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: Objective To evaluate the incidence , treatment and mortality of  acute respiratory failure ( ARF ) in Finnish intensive care units ( ICUs ) . Study design Prospect i ve multicentre cohort study . Methods All adult patients in 25 ICUs were screened for use of invasive or non-invasive ventilatory support during an 8-week period . Patients needing ventilatory support for more than 6 h were included and defined as ARF patients . Risk factors for ARF and details of prior chronic health status were assessed .  Ventilatory and concomitant treatments  were evaluated and recorded daily throughout the ICU stay . ICU and 90-day mortalities were assessed . Results A total of 958 ( 39 % ) from the 2,473 admitted patients were treated with ventilatory support for more than 6 h. Incidence of ARF , acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) was 149.5 , 10.6 and 5.0/100,000 per year , respectively . Ventilatory support was started with non-invasive interfaces in 183 of 958 ( 19 % ) patients . Ventilatory modes allowing triggering of spontaneous breaths were preferred ( 81 % ) . Median tidal volume/predicted body weight was 8.7 ( 7.6–9.9 ) ml/kg and plateau pressure 19 ( 16–23 ) cmH2O . The 90-day mortality of ARF was 31 % . Conclusions While the incidence of ARF requiring ventilatory support is higher , the incidence of ALI and ARDS seems to be lower in Finl and than previously reported in other countries . Tidal volumes are higher than recommended in the concept of lung protective strategy . However , restriction of peak airway pressure was used in the majority of ARF patients BACKGROUND Inhaled nitric oxide has been shown to improve oxygenation in select patients with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE The purpose of this study was to evaluate the clinical response to four concentrations of inhaled nitric oxide ( NO ) in 20 patients with ARDS . METHODS All patients with ARDS were eligible for the study . ARDS was defined as ( 1 ) the presence of a predisposing factor ; ( 2 ) a PaO2/FiO2 ratio < 200 ; ( 3 ) bilateral infiltrates on chest radiograph ; and ( 4 ) absence of evidence of congestive heart failure and pulmonary artery wedge pressure < 18 mm Hg . Patients received each of four doses ( 1 , 15 , 30 , and 60 ppm ) in r and om order , each for a 3-hour period . Cardiovascular variables were continuously monitored , and arterial and mixed venous blood gas measurements were obtained at 30 minutes and 3 hours . RESULTS Thirteen of the 20 patients demonstrated a significant increase in their PaO2/FiO2 ( > 20 % increase ) when treated with inhaled NO . The administration of inhaled NO was associated with an increase in oxygenation at doses of 1 , 15 , and 30 ppm , but not 60 ppm . Increasing NO dose to more than 1 ppm did not significantly improve response . Mean pulmonary artery pressure decreased with increasing NO concentration , but this did not reach statistical significance . Nine of the 13 responding patients and 2 of the 7 nonresponding patients survived . CONCLUSION Inhaled NO was successful in increasing PaO2/FiO2 by > 20 % in 65 % of the surgical patients in this trial . Response to NO could not be predicted by initial PaO2/FiO2 or pulmonary artery pressures . A trial of inhaled NO at a dose of < 10 ppm may be helpful in ARDS patients requiring increasing FiO2 and positive end-expiratory pressure BACKGROUND Recent data suggest that inhaled NO can inhibit platelet aggregation .  This study investigates whether inhaled NO affects the expression level and avidity of platelet membrane receptors that mediate platelet adhesion and aggregation . METHODS AND RESULTS In 30 healthy volunteers , platelet-rich plasma was incubated with an air/5 % CO2 mixture containing 0 , 100 , 450 , and 884 ppm inhaled NO . ADP- and collagen-induced platelet aggregation , the membrane expression of P-selectin , and the binding of fibrinogen to the platelet glycoprotein ( GP ) IIb/IIIa receptor were determined before ( t0 ) and during the 240 minutes of incubation . In addition , eight patients suffering from severe adult respiratory distress syndrome ( ARDS ) were investigated before and 120 minutes after the beginning of administration of 10 ppm inhaled NO . In vitro , NO led to a dose-dependent inhibition of both ADP-induced ( 3+/-3 % at 884 ppm versus 70+/-6 % at 0 ppm after 240 minutes ; P<.001 ) and collagen-induced ( 13+/-5 % versus 62+/-5 % ; P<.01 ) platelet aggregation . Furthermore , P-selectin expression ( 36+/-7 % of t0 value ; P<.01 ) and fibrinogen binding ( 33+/-11 % ; P<.01 ) were inhibited . In patients with ARDS , after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded , an increase in plasma cGMP , prolongation of in vitro bleeding time , and inhibition of platelet aggregation and P-selectin expression were observed , and fibrinogen binding was also inhibited ( 19+/-7 % versus 30+/-8 % ; P<.05 ) . CONCLUSIONS NO-dependent inhibition of platelet aggregation may be caused by a decrease in fibrinogen binding to the platelet GP IIb/IIIa receptor The aim of this prospect i ve study was to determine factors influencing effects of inhaled nitric oxide ( NO ) on the pulmonary circulation and on gas exchange in critically ill patients with acute lung injury . Twenty-one hypoxemic patients with acute respiratory failure ( PaO2 = 127 + /- 69 mm Hg during intermittent positive pressure ventilation , FiO2 = 1 ) , were mechanically ventilated with 2 ppm NO and pure oxygen . The effect of positive end-expiratory pressure ( PEEP ) on alveolar recruitment was assessed on an anatomic basis using a high-resolution and spiral thoracic computed tomographic ( CT ) scan . Four conditions were studied in r and om order : zero end-expiratory pressure ( ZEEP ) , ZEEP + 2 ppm NO , 10 cm H2O PEEP , 10 cm H2O PEEP + 2 ppm NO . During ZEEP and PEEP , NO significantly decreased pulmonary vascular resistance index ( PVRI ) , mean pulmonary arterial pressure ( MPAP ) , true pulmonary shunt ( Qs/QT ) , and alveolar dead space ( VDA/VT ) and significantly increased PaO2 ( p < 0.01 ) . During ZEEP , NO-induced decreases in PVRI ( delta PVRI ) and MPAP ( delta MPAP ) were significantly correlated to baseline PVRI and MPAP ( delta PVRI = -0.5 PVRI + 125 , r = 0.97 , p < 0.01 and delta MPAP = -0.28 MPAP + 4.8 , r = 0.69 , p < 0.05 ) . These changes were not potentiated by PEEP-induced alveolar recruitment . The NO-induced increase in PaO2 ( delta PaO2 ) was not significantly correlated with baseline PaO2 but was correlated with baseline PVRI ( delta PaO2 = 0.11 PVRI + 30 , r = 0.67 , p < 0.05 ) . In patients in whom PEEP was associated with alveolar recruitment , NO increased PaO2 by 66 + /- 24 mm Hg during ZEEP and by 104 + /- 26 mm Hg during PEEP ( p < 0.01 ) . In patients in whom PEEP did not induce alveolar recruitment , the NO-induced increase in PaO2 was similar during ZEEP and PEEP conditions ( + 70 + /- 15 mm Hg versus + 76 + /- 12 mm Hg , NS ) . In patients with adult respiratory distress syndrome , factors determining NO-induced improvement in arterial oxygenation and pulmonary vascular effects are PEEP-induced alveolar recruitment and the baseline level of pulmonary vascular resistance RATIONALE The 1994 American European Consensus Committee definitions of acute lung injury ( ALI ) and the acute respiratory distress syndrome ( ARDS ) have not been applied systematic ally in the pediatric population . OBJECTIVES The purpose of this study was to evaluate prospect ively the epidemiology and clinical risk factors associated with death and prolonged mechanical ventilation in all pediatric patients admitted to two large , pediatric intensive care units with ALI/ARDS using Consensus criteria . METHODS All pediatric patients meeting Consensus Committee definitions for ALI were prospect ively identified and included in a relational data base . MEASUREMENTS AND MAIN RESULTS There were 328 admissions for ALI/ARDS with a mortality of 22 % . Multivariate logistic regression analyses revealed ( 1 ) the initial severity of oxygenation defect , as measured by the Pa(O2)/FI(O2 ) ratio ; ( 2 ) the presence of nonpulmonary and non- central nervous system ( CNS ) organ dysfunction ; and ( 3 ) the presence of CNS dysfunction were independently associated with mortality and prolonged mechanical ventilation . A substantial fraction of patients ( 28 % ) did not require mechanical ventilation at the onset of ALI ; 46 % of these patients eventually required intubation for worsening ALI . CONCLUSIONS Mortality in pediatric ALI/ARDS is high and several risk factors have major prognostic value . In contrast to ALI/ARDS in adults , the initial severity of arterial hypoxemia in children correlates well with mortality . A significant fraction of patients with pediatric ALI/ARDS can be identified before endotracheal intubation is required . These patients provide a valuable group in whom new therapies can be tested OBJECTIVE : This population -based , prospect i ve , cohort study was design ed to determine the population incidence and outcomes of pediatric acute lung injury . METHODS : Between 1999 and 2000 , 1 year of screening was performed at all hospitals admitting critically ill children in King County , Washington . County residents 0.5 to 15 years of age who required invasive ( through endotracheal tube or tracheostomy ) or noninvasive ( through full face mask ) mechanical ventilation , regardless of the duration of mechanical ventilation , were screened . From this population , children meeting North American-European Consensus Conference acute lung injury criteria were eligible for enrollment . Postoperative patients who received mechanical ventilation for < 24 hours were excluded . Data collected included the presence of predefined cardiac conditions , demographic and physiological data , duration of mechanical ventilation , and deaths . US Census population figures were used to estimate incidence . Associations between outcomes and subgroups identified a priori were assessed . RESULTS : Thirty-nine children met the criteria for acute lung injury , result ing in a calculated incidence of 12.8 cases per 100000 person-years . Severe sepsis ( with pneumonia as the infection focus ) was the most common risk factor . The median 24-hour Pediatric Risk of Mortality III score was 9.0 , and the mean ± SD was 11.7 ± 7.5 . The hospital mortality rate was 18 % , lower than that reported previously for pediatric acute lung injury . There were no statistically significant associations between age , gender , or risk factors and outcomes . CONCLUSIONS : We present the first population -based estimate of pediatric acute lung injury incidence in the United States . Population incidence and mortality rates are lower than those for adult acute lung injury . Low mortality rates in pediatric acute lung injury may necessitate clinical trial outcome measures other than death 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.  
    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: Objective To evaluate the incidence , treatment and mortality of  acute respiratory failure ( ARF ) in Finnish intensive care units ( ICUs ) . Study design Prospect i ve multicentre cohort study . Methods All adult patients in 25 ICUs were screened for use of invasive or non-invasive ventilatory support during an 8-week period . Patients needing ventilatory support for more than 6 h were included and defined as ARF patients . Risk factors for ARF and details of prior chronic health status were assessed .  Ventilatory and concomitant treatments  were evaluated and recorded daily throughout the ICU stay . ICU and 90-day mortalities were assessed . Results A total of 958 ( 39 % ) from the 2,473 admitted patients were treated with ventilatory support for more than 6 h. Incidence of ARF , acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) was 149.5 , 10.6 and 5.0/100,000 per year , respectively . Ventilatory support was started with non-invasive interfaces in 183 of 958 ( 19 % ) patients . Ventilatory modes allowing triggering of spontaneous breaths were preferred ( 81 % ) . Median tidal volume/predicted body weight was 8.7 ( 7.6–9.9 ) ml/kg and plateau pressure 19 ( 16–23 ) cmH2O . The 90-day mortality of ARF was 31 % . Conclusions While the incidence of ARF requiring ventilatory support is higher , the incidence of ALI and ARDS seems to be lower in Finl and than previously reported in other countries . Tidal volumes are higher than recommended in the concept of lung protective strategy . However , restriction of peak airway pressure was used in the majority of ARF patients BACKGROUND Inhaled nitric oxide has been shown to improve oxygenation in select patients with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE The purpose of this study was to evaluate the clinical response to four concentrations of inhaled nitric oxide ( NO ) in 20 patients with ARDS . METHODS All patients with ARDS were eligible for the study . ARDS was defined as ( 1 ) the presence of a predisposing factor ; ( 2 ) a PaO2/FiO2 ratio < 200 ; ( 3 ) bilateral infiltrates on chest radiograph ; and ( 4 ) absence of evidence of congestive heart failure and pulmonary artery wedge pressure < 18 mm Hg . Patients received each of four doses ( 1 , 15 , 30 , and 60 ppm ) in r and om order , each for a 3-hour period . Cardiovascular variables were continuously monitored , and arterial and mixed venous blood gas measurements were obtained at 30 minutes and 3 hours . RESULTS Thirteen of the 20 patients demonstrated a significant increase in their PaO2/FiO2 ( > 20 % increase ) when treated with inhaled NO . The administration of inhaled NO was associated with an increase in oxygenation at doses of 1 , 15 , and 30 ppm , but not 60 ppm . Increasing NO dose to more than 1 ppm did not significantly improve response . Mean pulmonary artery pressure decreased with increasing NO concentration , but this did not reach statistical significance . Nine of the 13 responding patients and 2 of the 7 nonresponding patients survived . CONCLUSION Inhaled NO was successful in increasing PaO2/FiO2 by > 20 % in 65 % of the surgical patients in this trial . Response to NO could not be predicted by initial PaO2/FiO2 or pulmonary artery pressures . A trial of inhaled NO at a dose of < 10 ppm may be helpful in ARDS patients requiring increasing FiO2 and positive end-expiratory pressure BACKGROUND Recent data suggest that inhaled NO can inhibit platelet aggregation .  This study investigates whether inhaled NO affects the expression level and avidity of platelet membrane receptors that mediate platelet adhesion and aggregation . METHODS AND RESULTS In 30 healthy volunteers , platelet-rich plasma was incubated with an air/5 % CO2 mixture containing 0 , 100 , 450 , and 884 ppm inhaled NO . ADP- and collagen-induced platelet aggregation , the membrane expression of P-selectin , and the binding of fibrinogen to the platelet glycoprotein ( GP ) IIb/IIIa receptor were determined before ( t0 ) and during the 240 minutes of incubation . In addition , eight patients suffering from severe adult respiratory distress syndrome ( ARDS ) were investigated before and 120 minutes after the beginning of administration of 10 ppm inhaled NO . In vitro , NO led to a dose-dependent inhibition of both ADP-induced ( 3+/-3 % at 884 ppm versus 70+/-6 % at 0 ppm after 240 minutes ; P<.001 ) and collagen-induced ( 13+/-5 % versus 62+/-5 % ; P<.01 ) platelet aggregation . Furthermore , P-selectin expression ( 36+/-7 % of t0 value ; P<.01 ) and fibrinogen binding ( 33+/-11 % ; P<.01 ) were inhibited . In patients with ARDS , after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded , an increase in plasma cGMP , prolongation of in vitro bleeding time , and inhibition of platelet aggregation and P-selectin expression were observed , and fibrinogen binding was also inhibited ( 19+/-7 % versus 30+/-8 % ; P<.05 ) . CONCLUSIONS NO-dependent inhibition of platelet aggregation may be caused by a decrease in fibrinogen binding to the platelet GP IIb/IIIa receptor The aim of this prospect i ve study was to determine factors influencing effects of inhaled nitric oxide ( NO ) on the pulmonary circulation and on gas exchange in critically ill patients with acute lung injury . Twenty-one hypoxemic patients with acute respiratory failure ( PaO2 = 127 + /- 69 mm Hg during intermittent positive pressure ventilation , FiO2 = 1 ) , were mechanically ventilated with 2 ppm NO and pure oxygen . The effect of positive end-expiratory pressure ( PEEP ) on alveolar recruitment was assessed on an anatomic basis using a high-resolution and spiral thoracic computed tomographic ( CT ) scan . Four conditions were studied in r and om order : zero end-expiratory pressure ( ZEEP ) , ZEEP + 2 ppm NO , 10 cm H2O PEEP , 10 cm H2O PEEP + 2 ppm NO . During ZEEP and PEEP , NO significantly decreased pulmonary vascular resistance index ( PVRI ) , mean pulmonary arterial pressure ( MPAP ) , true pulmonary shunt ( Qs/QT ) , and alveolar dead space ( VDA/VT ) and significantly increased PaO2 ( p < 0.01 ) . During ZEEP , NO-induced decreases in PVRI ( delta PVRI ) and MPAP ( delta MPAP ) were significantly correlated to baseline PVRI and MPAP ( delta PVRI = -0.5 PVRI + 125 , r = 0.97 , p < 0.01 and delta MPAP = -0.28 MPAP + 4.8 , r = 0.69 , p < 0.05 ) . These changes were not potentiated by PEEP-induced alveolar recruitment . The NO-induced increase in PaO2 ( delta PaO2 ) was not significantly correlated with baseline PaO2 but was correlated with baseline PVRI ( delta PaO2 = 0.11 PVRI + 30 , r = 0.67 , p < 0.05 ) . In patients in whom PEEP was associated with alveolar recruitment , NO increased PaO2 by 66 + /- 24 mm Hg during ZEEP and by 104 + /- 26 mm Hg during PEEP ( p < 0.01 ) . In patients in whom PEEP did not induce alveolar recruitment , the NO-induced increase in PaO2 was similar during ZEEP and PEEP conditions ( + 70 + /- 15 mm Hg versus + 76 + /- 12 mm Hg , NS ) . In patients with adult respiratory distress syndrome , factors determining NO-induced improvement in arterial oxygenation and pulmonary vascular effects are PEEP-induced alveolar recruitment and the baseline level of pulmonary vascular resistance RATIONALE The 1994 American European Consensus Committee definitions of acute lung injury ( ALI ) and the acute respiratory distress syndrome ( ARDS ) have not been applied systematic ally in the pediatric population . OBJECTIVES The purpose of this study was to evaluate prospect ively the epidemiology and clinical risk factors associated with death and prolonged mechanical ventilation in all pediatric patients admitted to two large , pediatric intensive care units with ALI/ARDS using Consensus criteria . METHODS All pediatric patients meeting Consensus Committee definitions for ALI were prospect ively identified and included in a relational data base . MEASUREMENTS AND MAIN RESULTS There were 328 admissions for ALI/ARDS with a mortality of 22 % . Multivariate logistic regression analyses revealed ( 1 ) the initial severity of oxygenation defect , as measured by the Pa(O2)/FI(O2 ) ratio ; ( 2 ) the presence of nonpulmonary and non- central nervous system ( CNS ) organ dysfunction ; and ( 3 ) the presence of CNS dysfunction were independently associated with mortality and prolonged mechanical ventilation . A substantial fraction of patients ( 28 % ) did not require mechanical ventilation at the onset of ALI ; 46 % of these patients eventually required intubation for worsening ALI . CONCLUSIONS Mortality in pediatric ALI/ARDS is high and several risk factors have major prognostic value . In contrast to ALI/ARDS in adults , the initial severity of arterial hypoxemia in children correlates well with mortality . A significant fraction of patients with pediatric ALI/ARDS can be identified before endotracheal intubation is required . These patients provide a valuable group in whom new therapies can be tested OBJECTIVE : This population -based , prospect i ve , cohort study was design ed to determine the population incidence and outcomes of pediatric acute lung injury . METHODS : Between 1999 and 2000 , 1 year of screening was performed at all hospitals admitting critically ill children in King County , Washington . County residents 0.5 to 15 years of age who required invasive ( through endotracheal tube or tracheostomy ) or noninvasive ( through full face mask ) mechanical ventilation , regardless of the duration of mechanical ventilation , were screened . From this population , children meeting North American-European Consensus Conference acute lung injury criteria were eligible for enrollment . Postoperative patients who received mechanical ventilation for < 24 hours were excluded . Data collected included the presence of predefined cardiac conditions , demographic and physiological data , duration of mechanical ventilation , and deaths . US Census population figures were used to estimate incidence . Associations between outcomes and subgroups identified a priori were assessed . RESULTS : Thirty-nine children met the criteria for acute lung injury , result ing in a calculated incidence of 12.8 cases per 100000 person-years . Severe sepsis ( with pneumonia as the infection focus ) was the most common risk factor . The median 24-hour Pediatric Risk of Mortality III score was 9.0 , and the mean ± SD was 11.7 ± 7.5 . The hospital mortality rate was 18 % , lower than that reported previously for pediatric acute lung injury . There were no statistically significant associations between age , gender , or risk factors and outcomes . CONCLUSIONS : We present the first population -based estimate of pediatric acute lung injury incidence in the United States . Population incidence and mortality rates are lower than those for adult acute lung injury . Low mortality rates in pediatric acute lung injury may necessitate clinical trial outcome measures other than death 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.  
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