by George J. Dance
By now I am sure we have all heard of hydroxychloroquine (HCQ), the anti-malaria drug and arthritis treatment that may or may not be effective against COVID-19. There certainly has been plenty of debate on the drug online: A google search for "Hydroxychloroquine COVID" turns up 65 million hits. Sadly, though, for a debate supposed to be "guided by the science," little of that deals with science. As with mask wearing, HCQ has become a political "issue," and for much the same reasons. Masks are good or bad because the Orange Man doesn't wear them. HCQ is bad or good because the Orange Man uses it. (Choose an option depending on how you feel about the Orange Man.)
Unlike with masks, though, scientific information is needed to estimate the benefits and risks of HCQ. That is the main reason the blog has refrained from mentioning the drug; in all the debate I have followed, there has been nothing worth mentioning. There was a study in The Lancet that found using HCQ not only saved no lives but led to more deaths, from cardiac arrest; but before I could find space for it on the blog, Lancet had retracted the paper.
Today I discovered a new study, "Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19," by Samia Arshad et al., published in the International Journal of Infectious Diseases on July 1. The paper was an observational study conducted in the Henry Ford Health System (HFHS), a six-hospital chain in southwest Michigan, by the Henry Ford COVID-19 task force. The full study is online at ijid.com, and can also be found at https://doi.org/10.1016/j.ijid.2020.06.099
Arshad et al investigated the medical records of the more than 2,500 patients hospitalized as COVID-related admissions (defined as having a positive PCR-RT viral test in the hospital) between March 10 and May 2. Of those, some had been treated with HCQ; some with a combination of HCQ and azythromycin (AZM), an antiobiotc; some with AZM alone; and some with neither drug. The differences in mortality rates were striking:
Charted, the data gives a simple and clear picture: those receiving HCQ had a mortality rate almost 50% below those who received no drugs. Of course, that apparently simple and clear picture could actually be counfounded by numerous variables. The authors point out that those can include "1) patient demographics: age, gender, race, body mass index (BMI) on admission [as well as] 2) clinical characteristics: admission date, discharge date, length of stay (LOS), comorbidities including: cardiovascular disease (CVD), chronic lung disease, chronic kidney disease (CKD), hypertension, asthma, chronic obstructive pulmonary disease (COPD), diabetes mellitus, immunodeficiency, and cancer (defined as active or past/resolved)."
The task force "used Multivariable Cox regression models and Kaplan-Meier survival curves ... to compare survival among treatment groups while controlling for demographics (e.g., age, gender), preexisting medical conditions (e.g. CVD, lung disease) and clinical disease severity (mSOFA, O2 saturation). Bivariate comparisons of the 4 medication groups were made using analysis of variance or Kruskal-Wallis tests for continuous variables, and chi-square tests or Fisher exact tests for categorical variables."
In addition, the researchers were able to exactly match two cohorts - 190 who had received HCQ, and 190 who had not - with "identical underlying patient characteristics." "The Cox regression result for the two propensity matched groups ... indicates that treatment with hydroxychloroquine resulted in a mortality hazard ratio decrease of 51% (p = 0.009)."
"The results of this study," the authors conclude, "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." (They also demonstrate that HCQ used alone was associated with a greater reduction. than the combination.)
The Food and Drug Administration (FDA) cautions against use of HCQ "outside of the hospital setting or a clinical trial," but does not approve the drug's use within the hospital setting, either. The FDA approved an Emergency Use Authorization (EUA) for the drug in late March, but withdrew it on June 15 after the Lancet study. The latter study has since been retracted and its data discredited; and now its conclusions have been explicitly contradicted by the Henry Ford study.
The study's findings that the drug is effective (that it reduces COVID deaths) may be overstated or confounded with other unknown variables (such as steroid use); I agree with the the Journal's call for clinical trials of the drug. Undeniably, though, the safety of the drug has been proven (it does not even correlate with any increase in deaths); that and the possibility of dramatically cutting the COVID death toll warrant the FDA restoring the medicine's EUA.
By now I am sure we have all heard of hydroxychloroquine (HCQ), the anti-malaria drug and arthritis treatment that may or may not be effective against COVID-19. There certainly has been plenty of debate on the drug online: A google search for "Hydroxychloroquine COVID" turns up 65 million hits. Sadly, though, for a debate supposed to be "guided by the science," little of that deals with science. As with mask wearing, HCQ has become a political "issue," and for much the same reasons. Masks are good or bad because the Orange Man doesn't wear them. HCQ is bad or good because the Orange Man uses it. (Choose an option depending on how you feel about the Orange Man.)
Unlike with masks, though, scientific information is needed to estimate the benefits and risks of HCQ. That is the main reason the blog has refrained from mentioning the drug; in all the debate I have followed, there has been nothing worth mentioning. There was a study in The Lancet that found using HCQ not only saved no lives but led to more deaths, from cardiac arrest; but before I could find space for it on the blog, Lancet had retracted the paper.
Today I discovered a new study, "Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19," by Samia Arshad et al., published in the International Journal of Infectious Diseases on July 1. The paper was an observational study conducted in the Henry Ford Health System (HFHS), a six-hospital chain in southwest Michigan, by the Henry Ford COVID-19 task force. The full study is online at ijid.com, and can also be found at https://doi.org/10.1016/j.ijid.2020.06.099
Arshad et al investigated the medical records of the more than 2,500 patients hospitalized as COVID-related admissions (defined as having a positive PCR-RT viral test in the hospital) between March 10 and May 2. Of those, some had been treated with HCQ; some with a combination of HCQ and azythromycin (AZM), an antiobiotc; some with AZM alone; and some with neither drug. The differences in mortality rates were striking:
- Of 409 patients given neither drug, 108 died, or 26.4% [95% CI: 22.2%-31.0%].
- Of 147 patients given AZM alone, 33 died, or 22.4%. [95% CI: 16.0%-30.1%]
- Of 783 patients given HCQ and AZM, 157 died, or 20.1%. [95% CI: 17.3%-23.0%]).
- Of 1202 patients given HCQ alone, 162 died, or 13.5%. [95% CI: 11.6%-15.5%]).
Charted, the data gives a simple and clear picture: those receiving HCQ had a mortality rate almost 50% below those who received no drugs. Of course, that apparently simple and clear picture could actually be counfounded by numerous variables. The authors point out that those can include "1) patient demographics: age, gender, race, body mass index (BMI) on admission [as well as] 2) clinical characteristics: admission date, discharge date, length of stay (LOS), comorbidities including: cardiovascular disease (CVD), chronic lung disease, chronic kidney disease (CKD), hypertension, asthma, chronic obstructive pulmonary disease (COPD), diabetes mellitus, immunodeficiency, and cancer (defined as active or past/resolved)."
The task force "used Multivariable Cox regression models and Kaplan-Meier survival curves ... to compare survival among treatment groups while controlling for demographics (e.g., age, gender), preexisting medical conditions (e.g. CVD, lung disease) and clinical disease severity (mSOFA, O2 saturation). Bivariate comparisons of the 4 medication groups were made using analysis of variance or Kruskal-Wallis tests for continuous variables, and chi-square tests or Fisher exact tests for categorical variables."
In addition, the researchers were able to exactly match two cohorts - 190 who had received HCQ, and 190 who had not - with "identical underlying patient characteristics." "The Cox regression result for the two propensity matched groups ... indicates that treatment with hydroxychloroquine resulted in a mortality hazard ratio decrease of 51% (p = 0.009)."
"The results of this study," the authors conclude, "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." (They also demonstrate that HCQ used alone was associated with a greater reduction. than the combination.)
The Food and Drug Administration (FDA) cautions against use of HCQ "outside of the hospital setting or a clinical trial," but does not approve the drug's use within the hospital setting, either. The FDA approved an Emergency Use Authorization (EUA) for the drug in late March, but withdrew it on June 15 after the Lancet study. The latter study has since been retracted and its data discredited; and now its conclusions have been explicitly contradicted by the Henry Ford study.
The study's findings that the drug is effective (that it reduces COVID deaths) may be overstated or confounded with other unknown variables (such as steroid use); I agree with the the Journal's call for clinical trials of the drug. Undeniably, though, the safety of the drug has been proven (it does not even correlate with any increase in deaths); that and the possibility of dramatically cutting the COVID death toll warrant the FDA restoring the medicine's EUA.
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