RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.
French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.
Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). Concerns have been raised regarding this article, the substance of which relate to the articles' adherence to Elsevier's publishing ethics policies and the appropriate conduct of research involving human participants, as well as concerns raised by three of the authors themselves regarding the article's methodology and conclusions. Elsevier's Research Integrity and Publishing Ethics Team, in collaboration with the journal's co-owner, the International Society of Antimicrobial Chemotherapy (ISAC), and with guidance from an impartial field expert acting in the role of an independent Publishing Ethics Advisor, Dr. Jim Gray, Consultant Microbiologist at the Birmingham Children's and Women's Hospitals, U.K., conducted an investigation and determined that the below points constituted cause for retraction: • The journal has been unable to confirm whether any of the patients for this study were accrued before ethical approval had been obtained. The ethical approval dates for this article are stated as being 5th and 6th of March 2020 (ANSM and CPP respectively), while the article states that recruitment began in “early March”. The 17th author, Prof. Philippe Brouqui, has confirmed that the start date for patient accrual was 6th March 2020. The journal has not been able to establish whether all patients could have entered into the study in time for the data to have been analysed and included in the manuscript prior to its submission on the 20th March 2020, nor whether all patients were enrolled in the study upon admission as opposed to having been hospitalised for some time before starting the treatment described in the article. Additionally, the journal has not been able to establish whether there was equipoise between the study patients and the control patients. • The journal has not been able to establish whether the subjects in this study should have provided informed consent to receive azithromycin as part of the study. The journal has concluded that that there is reasonable cause to conclude that azithromycin was not considered standard care at the time of the study. The 17th author, Prof. Philippe Brouqui has attested that azithromycin treatment was not, at the time of the study, an experimental treatment but a possible treatment for, or preventative measure against, bacterial superinfections of viral pneumonia as described in section 2.4 of the article, and as such the treatment should be categorised as standard care that would not require informed consent. This does not fully address the journal's concerns around the use of azithromycin in the study. In section 3.1 of the article, it is stated that six patients received azithromycin to prevent (rather than treat) bacterial superinfection. All of these were amongst the patients who also received hydroxychloroquine (HCQ). None of the control patients are reported to have received azithromycin. This would indicate that only patients in the HCQ arm received azithromycin, all of whom were in one center. The recommendations for use of macrolides in France at the time the study was conducted indicate that azithromycin would not have been a logical agent to use as first-line prophylaxis against pneumonia due to the frequency of macrolide resistance amongst bacteria such as pneumococci. These two points suggest that azithromycin would not have been standard practice across southern France at the time the study was conducted and would have required informed consent. • Three of the authors of this article, Dr. Johan Courjon, Prof. Valérie Giordanengo, and Dr. Stéphane Honoré have contacted the journal to assert their opinion that they have concerns regarding the presentation and interpretation of results in this article and have stated they no longer wish to see their names associated with the article. • Author Prof. Valérie Giordanengo informed the journal that while the PCR tests administered in Nice were interpreted according to the recommendations of the national reference center, it is believed that those carried out in Marseille were not conducted using the same technique or not interpreted according to the same recommendations, which in her opinion would have resulted in a bias in the analysis of the data. This raises concerns as to whether the study was partially conducted counter to national guidelines at that time. The 17th author, Prof. Philippe Brouqui has attested that the PCR methodology was explained in reference 17 of the article. However, the article referred to by reference 17 describes several diagnostic approaches that were used (one PCR targeting the envelope protein only; another targeting the spike protein; and three commercially produced systems by QuantiNova, Biofire, and FTD). This reference does not clarify how the results were interpreted. It has also been noted during investigation of these concerns that only 76% (19/25) of patients were viral culture positive, resulting in uncertainty in the interpretation of PCR reports as has been raised by Prof. Giordanengo. As part of the investigation, the corresponding author was contacted and asked to provide an explanation for the above concerns. No response has been received within the deadline provided by the journal. Responses were received by the 3rd and 17th authors, Prof. Philippe Parola and Prof. Philippe Brouqui, respectively, and were reviewed as part of the investigation. These two authors, in addition to 1st author Dr. Philippe Gautret, 13th author Prof. Philippe Colson, and 15th author Prof. Bernard La Scola, disagreed with the retraction and dispute the grounds for it. Having followed due process and concluded the aforementioned investigation and based on the recommendation of Dr. Jim Gray acting in his capacity as independent Publishing Ethics Advisor, the co-owners of the journal (Elsevier and ISAC) have therefore taken the decision to retract the article.
Gautret P
，Lagier JC
，Parola P
，Hoang VT
，Meddeb L
，Mailhe M
，Doudier B
，Courjon J
，Giordanengo V
，Vieira VE
，Tissot Dupont H
，Honoré S
，Colson P
，Chabrière E
，La Scola B
，Rolain JM
，Brouqui P
，Raoult D
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Postpartum hospital use among survivors of intimate partner violence.
More than 1 in 3 individuals who identify as female, experience either intimate partner violence (IPV) or sexual assault during their lifetime, and sexual violence committed by an intimate partner is at its highest during their reproductive years.1 As many as 20% of pregnant individuals may experience IPV, and IPV during pregnancy has been associated with an increased risk for adverse maternal and neonatal outcomes, making pregnant individuals an especially vulnerable population.1 In fact, >50% of pregnancy-associated suicides and >45% of pregnancy-associated homicides are associated with IPV and these often occur during the postpartum period.2 Although >50% of maternal deaths occur postpartum,3 little research has examined whether IPV is associated with markers of postpartum maternal morbidity, including hospital readmission and emergency department (ED) visits.4 In addition, few studies have examined the feasibility of ascertaining IPV at the delivery hospitalization using billing codes. Although the International Classification of Diseases, Tenth Revision (ICD-10) codes include factors related to social determinants of health, ICD-10 codes are largely underutilized for the purpose of understanding risk of disease and adverse outcomes.5 The primary objective of this study was to investigate the association of IPV screening at delivery with the incidence of postpartum hospital use. Another objective was to examine the possibility of using ICD-10 codes at the delivery hospitalization to identify IPV in pregnant individuals.
This was a retrospective cohort of birth data linked with inpatient and outpatient hospital claims data, including deliveries of individuals residing in the New York City metropolitan area between 2016 and 2018. Thirty-day hospital use was ascertained by either a readmission or an ED visit within 30 days of discharge. We identified the incidence of IPV from the delivery hospital discharge records using 36 IPV-related ICD-10 codes that we identified in the literature, including those defined for adult psychological and sexual abuse. We estimated the associations between IPV identified during the delivery hospitalization and postpartum hospital use using a multivariable logistic regression and separately adjusting for demographic and structural determinants of health, psychosocial factors, comorbidities, and obstetrical complications. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). This study was approved by our institutional review board.
IPV was indicated on the discharge records of 348 individuals (0.11%). As shown in the Table, the overall incidence of ED visits among individuals with an IPV-related diagnosis was 12.9%. The incidence of a postpartum ED visit was significantly higher among individuals with an IPV diagnosis than among those without (odds ratio [OR], 2.8; 95% confidence interval [CI], 2.1-3.9), and this was true after sequentially adjusting for demographic and structural determinants of health (OR, 2.0; 95% CI, 1.4-2.7), comorbidities and pregnancy complications (OR, 1.9; 95% CI, 1.4-2.6), psychosocial factors (OR, 1.5; 95% CI, 1.1-2.0), and obstetrical complications (OR, 1.5; 95% CI, 1.1-2.0). The incidence of either a postpartum ED visit or readmission was also higher among those patients with an IPV-related diagnosis (OR, 2.7; 95% CI, 2.0-3.6). However, there was no significant difference in postpartum readmissions alone among patients with or without an IPV-related diagnosis.
This study established that postpartum ED visits are significantly higher among individuals with an IPV-related diagnosis during the delivery hospitalization in a large citywide database, even after adjusting for established risk factors for postpartum ED use. Because ED visits have been identified as a possible marker of maternal morbidity and mortality,4 this finding may suggest that individuals affected by IPV could benefit from screening throughout pregnancy, including during the delivery hospitalization, to prevent adverse postpartum outcomes. However, as established in this study, IPV identified solely by ICD-10 codes during the delivery hospitalization is rare and likely underreported. It is possible that underdetection of IPV is because of insufficient clinician screening, a lack of documentation in the medical records using ICD-10 codes, and the medical status of the pregnant individual at the time of delivery. This finding demonstrates a need to screen and record findings thoroughly during the pregnancy period, including at delivery hospitalization, for any IPV-related diagnoses. A limitation of our data is that we were not able to ascertain hospital use outside of New York City and did not include other time points during an individual's pregnancy. Future research should identify at which time points IPV screening occurs during care of a pregnant individual and whether this may affect postpartum ED visit rates. As a clinical outcome, maternal mortality is preventable and screening for risk factors such as IPV throughout the perinatal period, including at delivery admission and during the postpartum period, is imperative for comprehensive obstetrics care.
Rao MG
，Stone J
，Glazer KB
，Howell EA
，Janevic T
... -
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Association between intrapartum antibiotic prophylaxis for Group B Streptococcus colonization and clinical chorioamnionitis among patients undergoing induction of labor at term.
Rectovaginal colonization with Group B Streptococcus during pregnancy has historically been shown to be associated with an increased risk of clinical chorioamnionitis and peripartum infectious morbidity.
Newer observational data in the era of intrapartum antibiotic prophylaxis suggest a possible reversal of this association; however, it is unclear if this is related to differences in labor management for those with and without Group B Streptococcus colonization. We therefore sought to assess the association between intrapartum antibiotic prophylaxis for Group B Streptococcus colonization and clinical chorioamnionitis within the context of a randomized induction of labor trial with a standardized labor protocol.
We performed an exploratory secondary analysis of a randomized trial of patients undergoing term induction at a tertiary care center. Patients received third trimester Group B Streptococcus screening and intrapartum antibiotic prophylaxis as routine care. Group B Streptococcus detection was performed using a carrot broth-enhanced subculture to Group B Streptococcus Detect approach (Hardy Diagnostics, Santa Maria, CA). Labor management was protocolized per the trial. Patients with unknown Group B Streptococcus status or who did not receive intrapartum antibiotic prophylaxis, if indicated, were excluded. The primary outcome was diagnosis of clinical chorioamnionitis, compared between patients who received intrapartum antibiotic prophylaxis for known Group B Streptococcus positive status (by culture, history, or Group B Streptococcus bacteriuria) and those who were Group B Streptococcus negative and did not receive intrapartum antibiotic prophylaxis. Secondary outcomes included postpartum endometritis, wound infection, a composite maternal peripartum infectious morbidity, and neonatal outcomes.
A total of 491 patients were enrolled in the trial. Of these, 466 had a known Group B Streptococcus status and received or did not receive intrapartum antibiotic prophylaxis accordingly and were included in this analysis: 292 (62.7%) were Group B Streptococcus negative and did not receive intrapartum antibiotic prophylaxis, and 174 (37.3%) were Group B Streptococcus positive and received intrapartum antibiotic prophylaxis. The majority of patients were Non-Hispanic Black (78.1%) and nulliparous (59.7%). There were no differences in demographic, clinical, induction or labor characteristics between groups. Patients who were Group B Streptococcus positive had a 49% lower rate of clinical chorioamnionitis (8.1% vs 14.7%, odds ratio, 0.51; P=.03) and a lower rate of peripartum infectious morbidity (8.1% vs 15.8%, odds ratio, 0.47; P=.02) compared to those who were Group B Streptococcus negative. Infants born to patients who were Group B Streptococcus positive were significantly less likely to be admitted to the neonatal intensive care unit (3.4% vs 15.1%, P<.001).
Although Group B Streptococcus colonization has historically been considered a risk factor for clinical chorioamnionitis, in the era of universal antibiotic prophylaxis for Group B Streptococcus positive patients, our findings support the point that intrapartum antibiotic prophylaxis for Group B Streptococcus positivity is associated with lower rates of clinical chorioamnionitis and peripartum infectious morbidity among patients undergoing induction with protocolized labor management. These findings demonstrate that intrapartum antibiotic prophylaxis for Group B Streptococcus may protect against perinatal infectious morbidity, a phenomenon that warrants further investigation.
McCoy JA
，Bromwich K
，Gerson KD
，Levine LD
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ResearchGate
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