Comparative effectiveness and safety of antiviral agents for patients with COVID-19: Protocol for a systematic review and individual-patient data network meta-analysis.

BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We propose the protocol described below to perform an individual-patient data (IPD) network meta-analysis (NMA) in order to evaluate the efficacies of different antiviral drugs to treat patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: We will search the Medline, EMBASE, Cochrane Library, SinoMed, CNKI and VIP databases from their inceptions through July 2020. There will be no restrictions on language, publication year, or publication type. Randomized clinical trials (RCTs) and prospective cohort studies with antiviral treatments for COVID-19 will be considered. Two reviewers will independently select studies and collect data. Risk-of-bias assessments will be completed using the Cochrane risk-of-bias scale. Primary outcome will be the COVID-19 recovery rate. We will combine aggregated data from IPD with the NMA in a single model, compare the effects of different antiviral drugs on patient-relevant efficacy, and rank the results to decide which is the most effective. TRIAL REGISTRATION: PROSPERO registration number: CRD42020167038.

Indirect comparison of efficacy between different antibiotic prophylaxis against the intracranial infection after craniotomy.

BACKGROUND: Many studies had shown that prophylactic use of antibiotics could significantly reduce the intracranial infection (ICI) rate of craniotomy. However, there has been no comparison of these antibiotics. METHODS: An electronic database search was performed, from inception to June 102,020. Randomized controlled trials (RCT) using different intravenous antibiotics (IVA) against the ICIs after craniotomy were considered. The primary outcome was the incidence rates of ICIs. An indirect treatment comparison (ITC) was conducted to compare the protective effect among the diverse antibiotic prophylaxis to prevent ICIs after craniotomy. Risk of potential bias was assessed. RESULTS: A total of 3214 patients after craniotomy in 11 studies were included, 159 patients experienced postoperative ICI, including 33 patients in the antibacterial group and 126 in the control group. The calculate results of meta-analysis showed that except fusidic acid, preoperative intravenous injection of cephalosporin, clindamycin, vancomycin, and penicillin can significantly reduce the incidence of ICI after craniotomy, and ITC showed there was no statistically significance difference in the rates of post craniotomy ICI between the various antibiotics. CONCLUSION: The current evidence shows that low-grade antibacterial drugs can be selected to prevent ICI after craniotomy, but this may be due to the limited number of studies per antibiotic. It still needs more high-quality, large sample RCT to confirm. SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD42019133369.

Status and Challenges of Public Health Emergency Management in China Related to COVID-19.

Objective: This study aimed at exploring the current development status and problems of health emergency management in China and provides a reference for improving, constructing, and implementing a public health emergency management system. Methods: Cases of major and severe public health emergencies in China were analyzed along with the relevant health emergency management literature from the last decade. Results: China's health emergency system gradually improved during the study period. Monitoring and early warning systems were significantly strengthened. Material reserves and transfer management systems were constantly improved. However, the operational efficiency of command and decision systems was low, versatile talent accounted for a relatively small proportion, and emergency fund investment was insufficient. Conclusion: Constructing a sound and scientific emergency management mechanism is a lengthy and challenging process. To establish an emergency management mode for public health emergencies that is appropriate for China, it is necessary to solve existing problems and learn from the models and experiences of developed foreign countries.

Comparison of genotypic resistance mutations in treatment-naive HIV type 1-infected patients in Korea and China.

Seventy-six treatment-naive human immunodeficiency virus (HIV)-1-infected patients were recruited from Korea and China to evaluate transmitted drug resistance (TDR). Although no major TDR was observed within the study population, some resistance-associated mutations in the reverse transcriptase region were observed (V118I 9.2%, V179D 7.9%). The frequencies of resistance-associated mutations in NNRTI (V179D) and PI minor mutations were higher in Korean patients compared with Chinese patients (13.6% vs. 0%, 45.5% vs. 12.5%, p < 0.05). Although unique clustering was observed in phylogenetic analyses according to geographic sources, cautious monitoring is recommended due to increasing TDR reports in this area where the population shares close geographic and cultural aspects.

[Twenty-three cases of cytomegalovirus infection in acquired immunodeficiency syndrome].

OBJECTIVE: To investigate the clinical features, therapeutic approaches, outcomes and alterations of peripheral lymphocytes subsets in cytomegalovirus (CMV) infections in patients with AIDS. METHODS: Ninety-six cases of AIDS were treated in Peking Union Medical College Hospital and 23 of them had CMV infection. We analyzed the clinical features, peripheral lymphocytes subsets, outcomes, CMV pp65 antigen and/or specific anti-CMV IgM. RESULTS: In the 23 CMV patients, nonspecific symptoms including fever, cough, chest distress and diarrhea occurred in 18, 11, 9 and 8 patients, respectively. Thirteen patients had retinitis identified by ophthalmofundoscopy, 7 of them had blurred vision or floating as primary symptoms. Pneumocystis pneumonia, tuberculosis infection and other infection appeared in 18 patients. Fifteen (65.2%) of the patients had positive serum tests. The positive rates for CMV pp65 and specific anti-CMV-IgM were 43.5% and 30.4%, respectively. CD(4)(+)T cell count in CMV patients was remarkably decreased than that in non-CMV patients [14(4, 39) cells/microl vs (48(12, 128) cells/microl, P = 0.005] and the proportion of CD(8)(+)CD(38)(+)T cells in CMV patients was higher than that in non-CMV patients, whereas the difference of CD(8)(+)T cell was not statistically different between the 2 groups. CONCLUSIONS: CMV infection often occurs in advanced AIDS patients. In HIV/AIDS patients with CD(4)(+)T cell count

Three generic nevirapine-based antiretroviral treatments in Chinese HIV/AIDS patients: multicentric observation cohort.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection. METHODOLOGY: This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistance were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also compared in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44+/-0.68, 4.52+/-0.71 and 4.41+/-0.63 lg copies/ml in group A, B and C respectively (p = 0.628). At the end of the study, the plasma viral load reached 2.54+/-1.11, 1.89+/-0.46 and 1.92+/-0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response within any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR = 2.096, 95%CI: 1.106-3.973, P = 0.023) and higher CD4 baseline (CD4 count >250/ul) (OR = 2.096, 95%CI: 1.07-4.107, P = 0.031). CONCLUSION: Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00618176.

[The correlation of HIV-1 viral load to expression of CD8+ T lymphocyte activators CD38 and HLA-DR].

OBJECTIVE: To investigate the correlation of CD38 and HLA-DR abnormal activating expression on CD8+ T with plasma viral load (VL) and evaluate the possibility of the economical CD38 and HLA-DR test to substitute VL assay in HIV/AIDS patients. METHODS: A multi-point correlation study of the percentage of CD38 and HLA-DR on CD8+ T by flow cytometry with plasma VL by bDNA was performed in 103 HIV/AIDS patients during a 12-month highly active anti-retroviral therapy (HAART). The cutoff values of CD38 and HLA-DR were evaluated with ROC area, sensitivity and specificity for predictive VL < 50 copies/ml, < 500 copies/ml, > 1000 copies/ml and > 10,000 copies/ml respectively. RESULTS: The level of CD38 and HLA-DR on CD8+ T in 103 patients decreased gradually with the reduction of VL during a 12-month HAART. The correlation of CD38 and HLA-DR with VL in the year of HAART was 0.424, 0.376, 0.335, 0.326, 0.297, 0.285 and 0.377, 0.318, 0.333, 0.312, 0.361, 0.358 with significant P value. Moreover, the overall correlation of CD38 and HLA-DR with VL were 0.483 (P < 0.001) and 0.477 (P < 0.001). Depending on optimal ROC, sensitivity and specificity for the substitute method, the cutoffs percentage of CD38 were < 68.5% and < 72.5% for predictive VL < 50 copies/ml and < 500 copies/ml as well as > 39.5% and > 46.5% of HLA-DR cutoff to predict VL > 1000 copies/ml and > 10,000 copies/ml. CONCLUSION: The detection of CD38 and HLA-DR percentage expression on CD8+ T can be available for prediction about HIV VL assay as a substitute method to survey the disease progression and HAART outcome in some resource-limited areas of China.