Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

ObjectivesTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. DesignMulticenter, open-label, randomized controlled trial. Setting16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. InterventionsHCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. ResultsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. ConclusionsThe administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registrationChiCTR2000029868 What is already known on this topic-- The pandemic of coronavirus disease 2019 (COVID-19) imposes substantial burdens on individuals, communities, health-care facilities, markets, governments, etc. globally. -- There is no specific treatment approved for COVID-19 or vaccine to prevent infection with the novel coronavirus. -- During the urgent pandemic, media headlines the utility of drugs without solid evidence but buries the side-effects of these drugs. What this study adds-- In this randomized clinical trial of patients mainly with persistent mild to moderate COVID-19, exposure to hydroxychloroquine led to a similar probability of virus elimination comparing to the current standard-of-care. -- Adverse events, mostly gastrointestinal related, were significantly increased in patients who received hydroxychloroquine. -- Overall, the results from our trial do not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19. Print abstractO_ST_ABSStudy questionC_ST_ABSTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. MethodsThis is a multicenter, open-label, randomized controlled trial conducted in 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. A total of 150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. Among them, 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention to treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Study answer and limitationsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70) with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. What this study addsOur trial does not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19 due to limited effects on virus eliminating and significantly increased adverse events. Funding, competing interests, data sharingThis work was supported by the Emergent Projects of National Science and Technology (2020YFC0844500), National Natural Science Foundation of China (81970020, 81770025), National Key Research and Development Program of China (2016YFC0901104), Shanghai Municipal Key Clinical Specialty (shslczdzk02202, shslczdzk01103), National Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Discipline for Respiratory Diseases (2017ZZ02014), National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304007), Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period (2018ZX09206005-004, 2017ZX10202202-005-004, 2017ZX10203201-008). All authors declared no competing interests. Anonymized datasets can be made available on reasonable request after approval from the trial management committee. Study registrationChiCTR2000029868

Experts consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly / 中华内科杂志

Coronavirus disease 2019 (COVID-19) can cause great damage to the elderly patients and lead to high mortality. The clinical presentations and auxiliary examinations of the elderly patients with COVID-19 are atypical, due to the physiological ageing deterioration and basal pathological state. The treatment strategy for the elderly patients has its own characteristics and treatment protocol should be considered accordingly. To improve the diagnosis, treatment, and prevention of COVID-19 in the elderly, the Expert Committee of Geriatric Respiratory and Critical Care Medicine, China Society of Geriatrics established the "Expert consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly" . We focused on the clinical characteristics and key points for better treatment and prevention of COVID-19 in the elderly. (1) For diagnosis, atypical clinical presentation of COVID-19 in the elderly should be emphasized, which may be complicated by underlying disease. (2) For treatment, strategy of multiple disciplinary team (mainly the respiratory and critical care medicine) should be adopted and multiple systemic functions should be considered. (3) For prevention, health care model about integrated management of acute and chronic diseases, in and out of hospital should be applied.

Nasal high flow oxygen therapy for chronic obstructive pulmonary disease with hypercapnia / 中华全科医师杂志

Nasal high flow oxygen therapy (HFNC), an open nasal catheter system conveying heated and humidified air or oxygen, has been used to treat hypoxemic respiratory failure. At present, some researches indicated that HFNC can be applied for chronic obstructive pulmonary disease (COPD) with hypercapnia, which attenuates the retention of carbon dioxide by positive end-expiratory pressure effect, washing out anatomical dead space and reducing work of breath. HFNC is proved to decrease respiratory frequency, increase alveolar ventilation and end-expiratory lung volume, and its therapeutic effect is similar to non-invasive ventilation. Application of HFNC managed to be optimized in a way of increasing the flow rate in a single prong and mouth-closed breathing. This article summarizes the application of HFNC in COPD with hypercapnia.

Nasal high flow oxygen therapy for chronic obstructive pulmonary disease with hypercapnia / 中华全科医师杂志

Nasal high flow oxygen therapy (HFNC),an open nasal catheter system conveying heated and humidified air or oxygen,has been used to treat hypoxemic respiratory failure.At present,some researches indicated that HFNC can be applied for chronic obstructive pulmonary disease (COPD) with hypercapnia,which attenuates the retention of carbon dioxide by positive end-expiratory pressure effect,washing out anatomical dead space and reducing work of breath.HFNC is proved to decrease respiratory frequency,increase alveolar ventilation and end-expiratory lung volume,and its therapeutic effect is similar to non-invasive ventilation.Application of HFNC managed to be optimized in a way of increasing the flow rate in a single prong and mouth-closed breathing.This article summarizes the application of HFNC in COPD with hypercapnia.

Correlation Analysis between Carbapenem Consumption and Resistance to Carbapenems Among Gram Negative Bacteria Isolates / 医药导报

Objective To evaluate the correlation between carbapenem consumption and resistance to carbapenems among the frequent gram-negative bacteria and provide the basis for rational use of drugs. Methods Retrospective review was used to calculate the DDDs of carbapenems(impenem and meropenem) per 100 persons per day from the year of 2004 to 2016 and resistant rate of the frequent gram-negative bacteria(Acinetobacter baumannii,Pseudomonas aeruginosa,Klebsiella pneumoniae,and Escherich-ia coli).The correlation of drug usage and resistance were analyzed by SPSS 17.0 software. Results The study demonstrated that carbapenem usage was strongly correlated with imipenem and meropenem-resistant Acinetobacter baumannii,Klebsiella pneumoniae, while has no significant correlation with Pseudomonas aeruginosa,Escherichia coli. Conclusion The growing problem of gram-negative bacteria resistant to carbapenems was strongly related to the high consumption of carbapenems.It also suggested that opti-mum antibiotic use was necessary to alleviate the threat posed by resistant microorganisms at the hospital level.

Clinical manifestations and pulmonary radiological findings of primary anti-neutrophil cytoplasmic antibody-associated vasculitis / 中华全科医师杂志

Objective To analyze the clinical features and pulmonary radiological findings of primary anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis (AAV).Methods Clinical data of 271 ANCA positive primary AAV patients admitted in Shanghai Ruijin Hospital from January 2003 to November 2015 were retrospectively analyzed.Among 271 patients,there were 211 myeloperoxidase (MPO)-ANCA positive cases (MPO subgroup),52 proteinase 3 (PR3)-ANCA positive cases (PR3 subgroup),and 8 dual positive cases (dual subgroup) according to ANCA classification.The demography,clinical characteristics,pulmonary radiological manifestation and renal function were compared among three subgroups.Results MPO subgroup had more renal (x2 =4.968,P =0.026) and constitutional symptoms (x2.=8.901,P =0.003) than PR3 group,while PR3 group had more ENT symptoms (x2 =19.843,P ＜ 0.001),cough (x2 =6.623,P =0.010),hemoptysis (x2 =8.656,P =0.003),dyspnea (x2 =5.127,P =0.024),buccal and ocular mucosal symptoms (x2 =4.818,P =0.028) than MPO group.In lung radiology,interstitial manifestations were displayed more frequently in MPO than PR3 group (x2 =4.237,P =0.040),while pulmonary nodules was more frequent in PR3 than MPO group (x2 =4.503,P =0.034).Dual subgroup tended to have more nervous,respiratory and renal impairment.Renal function showed that MPO subgroup had higher creatinine (Z =-5.529,P ＜ 0.001),urea (Z =-4.646,P ＜ 0.001) and uric acid levels (Z =-2.331,P =0.020) than PR3 subgroup.Dual subgroup had higher creatinine (Z =-3.251,P =0.001) and urea (Z =-2.882,P =0.004) levels than PR3 subgroup,but there was no difference with MPO subgroup.Conclusion There are significant differences in both clinical and pulmonary radiological manifestations between the MPO and PR3-ANCA subgroup of primary AAV.

A case report of lung cancer presenting as interstitial pneumonia and a review of literatures / 中华全科医师杂志

A case of lung adenocarcinoma was reviewed.Its major symptoms were cough , sputum and progressive dyspnea.High resolution computed tomography presented ground-glass, bilateral fibrosis and some solid opacities.In conjunctions with the related literatures , its clinical manifestations and imaging features were analyzed for a better understanding of lung cancer.

Relationship between pulmonary arterial hypertension and fibrinolysis in elder patients with chronic obstructive pulmonary disease / 中华全科医师杂志

A total of 40 patients with COPD (excluding those with correlated/relevant diseases)were measured for inflammation parameters of erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) after hospital admission and some coagulation/fibrinolysis parameters including D-dimer,thrombinantithrombin (TAT),prothrombin fragment 1 + 2,(tissue plasminogen activator) tPA,plasminogen activator inhibitor 1 (PAI-1),von Willebrand factor (von WF),endothelin receptor A,thromboxane B2,P-selectin and pulmonary arterial pressure (PAP) by ultrasonic cardiography after the settling of the symptons of acute period.All patients were then divided into 2 groups according to PAP [＜ 40 mm Hg (1 mmHg=0.133 kPa) (n=24),＞40 mm Hg (n=16)].The values of CRP and ESRin the group with PAP ＞ 40 mm Hg were significantly higher than those in another group (P =0.044 and P =0.002respectively) while tPA was lower (P =0.04).A moderate positive correlation existed between tPA and TXB2 (r =0.547).Moreover,a highly positive correlation was found between TXB2 and PAl-1 (r =0.929).The results indicated that the COPD patients with pulmonary arterial hypertension (PAH) tend to have a higher level of inflammation,and their fibrinolysis becomes impaired leading to a prothrombotic state.