***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: Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use RATIONALE In a clinical trial by the Acute Respiratory Distress Syndrome Network ( ARDSNet ) , mechanical ventilation with tidal volumes of 6 ml/kg decreased mortality from acute lung injury . However , interpretations of these results generated controversy and it was unclear if this trial would change usual-care practice s. OBJECTIVES First , to determine if clinical practice s at ARDSNet hospitals changed after the tidal volume trial . Second , to determine if tidal volume and plateau pressure ( Pplat ) within 48 hours before r and omization affected hospital mortality in patients subsequently managed with 6 ml/kg predicted body weight ( PBW ) . METHODS We used preenrollment data from 2,451 patients enrolled in six trials ( 1996 - 2005 ) to describe changes in tidal volume over time . We used logistic regression to determine if preenrollment tidal volume or Pplat affected mortality . MEASUREMENTS AND MAIN RESULTS Median preenrollment tidal volume decreased from 10.3 ml/kg PBW ( range , 4.3 - 17.1 ) during the tidal volume trial ( 1996 - 1999 ) to 7.3 ml/kg PBW ( range , 3.9 - 16.2 ) after its completion ( P < 0.001 ) . Preenrollment tidal volume was not associated with mortality ( P = 0.566 ) . The odds of death increased multiplicatively with each cm H(2)O of preenrollment Pplat ( P < 0.001 ) ( e.g. , the odds of death was 1.37 times greater when preenrollment Pplat increased by 10 cm H(2)O ) . CONCLUSIONS Physicians used lower tidal volumes after publication of the tidal volume trial . Preenrollment Pplat was strongly associated with mortality , and may reflect disease severity independent of tidal volume . Pplat measured early in the course of acute lung injury , after accounting for tidal volume , is a respiratory system-specific value with strong prognostic significance We conducted clinical trials in patients with acute lung injury ( ALI ) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor , sivelestat sodium hydrate ( Sivelestat ) , to investigate the involvement of neutrophil elastase in ALI . In the phase III double-blind study ( Study 1 ) in 230 patients , the efficacy of Sivelestat was evaluated with the pulmonary function improvement ( PFI ) rating as the primary endpoint , and the weaning rate from mechanical ventilator , the discharge rate from intensive care unit ( ICU ) , and the survival rate as secondary endpoints . Afterwards , an unblinded study ( Study 2 ) in 20 patients was conducted using procedures for weaning from mechanical ventilation to reevaluate its efficacy with ventilator-free days ( VFD ) value , the primary endpoint , and to compare with that of Study 1 subgroup , which met the selection criteria used in Study 2 . Sivelestat increased PFI rating , reduced duration of mechanical ventilation , and shortened stay in ICU in Study 1 , although there was no significant efficacy on the survival rate . VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup , and increase in VFD value correlated with PFI rating and increase in ICU free days . It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans Sivelestat sodium hydrate ( sivelestat ) is a selective inhibitor of polymorphonuclear leukocyte elastase ( PMN-E ) . We administered sivelestat to patients with septic acute lung injury ( ALI ) to examine its usefulness . The primary endpoints in the study were the duration of artificial ventilation and pulmonary oxygenation ability , and the secondary endpoints were mortality and the concentrations of PMN-E , SP-D , TNF-alpha and IL-8 in blood . In the sivelestat group , the duration of artificial ventilation , pulmonary oxygenation ability , and the blood PMN-E , SP-D , TNF-alpha and IL-8 concentrations decreased significantly . Administration of sivelestat was found to reduce alveolar dysfunction and improve respiratory function , and it was suggested that early administration might be useful Objective To assess multicentre , r and omised , controlled trials ( MC- RCTs ) of systemic inflammatory response syndrome ( SIRS ) and sepsis conducted in Japan , published in Japanese and not available to English- language medical data bases . Design Method ological review .SubjectsAll Japanese RCTs relevant to SIRS and sepsis . Intervention Identification of manuscripts using a Japanese electronic library . Critical analysis of methodology and reporting quality using a modified Method ological Quality Assessment Score and the CONSORT group check list . Measurements and results Three MC- RCTs were identified . In the first , 147 patients with septic shock were r and omised to methylprednisolone ( 1000 mg i.v . ) or placebo . In the second , 221 patients were r and omised to 0.20 mg/kg per h or 0.004 mg/kg per h of sivelestat for acute lung injury with SIRS . In the third , 504 patients were r and omised to immunoglobulin ( 5 g for 3 days ) or to a control group . The average method ological quality score was higher than that of equivalent Western trials . The reporting quality ( CONSORT checklist ) was comparable to Western studies published during the same period . Conclusions Despite sound methodology and quality , the information obtained from relatively large Japanese critical care trials is not widely available to English-speaking investigators and therefore might be ignored in meta-analyses Evidence has linked neutrophil elastase to acute respiratory distress syndrome ( ARDS ) , suggesting that inhibiting the activity of this enzyme could prevent the development and progression of ARDS . However , few clinical trials have examined this notion . We therefore examined the effects of ONO-5046 ( sivelestat , a specific inhibitor of neutrophil elastase ; sodium N-[2-[4-(2,2-dimethylpropionyloxy ) phenylsulfonylaminobenzoyl]amino-acetate tetrahydrate ] ) in a r and omized , double-blinded trial in patients with ARDS . We r and omly assigned 24 patients with ARDS to groups that received conventional therapy without or with sivelestat ( 0.2 mg·kg−1·h−1 ) for 14 days . The variables of interest associated with clinical outcome were the duration of mechanical ventilation ; changes in oxygenation from baseline ; changes in cytokine levels from baseline ; number of patients alive at 30 days who did not need mechanical ventilation ; and mortality rate . The length of intensive care unit stay , number of ventilation days , and mortality rates did not statistically differ between groups . ARDS was more persistent in the control than in the sivelestat group ( control , 19.5 ± 7.4 days ; sivelestat , 13.5 ± 5.9 days ; P = 0.039 ) . Neutrophil elastase activity significantly differed between groups at 72 h after treatment . Levels of interleukin-6 were lower in the sivelestat group than in the controls at 24 , 48 , and 72 h after treatment . ONO-5046 apparently did not affect survival or the duration of mechanical ventilation Objective : Neutrophil elastase is believed to be an important mediator of acute lung injury .  Sivelestat ( ONO-5046 , Elaspol ) is a small molecular weight inhibitor of neutrophil elastase . The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days ( days alive and free from mechanical ventilation from day 1 to day 28 ) compared with placebo in mechanically ventilated patients with acute lung injury . Design : Multiple-center , double-blind , placebo-controlled trial administering a continuous infusion of sivelestat at a dose of 0.16 mg·kg−1·hr−1 . Setting : One hundred and five institutions in the United States , Canada , Belgium , Spain , Australia , and New Zeal and . Patients : A total of 492 mechanically ventilated patients with acute lung injury . Interventions : Patients were r and omized in a 1:1 fashion to sivelestat or placebo . Study drug was administered as a continuous infusion for the duration of mechanical ventilation plus 24 hrs for a maximum of 14 days . All patients were managed using low tidal volume mechanical ventilation . Measurements and Main Results : The study was stopped prematurely at the recommendation of an external Data and Safety Monitoring Board , which noted a negative trend in long-term mortality rate . Final analysis revealed no effect of sivelestat on the primary end points of ventilator-free days ( day 1–day 28 ) or 28-day all-cause mortality . There were 64 deaths in each treatment group within the 28-day study period , and the mean number of ventilator-free days was 11.4 and 11.9 in the sivelestat and placebo treatment groups , respectively ( p = .536 ) . There was no evidence of effect on measures of pulmonary function , including Pao2/Fio2 , static lung compliance , and time to meeting weaning criteria . There was no difference in adverse events or serious adverse events between treatment groups . A comparison of the Kaplan-Meier 180-day survival curves showed no difference between treatment groups ( p = .102 ) , but there was an increase in 180-day all-cause mortality in 
    Output:
    
Sivelestat was not associated with decreased mortality , even when including studies published in Japanese language