***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 Time-dependent bias occurs when future exposure status is analyzed as being known with start of observation . As this bias is common , we sought to determine whether it always leads to biased effect estimation . We also sought to determine the direction of the effect bias . STUDY DESIGN AND SETTING We derived an easy mathematical proof investigating the nature of time-dependent bias . We applied the general mathematical result to data from a prospect i ve cohort study on the incidence of hospital infection in intensive care : Here , we investigated the effect of time-dependent hospital infection status on intensive care unit stay . The nature of time-dependent bias was also illustrated graphically . RESULTS Biased effect estimation is a mathematically inevitable consequence of time-dependent bias , because the number of individuals at risk of exposure is distorted over the course of time . In case of a time-dependent exposure that prolongs time until the study endpoint , the prolonging effect will be overestimated . CONCLUSION Because time-dependent bias inevitably leads to erroneous findings , it is a major concern that it is common in the clinical literature . Time-dependent bias can be avoided by proper hazard-based analyses 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 authors compared five methods of study ing survival bias associated with time-to-treatment initiation in a drug effectiveness study using medical administrative data bases ( 1996 - 2002 ) from Quebec , Canada . The first two methods illustrated how survival bias could be introduced . Three additional methods were considered to control for this bias . Methods were compared in the context of evaluating statins for secondary prevention in elderly patients post-acute myocardial infa rct ion who initiated statins within 90 days after discharge and those who did not . Method 1 that classified patients into users and nonusers at discharge result ed in an overestimation of the benefit ( 38 % relative risk reduction at 1 year ) . In method 2 , following users from the time of the first prescription and nonusers from a r and omly selected time between 0 and 90 days attenuated the effect toward the null ( 10 % relative risk reduction ) . Method 3 controlled for survival bias by following patients from the end of the 90-day time window ; however , it suffered a major loss of statistical efficiency and precision . Method 4 matched prescription time distribution between users and nonusers at cohort entry . Method 5 used a time-dependent variable for treatment initiation . Methods 4 and 5 better controlled for survival bias and yielded similar results , suggesting a 20 % risk reduction of recurrent myocardial infa rct ion or death events Objective To determine the epidemiological features , course , and outcomes of critically ill pediatric patients with Influenza A ( H1N1 ) virus . Design Prospect i ve cohort of children in pediatric intensive care units ( PICUs ) due to Influenza A ( H1N1 ) virus infection . Setting Seventeen medical-surgical PICUs in tertiary care hospital in Argentina . Patients All consecutive patients admitted to the PICUs with influenza A ( H1N1 ) viral infection from 15 June to 31 July 2009 . Measurements and main results Of 437 patients with acute lower respiratory infection in PICUs , 147 ( 34 % ) were diagnosed with influenza A ( H1N1 ) related to critical illness . The median age of these patients was 10 months ( IQR 3–59 ) .  Invasive mechanical ventilation  was used in 117 ( 84 % ) on admission . The rate of acute respiratory distress syndrome ( ARDS ) was 80 % ( 118 of 147 patients ) . Initial  non-invasive ventilation  failed in 19 of 22 attempts ( 86 % ) . Mortality at 28 days was 39 % ( n = 57 ) . Chronic complex conditions ( CCCs ) , acute renal dysfunction ( ARD ) and ratio PaO2/FiO2 at day 3 on MV were independently associated with a higher risk of mortality . The odds ratio ( OR ) for CCCs was 3.06 , ( CI 95 % 1.36–6.84 ) ; OR for ARD , 3.38 , ( CI 95 % 1.45–10.33 ) ; OR for PaO2/FiO2 , 4 ( CI 95 % 1.57–9.59 ) . The administration of oseltamivir within 24 h after admission had a protective effect : OR 0.2 ( CI 95 % 0.07–0.54 ) . Conclusions In children with ARDS , H1N1 as an etiologic agent confers high mortality , and the presence of CCCs in such patients increases the risk of death 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 zanam 
    Output:
    
Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults .
The use of oseltamivir increases the risk of nausea , vomiting , psychiatric events in adults and vomiting in children .
Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza .
Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households .