***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: Laninamivir octanoate , a long-acting neuraminidase inhibitor , is an effective treatment for influenza . However , its effectiveness for the prevention of influenza has not yet been demonstrated . We conducted a double-blind , multicenter , r and omized , placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts . Eligible participants , who were household members who did not have influenza and were in contact with an influenza-infected index patient , were r and omly assigned ( 1:1:1 ) to one of three groups : 20 mg of laninamivir octanoate once daily for 2 days ( LO-2 ) , 20 mg of laninamivir octanoate once daily for 3 days ( LO-3 ) , or a placebo . The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period . A total of 1711 participants were enrolled , and 1451 participants were included in the primary analysis . The proportion of participants with clinical influenza was 3.9 % ( 19/487 ) in the LO-2 group , 3.7 % ( 18/486 ) in the LO-3 group , and 16.9 % ( 81/478 ) in the placebo group ( P < 0.001 for each of the laninamivir octanoate group ) . The relative risk reductions , compared with the placebo group , were 77.0 % [ 95 % confidence interval ( CI ) 62.7–85.8 ] and 78.1 % ( 95 % CI 64.1–86.7 % ) for the LO-2 and LO-3 groups , respectively . The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group . The inhalation of 20 mg of laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts BACKGROUND Influenza causes lower respiratory tract complications ( LRTCs ) , particularly bronchitis and pneumonia , in both otherwise healthy adults and those with underlying conditions . The aim of this study was to assess the effect of oseltamivir treatment on the incidence of LRTCs leading to antibiotic treatment and hospitalizations following influenza illness . METHODS We analyzed prospect ively collected data on LRTCs and antibiotic use from 3564 subjects ( age range , 13 - 97 years ) with influenzalike illness enrolled in 10 placebo-controlled , double-blind trials of oseltamivir treatment .  RESULTS In adults and adolescents with a proven influenza illness , oseltamivir treatment reduced overall antibiotic use for any reason by 26.7 % ( 14.0 % vs 19.1 % with placebo ; P<.001 ) and the incidence of influenza-related LRTCs result ing in antibiotic therapy by 55 % ( 4.6 % vs 10.3 % with placebo ; P<.001 ) . In those subjects considered at increased risk of complications , 74 ( 18.5 % ) of 401 placebo recipients developed an LRTC leading to antibiotic use compared with 45 ( 12.2 % ) of 368 oseltamivir recipients ( 34.0 % reduction ; P = .02 ) . Hospitalization for any cause occurred in 18 ( 1.7 % ) of 1063 placebo recipients compared with 9 ( 0.7 % ) of 1350 oseltamivir-treated patients ( 59 % reduction ; P = .02 ) . In contrast , among subjects with an influenzalike illness but without a confirmed influenza infection , the incidence of LRTCs ( 6.7 % vs 5.3 % ) , overall antibiotic use ( 19.7 % vs 19.3 % ) , or hospitalizations ( 1.7 % vs 1.9 % ) was similar between placebo and oseltamivir recipients , respectively . CONCLUSION Oseltamivir treatment of influenza illness reduces LRTCs , antibiotic use , and hospitalization in both healthy and " at-risk " adults Objective We assessed the adequacy of r and omized controlled trial ( RCT ) registration , changes to registration data and reporting completeness for articles in ICMJE journals during 2.5 years after registration requirement policy . Methods For a set of 149 reports of 152 RCTs with Clinical Trials.gov registration number , published from September 2005 to April 2008 , we evaluated the completeness of 9 items from WHO 20-item Minimum Data Set relevant for assessing trial quality . We also assessed changes to the registration elements at the Archive site of Clinical Trials.gov and compared published and registry data . Results RCTs were mostly registered before 13 September 2005 deadline ( n = 101 , 66.4 % ) ; 118 ( 77.6 % ) started recruitment before and 31 ( 20.4 % ) after registration . At the time of registration , 152 RCTs had a total of 224 missing registry fields , most commonly ‘ Key secondary outcomes ’ ( 44.1 % RCTs ) and ‘ Primary outcome ’ ( 38.8 % ) . More RCTs with post- registration recruitment had missing Minimum Data Set items than RCTs with pre- registration recruitment : 57/118 ( 48.3 % ) vs. 24/31 ( 77.4 % ) ( χ2 1 = 7.255 , P = 0.007 ) . Major changes in the data entries were found for 31 ( 25.2 % ) RCTs . The number of RCTs with differences between registered and published data ranged from 21 ( 13.8 % ) for Study type to 118 ( 77.6 % ) for Target sample size . Conclusions ICMJE journals published RCTs with proper registration but the registration data were often not adequate , underwent substantial changes in the registry over time and differed in registered and published data . Editors need to establish quality control procedures in the journals so that they continue to contribute to the increased transparency of clinical trials The local immune response to influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid sample s from 15 volunteers experimentally infected with influenza A/Texas/36/91 ( H1N1 ) . The study was part of a r and omized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir ( 600 mg 2x/day for 5 days ) , a highly selective inhibitor of influenza A and B virus neuraminidases , on the clinical symptoms of influenza infection .  Nasal lavage fluid levels of interleukin (IL)-6 , tumor necrosis factor-alpha , interferon-gamma , IL-10 , monocyte chemotactic protein-1 , and macrophage inflammatory protein-1alpha and -1beta increased in response to influenza virus infection and correlated statistically with the magnitude and time course of the symptoms . Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses . These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of influenza Objectives Long-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks . We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks . Methods We conducted a parallel group , double blind , 2 ( active drug ) :1 ( placebo ) r and omized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy , Thai hospital professionals at two Bangkok hospitals . The primary endpoint was study withdrawal due to drug-related ( possibly , probably , definitely ) serious or adverse events ( AEs ) grade d ≥2 . Results Recruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo . A total of 102 grade ≥2 AEs were reported or detected in 69 subjects : 23/129 ( 17.8 % ) versus 15/65 ( 23.1 % ) ( P = 0.26 ) , and 23/131 ( 17.6 % ) versus 8/65 ( 12.3 % ) ( P = 0.28 ) . Intercurrent infections/fevers [ 26/102 ( 25.5 % ) ] , abnormal biochemistry [ 25/102 ( 24.5 % ) ] and gastrointestinal symptoms [ 18/102 ( 17.6 % ) ] were the most frequently reported AEs . There were no drug-related study withdrawals . Eight serious AEs were all due to intercurrent illnesses . Laboratory , lung function and ECG parameters were similar between drugs and placebos . Conclusions Oseltamivir and zanamivir were well tolerated in healthy hospital professionals . Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks CONTEXT Influenza virus neuraminidase is thought to be essential for virus replication in humans ; however , to date , available neuraminidase inhibitors are limited to zanamivir , which is topically administered . OBJECTIVE To determine the safety , tolerability , and antiviral activity of oral neuraminidase inhibitor oseltamivir ( GS4104/Ro64 - 0796 ) for prevention and the early treatment of influenza in experimentally infected humans . DESIGN Two r and omized , double-blind , placebo-controlled trials conducted between June and July 1997 . SETTING Individual hotel rooms ; 2 large US university medical schools . PARTICIPANTS A total of 117 healthy adult volunteers ( aged 18 - 40 years ; median age , 21 years ) who were susceptible ( hemagglutination-inhibition antibody titer < or = 1:8 ) . INTERVENTIONS All subjects were inoculated intranasally with influenza A/Texas/36/91 ( H1N1 ) virus . For the prophylaxis study , oral oseltamivir ( 100 mg once daily [ n = 12 ] , 100 mg twice daily [ n = 12 ] , or matching placebo [ n = 13 ] , starting 26 hours before virus inoculation ) was administered . For the treatment study , the same drug was given ( 20 mg , 100 mg , or 200 mg twice daily , 200 mg once daily , or matching placebo [ n = 16 ] , in each group starting 28 hours after inoculation ) . All regimens were continued for 5 days . MAIN OUTCOME MEASURES Comparing placebo groups with pooled treatment groups , for prophylaxis , outcomes included frequency of infection and viral shedding ; for treatment , viral shedding in titers . RESULTS In the prophylaxis study , 8 ( 67 % ) of 12 placebo and 8 ( 38 % ) of 21 oseltamivir recipients became infected ( P = .16 ; efficacy , 61 % ) ; 6 ( 50 % ) placebo compared with 0 oseltamivir recipients shed virus ( P<.001 ; efficacy , 100 % ) , and 33 % of placebo but no oseltamivir recipient had infection-related respiratory illness ( P<.01 ) . Among infected subjects in the treatment study ( n = 69 ) , the viral titer area under the curve of the combined oseltamivir groups ( n = 56 ) was lower ( median [ interquartile range [ IQR ] ] , 80 [ 23 - 151 ] vs 273 [ 79 - 306 ] log10 tissue culture-infective doses50 per milliliter x hour ; P = .02 ) than the placebo group ( n = 13 ) , and the median ( IQR ) duration of viral shedding with therapy was reduced from 107 ( 83 - 131 ) to 58 ( 35 - 59 ) hours ( P = .003 ) . Oseltamivir treatment also reduced symptom scores ( median [ IQR ] score-hours , 225 [ 97 - 349 ] vs 400 [ 189 - 645 ] ; P = .05 ) , and nasal proinflammatory cytokine levels . Transient mild to moderate nausea after dosing was observed in 15 ( 17 % ) of 88 oseltamivir and 2 ( 7 % ) of 29 placebo recipients ( 95 % confidence interval for difference , -11 % to 68 % ) , which was largely prevented by ingestion with food . CONCLUSIONS In these trials , prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza Please cite this paper as : Dharan et al. ( 2011 ) Clinical and virologic outcomes in patients with oseltamivir‐resistant seasonal influenza A ( H1N1 ) infections : results from a clinical trial . Influenza and Other Respiratory Viruses 6(3 ) , 153–158 . Nineteen patients with oseltamivir‐resistant seasonal influenza A ( H1N1 ) infections were r and omized to 
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Time to first symptom alleviation .
Serious influenza complications or those leading to study withdrawal .
There was no significant effect on  unverified pneumonia in children .
There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia .
Harms of treatment .
Oseltamivir and zanamivir have small , non-specific effects on reducing the time to alleviation of influenza symptoms in adults , but not in asthmatic children .
Using either drug as prophylaxis reduces the risk of developing symptomatic influenza .
Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza ( such as pneumonia ) are reduced , because of a lack of diagnostic definitions .
The use of oseltamivir increases the risk of adverse effects , such as nausea , vomiting , psychiatric effects and renal events in adults and vomiting in children .
The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir .