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: CONTEXT Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS . DESIGN , SETTING , AND PATIENTS The Prone-Supine II Study , a multicenter , unblinded , r and omized controlled trial conducted in 23 centers in Italy and 2 in Spain . Patients were 342 adults with ARDS receiving mechanical ventilation , enrolled from February 2004 through June 2008 and prospect ively stratified into subgroups with moderate ( n = 192 ) and severe ( n = 150 ) hypoxemia . INTERVENTIONS Patients were r and omized to undergo supine ( n = 174 ) or prone ( 20 hours per day ; n = 168 ) positioning during ventilation . MAIN OUTCOME MEASURES The primary outcome was 28-day all-cause mortality . Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge , organ dysfunctions , and the complication rate related to prone positioning . RESULTS Prone and supine patients from the entire study population had similar 28-day ( 31.0 % vs 32.8 % ; relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.84 - 1.13 ; P = .72 ) and 6-month ( 47.0 % vs 52.3 % ; RR , 0.90 ; 95 % CI , 0.73 - 1.11 ; P = .33 ) mortality rates , despite significantly higher complication rates in the prone group . Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days ( 25.5 % vs 22.5 % ; RR , 1.04 ; 95 % CI , 0.89 - 1.22 ; P = .62 ) and at 6 months ( 42.6 % vs 43.9 % ; RR , 0.98 ; 95 % CI , 0.76 - 1.25 ; P = .85 ) . The 28-day mortality of patients with severe hypoxemia was 37.8 % in the prone and 46.1 % in the supine group ( RR , 0.87 ; 95 % CI , 0.66 - 1.14 ; P = .31 ) , while their 6-month mortality was 52.7 % and 63.2 % , respectively ( RR , 0.78 ; 95 % CI , 0.53 - 1.14 ; P = .19 ) . CONCLUSION Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00159939 Objective : Both prone position and high-frequency oscillatory ventilation ( HFOV ) have the potential to facilitate lung recruitment , and their combined use could thus be synergetic on gas exchange . Keeping the lung open could also potentially be lung protective . The aim of this study was to compare physiologic and proinflammatory effects of HFOV , prone positioning , or their combination in severe acute respiratory distress syndrome ( ARDS ) . Design : Prospect i ve , comparative r and omized study . Setting : A medical intensive care unit . Patients : Thirty-nine ARDS patients with a Pao2/Fio2 ratio < 150 mm Hg at positive end-expiratory pressure ≥5 cm H2O . Interventions : After 12 hrs on conventional lung-protective mechanical ventilation ( tidal volume 6 mL/kg of ideal body weight , plateau pressure not exceeding the upper inflection point , and a maximum of 35 cm H2O ; supine-CV ) , 39 patients were r and omized to receive one of the following 12-hr periods : conventional lung-protective mechanical ventilation in prone position ( prone-CV ) , HFOV in supine position ( supine-HFOV ) , or HFOV in prone position ( prone-HFOV ) . Measurements and Main Results : Prone-CV ( from 138 ± 58 mm Hg to 217 ± 110 mm Hg , p < .0001 ) and prone-HFOV ( from 126 ± 40 mm Hg to 227 ± 64 mm Hg , p < 0.0001 ) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio ( from 134 ± 57 mm Hg to 138 ± 48 mm Hg ) . The oxygenation index ( { mean airway pressure × Fio2 × 100}/Pao2 ) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group . Interleukin-8 increased significantly in the bronchoalveolar lavage fluid ( BALF ) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV . Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group . Conclusions : Although HFOV in the supine position does not improve oxygenation or lung inflammation , the prone position increases oxygenation and reduces lung inflammation  in ARDS patients .  Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation . In contrast , supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation 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 Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising  studies  for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as 
    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: CONTEXT Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS . DESIGN , SETTING , AND PATIENTS The Prone-Supine II Study , a multicenter , unblinded , r and omized controlled trial conducted in 23 centers in Italy and 2 in Spain . Patients were 342 adults with ARDS receiving mechanical ventilation , enrolled from February 2004 through June 2008 and prospect ively stratified into subgroups with moderate ( n = 192 ) and severe ( n = 150 ) hypoxemia . INTERVENTIONS Patients were r and omized to undergo supine ( n = 174 ) or prone ( 20 hours per day ; n = 168 ) positioning during ventilation . MAIN OUTCOME MEASURES The primary outcome was 28-day all-cause mortality . Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge , organ dysfunctions , and the complication rate related to prone positioning . RESULTS Prone and supine patients from the entire study population had similar 28-day ( 31.0 % vs 32.8 % ; relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.84 - 1.13 ; P = .72 ) and 6-month ( 47.0 % vs 52.3 % ; RR , 0.90 ; 95 % CI , 0.73 - 1.11 ; P = .33 ) mortality rates , despite significantly higher complication rates in the prone group . Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days ( 25.5 % vs 22.5 % ; RR , 1.04 ; 95 % CI , 0.89 - 1.22 ; P = .62 ) and at 6 months ( 42.6 % vs 43.9 % ; RR , 0.98 ; 95 % CI , 0.76 - 1.25 ; P = .85 ) . The 28-day mortality of patients with severe hypoxemia was 37.8 % in the prone and 46.1 % in the supine group ( RR , 0.87 ; 95 % CI , 0.66 - 1.14 ; P = .31 ) , while their 6-month mortality was 52.7 % and 63.2 % , respectively ( RR , 0.78 ; 95 % CI , 0.53 - 1.14 ; P = .19 ) . CONCLUSION Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00159939 Objective : Both prone position and high-frequency oscillatory ventilation ( HFOV ) have the potential to facilitate lung recruitment , and their combined use could thus be synergetic on gas exchange . Keeping the lung open could also potentially be lung protective . The aim of this study was to compare physiologic and proinflammatory effects of HFOV , prone positioning , or their combination in severe acute respiratory distress syndrome ( ARDS ) . Design : Prospect i ve , comparative r and omized study . Setting : A medical intensive care unit . Patients : Thirty-nine ARDS patients with a Pao2/Fio2 ratio < 150 mm Hg at positive end-expiratory pressure ≥5 cm H2O . Interventions : After 12 hrs on conventional lung-protective mechanical ventilation ( tidal volume 6 mL/kg of ideal body weight , plateau pressure not exceeding the upper inflection point , and a maximum of 35 cm H2O ; supine-CV ) , 39 patients were r and omized to receive one of the following 12-hr periods : conventional lung-protective mechanical ventilation in prone position ( prone-CV ) , HFOV in supine position ( supine-HFOV ) , or HFOV in prone position ( prone-HFOV ) . Measurements and Main Results : Prone-CV ( from 138 ± 58 mm Hg to 217 ± 110 mm Hg , p < .0001 ) and prone-HFOV ( from 126 ± 40 mm Hg to 227 ± 64 mm Hg , p < 0.0001 ) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio ( from 134 ± 57 mm Hg to 138 ± 48 mm Hg ) . The oxygenation index ( { mean airway pressure × Fio2 × 100}/Pao2 ) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group . Interleukin-8 increased significantly in the bronchoalveolar lavage fluid ( BALF ) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV . Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group . Conclusions : Although HFOV in the supine position does not improve oxygenation or lung inflammation , the prone position increases oxygenation and reduces lung inflammation  in ARDS patients .  Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation . In contrast , supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation 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 Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising  studies  for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as 
    Output:
    