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 ) 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 Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction 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 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 To identify the potential impact of novel therapeutic approaches , we studied the early predictive factors of survival at the onset of acute respiratory distress syndrome ( ARDS ) in a 24-bed medical ICU of an academic tertiary care hospital . Over a 48-mo period , a total of 3,511 adult patients were admitted and 259 mechanically ventilated patients met ARDS criteria , as defined by American-European consensus conference , i.e. , bilateral pulmonary infiltrates and PaO2/FIO2 lower than 200 without left atrial hypertension . These patients were r and omly included in a developmental sample ( 177 patients ) and a validation sample ( 82 patients ) . Demographic variables , hemodynamic and respiratory parameters , underlying diseases , as well as several severity scores ( SAPS , SAPS-II , OSF ) and Lung Injury Score ( LIS ) were collected . These variables were compared between survivors and nonsurvivors and entered into a step 
    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 ) 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 Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction 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 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 To identify the potential impact of novel therapeutic approaches , we studied the early predictive factors of survival at the onset of acute respiratory distress syndrome ( ARDS ) in a 24-bed medical ICU of an academic tertiary care hospital . Over a 48-mo period , a total of 3,511 adult patients were admitted and 259 mechanically ventilated patients met ARDS criteria , as defined by American-European consensus conference , i.e. , bilateral pulmonary infiltrates and PaO2/FIO2 lower than 200 without left atrial hypertension . These patients were r and omly included in a developmental sample ( 177 patients ) and a validation sample ( 82 patients ) . Demographic variables , hemodynamic and respiratory parameters , underlying diseases , as well as several severity scores ( SAPS , SAPS-II , OSF ) and Lung Injury Score ( LIS ) were collected . These variables were compared between survivors and nonsurvivors and entered into a step 
    Output:
    