To stall with the hope of detecting (in a security context) if nothing else.

            Why double blind? Because people are people even when they're not intentionally being the absolute worst.

            IMO,

          • by q_e_t ( 5104099 )
            The problem with trying to define comparable subgroups at this stage is that without fully understanding the risk factors for death in COVID cases such that you can truly select comparable subgroups, it's difficult to know if you have comparable subgroups. I think it would be reasonable to suggest that you can probably get close, but there is still a chance of confounding factors. The level of effect suggested by the study is also very strong.
          • Unless you can show that your sample group and the control group are actually comparable, any kind of comparison is bollocks.

            That is exactly what the Henry Ford Health System study and the NY study (and others by the way) tried to achieve: define comparable sample groups, so to get some sensible results.

            This is exactly what the two studies did not do.

            There was no attempt in either this study or the NY study to match the groups. Read the summary.

            That's why this study is so heavily criticized.

            Furthermore, I'd like to point out the fact that the double-blind is not a method about picking good sample groups.

            Good point. The correctly phrased criticism is that this study was not controlled.

            With no matched control group, you don't know what it means.

      • Re:Simple ruling (Score:5, Insightful)

        by dirk ( 87083 ) <dirk@one.net> on Sunday July 05, 2020 @07:39AM (#60263354) Homepage

        The fact this is voted up as "insightful" shows how many people have no idea no idea how medicine works. There was no study to determine who COVID19 is more dangerous to because that is not what a study is for. That is an observation and is figured out by looking at the data and extrapolating from it. This is similar to saying "more people die in high speed car crashes than low speed crashes". You looks at the data and see what it tells you. It does not tell you if something works, it tell you what happens based on what has already happened.

        Drug studies are meant to determine if a drug first is relatively safe (compared to the results expected), second if it does what it claims, and third if it does it better than other things already available. To determine points 2 and 3, there are very specific rules that must be followed to eliminate bias and bad results. The biggest one is the study being double-blind. This means not only do the patients not know what they are receiving (the experimental drugs, a different drug, or placebo depending on the study) but the doctor does not either. This eliminates any biases based on knowing what the patient is receiving. The second rule is that patients should not be receiving any other treatments that can affect the results (and if other treatments are given, they should be as close as possible across all groups). For example in this case, steroid use in HCQ patients was double that of the other group.This could mean that steroid us, not HCQ, causes better results. If this was the only study to be conducted, these results would be important. But since other studies have already been done with more rigorous standards, these results are fairly meaningless. The fact it is even being talked about is just a result of the politics at play.

      • by XXongo ( 3986865 )

        Was it double blind? No? Chuck it in the bin.

        That is utterly idiotic.

        Unfortunately, it's not. The study was badly done.

        Unless the group given the treatment is identical to the group not given the treatment, you can't conclude anything..

        Really, this is the very first rule of science.

        When they say that Covid-19 is more dangerous to elders, did they perform a double-blind to judge that?

        Since the researchers didn't select which elders to expose to the disease, yes. If they had compared, say, people over 60 in France to people under 60 in Germany, that would be a failure.

        Since, however, the population of seniors were not necessarily exposed under identical conditions: no. You

        • Was it double blind? No? Chuck it in the bin.

          That is utterly idiotic.

          Unfortunately, it's not. The study was badly done.

          Unless the group given the treatment is identical to the group not given the treatment, you can't conclude anything..

          And that has nothing to do with double-blind. Cheers.

        • Unless the group given the treatment is identical to the group not given the treatment, you can't conclude anything..
          Really, this is the very first rule of science.

          That's not the first rule of science.

    • Re:Simple ruling (Score:4, Insightful)

      by xonen ( 774419 ) on Sunday July 05, 2020 @05:34AM (#60263176) Journal

      If any, this whole topic shows that people will just believe what they already believe in, and selectively absorb information. This confirmation bias leads nowhere, or actually it leads somewhere: polarization.

      Only very few people i know or i encounter on the internet dare to be open-minded and inform themselves of all sides of the story, without judging too fast. How can you be so very sure of what you think? I for myself don't. I have an opinion, but i'm not sure i'm right. But i do observe that many people are loosing their sense of proportionality, or blindly stick to their believes discarding any evidence that not match that world views.

      I can summarize this all by asking: Where is the love. Where is the adult debate. Without calling each other idiots.

      Personally i try to stick with this quote: 'i disagree with what you say, but i'll defend to the death your right to say it' (Voltaire). But please say it polite and respectful.

      • Re: (Score:3, Interesting)

        by Opportunist ( 166417 )

        I don't say that chloroquine does not work. I only say that this study proves nothing. If you want to know whether hydrochloroquine is a suitable cure or treatment, you'd have to do a double blind study with a sensibly selection of a study group. Even if the benefit only marginally beats the side effects, it would certainly be a better choice than doing nothing. Unfortunately, hydrochloroquine does have side effects that may even be deadly with patients that have coronary diseases and you better not be a di

        • by q_e_t ( 5104099 )
          You don't have to do a double-blind study. Indeed, many treatments are not determined by double-blind studies as it would be unethical to do so. A double-blind study will show you more clearly which is the best treatment, but it isn't the only way if the effect is sufficiently large.
          • Again, if you have SO many variables as you have with this infection, the potential for abuse is too large to consider any kind of study credible that doesn't ensure that those variables are all taken into account.

    • I don't know if that is the standard on which this should be based, but this study doesn't even have a control group. So by any reasonable standard, this study is useless at best.

    • It wasn't even single blind. Or random. And no control.

      This is the type of purely-observational science you resort to only when there is nothing else available to draw conclusions from.

    • More than likely as an infection the answer is that it's not simple. This study says at best HCQ may help in boosting survival rates. It however definitively says that HCQ is not some sort of cure. There are also a lot of questions that come arise from the conclusions of the study that will need further investigation.
    • by fermion ( 181285 )
      This is how it gets started, a single of a few studies, often paid for by a special interest, gets disproportionate consideration, and the science is gone. Smoking is beneficial and necessary. Dangerous drugs are safe. Climate change is a Chinese Hoax.
    • Double blind would have been criminally irresponsible. Hydroxychloroquine has some known , potentially fatal, side effects that physicians have to be alert to. If one of those side effects manifests, a physician has to be able to respond appropriately with the knowledge that .hydroxychloroquine was in use.
    • Well, among FPs on Slashdot 2020, that one is not too bad. However I think your [Opportunist's] focus was rather too narrow for the Insightful moderation, even though you were focusing on a key aspect. Let me try to clarify, then I can look deeper to see if anyone went there...

      There are two research paths we can consider. For hypothesis-driven research, you [a scientist or researcher (selected at random?)] figure out IN ADVANCE what the specific research question is and then you design an experiment or stud

  • Hopefully it will put to rest the stupid goal shifting since the mortality rate of HCQ is lower than the mortality rate of HCQ when combined with whatever goal shifting medicine is in vogue for Trump supporters to promote today.

  • by Zorpheus ( 857617 ) on Sunday July 05, 2020 @04:56AM (#60263138)
    This sentence at the end of the summary is most important:
    "concomitant steroid use in patients receiving hydroxychloroquine was more than double the non-treated group. This is relevant considering the recent RECOVERY trial that showed a mortality benefit with dexamethasone"
    • Personally I would go with the double blind placebo controlled trial that says steroids cut death rates by 30% for ventilated patients and 20% for patients on oxygen. The retrospective study reported here is unable to distinguish what benefit any of the treatment regimes might have had..

      • by eclectro ( 227083 ) on Sunday July 05, 2020 @06:06AM (#60263204)

        Actually there's more to it than just that. The steroid dexamethasone appears to be only useful when patients have to be put on a ventallator, I.e. at later stages of the disease and not before. Whereas the HCQ as stated above was done early as possible in the course of the disease. By time later stages of the disease have arrived, HCQ (and remdessivir also for that matter) was ineffective.

        So, all those studies that "proved" that HCQ was ineffective may be outright wrong without taking the "stage" of the disease in account. Considering the rancid political environment it does beg the question if this carelessness was purposeful or not.

        • So far, every study I saw that 'proves it works' was for relatively low dose early intervention (400 ug) to dampen a cytokine storm and every study that 'proves it doesn't work', was for late stage high dose (2000 ug) treatment when the patient was almost dead already. So all the studies are quite correct. It just depends on what the doctors want to achieve: Help people = small doses early; Kill people = high doses too late.
          • by XXongo ( 3986865 )

            So far, every study I saw that 'proves it works' was for relatively low dose early intervention (400 ug) to dampen a cytokine storm and every study that 'proves it doesn't work', was for late stage high dose (2000 ug) treatment when the patient was almost dead already. So all the studies are quite correct. It just depends on what the doctors want to achieve: Help people = small doses early; Kill people = high doses too late.

            Yes, that's the hypothesis which needs to be tested:

            Unfortunately, because there were selection effects and no control group, this particular study does not confirm that hypothesis (nor contradict it).

            So far, there isn't any study that confirms that hypothesis. It's still a hypothesis.

        • by q_e_t ( 5104099 )
          But those receiving the steroid throughout are also receiving it if they are on a ventilator, so it's not clear to me how you would disambiguate the steroid effect here.
      • Personally I would go with the double blind placebo controlled trial that says steroids cut death rates by 30% for ventilated patients and 20% for patients on oxygen.

        Given that the claimed benefit was more than twice that of the RECOVERY study, the numbers don't argue that that the steroid benefits observed there are the full explanation. Nor do they argue that this plus the difference between a double-blind and a retrospective data-mining inadequately controlling correlated differences between the groups

  • by Futurepower(R) ( 558542 ) on Sunday July 05, 2020 @05:15AM (#60263164) Homepage
    Posted March 30, 2020:

    Coronavirus successful treatment: Costs only $20. [slashdot.org]

    Quote: "We know that hydroxychloroquine helps Zinc enter the cell. We know that Zinc slows viral replication within the cell."

    Research, published June 12, 2020: Zinc, a micronutrient required for immunocompetence, is found deficient in populations. [medrxiv.org]
  • A difference _this_ large would have shown up in other studies, even if smaller. It did not. This study was either botched due to incompetence or due to gross scientific misconduct.

    • It's not so much that the study is botched, but this type of retrospective observational study is extremely prone to bias, and the biases can be surprisingly large. This is why the gold-standard for an intervention trial is a randomised controlled trial, preferably double blinded.

      For example, the different treatments were chosen on an ad hoc basis - while there may not have been a formal protocol for choosing a treatment, the prescribing doctors may have been going on "gut instinct" - this person is high
    • A difference _this_ large would have shown up in other studies, even if smaller. It did not. This study was either botched due to incompetence or due to gross scientific misconduct.

      I wouldn't say botched as much as all these studies may have uncontrolled factors that affect the conclusion. Under controlled circumstances, these factors can be minimized or removed by selection or experimental design; however, during the current pandemic, some factors are beyond the study's control.

    • Other studies have found [kataeb.org] found [ny1.com] it works. So much so even Governor Cuomo grudgingly admitted it seems to work [breitbart.com]. But we refuse to accept that data, so we tear each study down for some small reason or another.
  • Of course they were. They go against the rhetoric.
    • HCQ seems to be a very politically convenient drug. Depending on the dose, one can either help people (low dose), or kill people (high dose). It seems that Republicans prefer the former and Democrats the latter. That the drug is extremely cheap, probably also helps the high dosers.
      • One of the problems with hydroxychloroquinine is the very narrow theraputic window - the amount you need to be effective is only slightly less than the lethal dose, so the doctors have to pay close attention to dosing and monitoring patients. Perfectly safe, if you have well-trained and attentive doctors - but not safe if unqualified quacks are handing it out, or even in a hospital environment operating far above capacity where there is an increased probability of error.

      • Any drug would be politically convenient. If there were a drug that would cure the disease with a quick pill, then the whole lockdown mess would be instantly pointless - the economic disaster could be averted, and life would go back to normal. So a lot of people are really desperate for such a magic bullet, and not above clutching at straws.

  • ... if your elderly parent or child got infected with COVID-19?

    • by dfghjk ( 711126 )

      Would my doctor recommend it? No he wouldn't and yes I would. Also, why would I be offered a treatment to "turn down" when someone else got infected?

  • but to get it to do that you have to dose so high you risk heart complications. This has been known for ages. The drug fights viruses but it's likely to give you a heart attack at doses high enough to do that.

    I can cure you completely with a spoonful of arsenic, but the side effect is death.
  • May be someone other than the covid-19 patients.

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