3 ms·

Outcomes of hydroxychloroquine usage in US veterans hospitalized with Covid-19 [pdf]

17 points by origgm 6y ago

foxyv 6y ago
So in other words, still no positive results for Hydroxycloroquine treatment of Covid-19. Bummer.
KarlKemp 6y ago
Three times as many deaths with Trump’s “miracle drug” compared to control! Even HN was full of “but it’s possibly helpful and totally safe” comments. Long after that initial French study had been retracted and exposed as borderline fraudulent. This study alone killed 20 patients. I wonder what the ratio of changed minds / deaths is. And at what number this whole exercise could be considered worthwhile. But I guess the true believer will bemoan the lack of zinc (edit: nailed it!), or this “obviously” being the wrong group of patients, or asking for tests of smoked HC because it can’t get to the lungs otherwise. Or learn from the master and pivot to the next shiny policy. Which is, apparently, not processing a few thousand Green Card applications?
- adamiscool8 6y ago
  This is, most charitably, an uninformed (and presumably partisan) reading of the study. Let's try reading this paper the proper way, starting at the end: >the findings from this retrospective study suggest caution in using hydroxychloroquine in hospitalized Covid-19 patients, particularly when not combined with azithromycin. So that's not saying HCQ can't be helpful, or is a waste of time as you implied. That just says it requires caution, which is totally fair -- this is uncharted territory. What else do we have? >Our study cohort comprised only men whose median age was over 65 years. Therefore, the results may not necessarily reflect outcomes in women or in younger hospitalized populations OK, so we know the paper itself is a lot narrower in it's prescriptions than the many headlines that will be generate from it. It certainly didn't "kill 20 patients". >hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease, as assessed by baseline ventilatory status and metabolic and hematologic parameters. Thus, as expected, increased mortality was observed in patients treated with hydroxychloroquine, both with and without azithromycin. Nevertheless, the increased risk of overall mortality in the hydroxychloroquine-only group persisted after adjusting for the propensity of being treated with the drug. So the people who received HCQ+AZ were worse off from the jump, but they adjusted for propensity of treatment, now how was that done? >we created propensity scores for hydroxychloroquine use alone and hydroxychloroquine and azithromycin use during the hospital stay. Propensity scores were estimated via multinomial logistic regression of treatment group. All baseline covariates were included in the propensity score models. The propensity scores were entered into the outcome models with restricted cubic splines. Well, I don't know what that all means, but I can Googles -- here's a paper called "A Tutorial on Propensity Score Estimation for Multiple Treatments Using Generalized Boosted Models" [0], what does that have to say about this method? >If there are unmeasured variables that predict outcomes and differ among treatment groups then the estimates can be biased. This limitation, however, is not specific to the methods we present; indeed, all causal modeling strategies that use observational study data must contend with this limitation in one way or another. Hmm, so that's a weak point in this study for sure. How did the VA study contend with that? >We did, however adjust for a large number of Covid19-relevant confounders including comorbidities, medications, clinical and laboratory abnormalities. Despite propensity score adjustment for a large number of relevant confounders, we cannot rule out the possibility of selection bias or residual confounding. OK, so what did this study really find? That for men aged 65+ and above hospitalized with COVID-19, based on an adjusted and possibly confounded model of when HCQ/+AZ would be prescribed, those who received HCQ alone may have a 1.1-6.2x increased risk of mortality, but when combined with AZ did not lead to an increase in overall mortality, and in fact could reduce it by nearly half. But of course, that's not a sexy headline, and it certainly won't rally the right people. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710547/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710547/
  - woliveirajr 6y ago
    If I understand it correctly the groups had their risk of hazard adjusted, i.e., there was some estimative of the expected outcome if the HC wasn't used. Well, the HC adjust factor was 2.61, i.e., it was expected to have 2.61 more deaths than the no-HC group. So 11.4% x 2.61 = 29.75% and the final death rate in the group was 27.8%. It might not be an improvement but it doesn't seem to be something that killed the patients. Or where I'm wrong ?
vondur 6y ago
I thought the other major part of the treatment was including a zinc supplement in addition to the Azithromycin and Hydroxychloroquine?
- WilsonPaige 6y ago
  Yes. One of the earliest proponents of that was Dr. Zev Zelenko: https://www.youtube.com/watch?v=4ulqf5NXhms https://www.youtube.com/watch?v=4ulqf5NXhms and https://twitter.com/RossFairchild/status/1242263727325483010 https://twitter.com/RossFairchild/status/1242263727325483010? "Dr Zelenko statistics – 699 cases / 0 deaths = 0% death rate PATIENTS TREATED WITH THREE DRUG REGIMEN 1- hydroxychloroquine 200mg twice a day for 5 days 2- azithromycin 500mg once a day for five days 3- zinc sulfate 220mg once a day for five days CONCLUSION – TREAT AS EARLY AND AS AGGRESSIVELY AS POSSIBLE IN THE OUTPATIENT SETTING Respectfully, Dr. Vladimir (Zev) Zelenko" But Zelenko treated his patients _early_; he didn't wait until they had pneumonia or other lung problems to administer the triad of drugs. The recent studies that "disprove hydroxychloroquine/chloroquin" differ from Zelenko's suggested treatment in that: a) they select patients where disease is in an advanced stage, i.e., in in the lungs and/or pneumonia/SARS/ARDS has developed, b) they don't administer zinc at all: they may not administer azithromycin, c) these studies usually _overdose_ the hydroxychloroquine/chloroquin. Note that Zelenko used only 200mg hydroxychloroquine twice a day. Zelenko makes it clear that his goal was to defeat the virus early (ergo the zinc sulfate + hydroxychloroquine as a zinc ionophore, which allows the zinc zn++ ion to move from the bloodstream into each cell's cytoplasm where viral replication takes polace. Zelenko also clearly notes (in other places) that the azithromycin was a trick taken from ICU doctors, a drug intended to _prevent_ opportunistic bacterial infection consequent to the virus damaging lung tissue. Waiting for pheumonia/SARS/ARDS to develop before deploying azithromycin or other antibiotics should be considered medical negligence. Even medicine can't avoid politics these days.
- IAmEveryone 6y ago
  Funny, your comment from 23 days ago only mentions Hydroxychloroquine and Azithromycin: https://news.ycombinator.com/item?id=22721807 https://news.ycombinator.com/item?id=22721807

17 points by origgm 6y ago

So in other words, still no positive results for Hydroxycloroquine treatment of Covid-19. Bummer.

Three times as many deaths with Trump’s “miracle drug” compared to control! Even HN was full of “but it’s possibly helpful and totally safe” comments. Long after that initial French study had been retracted and exposed as borderline fraudulent. This study alone killed 20 patients. I wonder what the ratio of changed minds / deaths is. And at what number this whole exercise could be considered worthwhile. But I guess the true believer will bemoan the lack of zinc (edit: nailed it!), or this “obviously” being the wrong group of patients, or asking for tests of smoked HC because it can’t get to the lungs otherwise. Or learn from the master and pivot to the next shiny policy. Which is, apparently, not processing a few thousand Green Card applications?

adamiscool8 6y ago
This is, most charitably, an uninformed (and presumably partisan) reading of the study. Let's try reading this paper the proper way, starting at the end: >the findings from this retrospective study suggest caution in using hydroxychloroquine in hospitalized Covid-19 patients, particularly when not combined with azithromycin. So that's not saying HCQ can't be helpful, or is a waste of time as you implied. That just says it requires caution, which is totally fair -- this is uncharted territory. What else do we have? >Our study cohort comprised only men whose median age was over 65 years. Therefore, the results may not necessarily reflect outcomes in women or in younger hospitalized populations OK, so we know the paper itself is a lot narrower in it's prescriptions than the many headlines that will be generate from it. It certainly didn't "kill 20 patients". >hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease, as assessed by baseline ventilatory status and metabolic and hematologic parameters. Thus, as expected, increased mortality was observed in patients treated with hydroxychloroquine, both with and without azithromycin. Nevertheless, the increased risk of overall mortality in the hydroxychloroquine-only group persisted after adjusting for the propensity of being treated with the drug. So the people who received HCQ+AZ were worse off from the jump, but they adjusted for propensity of treatment, now how was that done? >we created propensity scores for hydroxychloroquine use alone and hydroxychloroquine and azithromycin use during the hospital stay. Propensity scores were estimated via multinomial logistic regression of treatment group. All baseline covariates were included in the propensity score models. The propensity scores were entered into the outcome models with restricted cubic splines. Well, I don't know what that all means, but I can Googles -- here's a paper called "A Tutorial on Propensity Score Estimation for Multiple Treatments Using Generalized Boosted Models" [0], what does that have to say about this method? >If there are unmeasured variables that predict outcomes and differ among treatment groups then the estimates can be biased. This limitation, however, is not specific to the methods we present; indeed, all causal modeling strategies that use observational study data must contend with this limitation in one way or another. Hmm, so that's a weak point in this study for sure. How did the VA study contend with that? >We did, however adjust for a large number of Covid19-relevant confounders including comorbidities, medications, clinical and laboratory abnormalities. Despite propensity score adjustment for a large number of relevant confounders, we cannot rule out the possibility of selection bias or residual confounding. OK, so what did this study really find? That for men aged 65+ and above hospitalized with COVID-19, based on an adjusted and possibly confounded model of when HCQ/+AZ would be prescribed, those who received HCQ alone may have a 1.1-6.2x increased risk of mortality, but when combined with AZ did not lead to an increase in overall mortality, and in fact could reduce it by nearly half. But of course, that's not a sexy headline, and it certainly won't rally the right people. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710547/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710547/
- woliveirajr 6y ago
  If I understand it correctly the groups had their risk of hazard adjusted, i.e., there was some estimative of the expected outcome if the HC wasn't used. Well, the HC adjust factor was 2.61, i.e., it was expected to have 2.61 more deaths than the no-HC group. So 11.4% x 2.61 = 29.75% and the final death rate in the group was 27.8%. It might not be an improvement but it doesn't seem to be something that killed the patients. Or where I'm wrong ?

vondur 6y ago

I thought the other major part of the treatment was including a zinc supplement in addition to the Azithromycin and Hydroxychloroquine?

WilsonPaige 6y ago
Yes. One of the earliest proponents of that was Dr. Zev Zelenko: https://www.youtube.com/watch?v=4ulqf5NXhms https://www.youtube.com/watch?v=4ulqf5NXhms and https://twitter.com/RossFairchild/status/1242263727325483010 https://twitter.com/RossFairchild/status/1242263727325483010? "Dr Zelenko statistics – 699 cases / 0 deaths = 0% death rate PATIENTS TREATED WITH THREE DRUG REGIMEN 1- hydroxychloroquine 200mg twice a day for 5 days 2- azithromycin 500mg once a day for five days 3- zinc sulfate 220mg once a day for five days CONCLUSION – TREAT AS EARLY AND AS AGGRESSIVELY AS POSSIBLE IN THE OUTPATIENT SETTING Respectfully, Dr. Vladimir (Zev) Zelenko" But Zelenko treated his patients _early_; he didn't wait until they had pneumonia or other lung problems to administer the triad of drugs. The recent studies that "disprove hydroxychloroquine/chloroquin" differ from Zelenko's suggested treatment in that: a) they select patients where disease is in an advanced stage, i.e., in in the lungs and/or pneumonia/SARS/ARDS has developed, b) they don't administer zinc at all: they may not administer azithromycin, c) these studies usually _overdose_ the hydroxychloroquine/chloroquin. Note that Zelenko used only 200mg hydroxychloroquine twice a day. Zelenko makes it clear that his goal was to defeat the virus early (ergo the zinc sulfate + hydroxychloroquine as a zinc ionophore, which allows the zinc zn++ ion to move from the bloodstream into each cell's cytoplasm where viral replication takes polace. Zelenko also clearly notes (in other places) that the azithromycin was a trick taken from ICU doctors, a drug intended to _prevent_ opportunistic bacterial infection consequent to the virus damaging lung tissue. Waiting for pheumonia/SARS/ARDS to develop before deploying azithromycin or other antibiotics should be considered medical negligence. Even medicine can't avoid politics these days.
IAmEveryone 6y ago
Funny, your comment from 23 days ago only mentions Hydroxychloroquine and Azithromycin: https://news.ycombinator.com/item?id=22721807 https://news.ycombinator.com/item?id=22721807