[Systematic review and Meta-analysis of Lianhua Qingwen preparations combined with Oseltamivir in treatment of influenza].

This study aims to explore the efficacy and safety of Lianhua Qingwen preparations combined with Oseltamivir in the treatment of influenza patients. PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang, and VIP were searched for the randomized controlled trials(RCTs) involving the comparison between the influenza patients treated with Lianhua Qingwen preparations combined with Oseltamivir and those treated with Oseltamivir alone. Fever clearance time was taken as the primary outcome indicator. Clinical effective rate(markedly effective and effective), time to muscle pain relief, time to sore throat relief, time to cough relief, time to nasal congestion and runny nose relief, time to negative result of viral nucleic acid test, and adverse reactions were taken as the secondary outcome indicators. The data were extracted based on the outcome indicators and then combined. The Cochrane collaboration's tool for assessing risk of bias was used to evaluate the quality of a single RCT, and the grading of recommendations assessment, development and evaluations(GRADE) system to assess the quality of a single outcome indicator. RevMan 5.3 was employed to analyze data and test heterogeneity. Finally, 16 RCTs involving 1 629 patients were included for analysis. The Meta-analysis showed that Lianhua Qingwen preparations combined with Oseltamivir was superior to Oseltamivir alone in the treatment of influenza in terms of clinical effective rate(RR=1.16, 95%CI [1.12, 1.20], P<0.000 01), fever clearance time(SMD=-2.02, 95%CI [-2.62,-1.41], P<0.000 01), time to muscle pain relief(SMD=-2.50, 95%CI [-3.84,-1.16], P=0.000 2), time to sore throat relief(SMD=-1.40, 95%CI [-1.93,-0.85], P<0.000 01), time to cough relief(SMD=-1.81, 95%CI [-2.44,-1.19], P<0.000 01), time to nasal congestion and runny nose(SMD=-2.31, 95%CI [-3.61,-1.01], P=0.000 5), and time to negative result of viral nucleic acid test(SMD=-0.68, 95%CI [-1.19,-0.16], P=0.01). However, due to the low quality of the trials, the above conclusions need to be proved by more high-quality clinical studies. In addition, we still need to attach importance to the adverse reactions of the integrated application of Chinese and western medicines.

Clinical Efficacy and Safety of Chinese Patent Medicine Combined with Oseltamivir for the Treatment of Adult Influenza: A Systematic Review and Meta-Analysis.

Influenza is a sudden and serious viral breathing and lung-related infectious disease that causes significant deadliness and death worldwide. Now, the international treatment is oseltamivir. Chinese patent medicine (CPM) as a kind of different therapy is used in the treatment of influenza in China. The aim of this study was to interpret the clinical efficacy and safety of CPM combined with oseltamivir in the treatment of adult influenza by reviewing all relevant randomized controlled trials, and to provide new ideas and methods for the treatment of influenza. PubMed, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Database were searched from the date of beginning until 1 June 2021, for the references on treatment of influenza with CPM. According to standard information extraction tables, two people worked to find and aggregate information independently. Review Manager 5.2 was used to study data carefully and evaluate risk of bias. A total of nine trials of 906 patients were included. Based on the meta-analysis, compared to oseltamivir, CPM combined with oseltamivir had better effect in the time of defervescence [MD = -17.68, 95% CI (-25.93, -9.44), P < 0.0001], the time of symptom improvement [MD = -22.28, 95% CI (-26.77, -17.80), P < 0.00001], and the time of hospitalization [MD = -2.04, 95% CI (-3.45, -0.63), P = 0.005]. Related to safety [RR = 0.69, 95% CI (0.38, 1.23), P = 0.21], the experimental group had fewer adverse reactions than the control group, but there is no statistical significance. The findings show that CPM combined with oseltamivir in adult influenza has a better efficacy in shortening the time of defervescence and symptom improvement, reducing the time of hospitalization. However, publication bias is inevitable due to the low methodological quality check of the clinical research about diagnostic criteria, definition of adult influenza, and small number of articles, and further large sample sizes and multi-center clinical trials are needed to give better proof for its efficacy and safety.

Herbal Medicine Treatment for Influenza: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The aim of this research is to evaluate the clinical evidence of an herbal medicine (HM) treatment on influenza and describe the potential benefits and adverse events by reviewing all relevant randomized controlled trials. All papers published from 2010 to 2019 in all languages in six databases were searched, including all randomized controlled trials on adults and children, testing herbal medicine for treatment of influenza, alone or in combination with conventional antiviral therapy. The main outcome parameters of interest were total effective rate, time to resolution of fever, adverse events, complications, and duration of viral shedding. 25 trials of 3044 patients were included. Herbal medicine compared to placebo significantly reduced time to fever resolution by 4.96[Formula: see text]h (mean difference, [Formula: see text]4.96; 95% CI, [Formula: see text]7.11 to [Formula: see text]2.80; [Formula: see text]), herbal medicine compared to oseltamivir showed no significant difference (mean difference, [Formula: see text]1.82; 95% CI, [Formula: see text]6.08 to 2.44; [Formula: see text]), and herbal medicine plus oseltamivir combined treatment significantly reduced duration of fever by 7.84[Formula: see text]h compared to a single treatment with oseltamivir (mean difference, [Formula: see text]7.84; 95% CI, [Formula: see text]12.51 to [Formula: see text]3.17; [Formula: see text]). Herbal medicine compared to placebo showed a significantly better total effective rate (risk ratio, 1.90; 95% CI, 1.18 to 3.07; [Formula: see text]), herbal medicine compared to oseltamivir indicated significantly better effective rate (risk ratio, 1.15; 95% CI, 1.03 to 1.29; [Formula: see text]), and combined treatment showed a significantly better total effective rate compared to a single treatment with oseltamivir (risk ratio, 1.20; 95% CI, 1.06 to 1.36; [Formula: see text]). Regarding safety, no serious adverse events were reported in HM treatment. HM presented fewer adverse events compared to oseltamivir, but the difference was not significant (risk difference, [Formula: see text]0.04; 95% CI, [Formula: see text]0.09 to 0.00; [Formula: see text]), and the combined treatment did not increase adverse events compared to oseltamivir (risk difference, [Formula: see text]0.02; 95% CI, [Formula: see text]0.06 to 0.02; [Formula: see text]). Research findings show that herbal medicine treatments have beneficial therapeutic effects on influenza and could decrease duration of fever and improve total effective rate. In addition, herbal medicine plus oseltamivir combined therapy could increase the therapeutic effect compared to a single treatment with oseltamivir.

Functionalized selenium nanoparticles enhance the anti-EV71 activity of oseltamivir in human astrocytoma cell model.

Enterovirus 71 (EV71) which commonly caused the hand-foot-mouth disease (HFMD) has become one of public health challenges worldwide. However, no effective vaccines or drugs for this disease has been developed. Thus, there is an urgent need to find a new strategy for treating the EV71 infection. Oseltamivir (OT) is an effective antiviral agent, but continuous use of oseltamivir leads to a diminished therapeutic effect in the clinic. In order to improve the antiviral activity of oseltamivir, oseltamivir was loaded onto surfaces of selenium nanoparticles (SeNPs) to fabricate a functionalized antiviral nanoparticles SeNPs@OT. The size of SeNPs@OT was tested by TEM and dynamic light scattering. The chemical structure and elemental composition of SeNPs@OT were analyzed by FT-IR and EDX, respectively. SeNPs@OT exhibited good stability and effective drug release in serum and PBS. SeNPs@OT efficiently entered into human astrocyte U251 cells (host cells) via clathrin-associated endocytosis and inhibited EV71 proliferation, which could protect EV71-infected U251 cells from apoptosis through mitochondrial pathway. Furthermore, SeNPs@OT inhibited EV71 activity probably by reducing the generation of reactive oxygen species in EV71-infected U251 cells. Interestingly, SeNPs obviously enhanced antiviral activity of oseltamivir in the anti-EV71 cell model. Taken together, SeNPs@OT is a promising antiviral drug candidate for EV71 infection.

Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program.

[Influenza A, pregnancy and neuraminidase inhibitors]. / Gripe A, embarazo y antivíricos inhibidores de la neuraminidasa.

Following the explosion of the influenza A pandemic (H1N1) during the first semester of 2009, oseltamivir and zanamivir were used as the treatment of choice in the absence of rigorous clinical studies demonstrating their efficacy in the treatment and prophylaxis of this disease. Knowledge of seasonal influenza, flu pandemics and particularly the H1N1, which produces more severe infection and a higher mortality rate during pregnancy, led to the use of antiviral treatment despite the scarcity of clinical studies on their efficacy and effectiveness, mainly due to the influence of the media. This study reviewed the experimental and clinical studies performed on the safety of oseltamivir and zanamivir in pregnancy. Likewise, the recommendations made by the different health care and governmental authorities as well as other institutions and scientific and health care organizations on the therapeutic management and prophylaxis of influenza A 2009 in pregnant women were reviewed.

Safety of oseltamivir in pregnancy: a review of preclinical and clinical data.

Pregnant women with influenza are at increased risk of morbidity, particularly due to respiratory complications. A high excess mortality rate among pregnant women has been observed in previous influenza pandemics and healthcare agencies have provided recommendations on the use of oseltamivir to treat pregnant women who are infected with the pandemic (H1N1) 2009 virus. This article reviews pre-clinical and clinical data to assess the safety of oseltamivir administered during pregnancy, in the context of the effects of influenza on adverse pregnancy outcomes and fetal malformations. The effects of influenza during pregnancy, whether mediated directly by the virus or by fever or other events secondary to the underlying infection, are not yet well understood, but some data indicate an increased risk of birth defects in women infected with influenza during the first trimester. Animal and toxicology studies do not suggest that clinically effective dosages of oseltamivir have the potential to produce adverse effects on fetal development. Additionally, transplacental transfer of the drug and its active metabolite was very limited and not detectable at normal therapeutic doses in an ex vivo human placenta model. To investigate the safety of oseltamivir in pregnancy, the Roche oseltamivir safety database was searched for all exposures to oseltamivir during pregnancy in the 9 years up to 14 December 2008. In addition, a search of the literature was carried out. Of 232 maternal exposures to oseltamivir in the Roche database, pregnancy outcomes were known for 115 of these exposures. The incidence of adverse pregnancy outcomes was as follows: spontaneous abortions 6.1% (7/115), therapeutic abortions 11.3% (13/115) and pre-term deliveries 2.1% (2/94 live births), values that are not higher than background incidence rates. Fetal outcomes were known in 100 of the 232 exposures. For the nine cases of birth defect that were reported, the timing of oseltamivir exposure in relation to the sensitive period for inducing the birth defect was analysed. Two cases of ventricular septal defect, a more common birth defect, and one case of anophthalmos, an uncommon birth defect, were consistent with exposure to oseltamivir during the sensitive period for these birth defects. For other birth defects, there was either no exposure to oseltamivir during the sensitive period for the defect or insufficient information for assessment. These findings were consistent with other reports in the published literature, including a series of 79 Japanese women exposed to oseltamivir during the first trimester. Together with the other evidence reviewed herein, review of the company safety database suggests that oseltamivir is unlikely to cause adverse pregnancy or fetal outcomes, but available data are limited. Clinicians who use oseltamivir in pregnant women should consider the available safety information, the pathogenicity of the circulating influenza virus strain, the woman's general health and the guidance provided by health authorities. Roche will continue to monitor all reports of oseltamivir use during pregnancy.

Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice.

The development of novel antiviral drugs is necessary for the prevention and treatment of a potential avian influenza pandemic. The aim of this study was to evaluate the efficacy and safety of a novel statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in a murine model. In H5N1-, H3N2- and H1N1-infected BALB/c mice, 50mug statin/200mug caffeine effectively ameliorated lung damage and inhibited viral replication and was at least as effective as oseltamivir and ribavirin. The statin/caffeine combination also appeared to be more effective when administered preventatively rather than as treatment. These findings provide justification for further research into this novel antiviral formulation.