Posted by Jeff Id on July 3, 2020
Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
A new study of over 2000 hospitalized patients reveals that Hydroxychloroquine works very well in treatment of COVID. The reason I’m so excited about this one is because unlike the poor studies that I’ve written about already, this study controlled the dosages, use the correct levels of HCQ and Azythromycin per other studies, and matched patients to each other by their own health situations. This matching of health condition is the proper method to control the confounding factors in a situation where testing cannot be double-blind. The health of the patient is what the frustratingly fake studies didn’t correct for, but certain political pressures made them popular.
This is absolutely the most conclusive research produced to date by anyone, due mostly to the quality of the approach. No one has published this quality level of work on HCQ on humans prior to this.
HCQ reduced deaths by half from the untreated patients.
Of note, this was a very large study:
The results of this study demonstrate that in a strictly monitored protocol-driven in-hospital setting, treatment with hydroxychloroquine alone and hydroxychloroquine + azithromycin was associated with a significant reduction in mortality among patients hospitalized with COVID-19. In this study, among one of the largest COVID-19 hospital patient cohorts (n = 2,541) assembled in a single institution, overall in-hospital COVID-19 associated mortality was 18.1% reflecting a high prevalence of co-morbid conditions in COVID-19 patients admitted to our institution.
And Safe:
To mitigate potential limitations associated with missing or inaccurate documentation in electronic medical records, we manually reviewed all deaths to confirm the primary mortality outcome and ascertain the cause of death. A review of our COVID-19 mortality data demonstrated no major cardiac arrhythmias; specifically, no torsades de pointes that has been observed with hydroxychloroquine treatment.
My bold of course. That means that HCQ is still not dangerous folks!!
Look at this powerful result:
The Cox regression result for the two propensity matched groups (Table 4) indicates that treatment with hydroxychloroquine resulted in a mortality hazard ratio decrease of 51% (p = 0.009). The resulting Kaplan-Meier survival curves within the propensity matched setting displayed significantly better survival in the hydroxychloroquine treated group, with the enhanced survival persisting all the way out to 28 days from admission (Fig. 2).
Also:
I found it very interesting that the Azythromycin didn’t work as well in combination with HCQ but it did better by itself than no treatment. I also found it a little overly deferential in its recognition of the bad papers which others have produced, but those who know me probably aren’t surprised by that.
I want to thank all of these researchers who did their job so well. Saving lives the right way.
Samia Arshad, Paul Kilgore, Zohra S. Chaudhry, Gordon Jacobsen, Dee Dee Wang, Kylie Huitsing, Indira Brar, George J. Alangaden, Mayur S. Ramesh, John E. McKinnon, William O’Neill, Marcus Zervos, Henry Ford COVID-19 Task Force<ce:author-group id=”aug0010″>, Varidhi Nauriyal, Asif Abdul Hamed, Owais Nadeem, Jennifer Swiderek, Amanda Godfrey, Jeffrey Jennings, Jayna Gardner-Gray, Adam M Ackerman, Jonathan Lezotte, Joseph Ruhala, Raef Fadel, Amit Vahia, Smitha Gudipati, Tommy Parraga, Anita Shallal, Gina Maki, Zain Tariq, Geehan Suleyman, Nicholas Yared, Erica Herc, Johnathan Williams, Odaliz Abreu Lanfranco, Pallavi Bhargava, Katherine Reyes, Anne Chen
Well done!
Please watch this video. Two doctors (one ER one cardiologist) speak on Pandemic. Allegations are made. 1. moving covid positive patients to nursing homes; 2. mischaracterization of hydroxychloroquine. Vital information to anyone who wants to cut through the media narrative and who really wants to save lives.
https://forbiddenknowledgetv.net/doctors-break-down-covid-response-and-the-demonization-of-hcq/
For the memory impaired:
“Hydroxychloroquine is the most disappointing, disavowed drug that researchers keep studying for COVID-19
Barely three months ago, the anti-malarial drug that President Trump touted seemed like such a sure bet against COVID-19 that Susanna Naggie had a tough time setting up a national clinical trial comparing it to placebo. Colleagues said giving a fake pill would be unethical since the real thing might save lives.
Now, hydroxychloroquine, or HCQ, has fallen into such disfavor that healthcare workers are leery of Naggie’s trial. Called HERO (a loose acronym for HEalth Care Worker pROphylaxis Against COVID-19) it is designed to see if the drug can protect them from infection.
“Our original recruitment goal was 15,000,” said Naggie, vice dean for clinical research at Duke University School of Medicine. “We are reevaluating that because, with everything that’s happened, it has certainly decreased interest among healthcare workers in participating.”
Coronavirus Coverage
Of all the hundreds of existing drugs being tested against the coronavirus, it is safe to say HCQ and its cousin chloroquine have been the most contentious. HCQ was rushed into clinical use based mostly on desperation and Trump’s endorsement of what he called “a game-changer.” So much was diverted that people who use the drug for its proven uses feared shortages and escalating prices.
Then rigorous studies showed it didn’t help treat or prevent COVID-19. Last month, the U.S. Food and Drug Administration revoked its emergency use authorization, and warned of potentially deadly side effects. Soon after that, the World Health Organization stopped an international treatment trial of HCQ, and the National Institutes of Health pulled the plug on two big studies — one that appeared to be futile, and another that couldn’t recruit enough participants.
Yet researchers are not giving up on HCQ. Far from it. Hundreds of studies around the world — including dozens in the U.S. and some in Philadelphia — are continuing, according to clinicaltrials.gov, the U.S. government website that lists trials. (The FDA now says the drug shouldn’t be prescribed for treating or preventing the coronavirus except in a trial.)
Why keep investing in a seeming loser? The most common answers: Studies to date have not been definitive. Results need to be confirmed, or “reproduced,” by different research groups. And finding even a glimmer of benefit would be valuable against a virus that is so far unstoppable.
But pride, prejudice, and protocols may also be driving hope against hope.
The University of Pennsylvania is continuing two trials — at least until the independent board that monitors safety analyzes the latest data. One trial is testing HCQ as a treatment for COVID-19 patients quarantined at home. The other study is testing HCQ to prevent infection in health care workers who are high risk because of their jobs.
“The overall enrollment rate into research studies has decreased primarily because the numbers of COVID cases has decreased” locally, emailed Emma Meagher, chief clinical research officer for Penn’s Perelman School of Medicine. ”COVID-positive patients and healthcare workers continue to be enrolled in the two trials.”
Hints of effectiveness
HCQ has long been used to treat malaria and rheumatoid conditions such as arthritis and lupus.
In theory, HCQ could curb the coronavirus by reducing inflammation, inhibiting viral replication, and blocking enzymes that the virus uses to break into lung cells. Scientists in China, where the virus emerged in December, found HCQ kept the coronavirus from infecting monkey cells in lab dishes. Circumstantial evidence from small studies of hospitalized patients also hinted at effectiveness.
But gold standard studies — which compare a drug to a placebo or usual care to see whether changes in the test group result from the treatment — have repeatedly dashed hopes.
Last month, British researchers abruptly stopped a large trial of HCQ because it did not help hospitalized patients. After 28 days, 25.7 percent of patients on the drug had died, compared to 23.5 percent who received usual care — a difference that was not statistically significant, meaning it could be by chance. There was no beneficial effect on length of hospital stay or other outcomes.
“Hydroxychloroquine and chloroquine have been used very widely to treat COVID patients despite the absence of any good evidence,” said study leader Peter Horby, an infectious diseases specialist at the University of Oxford. “Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs.”
The potential of HCQ has been dimmed not just by bad results, but suspected fraud. In early June, the Lancet retracted a headline-making study that concluded HCQ might actually increase the risk of death. “We can no longer vouch for the veracity of the primary data sources,” the journal said.
A matter of timing
The hope that HCQ might work to prevent disease was undermined by a University of Minnesota study published in the New England Journal of Medicine. The drug or placebo was given to 821 people who had recent close contact with a confirmed case of COVID-19. About 12 percent of those on the drug got sick, compared to 14 percent on placebo — again, a difference that could have been by chance.
However, the study had a big limitation: most people who got sick did not have a diagnostic molecular test to confirm COVID-19.
“Testing was in very short supply at that time,” explained Radha Rajasingham, an infectious disease specialist and co-leader of the study.
The Minnesota trial also could not rule out the possibility that HCQ can decrease the chance of infection if taken before exposure to the virus.
Minnesota is now doing a study of “pre-exposure prophylaxsis,” or PreP.
“I think for something to be used across the country, it would be nice to see a strong reduction in infections — 50 percent,” said Rajasingham. “If it’s something more modest, it would be hard to say whether the side effects are worth it. The drug can cause diarrhea, nausea, drug interactions, and heart arrhythmias.”
The HERO study, led by Naggie at Duke, is also testing pre-exposure prevention. But Naggie thinks even a 20 percent reduction in infection risk would be a win. And she stresses that HCQ is generally well tolerated.
“As long as there is no evidence of harm and there is potential benefit, we should complete the study to get a definitive answer,” Naggie said. “We need definitive answers so we don’t continue to rehash these questions.””
https://www.msn.com/en-us/health/medical/hydroxychloroquine-is-the-most-disappointing-disavowed-drug-that-researchers-keep-studying-for-covid-19/ar-BB16glaE
McGinley
So you too want to add a smoke screen to the results of this post that highlights a 50% reduction of deaths from covid19. How disingenuous can you be. What is your agenda.
Bixler,
The people who have know me here from many years of commentary know I have no agenda except to inform based on what can be shown true based on evidence.
I am the least disingenuous person you might ever hear from in your entire life.
No one can find anything out of the many thousands of comments and articles I have written, ever, in which I made anything up, or represented my opinions, or those of anyone else, as something other than opinions. I also know enough to be able to discern evidence from what can be shown to be based on opinions, faulty reasoning, bad data, and plain old making stuff up.
Your agenda seems clear, given your objection to what seems to me to be an unbiased article that discusses the pro and con case and the state of current research.
You do not want anyone contradicting your beliefs.
I am a trained multidisciplinary scientist.
I operate on the level of the scientific method, in my thinking and in what I communicate.
You might try it some time.
Terry,
I haven’t seen him (her?) here for years. So ….
“Why keep investing in a seeming loser? The most common answers: Studies to date have not been definitive. Results need to be confirmed, or “reproduced,” by different research groups. And finding even a glimmer of benefit would be valuable against a virus that is so far unstoppable.”
I think that explains things pretty well. The jury is still out.
There are numerous juries, not one.
I think looking at the whole story explains things even better than “pretty well”, personally.
Which is why I posted the entire article.
I did not edit out the parts I find objectionable, like repeated and gratuitous references to Trump and leftist talking points.
Some of these researchers are continuing because they hope to tease out any “glimmer” or “hint” of benefit
Many of the juries have ended deliberations and thrown the case out of court, with prejudice:
“Then rigorous studies showed it didn’t help treat or prevent COVID-19. Last month, the U.S. Food and Drug Administration revoked its emergency use authorization, and warned of potentially deadly side effects. Soon after that, the World Health Organization stopped an international treatment trial of HCQ, and the National Institutes of Health pulled the plug on two big studies — one that appeared to be futile, and another that couldn’t recruit enough participants.”
“But pride, prejudice, and protocols may also be driving hope against hope.”
“The University of Pennsylvania is continuing two trials — at least until the independent board that monitors safety analyzes the latest data.
Last month, British researchers abruptly stopped a large trial of HCQ because it did not help hospitalized patients. After 28 days, 25.7 percent of patients on the drug had died, compared to 23.5 percent who received usual care — a difference that was not statistically significant, meaning it could be by chance. There was no beneficial effect on length of hospital stay or other outcomes.”
“…gold standard studies — which compare a drug to a placebo or usual care to see whether changes in the test group result from the treatment — have repeatedly dashed hopes.”
“Hydroxychloroquine and chloroquine have been used very widely to treat COVID patients despite the absence of any good evidence,” said study leader Peter Horby, an infectious diseases specialist at the University of Oxford. “Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs.”
“The hope that HCQ might work to prevent disease was undermined by a University of Minnesota study published in the New England Journal of Medicine. The drug or placebo was given to 821 people who had recent close contact with a confirmed case of COVID-19. About 12 percent of those on the drug got sick, compared to 14 percent on placebo — again, a difference that could have been by chance.”
The best evidence, the double blind and randomized clinical trials, is that there is no benefit.
This New York based study is very interesting, as was the one in Detroit a few days ago.
They are interesting because hospitalization is not the best opportunity for using HCL (and AZT).
The best moment is very early after infection, as demonstrated by Didier Raoult’ s latest study published
https://www.sciencedirect.com/science/article/pii/S1477893920302817
In Marseille Raoult’s team tested all volunteering patients and detected 5000+ infected people, and immediately started curing all of them, selecting HCL+AZT as often as possible, but avoiding cases where HCL might have secondary effects. The objective was a) to reduce virus workload of infected, b) reduce contagion risk and C) avoid hospitalization as well as d) secondary effects in lungs or other organs.
, they had 18 death cases only, 0,5% of identified cases, with only 16% fatalities in ICU cases versus 25% or 40% in most hospitals
Best. Daniel
18 deaths and 0.5 fatality rate on those cases treated with HCL and AZT
Regarding the Recovery trial in UK monitored by Oxford professors, they did’ it publish yet and may never due to some study crazy features.
One is the fact that they administered an HCL regimen 4 times stronger than any official reco or any other practice. Indian authorities reached out to UK ones to warn of this apparent huge mistake which may explain why so many patients died.
An other particularity is that they included 10 or 20% of patients who were not COVID-19 cases .
They also have 40% Average fatality rate which seems particularly high for Covid cases at hospital.
HCQ+ zinc = life, covid 19. demise
Provably false assertions, even just using the study examined in the headline article and the known rates of mortality of those who become exposed to and infected with COVID-19.
Even this problematic retrospective, hailed as proof of efficacy, shows the vast majority live even if they get infected, no matter what they do or do not take.
And the ones who take HCQ are shown to still die in many cases.
Overall a tiny fraction of people who are infected will die from COVID-19.
So the virus is not equal to demise, and HCQ plus zinc does not equal life.
Even the advocates who started who whole thing do not show evidence of much of an effect, when overall mortality of the people they treated is compared to overall mortality of everyone in a population.
Even after they massaged their data beyond any semblance of acceptable analysis.
“This is absolutely the most conclusive research produced to date by anyone, due mostly to the quality of the approach. No one has published this quality level of work on HCQ on humans prior to this.”
This study is absolutely not the most conclusive research on this topic. This is a retrospective analysis of hospital data using multivariate correlational methods. There are issues with interpretaion of results due to multicollinearity and restriction of range in variables. And most significant, correlational analytic techniques will not demonstrate causality between the treatment and the effects. This type of study will “suggest potential benefit” in the words of the authors. Also, “…our results should be interpreted with some caution and should not be applied to patients treated outside of hospital settings. Our results also require further confirmation in prospective, randomized controlled trials…”. This is an “exploratory” design which needs to be confirmed with more rigorous research.
The most conclusive to date. Tay appension.
The comparisons done in table 3 are all you can really do as someone points out above. Do you think we will give fake vaccines to people to prove the vaccine works? I don’t think anyone expects that.
You will examine it retrospectively.
Yes in fact vaccine testing is done is phases that include ramdom experimental designs with placebo and/or alternative vaccines; and so, not at all in any way “retrospective in design”, which by the way, has a very specific technical meaning.
To all above, thanks for the comments and critiques. What I liked about this study was the extra effort the authors put into trying to match up two population groups based on confounding factors. They also used MV regression to remove these factors and had a similar result, confirming that it is unlikely true that confounding factors were a problem in the larger mass of data. We climate geeks all know what happens when you jam data into a giant MV regression.
Is the study perfect—no.
Is it amazingly good — yes it really is.
I don’t agree whatsoever that a study MUST be double blind to make a conclusion. Post collection data analysis is really common and can be done to a high statistical certainty. Does anyone truly expect that placebo vaccines will be given to people to prove the vaccine works? I don’t think you do. Maybe someone in China will but it is not required to get to the efficacy answer.
The first place I heard about HCQ for viral treatment was right here at WUWT. This study matches the in vitro results amazingly well, controls the dosage and matched the time when dosages were given.
I also agree with the folks that mentioned we don’t have a time based result. Given early or later in the progression. In vitro, and in the French studies that was an important factor. With so much negativity in the world about this disease, we have a real opportunity to help people in front of us and our lousy governments are making the most unhelpful rules imaginable.
I believe, unfortunately, that several of your statements above display a lack of expertise in research design. Yes “Post collection data analysis is really common and can be done to a high statistical certainty”, yes, high statistical (correlational) but not *causal*. And, as I mentioned some issues above, multicollinearity for example, which can easily lead to spurious results from multiple regression techniques, vs. “strong” designs double blind/randomized, which are considered the standard for drawing *causal* conclusions, which is what we are really looking for. Sorry I popped in (based on a friend’s comment on Linkedin) but if feel it is unfortunate that this has devolved into a political rather than a medical/scientific issue, so I thought I’d bring up some of the scientific and methodological issues. The study is commendable, it is preliminary and exploratory and in no way conclusive. As a reviewer, I would ask for results/discussion of multicollinearity, I don’t see it addressed. And again, yes, vaccine testing includes randomized designs (per the CDC process.) I am not a medical researcher, immunologist, epidemiologist, or virologist, although I have lots of confidence in the body of work that they are producing. I am an expert in experimental designs, multivariate statistcial analysis and related research areas, so I will leave the rest up to the expertise of the medical researchers.
Everyone here is doing their best to describe the “gold standard” vs how humans are keenly good at seeing and learning from good observation.
I think this needs to be said at this point in this post:
What I see happening is people talking right past each other and some believe only conclusions from any study that’s badged with double blind placebo controlled –the gold standard.
With the gold standard, we often get a flu shot that is no better than getting a saline shot. We get people being prescribed acid reflux medicines that literally destroy the way our bodies are supposed to function to digest properly. But don’t worry, they used the gold standard and it’s FDA approved and my doctor told me it would cure acid reflux. Nonsense.
I fear common sense is being disregarded because some people attach purity with the use of the gold standard –that goes well beyond the structure of the the gold standard. It’s as if when its use is claimed, the results are not to be questioned, everyone behind it is honest and no one has put any bias [into the process or the data].
Some attach all other virtues and power to the study leading to a blind loss of reason. The complexity benefits those in authority who tell you it’s too confusing for you to understand, so don’t question us.
So don’t question the data or how the study was conducted. We have seen atrocious problems with these studies by exposing them to good skeptical human observation. That’s the beauty of science, it forces us to think.
I agree with you 100%. Science, including medical science, progresses incrementally. The use of the term “gold standard” is a deception because it implies that there is the one and only study to be done. Experiments are designed and completed after significant prior observational, retrospective, correlational, and all sorts of other methodologies are completed, reviewed, questioned, critiqued and revised. The results and conclusions from the prior research feed into the designs of the experimental research. And then we replicate and confirm. As a young assistant research professor (three years into my post-doctoral career) I spent some time reviewing grant proposals for the NSF. I critiqued a proposal from a stellar researcher in my narrow field of study and found a hole in his logic and design. After some serious push back from the external committee and the NSF Section Head, the consensus among the committee – “send it back!” As it should be.
Exactly!
In many cases, garbage in worse than garbage out… since the outed garbage is then branded as food… “…don’t question it, you are not qualified if you disagree with the gold standard.”
Think The Lancet, Surgisphere et. al.
Multicollinearity. I think that I not only agree but explained this problem.
If you read the study, actually read it this time, you will see that not only did they stuff the data into the multivariate meat grinder, they took the time to manually separate the multicolinearities- needs more suffixes to be fun I think.
The neat thing is that the manual symptom matching in Table 3 actually matched the meat grinder multivariate approach pretty well. Fifty percent improvement in people so sick that they are being hospitalized. The MV isn’t splotched this time.
It shows that when the correlated health data is removed, you have a solid result with HCQ.
Multicollinearity. I think that I not only agree but explained this problem.
If you read the study, you will see that not only did they stuff the data into the multivariate meat grinder and check for confounding variables, they took the time to manually separate the ‘multicolinearities’- needs more suffixes to be fun I think.
The neat thing is that the manual condition matching in Table 3 actually approximated the multivariate meat grinder pretty well. Fifty percent better survival in people so sick that they are being hospitalized. Shows that the MV likely isn’t splotched this time but even without it, the results are strong.
Actually, they did not address the multicollinearity. Table 3 attempts to address, that is, control for the effects of the “propensity” variables. However, it does in no way address the multicollinearity in the data. Sorry about that but they missed this one. High multicollinearity in predictors can easily lead to spurious results. It needs to be addressed by the authors. I am not a big fan of much in the medical research literature that I read for this reason, design and analysis can at times be amateurish.
I’ve heard is said that drinking water is the common factor across all Covid deaths, hence it’s clear evidence that water was the culprit. The people who had no access to water died before contracting the disease, and were therefore saved from Covid 19. Conclusion, water is the cause of Covid 19.
Later is was argued that the above study was flawed, but followed the gold standard.