回答: 紧急求助：华人博士溺亡，家人因疫情无法赴美 由 lgc213 于 2020-04-20 8:53

Outcomes of hydroxychloroquine usage in United States veterans hospitalized
with Covid-19
Joseph Magagnoli, M.S.1,2,*, Siddharth Narendran, M.D.4,5,*, Felipe Pereira M.D.4,5,*, Tammy
Cummings, Ph.D.1
, James W. Hardin, Ph.D.3
, S. Scott Sutton, Pharm.D.1,2, Jayakrishna Ambati,
M.D.4,5,6,7
1
Dorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina, USA.
2
Department of Clinical Pharmacy & Outcomes Sciences, College of Pharmacy, University of
South Carolina, Columbia, South Carolina, USA
3
Department of Epidemiology & Biostatistics, University of South Carolina, Columbia, South
Carolina, USA
4
Center for Advanced Vision Science, University of Virginia School of Medicine,
Charlottesville, Virginia, USA.
5
Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville,
Virginia, USA.
6
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia,
USA.
7
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School
of Medicine, Charlottesville, Virginia, USA.
*Mr. Magagnoli, Dr. Narendran, and Dr. Pereira contributed equally to this article
Correspondence should be addressed to Dr. J. Ambati at ja9qr@virginia.edu or Dr. S.S. Sutton at
sutton@cop.sc.edu.
ABSTRACT
BACKGROUND:
Despite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19,
the U.S. Food and Drug Administration has authorized the emergency use of this drug when
clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with
azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited
observational evidence.
METHODS:
We performed a retrospective analysis of data from patients hospitalized with confirmed SARSCoV-2
infection in all United States Veterans Health Administration medical centers until April
11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC)
or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for
Covid-19. The two primary outcomes were death and the need for mechanical ventilation. We
determined the association between treatment and the primary outcomes using competing risk
hazard regression adjusting for clinical characteristics via propensity scores. Discharge and death
were taken into account as competing risks and subdistribution hazard ratios are presented.
RESULTS:
A total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of
death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of
ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. 
Compared to the no HC group, the risk of death from any cause was higher in the HC group
(adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group
(adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72). The risk of ventilation was similar in
the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ
group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group.
CONCLUSIONS:
In this study, we found no evidence that use of hydroxychloroquine, either with or without
azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19.
An association of increased overall mortality was identified in patients treated with
hydroxychloroquine alone. These findings highlight the importance of awaiting the results of
ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.
The rapidity of the Covid-19 pandemic has exerted inordinate pressure on clinicians and drug
regulatory agencies throughout the world to expedite development, approval, and deployment of
both experimental drugs and repurposing of existing therapeutics. Among the myriad
therapeutics advanced as potential repurposing candidates for Covid-19, the antimalarial and
immunomodulatory drug hydroxychloroquine has captured great attention following an openlabel,
non-randomized, single treatment center study that reported efficacy of
hydroxychloroquine and a potential synergistic effect with the macrolide antibiotic azithromycin,
in improving viral clearance in Covid-19 patients.1 The resulting spotlight and public interest has
led to its soaring utilization in Covid-19, drug shortages impacting its use in labeled indications,
and stockpiling by countries.
Subsequent studies have not identified a similar benefit of hydroxychloroquine in Covid-192-5
and concerns have been raised about the original positive study.6,7 Nevertheless, the United
States Food and Drug Administration used its emergency authority for only the second time ever
to permit the use of a drug for an unapproved indication8 in the case of hydroxychloroquine for
Covid-19 in situations where clinical trials are unavailable or infeasible.9
Multiple prospective, randomized trials of hydroxychloroquine are now underway and will, in
due course, provide valuable information about safety and efficacy. However, given its
increasingly widespread use, not only as therapy but also as prophylaxis for Covid-19, there is a
great and immediate need to obtain insights into the clinical outcomes among patients currently
treated with hydroxychloroquine, particularly because of the non-negligible toxicities associated
with its use.
Therefore, we conducted a retrospective analysis of patients hospitalized with Covid-19 in all the
Veterans Health Administration medical centers across the United States to analyze the
associations between hydroxychloroquine and azithromycin use and clinical outcomes. The
findings of this nationwide study of one of the most complete national datasets in the United
States can accelerate our understanding of the outcomes of these drugs in Covid-19 while we
await the results of the ongoing prospective trials.
METHODS
STUDY DESIGN
This national retrospective cohort study evaluated information on hospitalized patients with
confirmed SARS-CoV-2 infection using data from the Department of Veterans Affairs (VA).
Data were extracted from the Veterans Affairs Informatics and Computing Infrastructure
(VINCI), which includes inpatient, outpatient data (coded with International Classification of
diseases (ICD) revision 9-CM, revision 10-CM), laboratory, and pharmacy claims. The
completeness, utility, accuracy, validity, and access methods are described on the VA website,
http://www.virec.research.va.gov. This study was conducted in compliance with the Department
of Veterans Affairs requirements, received VA Institutional Review Board, and VA Research &
Development approval.
STUDY POPULATION
We developed a cohort comprising patients with laboratory confirmed SARS-CoV-2 infection in
an inpatient setting. SARS-CoV-2 status was classified by laboratory results that were extracted
from VA laboratory data. A text search for SARS-CoV-2 laboratory tests was used to query VA
lab results. The study index date was defined as the date of a hospitalization with a positive
SARS-CoV-2 laboratory test. Index dates range from March 9, 2020 to April 11, 2020, and
patients were followed from index until hospital discharge or death. The period prior to index is
designated as the baseline period and on or after index is designated the follow-up period. 
Patients were included in the study if their information included 1) a body mass index, 2) vital signs during an encounter (temperature, heart rate and blood pressure), and 3) discharge
disposition status available for the hospitalization.
OUTCOMES AND EXPOSURE CODING 
The study outcomes are the result of the hospitalization (discharge or death), whether ventilation
was required, and the result of hospitalization among patients requiring ventilation. Ventilator
usage was coded using HCPCS/CPT codes (31500, 94003, 94002, E0463) and ICD-10-PCS
codes (5A0955, 5A0945, 5A0935, 5A1522F, 5A1522G, 5A1522H). The results of the
hospitalization were coded from the discharge disposition status on the inpatient
record. Hospitalization data were taken from the VA inpatient hospitalization data.
Patients were assigned to one of three cohorts based on medication exposure to
hydroxychloroquine (HC) and azithromycin (AZ): 1) HC-treated; 2) HC- and AZ-treated; or 3)
HC-untreated. Patients were exposed to hydroxychloroquine if they had a dispensed drug from
the VA bar code medication administration (BCMA) data file during their hospitalization.
Similarly, if patients received azithromycin with hydroxychloroquine during their
hospitalization they were categorized HC- and AZ-treated. Patients with no hydroxychloroquine
exposure were coded as HC unexposed. To examine the association with ventilation, the time of
hydroxychloroquine and azithromycin dispense was coded dynamically, before or after ventilator
support.
COVARIATES