human
***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: Objectives : To evaluate the association between interleukin-6 , interleukin-8 , and interleukin-10 and clinical outcomes including mortality in patients with acute lung injury and to determine whether lower tidal volume ventilation was associated with a decrease in plasma cytokines in patients with acute lung injury . Design : Multiple-center , r and omized trial . Setting : Intensive care units in ten university centers . Patients : The study included 861 patients enrolled in the National Heart , Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial of lower tidal volumes compared with traditional tidal volumes for acute lung injury . Interventions : Patients were r and omized to a 6 mL/kg or a 12 mL/kg tidal volume strategy that has been previously described . Measurements and Main Results : Baseline plasma levels of interleukin-6 , interleukin-8 , and interleukin-10 were each associated with an increased risk of death in both logistic regression analyses controlling for ventilator group ( odds ratio 1.63 per log-10 increment , 95 % confidence interval 1.33–1.98 ; odds ratio 2.33 per log-10 increment , 95 % confidence interval 1.79–3.03 ; odds ratio 2.02 per log-10 increment , 95 % confidence interval 1.47–2.76 , respectively ) and multivariate analyses controlling for ventilation strategy , Acute Physiology and Chronic Health Evaluation III score , Pao2/Fio2 ratio , creatinine , platelet count , and vasopressor use ( odds ratio 1.63 per log-10 increment , 95 % confidence interval 0.93–1.49 ; odds ratio 1.73 per log-10 increment , 95 % confidence interval 1.29–2.34 ; odds ratio 1.23 per log-10 increment , 95 % confidence interval 0.86–1.76 , respectively ) . Interleukin-6 and interleukin-8 levels were also associated with a significant decrease in ventilator free and organ failure free days .  Patients with sepsis had the highest cytokine levels and the greatest risk of death per cytokine elevation . By day 3 , the 6 mL/kg strategy was associated with a greater decrease in interleukin-6 and interleukin-8 levels . There was a 26 % reduction in interleukin-6 ( 95 % confidence interval , 12–37 % ) and a 12 % reduction in interleukin-8 ( 95 % confidence interval , 1–23 % ) in the 6 mL/kg group compared with the 12 mL/kg group . Conclusions : In patients with acute lung injury , plasma interleukin-6 and interleukin-8 levels are associated with morbidity and mortality . The severity of inflammation varies with clinical risk factor , suggesting that clinical risk factor should be considered when both developing and testing therapeutic interventions . Low tidal volume ventilation is associated with a more rapid attenuation of the inflammatory response Background Acute respiratory distress syndrome ( ARDS ) is a potentially fatal disease with high mortality . Our aim was to summarize the current evidence for use of neuromuscular blocking agents ( NMBA ) in the early phase of ARDS . Methods Systematic review and meta- analysis of publications between 1966 and 2012 . The Medline and CENTRAL data bases were search ed for studies on  NMBA in patients with ARDS . The meta- analysis was limited to : 1 ) r and omized controlled trials ; 02 ) adult human patients with ARDS or acute lung injury ; and 03 ) use of any NMBA in one arm of the study compared with another arm without NMBA . The outcomes assessed were : overall mortality , ventilator-free days , time of mechanical ventilation , adverse events , changes in gas exchange , in ventilator setting s , and in respiratory mechanics . Results Three r and omized controlled trials covering 431 participants were included . Patients treated with NMBA showed less mortality ( Risk ratio , 0.71 [ 95 % CI , 0.55 – 0.90 ] ; number needed to treat , 1 – 7 ) , more ventilator free days at day 28 ( p = 0.020 ) , higher PaO2 to FiO2 ratios ( p = 0.004 ) , and less barotraumas ( p = 0.030 ) . The incidence of critical illness neuromyopathy was similar ( p = 0.540 ) . Conclusions The use of NMBA in the early phase of ARDS improves outcome A r and omized , controlled clinical trial was performed with patients with acute respiratory distress syndrome ( ARDS ) to compare the effect of conventional therapy or inhaled nitric oxide ( iNO ) on oxygenation .  Patients were r and omized to either conventional therapy or conventional therapy plus iNO for 72 h. We tested the following hypotheses : ( 1 ) that iNO would improve oxygenation during the 72 h after r and omization , as compared with conventional therapy ; and ( 2 ) that iNO would increase the likelihood that patients would improve to the extent that the FI(O2 ) could be decreased by > or = 0.15 within 72 h after r and omization . There were two major findings . First , That iNO as compared with conventional therapy increased Pa(O2)/FI(O2 ) at 1 h , 12 h , and possibly 24 h. Beyond 24 h , the two groups had an equivalent improvement in Pa(O2)/FI(O2 ) . Second , that patients treated with iNO therapy were no more likely to improve so that they could be managed with a persistent decrease in FI(O2 ) > or = 0.15 during the 72 h following r and omization ( 11 of 20 patients with iNO versus 9 of 20 patients with conventional therapy , p = 0.55 ) . In patients with severe ARDS , our results indicate that iNO does not lead to a sustained improvement in oxygenation as compared with conventional therapy & NA ; The Reevaluation of Systemic Early Neuromuscular Blockade ( ROSE ) trial is a multicenter , r and omized trial design ed to assess the efficacy and safety of  early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome . This document provides background for interpretation of the trial results , and highlights unique design approaches that may inform future trials of acute illness . We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury Network , provide the trial methodology using the Consoli date d St and ards of Reporting Trials framework , and discuss key design challenges and their resolution . Four key design issues proved challenging — feasibility , choice of sedation depth in the control group , impact of emphasizing early treatment on enrollment criteria and protocol execution , and choice of positive end‐expiratory pressure strategy . We used literature , an iterative consensus model , and internal surveys of current practice to inform design choice . ROSE will provide definitive , Consoli date d St and ards of Reporting Trials adherent data on early neuromuscular blockade for future patients with acute respiratory distress syndrome . Our multidisciplinary approach to trial design may be of use to other trials of acute illness . Clinical trial registered with www . clinical trials.gov ( NCT02509078 ) RATIONALE Critical illness polyneuropathy/myopathy causes limb and respiratory muscle weakness , prolongs mechanical ventilation , and extends hospitalization of intensive care patients . Besides controlling risk factors , no specific prevention or treatment exists . Recently , intensive insulin therapy prevented critical illness polyneuropathy in a surgical intensive care unit . OBJECTIVES To investigate the impact of intensive insulin therapy on polyneuropathy/myopathy and treatment with prolonged mechanical ventilation in medical patients in the intensive care unit for at least 7 days . METHODS This was a prospect ively planned sub analysis of a r and omized controlled trial evaluating the effect of intensive insulin versus conventional therapy on morbidity and mortality in critically ill medical patients . All patients who were still in intensive care on Day 7 were screened weekly by electroneuromyography . The effect of intensive insulin therapy on critical illness polyneuropathy/myopathy and the relationship with duration of mechanical ventilation were assessed . MEASUREMENTS AND MAIN RESULTS Independent of risk factors , intensive insulin therapy reduced incidence of critical illness polyneuropathy/myopathy ( 107/212 [ 50.5 % ] to 81/208 [ 38.9 % ] , p = 0.02 ) . Treatment with prolonged ( > or = 14 d ) mechanical ventilation was reduced from 99 of 212 ( 46.7 % ) to 72 of 208 ( 34.6 % ) ( p = 0.01 ) . This was statistically only partially explained by prevention of critical illness polyneuropathy/myopathy . CONCLUSION In a subset of medical patients in the intensive care unit for at least 7 days , enrolled in a r and omized controlled trial of intensive insulin therapy , those assigned to intensive insulin therapy had a reduced incidence of critical illness polyneuropathy/myopathy and were treated with prolonged mechanical ventilation less frequently BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water . Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients . METHODS We r and omly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels , which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen . RESULTS Mean ( + /-SD ) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group ( P<0.001 ) . The rates of death before hospital discharge were 24.9 percent and 27.5 percent , respectively ( P=0.48 ; 95 percent confidence interval for the difference between groups , -10.0 to 4.7 percent ) . From day 1 to day 28 , breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group ( P=0.50 ) . CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water , clinical outcomes are similar whether lower or higher PEEP levels are used Abstract Although numerous clinical , laboratory , and pharmacological variables have been reported as significant risk factors for critical illness polyneuromyopathy ( CIPM ) , there is still no consensus on the aetiology of this condition . Objectives of the study were to assess the clinical and electrophysiological incidence and risk factors for CIPM.A  cohort of critically ill patients was observed prospect ively for a one – month period and the association between neuromuscular involvement and various potential risk factors was evaluated . Sixty one critically ill patients completed the follow – up ( 30 women , 31 men , median age 59 years).CIPM  development was detected clinical ly in 17 patients ( 27.9 % ) and electrophysiologically in 35 patients ( 57.4 % ) . CIPM was significantly associated with the presence and duration of systemic inflammatory response syndrome and the severity of multiple , respiratory , central nervous , and cardiovascular organ failures . The median duration of mechanical ventilation was significantly longer in patients with CIPM than in those without ( 16 vs 3 days , p < 0.001 ) . Independent predictors of CIPM obtainable within the 1st week of critical illness were the admission sequential organ failure assessment score ( odds ratio [ OR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02–1.36 ) , the 1st week total sequential organ failure assessment scores ( OR , 1.14 ; 95 % CI , 1.06–1.46 ) and the 1st week duration of systemic inflammatory response syndrome ( OR , 1.05 ; 95 % CI , 1.01–1.15 ) . They were able to correctly predict the development of CIPM at the end of the 1st week in about 80 % of critically ill cases . In conclusion , the presence and duration of systemic inflammatory response syndrome and the severity of multiple and several organ failures are associated with increased risk of the development of CIPM BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP 
    Output:
    
agent
***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: Objectives : To evaluate the association between interleukin-6 , interleukin-8 , and interleukin-10 and clinical outcomes including mortality in patients with acute lung injury and to determine whether lower tidal volume ventilation was associated with a decrease in plasma cytokines in patients with acute lung injury . Design : Multiple-center , r and omized trial . Setting : Intensive care units in ten university centers . Patients : The study included 861 patients enrolled in the National Heart , Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial of lower tidal volumes compared with traditional tidal volumes for acute lung injury . Interventions : Patients were r and omized to a 6 mL/kg or a 12 mL/kg tidal volume strategy that has been previously described . Measurements and Main Results : Baseline plasma levels of interleukin-6 , interleukin-8 , and interleukin-10 were each associated with an increased risk of death in both logistic regression analyses controlling for ventilator group ( odds ratio 1.63 per log-10 increment , 95 % confidence interval 1.33–1.98 ; odds ratio 2.33 per log-10 increment , 95 % confidence interval 1.79–3.03 ; odds ratio 2.02 per log-10 increment , 95 % confidence interval 1.47–2.76 , respectively ) and multivariate analyses controlling for ventilation strategy , Acute Physiology and Chronic Health Evaluation III score , Pao2/Fio2 ratio , creatinine , platelet count , and vasopressor use ( odds ratio 1.63 per log-10 increment , 95 % confidence interval 0.93–1.49 ; odds ratio 1.73 per log-10 increment , 95 % confidence interval 1.29–2.34 ; odds ratio 1.23 per log-10 increment , 95 % confidence interval 0.86–1.76 , respectively ) . Interleukin-6 and interleukin-8 levels were also associated with a significant decrease in ventilator free and organ failure free days .  Patients with sepsis had the highest cytokine levels and the greatest risk of death per cytokine elevation . By day 3 , the 6 mL/kg strategy was associated with a greater decrease in interleukin-6 and interleukin-8 levels . There was a 26 % reduction in interleukin-6 ( 95 % confidence interval , 12–37 % ) and a 12 % reduction in interleukin-8 ( 95 % confidence interval , 1–23 % ) in the 6 mL/kg group compared with the 12 mL/kg group . Conclusions : In patients with acute lung injury , plasma interleukin-6 and interleukin-8 levels are associated with morbidity and mortality . The severity of inflammation varies with clinical risk factor , suggesting that clinical risk factor should be considered when both developing and testing therapeutic interventions . Low tidal volume ventilation is associated with a more rapid attenuation of the inflammatory response Background Acute respiratory distress syndrome ( ARDS ) is a potentially fatal disease with high mortality . Our aim was to summarize the current evidence for use of neuromuscular blocking agents ( NMBA ) in the early phase of ARDS . Methods Systematic review and meta- analysis of publications between 1966 and 2012 . The Medline and CENTRAL data bases were search ed for studies on  NMBA in patients with ARDS . The meta- analysis was limited to : 1 ) r and omized controlled trials ; 02 ) adult human patients with ARDS or acute lung injury ; and 03 ) use of any NMBA in one arm of the study compared with another arm without NMBA . The outcomes assessed were : overall mortality , ventilator-free days , time of mechanical ventilation , adverse events , changes in gas exchange , in ventilator setting s , and in respiratory mechanics . Results Three r and omized controlled trials covering 431 participants were included . Patients treated with NMBA showed less mortality ( Risk ratio , 0.71 [ 95 % CI , 0.55 – 0.90 ] ; number needed to treat , 1 – 7 ) , more ventilator free days at day 28 ( p = 0.020 ) , higher PaO2 to FiO2 ratios ( p = 0.004 ) , and less barotraumas ( p = 0.030 ) . The incidence of critical illness neuromyopathy was similar ( p = 0.540 ) . Conclusions The use of NMBA in the early phase of ARDS improves outcome A r and omized , controlled clinical trial was performed with patients with acute respiratory distress syndrome ( ARDS ) to compare the effect of conventional therapy or inhaled nitric oxide ( iNO ) on oxygenation .  Patients were r and omized to either conventional therapy or conventional therapy plus iNO for 72 h. We tested the following hypotheses : ( 1 ) that iNO would improve oxygenation during the 72 h after r and omization , as compared with conventional therapy ; and ( 2 ) that iNO would increase the likelihood that patients would improve to the extent that the FI(O2 ) could be decreased by > or = 0.15 within 72 h after r and omization . There were two major findings . First , That iNO as compared with conventional therapy increased Pa(O2)/FI(O2 ) at 1 h , 12 h , and possibly 24 h. Beyond 24 h , the two groups had an equivalent improvement in Pa(O2)/FI(O2 ) . Second , that patients treated with iNO therapy were no more likely to improve so that they could be managed with a persistent decrease in FI(O2 ) > or = 0.15 during the 72 h following r and omization ( 11 of 20 patients with iNO versus 9 of 20 patients with conventional therapy , p = 0.55 ) . In patients with severe ARDS , our results indicate that iNO does not lead to a sustained improvement in oxygenation as compared with conventional therapy & NA ; The Reevaluation of Systemic Early Neuromuscular Blockade ( ROSE ) trial is a multicenter , r and omized trial design ed to assess the efficacy and safety of  early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome . This document provides background for interpretation of the trial results , and highlights unique design approaches that may inform future trials of acute illness . We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury Network , provide the trial methodology using the Consoli date d St and ards of Reporting Trials framework , and discuss key design challenges and their resolution . Four key design issues proved challenging — feasibility , choice of sedation depth in the control group , impact of emphasizing early treatment on enrollment criteria and protocol execution , and choice of positive end‐expiratory pressure strategy . We used literature , an iterative consensus model , and internal surveys of current practice to inform design choice . ROSE will provide definitive , Consoli date d St and ards of Reporting Trials adherent data on early neuromuscular blockade for future patients with acute respiratory distress syndrome . Our multidisciplinary approach to trial design may be of use to other trials of acute illness . Clinical trial registered with www . clinical trials.gov ( NCT02509078 ) RATIONALE Critical illness polyneuropathy/myopathy causes limb and respiratory muscle weakness , prolongs mechanical ventilation , and extends hospitalization of intensive care patients . Besides controlling risk factors , no specific prevention or treatment exists . Recently , intensive insulin therapy prevented critical illness polyneuropathy in a surgical intensive care unit . OBJECTIVES To investigate the impact of intensive insulin therapy on polyneuropathy/myopathy and treatment with prolonged mechanical ventilation in medical patients in the intensive care unit for at least 7 days . METHODS This was a prospect ively planned sub analysis of a r and omized controlled trial evaluating the effect of intensive insulin versus conventional therapy on morbidity and mortality in critically ill medical patients . All patients who were still in intensive care on Day 7 were screened weekly by electroneuromyography . The effect of intensive insulin therapy on critical illness polyneuropathy/myopathy and the relationship with duration of mechanical ventilation were assessed . MEASUREMENTS AND MAIN RESULTS Independent of risk factors , intensive insulin therapy reduced incidence of critical illness polyneuropathy/myopathy ( 107/212 [ 50.5 % ] to 81/208 [ 38.9 % ] , p = 0.02 ) . Treatment with prolonged ( > or = 14 d ) mechanical ventilation was reduced from 99 of 212 ( 46.7 % ) to 72 of 208 ( 34.6 % ) ( p = 0.01 ) . This was statistically only partially explained by prevention of critical illness polyneuropathy/myopathy . CONCLUSION In a subset of medical patients in the intensive care unit for at least 7 days , enrolled in a r and omized controlled trial of intensive insulin therapy , those assigned to intensive insulin therapy had a reduced incidence of critical illness polyneuropathy/myopathy and were treated with prolonged mechanical ventilation less frequently BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water . Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients . METHODS We r and omly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels , which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen . RESULTS Mean ( + /-SD ) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group ( P<0.001 ) . The rates of death before hospital discharge were 24.9 percent and 27.5 percent , respectively ( P=0.48 ; 95 percent confidence interval for the difference between groups , -10.0 to 4.7 percent ) . From day 1 to day 28 , breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group ( P=0.50 ) . CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water , clinical outcomes are similar whether lower or higher PEEP levels are used Abstract Although numerous clinical , laboratory , and pharmacological variables have been reported as significant risk factors for critical illness polyneuromyopathy ( CIPM ) , there is still no consensus on the aetiology of this condition . Objectives of the study were to assess the clinical and electrophysiological incidence and risk factors for CIPM.A  cohort of critically ill patients was observed prospect ively for a one – month period and the association between neuromuscular involvement and various potential risk factors was evaluated . Sixty one critically ill patients completed the follow – up ( 30 women , 31 men , median age 59 years).CIPM  development was detected clinical ly in 17 patients ( 27.9 % ) and electrophysiologically in 35 patients ( 57.4 % ) . CIPM was significantly associated with the presence and duration of systemic inflammatory response syndrome and the severity of multiple , respiratory , central nervous , and cardiovascular organ failures . The median duration of mechanical ventilation was significantly longer in patients with CIPM than in those without ( 16 vs 3 days , p < 0.001 ) . Independent predictors of CIPM obtainable within the 1st week of critical illness were the admission sequential organ failure assessment score ( odds ratio [ OR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02–1.36 ) , the 1st week total sequential organ failure assessment scores ( OR , 1.14 ; 95 % CI , 1.06–1.46 ) and the 1st week duration of systemic inflammatory response syndrome ( OR , 1.05 ; 95 % CI , 1.01–1.15 ) . They were able to correctly predict the development of CIPM at the end of the 1st week in about 80 % of critically ill cases . In conclusion , the presence and duration of systemic inflammatory response syndrome and the severity of multiple and several organ failures are associated with increased risk of the development of CIPM BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP 
    Output:
    