***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The herbal medicine , maoto , has been traditionally prescribed to patients with influenza in Japan . To better underst and the efficacy of maoto for the treatment of influenza , a r and omized trial was conducted for comparison with oseltamivir or zanamivir .  Adult patients with influenza symptoms , including fever , positive for quick diagnostic kit for influenza within 48 h of fever onset were assessed for enrollment . The data of 28 patients r and omly assigned to maoto ( n = 10 ) , oseltamivir ( n = 8) , or zanamivir ( n = 10 ) were analyzed for the duration of fever ( > 37.5 ° C ) and total symptom score from symptom cards recorded by the patient . Viral isolation and serum cytokine measurements were also done on days 1 , 3 , and 5 . Maoto granules , a commercial medical dosage form , are made from four plants : Ephedra Herb , Apricot Kernel , Cinnamon Bark , and Glycyrrhiza Root . Median duration s of fever of patients assigned maoto , oseltamivir , or zanamivir were 29 , 46 , or 27 h , respectively , significantly different for maoto and oseltamivir . No significant between-group differences were found in total symptom score among three groups . Viral persistent rates and serum cytokine levels ( IFN-α , IL-6 , IL-8 , IL-10 , and TNF-α ) during the study period showed no differences among three groups . The administration of oral maoto granules to healthy adults with seasonal influenza was well tolerated and associated with equivalent clinical and virological efficacy to neuraminidase inhibitors Background : In an influenza season where reduced effectiveness of oseltamivir was observed , we investigated the effectiveness of Maoto for influenza infection in children . Methods : Patients diagnosed with influenza by rapid diagnostic kit underwent treatment in one of the following groups : Maoto-treated group ( group 1 ( M ) ) ; oseltamivir-treated group ( group 2 ( O ) ) ; Maoto+oseltamivir-treated group ( group 3 ( M+O ) ) ; zanamivir-treated group ( group 4 ( Z ) ) ; and Maoto+zanamivir-treated group ( group 5 ( M+Z ) ) . Results : In influenza A patients who completed the study ( n = 150 ) , the mean duration of fever after administration ( DFA ) was significantly shorter in group 3 ( M+O ) ( 31.1 h , p < 0.01 ) and in group 4 ( Z ) ( 35.2 h , p < 0.05 ) , as compared to group 2 ( O ) ( 56.0 h ) . Among these , in patients aged ≤5 years ( n = 54 ) , DFA was significantly shorter in group 1 ( M ) ( 33.2 h , p < 0.05 ) and in group 3 ( M+O ) ( 34.6 h , p < 0.05 ) , as compared to group 2 ( O ) ( 61.4 h ) . In influenza B patients who completed the study ( n = 70 ) , no significant differences in DFA were observed among the groups . Conclusion : Maoto may be useful , particularly in cases of influenza with low sensitivity to oseltamivir and in patients aged ≤5 years for whom the use of zanamivir is difficult Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies We previously reported in r and omized controlled trials that maoto , a traditional herbal medicine , showed clinical and virological efficacy for seasonal influenza . In this study , a culturing system for influenza was used to test the effect of maoto .  A549 cells in the culture were infected with influenza virus A ( PR8 ) and followed after treatment with maoto ; the virus titers in the culture supernatant , intracellular viral proteins , and viral RNA were determined . When infected cells were cultured with maoto for 24 hr , the virus titer and protein were significantly reduced compared with medium only . Other subtypes , A/H3N2 , H1N1pdm , and B , were also inhibited by maoto .  Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase , especially in the first 30 min . Focusing on the entry step of the influenza virus , we found that endosomal pH , regulated by vacuolar-type H+ ATPase ( V-ATPase ) located in the membrane , was increased when treated with maoto . We also found that uncoating of influenza viruses was also inhibited by maoto , result ing in the increase of the number of virus particles in endosomes . These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm , probably through the inhibition of V-ATPase . The present study provides evidence that supports the clinical use of maoto for the treatment of influenza BACKGROUND Baloxavir marboxil is a selective inhibitor of influenza cap‐dependent endonuclease . It has shown therapeutic activity in pre clinical models of influenza A and B virus infections , including strains resistant to current antiviral agents . METHODS We conducted two r and omized , double‐blind , controlled trials involving otherwise healthy out patients with acute uncomplicated influenza . After a dose‐ranging ( 10 to 40 mg ) placebo‐controlled trial , we undertook a placebo‐ and oseltamivir‐controlled trial of single , weight‐based doses of baloxavir ( 40 or 80 mg ) in patients 12 to 64 years of age during the 2016–2017 season . The dose of oseltamivir was 75 mg twice daily for 5 days . The primary efficacy end point was the time to alleviation of influenza symptoms in the intention‐to‐treat infected population . RESULTS In the phase 2 trial , the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group ( P<0.05 ) . In the phase 3 trial , the intention‐to‐treat infected population included 1064 patients ; 84.8 to 88.1 % of patients in each group had influenza A(H3N2 ) infection . The median time to alleviation of symptoms was 53.7 hours ( 95 % confidence interval [ CI ] , 49.5 to 58.5 ) with baloxavir , as compared with 80.2 hours ( 95 % CI , 72.6 to 87.1 ) with placebo ( P<0.001 ) . The time to alleviation of symptoms was similar with baloxavir and oseltamivir . Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir . Adverse events were reported in 20.7 % of baloxavir recipients , 24.6 % of placebo recipients , and 24.8 % of oseltamivir recipients . The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced  susceptibility to baloxavir occurred in 2.2 % and 9.7 % of baloxavir recipients in the phase 2 trial and phase 3 trial , respectively . CONCLUSIONS Single‐dose baloxavir was without evident safety concerns , was superior to placebo in alleviating influenza symptoms , and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza . Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed . ( Funded by Shionogi ; JapicCTI number , 153090 , and CAPSTONE‐1 Clinical Trials.gov number , NCT02954354 . 
    Output:
    
The duration of symptoms or virus isolation did not differ between maoto and NAIs .
No severe side effects or adverse reactions were reported related to maoto or NAIs .
Conclusions Although we could not reach a definitive conclusion because of the small sample sizes and high risk of bias in the analysed studies , maoto may lower the duration of fever when it is used alone or in combination with NAIs and may be a well-tolerated treatment .