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: The objective of this study was to refine the APACHE ( Acute Physiology , Age , Chronic Health Evaluation ) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults . We prospect ively collected data on 17,440 unselected adult medical/surgical intensive care unit ( ICU ) admissions at 40 US hospitals ( 14 volunteer tertiary-care institutions and 26 hospitals r and omly chosen to represent intensive care services nationwide ) . We analyzed the relationship between the patient 's likelihood of surviving to hospital discharge and the following predictive variables : major medical and surgical disease categories , acute physiologic abnormalities , age , preexisting functional limitations , major comorbidities , and treatment location immediately prior to ICU admission . The APACHE III prognostic system consists of two options : ( 1 ) an APACHE III score , which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups ; and ( 2 ) an APACHE III predictive equation , which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients . A five-point increase in APACHE III score ( range , 0 to 299 ) is independently associated with a statistically significant increase in the relative risk of hospital death ( odds ratio , 1.10 to 1.78 ) within each of 78 major medical and surgical disease categories . The overall predictive accuracy of the first-day APACHE III equation was such that , within 24 h of ICU admission , 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed ( r2 = 0.41 ; receiver operating characteristic = 0.90 ) . Recording changes in the  APACHE III score on each subsequent day of ICU therapy provided daily up date s in these risk estimates . When applied across the individual ICUs , the first-day APACHE III equation accounted for the majority of variation in observed death rates ( r2 = 0.90 , p less than 0.0001 ) CONTEXT The need for lung protection is universally accepted , but the optimal level of positive end-expiratory pressure ( PEEP ) in patients with acute lung injury ( ALI ) or acute respiratory distress syndrome remains debated . OBJECTIVE To compare the effect on outcome of a strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation to one aim ed at minimizing alveolar distension in patients with ALI . DESIGN , SETTING , AND PATIENTS A multicenter r and omized controlled trial of 767 adults ( mean [ SD ] age , 59.9 [ 15.4 ] years ) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005 . INTERVENTION Tidal volume was set at 6 mL/kg of predicted body weight in both strategies . Patients were r and omly assigned to a moderate PEEP strategy ( 5 - 9 cm H(2)O ) ( minimal distension strategy ; n = 382 ) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O ( increased recruitment strategy ; n = 385 ) . MAIN OUTCOME MEASURES The primary end point was mortality at 28 days . Secondary end points were hospital mortality at 60 days , ventilator-free days , and organ failure-free days at 28 days . RESULTS The 28-day mortality rate in the minimal distension group was 31.2 % ( n = 119 ) vs 27.8 % ( n = 107 ) in the increased recruitment group ( relative risk , 1.12 [ 95 % confidence interval , 0.90 - 1.40 ] ; P = .31 ) . The hospital mortality rate in the minimal distension group was 39.0 % ( n = 149 ) vs 35.4 % ( n = 136 ) in the increased recruitment group ( relative risk , 1.10 [ 95 % confidence interval , 0.92 - 1.32 ] ; P = .30 ) . The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days ( 7 [ interquartile range { IQR } , 0 - 19 ] vs 3 [ IQR , 0 - 17 ] ; P = .04 ) and organ failure-free days ( 6 [ IQR , 0 - 18 ] vs 2 [ IQR , 0 - 16 ] ; P = .04 ) . This strategy also was associated with higher compliance values , better oxygenation , less use of adjunctive therapies , and larger fluid requirements . CONCLUSIONS A strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality . However , it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00188058 Objective : To evaluate the prevalence and outcome of the acute respiratory distress syndrome ( ARDS ) among patients requiring mechanical ventilation . Design : A prospect i ve , multi-institutional , initial cohort study including 28-day follow-up . Setting s : Thirty-six French intensive care units ( ICUs ) from a working group of the French Intensive Care Society ( SRLF ) . Patients : All the patients entering the ICUs during a 14-day period were screened prospect ively . Hypoxemic patients , defined as having a PaO2/FIO2 ratio ( P/F ) of 300 mmHg or less and receiving mechanical ventilation  , were classified into three groups , according to the Consensus Conference on ARDS : group 1 refers to ARDS ( P/F : 200 mmHg or less and bilateral infiltrates on the chest X-ray ) ; group 2 to acute lung injury ( ALI ) without having criteria for ARDS ( 200 < P/F ≤ 300 mmHg and bilateral infiltrates ) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups . Results : Nine hundred seventy-six patients entered the ICUs during the study period , 43 % of them being mechanically ventilated and 213 ( 22 % ) meeting the criteria for one of the three groups . Among all the ICU admissions , ARDS , ALI and group 3 patients amounted , respectively , to 6.9 % ( 67 ) , 1.8 % ( 17 ) and 13.3 % ( 129 ) of the patients , and represented 31.5 % , 8.1 % and 60.2 % of the hypoxemic , ventilated patients . The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others ( 60 % vs 31 % p < 0.01 ) . In group 3 , 42 patients had P/F less than 200 mmHg associated with unilateral lung injury ; mortality was significantly lower ( 40.5 % ) than in the ARDS group . In the whole group of hypoxemic , ventilated patients , septic shock and severity indices but not oxygenation indices were significantly associated with mortality , while the association with immunosuppression revealed only a trend ( p = 0.06 ) . Conclusions : In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high CONTEXT Health-related quality of life ( HRQL ) is reduced in patients who survive acute respiratory distress ( ARDS ) , but whether this decline in HRQL is caused by ARDS or other aspects of the patient 's illness or injury is unknown . OBJECTIVE To determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS . DESIGN Prospect i ve , matched , parallel cohort study . SETTING A 411-bed municipal medical and regional level I trauma center . PATIENTS Seventy-three pairs of ARDS survivors and severity-matched controls with the clinical risk factors for ARDS of sepsis and trauma admitted between January 1 , 1994 , and July 30 , 1996 . MAIN OUTCOME MEASURES The HRQL of ARDS survivors and controls , assessed by generic and pulmonary disease-specific HRQL instruments ( Medical Outcomes Study 36-Item Short Form Health Survey , St and ard Form [ SF-36 ] and St George 's Respiratory Question naire [ SGRQ ] , respectively ) . RESULTS Clinical ly meaningful and statistically significant reductions in HRQL scores of ARDS survivors ( n = 73 ) were seen in 7 of 8 SF-36 domains and 3 of 3 SGRQ domains compared with matched controls ( P<.001 for all reductions ) . The largest decrements in the HRQL were seen in physical function and pulmonary symptoms and limitations . Analysis of trauma-matched pairs ( n = 46 ) revealed significant reductions in 7 of 8 SF-36 domains ( P < or = .02 ) and 3 of 3 SGRQ domains ( P < or = .003 ) . Analysis of sepsis-matched pairs ( n = 27 ) revealed significant reductions in 6 of 8 SF-36 domains ( P < or = .05 ) and 3 of 3 SGRQ domains ( P < or = .002 ) . CONCLUSIONS Survivors of ARDS have a clinical ly significant reduction in HRQL that appears to be caused exclusively by ARDS and its sequelae . Reductions were primarily noted in physical functioning and pulmonary disease-specific domains To which groups of patients can the results of clinical trials be applied ? This question is often inappropriately answered by reference to the trial entry criteria . Instead , the benefit and harm ( adverse events , discomfort of treatment , etc ) of treatment could be assessed separately for individual patients . Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed . To assess net benefit , the relative risks should come from ( a meta- analysis of ) r and omised trials ; the risk in individual patients should come from multivariate risk equations derived from cohort studies . However , before making firm conclusions , the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked Objectives : To evaluate the outcome in patients with severe adult respiratory distress syndrome ( ARDS ) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O , low tidal volumes ( 4 to 7 mL/kg ) , spontaneous breathing using synchronized intermittent m and atory ventilation from the start of ventilation , and permissive hypercapnia without the use of bicarbonate to buffer acidosis . Also , to compare hospital mortality rate with that predicted by the Acute Physiology and Chronic Health Evaluation ( APACHE ) II scoring system and the “ ventilator score . ” Setting : A ten‐bed general intensive care unit in a university hospital . Design : Prospect i ve , descriptive study . Patients : Fifty‐three patients with severe ARDS having a lung injury score of ≥2.5 . Interventions : Data recording . Results : The hospital mortality rate was significantly lower than that predicted by the APACHE II scores ( 26.4 % vs. 53.3 % , p = .004 ) , even after correcting the latter for the effect of hypercapnic acidosis ( 26.4 % vs. 51.1 % , p = .008 ) . The mortality rate increased with increasing number of organ failures , but was only 43 % in patients with ≥4 organ failures , 20.5 % with ≤3 organ failures , and 6.6 % with only respiratory failure . The mean maximum Paco2 was 66.5 torr ( range 38 to 158 torr [ 8.87 kPa , range 5.07 to 21.07 ] ) , and the mean arterial pH at the same time was 7.23 ( range 6.79 to 7.45 ) . There was no correlation between the maximum Paco2 or the corresponding pH and the total respiratory rate at the same time . No pneumothoraces developed during mechanical ventilation . Conclusions : These results lend further support to the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator‐induced lung injury and improve outcome in severe ARDS . This hypothesis is supported by a large body of experimental evidence , which also suggests that ventilator‐induced lung injury may result in the release of inflammatory mediators , and thus may have the potential to augment the development of multiple organ dysfunction . However , the hypothesis requires testing in a r and omized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects . ( Crit Care Med 1994 ; 22:1568–1578 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 breath 
    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: The objective of this study was to refine the APACHE ( Acute Physiology , Age , Chronic Health Evaluation ) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults . We prospect ively collected data on 17,440 unselected adult medical/surgical intensive care unit ( ICU ) admissions at 40 US hospitals ( 14 volunteer tertiary-care institutions and 26 hospitals r and omly chosen to represent intensive care services nationwide ) . We analyzed the relationship between the patient 's likelihood of surviving to hospital discharge and the following predictive variables : major medical and surgical disease categories , acute physiologic abnormalities , age , preexisting functional limitations , major comorbidities , and treatment location immediately prior to ICU admission . The APACHE III prognostic system consists of two options : ( 1 ) an APACHE III score , which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups ; and ( 2 ) an APACHE III predictive equation , which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients . A five-point increase in APACHE III score ( range , 0 to 299 ) is independently associated with a statistically significant increase in the relative risk of hospital death ( odds ratio , 1.10 to 1.78 ) within each of 78 major medical and surgical disease categories . The overall predictive accuracy of the first-day APACHE III equation was such that , within 24 h of ICU admission , 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed ( r2 = 0.41 ; receiver operating characteristic = 0.90 ) . Recording changes in the  APACHE III score on each subsequent day of ICU therapy provided daily up date s in these risk estimates . When applied across the individual ICUs , the first-day APACHE III equation accounted for the majority of variation in observed death rates ( r2 = 0.90 , p less than 0.0001 ) CONTEXT The need for lung protection is universally accepted , but the optimal level of positive end-expiratory pressure ( PEEP ) in patients with acute lung injury ( ALI ) or acute respiratory distress syndrome remains debated . OBJECTIVE To compare the effect on outcome of a strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation to one aim ed at minimizing alveolar distension in patients with ALI . DESIGN , SETTING , AND PATIENTS A multicenter r and omized controlled trial of 767 adults ( mean [ SD ] age , 59.9 [ 15.4 ] years ) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005 . INTERVENTION Tidal volume was set at 6 mL/kg of predicted body weight in both strategies . Patients were r and omly assigned to a moderate PEEP strategy ( 5 - 9 cm H(2)O ) ( minimal distension strategy ; n = 382 ) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O ( increased recruitment strategy ; n = 385 ) . MAIN OUTCOME MEASURES The primary end point was mortality at 28 days . Secondary end points were hospital mortality at 60 days , ventilator-free days , and organ failure-free days at 28 days . RESULTS The 28-day mortality rate in the minimal distension group was 31.2 % ( n = 119 ) vs 27.8 % ( n = 107 ) in the increased recruitment group ( relative risk , 1.12 [ 95 % confidence interval , 0.90 - 1.40 ] ; P = .31 ) . The hospital mortality rate in the minimal distension group was 39.0 % ( n = 149 ) vs 35.4 % ( n = 136 ) in the increased recruitment group ( relative risk , 1.10 [ 95 % confidence interval , 0.92 - 1.32 ] ; P = .30 ) . The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days ( 7 [ interquartile range { IQR } , 0 - 19 ] vs 3 [ IQR , 0 - 17 ] ; P = .04 ) and organ failure-free days ( 6 [ IQR , 0 - 18 ] vs 2 [ IQR , 0 - 16 ] ; P = .04 ) . This strategy also was associated with higher compliance values , better oxygenation , less use of adjunctive therapies , and larger fluid requirements . CONCLUSIONS A strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality . However , it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00188058 Objective : To evaluate the prevalence and outcome of the acute respiratory distress syndrome ( ARDS ) among patients requiring mechanical ventilation . Design : A prospect i ve , multi-institutional , initial cohort study including 28-day follow-up . Setting s : Thirty-six French intensive care units ( ICUs ) from a working group of the French Intensive Care Society ( SRLF ) . Patients : All the patients entering the ICUs during a 14-day period were screened prospect ively . Hypoxemic patients , defined as having a PaO2/FIO2 ratio ( P/F ) of 300 mmHg or less and receiving mechanical ventilation  , were classified into three groups , according to the Consensus Conference on ARDS : group 1 refers to ARDS ( P/F : 200 mmHg or less and bilateral infiltrates on the chest X-ray ) ; group 2 to acute lung injury ( ALI ) without having criteria for ARDS ( 200 < P/F ≤ 300 mmHg and bilateral infiltrates ) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups . Results : Nine hundred seventy-six patients entered the ICUs during the study period , 43 % of them being mechanically ventilated and 213 ( 22 % ) meeting the criteria for one of the three groups . Among all the ICU admissions , ARDS , ALI and group 3 patients amounted , respectively , to 6.9 % ( 67 ) , 1.8 % ( 17 ) and 13.3 % ( 129 ) of the patients , and represented 31.5 % , 8.1 % and 60.2 % of the hypoxemic , ventilated patients . The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others ( 60 % vs 31 % p < 0.01 ) . In group 3 , 42 patients had P/F less than 200 mmHg associated with unilateral lung injury ; mortality was significantly lower ( 40.5 % ) than in the ARDS group . In the whole group of hypoxemic , ventilated patients , septic shock and severity indices but not oxygenation indices were significantly associated with mortality , while the association with immunosuppression revealed only a trend ( p = 0.06 ) . Conclusions : In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high CONTEXT Health-related quality of life ( HRQL ) is reduced in patients who survive acute respiratory distress ( ARDS ) , but whether this decline in HRQL is caused by ARDS or other aspects of the patient 's illness or injury is unknown . OBJECTIVE To determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS . DESIGN Prospect i ve , matched , parallel cohort study . SETTING A 411-bed municipal medical and regional level I trauma center . PATIENTS Seventy-three pairs of ARDS survivors and severity-matched controls with the clinical risk factors for ARDS of sepsis and trauma admitted between January 1 , 1994 , and July 30 , 1996 . MAIN OUTCOME MEASURES The HRQL of ARDS survivors and controls , assessed by generic and pulmonary disease-specific HRQL instruments ( Medical Outcomes Study 36-Item Short Form Health Survey , St and ard Form [ SF-36 ] and St George 's Respiratory Question naire [ SGRQ ] , respectively ) . RESULTS Clinical ly meaningful and statistically significant reductions in HRQL scores of ARDS survivors ( n = 73 ) were seen in 7 of 8 SF-36 domains and 3 of 3 SGRQ domains compared with matched controls ( P<.001 for all reductions ) . The largest decrements in the HRQL were seen in physical function and pulmonary symptoms and limitations . Analysis of trauma-matched pairs ( n = 46 ) revealed significant reductions in 7 of 8 SF-36 domains ( P < or = .02 ) and 3 of 3 SGRQ domains ( P < or = .003 ) . Analysis of sepsis-matched pairs ( n = 27 ) revealed significant reductions in 6 of 8 SF-36 domains ( P < or = .05 ) and 3 of 3 SGRQ domains ( P < or = .002 ) . CONCLUSIONS Survivors of ARDS have a clinical ly significant reduction in HRQL that appears to be caused exclusively by ARDS and its sequelae . Reductions were primarily noted in physical functioning and pulmonary disease-specific domains To which groups of patients can the results of clinical trials be applied ? This question is often inappropriately answered by reference to the trial entry criteria . Instead , the benefit and harm ( adverse events , discomfort of treatment , etc ) of treatment could be assessed separately for individual patients . Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed . To assess net benefit , the relative risks should come from ( a meta- analysis of ) r and omised trials ; the risk in individual patients should come from multivariate risk equations derived from cohort studies . However , before making firm conclusions , the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked Objectives : To evaluate the outcome in patients with severe adult respiratory distress syndrome ( ARDS ) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O , low tidal volumes ( 4 to 7 mL/kg ) , spontaneous breathing using synchronized intermittent m and atory ventilation from the start of ventilation , and permissive hypercapnia without the use of bicarbonate to buffer acidosis . Also , to compare hospital mortality rate with that predicted by the Acute Physiology and Chronic Health Evaluation ( APACHE ) II scoring system and the “ ventilator score . ” Setting : A ten‐bed general intensive care unit in a university hospital . Design : Prospect i ve , descriptive study . Patients : Fifty‐three patients with severe ARDS having a lung injury score of ≥2.5 . Interventions : Data recording . Results : The hospital mortality rate was significantly lower than that predicted by the APACHE II scores ( 26.4 % vs. 53.3 % , p = .004 ) , even after correcting the latter for the effect of hypercapnic acidosis ( 26.4 % vs. 51.1 % , p = .008 ) . The mortality rate increased with increasing number of organ failures , but was only 43 % in patients with ≥4 organ failures , 20.5 % with ≤3 organ failures , and 6.6 % with only respiratory failure . The mean maximum Paco2 was 66.5 torr ( range 38 to 158 torr [ 8.87 kPa , range 5.07 to 21.07 ] ) , and the mean arterial pH at the same time was 7.23 ( range 6.79 to 7.45 ) . There was no correlation between the maximum Paco2 or the corresponding pH and the total respiratory rate at the same time . No pneumothoraces developed during mechanical ventilation . Conclusions : These results lend further support to the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator‐induced lung injury and improve outcome in severe ARDS . This hypothesis is supported by a large body of experimental evidence , which also suggests that ventilator‐induced lung injury may result in the release of inflammatory mediators , and thus may have the potential to augment the development of multiple organ dysfunction . However , the hypothesis requires testing in a r and omized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects . ( Crit Care Med 1994 ; 22:1568–1578 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 breath 
    Output:
    