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: 200 adult respiratory distress syndrome patients were included in a prospect i ve multicenter r and omized trial to determine the efficacy of computerized decision support . The study was done in 10 medical centers across the United States . There was no significant difference in survival between the two treatment groups ( mean 2 = 0.49 p = 0.49 ) or in ICU length of stay between the two treatment groups when controlling for survival ( F(1df ) = 0.88 , p = 0.37 . ) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group ( F(1df ) = 4.1 , p = 0.04 ) as well as significantly lower incidence and severity of overdistension lung injury ( F(1df ) = 45.2 , p < 0.001 ) . We rejected the null hypothesis . Efficacy was best for the protocol group . Protocol s were used for 32,055 hours ( 15 staff person years , 3.7 patient years or 1335 patient days ) . Protocol s were active 96 % of the time . 38,546 instructions were generated . 94 % were followed . This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical setting s and significantly improve patient morbidity 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 ) 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 The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 )  , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS The associated use of permissive hypercapnia ( PHY ) and high PEEP levels ( PEEP(IDEAL ) ) has been recently indicated as part of a lung-protective-approach ( LPA ) in acute respiratory distress syndrome ( ARDS ) . However , the net hemodynamic effect produced by this association is not known . We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients ( mean age 34 + /- 13 yr ) with ARDS , focusing on its immediate ( after 1 h ) , early ( first 36 h ) , and late ( 2nd-7th d ) consequences . Twenty-five patients were su bmi tted to LPA -- with the combined use of permissive hypercapnia ( PHY ) , VT < 6 ml/kg , distending pressures above PEEP < 20 cm H2O , and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve ( P(FLEX))- and 23 control patients were su bmi tted to conventional mechanical ventilation .  LPA was initiated at once , result ing in an immediate increase in heart rate ( p = 0.0002 ) , cardiac output ( p = 0.0002 ) , oxygen delivery ( DO2l , p = 0.0003 ) , and mixed venous Po2 ( p = 0.0006 ) , with a maintained systemic oxygen consumption ( p = 0.52 ) . The mean pulmonary arterial pressure markedly increased ( mean increment 8.8 mm Hg ; p < 0.0001 ) , but the pulmonary vascular resistance did not change ( p = 0.32 ) . Cardiac filling pressures increased ( p < 0.001 ) and the systemic vascular resistance fell ( p = 0.003 ) . All these alterations were progressively attenuated in the course of the first 36 h , despite persisting hypercapnia . Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients ( p < 0.0001 ) . No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved . A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis , with no depressant effects ascribed to high PEEP levels . In contrast , high plateau pressures were associated with cardiovascular depression . Thus , as long as sufficiently low distending pressures are concomitantly applied , the sudden installation of PHY plus PEEP(IDEAL ) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals su bmi tted to  artificial ventilation  . To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome ( ARDS ) su bmi tted to conventional mechanical ventilation ( MV ) , we evaluated the impact of 
    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: 200 adult respiratory distress syndrome patients were included in a prospect i ve multicenter r and omized trial to determine the efficacy of computerized decision support . The study was done in 10 medical centers across the United States . There was no significant difference in survival between the two treatment groups ( mean 2 = 0.49 p = 0.49 ) or in ICU length of stay between the two treatment groups when controlling for survival ( F(1df ) = 0.88 , p = 0.37 . ) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group ( F(1df ) = 4.1 , p = 0.04 ) as well as significantly lower incidence and severity of overdistension lung injury ( F(1df ) = 45.2 , p < 0.001 ) . We rejected the null hypothesis . Efficacy was best for the protocol group . Protocol s were used for 32,055 hours ( 15 staff person years , 3.7 patient years or 1335 patient days ) . Protocol s were active 96 % of the time . 38,546 instructions were generated . 94 % were followed . This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical setting s and significantly improve patient morbidity 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 ) 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 The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 )  , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS The associated use of permissive hypercapnia ( PHY ) and high PEEP levels ( PEEP(IDEAL ) ) has been recently indicated as part of a lung-protective-approach ( LPA ) in acute respiratory distress syndrome ( ARDS ) . However , the net hemodynamic effect produced by this association is not known . We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients ( mean age 34 + /- 13 yr ) with ARDS , focusing on its immediate ( after 1 h ) , early ( first 36 h ) , and late ( 2nd-7th d ) consequences . Twenty-five patients were su bmi tted to LPA -- with the combined use of permissive hypercapnia ( PHY ) , VT < 6 ml/kg , distending pressures above PEEP < 20 cm H2O , and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve ( P(FLEX))- and 23 control patients were su bmi tted to conventional mechanical ventilation .  LPA was initiated at once , result ing in an immediate increase in heart rate ( p = 0.0002 ) , cardiac output ( p = 0.0002 ) , oxygen delivery ( DO2l , p = 0.0003 ) , and mixed venous Po2 ( p = 0.0006 ) , with a maintained systemic oxygen consumption ( p = 0.52 ) . The mean pulmonary arterial pressure markedly increased ( mean increment 8.8 mm Hg ; p < 0.0001 ) , but the pulmonary vascular resistance did not change ( p = 0.32 ) . Cardiac filling pressures increased ( p < 0.001 ) and the systemic vascular resistance fell ( p = 0.003 ) . All these alterations were progressively attenuated in the course of the first 36 h , despite persisting hypercapnia . Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients ( p < 0.0001 ) . No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved . A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis , with no depressant effects ascribed to high PEEP levels . In contrast , high plateau pressures were associated with cardiovascular depression . Thus , as long as sufficiently low distending pressures are concomitantly applied , the sudden installation of PHY plus PEEP(IDEAL ) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals su bmi tted to  artificial ventilation  . To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome ( ARDS ) su bmi tted to conventional mechanical ventilation ( MV ) , we evaluated the impact of 
    Output:
    