human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To evaluate the safety and efficacy of high-frequency oscillatory ventilation ( HFOV ) in adult patients with the acute respiratory distress syndrome ( ARDS ) and oxygenation failure . Design Prospect i ve , clinical study . Setting Intensive care and burn units of two university teaching hospitals . Patients Twenty-four adults ( 10 females , 14 males , aged 48.5 ± 15.2 yrs , Acute Physiology and Chronic Health Evaluation II score 21.5 ± 6.9 ) with ARDS ( lung injury score 3.4 ± 0.6 , Pao2/Fio2 98.8 ± 39.0 mm Hg , and oxygenation index 32.5 ± 19.6 ) who met one of the following criteria : Pao2 ≤65 mm Hg with Fio2 ≥0.6 , or plateau pressure ≥35 cm H2O . Interventions HFOV was initiated in patients with ARDS after varying periods of conventional ventilation ( CV ) . Mean airway pressure ( Paw ) was initially set 5 cm H2O greater than Paw during CV , and was subsequently titrated to maintain oxygen saturation between 88 % and 93 % and Fio2 ≤0.60 . Measurements and Main Results Fio2 , Paw , pressure amplitude of oscillation , frequency , blood pressure , heart rate , and arterial blood gases were monitored during the transition from CV to HFOV , and every 8 hrs thereafter for 72 hrs . In 16 patients who had pulmonary artery catheters in place  , cardiac hemodynamics were recorded at the same time intervals . Throughout the HFOV trial , Paw was significantly higher than that applied during CV . Within 8 hrs of HFOV application , and for the duration of the trial , Fio2 and Paco2 were lower , and Pao2/Fio2 was higher than baseline values during CV . Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure ( at 8 and 40 hrs ) and central venous pressure ( at 16 and 40 hrs ) , and a reduction in cardiac output throughout the course of the study . There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV . Complications occurring during HFOV  included pneumothorax in two patients and desiccation of secretions in one patient . Survival at 30 days was 33 % , with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors ( 1.6 ± 1.2 vs. 7.8 ± 5.8 days;p = .001 ) . Conclusions These findings suggest that HFOV has beneficial effects on oxygenation and ventilation , and may be a safe and effective rescue therapy for patients with severe oxygenation failure . In addition , early institution of HFOV may be advantageous 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 To evaluate the safety and effectiveness of high-frequency oscillatory ventilation using a protocol design ed to recruit and maintain optimal lung volume in patients with severe adult respiratory distress syndrome ( ARDS ) . SETTING Surgical and medical intensive care units in a tertiary care , military teaching hospital . DESIGN A prospect i ve , clinical study . PATIENTS Seventeen patients , 17 yrs to 83 yrs of age , with severe ARDS ( Lung Injury Score of 3.81 + /- 0.23 ) failing inverse ratio mechanical conventional ventilation  ( PaO2/FiO2 ratio of 68.6 + /- 21.6 , peak inspiratory pressure of 54.3 + /- 12.7 cm H2O , positive end-expiratory pressure of 18.2 + /- 6.9 cm H2O ) . INTERVENTIONS High-frequency oscillatory ventilation was instituted after varying periods of conventional ventilation ( 5.12 + /- 4.3 days ) . We employed lung volume recruitment strategy that consisted of incremental increases in mean airway pressure to achieve a PaO2 of > or = 60 torr ( > or = 8.0 kPa ) , with an FiO2 of < or = 0.6 . MEASUREMENTS AND MAIN RESULTS  High-frequency oscillator ventilator setting s ( FiO2 , mean airway pressure , pressure amplitude of oscillation [ delta P ] frequency ) and hemodynamic parameters ( cardiac output , oxygen delivery [ DO2 ] ) , mean systemic and pulmonary arterial pressures , and the oxygenation index ( oxygenation index = [ FiO2 x mean airway pressure x 100]/PaO2 ) were monitored during the transition to high-frequency oscillatory ventilation and throughout the course of the high-frequency protocol . Thirteen patients demonstrated improved gas exchange and an overall improvement in PaO2/FiO2 ratio ( p < .02 ) . Reductions in the oxygenation index ( p < .01 ) and FiO2 ( p < .02 ) at 12 , 24 , and 48 hrs after starting high-frequency oscillatory ventilation were observed . No significant compromise in cardiac output or DO2 was observed , despite a significant increase in mean airway pressure ( 31.2 + /- 10.3 to 34.0 + /- 6.7 cm H2O , p < .05 ) on high-frequency oscillatory ventilation . The overall survival rate at 30 days was 47 % . A greater number of pretreatment days on conventional ventilation ( p < .009 ) and an entry oxygenation index of > 47 ( sensitivity 100 % , specificity 100 % ) were associated with mortality . CONCLUSIONS High-frequency oscillatory ventilation is both safe and effective in adult patients with severe ARDS failing conventional ventilation . A lung volume recruitment strategy during high-frequency oscillatory ventilation produced improved gas exchange without a compromise in DO2 . These results are encouraging and support the need for a prospect i ve , r and omized trial of algorithm-controlled conventional ventilation vs. high-frequency oscillatory ventilation for adults with severe ARDS 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 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-Bu 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To evaluate the safety and efficacy of high-frequency oscillatory ventilation ( HFOV ) in adult patients with the acute respiratory distress syndrome ( ARDS ) and oxygenation failure . Design Prospect i ve , clinical study . Setting Intensive care and burn units of two university teaching hospitals . Patients Twenty-four adults ( 10 females , 14 males , aged 48.5 ± 15.2 yrs , Acute Physiology and Chronic Health Evaluation II score 21.5 ± 6.9 ) with ARDS ( lung injury score 3.4 ± 0.6 , Pao2/Fio2 98.8 ± 39.0 mm Hg , and oxygenation index 32.5 ± 19.6 ) who met one of the following criteria : Pao2 ≤65 mm Hg with Fio2 ≥0.6 , or plateau pressure ≥35 cm H2O . Interventions HFOV was initiated in patients with ARDS after varying periods of conventional ventilation ( CV ) . Mean airway pressure ( Paw ) was initially set 5 cm H2O greater than Paw during CV , and was subsequently titrated to maintain oxygen saturation between 88 % and 93 % and Fio2 ≤0.60 . Measurements and Main Results Fio2 , Paw , pressure amplitude of oscillation , frequency , blood pressure , heart rate , and arterial blood gases were monitored during the transition from CV to HFOV , and every 8 hrs thereafter for 72 hrs . In 16 patients who had pulmonary artery catheters in place  , cardiac hemodynamics were recorded at the same time intervals . Throughout the HFOV trial , Paw was significantly higher than that applied during CV . Within 8 hrs of HFOV application , and for the duration of the trial , Fio2 and Paco2 were lower , and Pao2/Fio2 was higher than baseline values during CV . Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure ( at 8 and 40 hrs ) and central venous pressure ( at 16 and 40 hrs ) , and a reduction in cardiac output throughout the course of the study . There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV . Complications occurring during HFOV  included pneumothorax in two patients and desiccation of secretions in one patient . Survival at 30 days was 33 % , with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors ( 1.6 ± 1.2 vs. 7.8 ± 5.8 days;p = .001 ) . Conclusions These findings suggest that HFOV has beneficial effects on oxygenation and ventilation , and may be a safe and effective rescue therapy for patients with severe oxygenation failure . In addition , early institution of HFOV may be advantageous 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 To evaluate the safety and effectiveness of high-frequency oscillatory ventilation using a protocol design ed to recruit and maintain optimal lung volume in patients with severe adult respiratory distress syndrome ( ARDS ) . SETTING Surgical and medical intensive care units in a tertiary care , military teaching hospital . DESIGN A prospect i ve , clinical study . PATIENTS Seventeen patients , 17 yrs to 83 yrs of age , with severe ARDS ( Lung Injury Score of 3.81 + /- 0.23 ) failing inverse ratio mechanical conventional ventilation  ( PaO2/FiO2 ratio of 68.6 + /- 21.6 , peak inspiratory pressure of 54.3 + /- 12.7 cm H2O , positive end-expiratory pressure of 18.2 + /- 6.9 cm H2O ) . INTERVENTIONS High-frequency oscillatory ventilation was instituted after varying periods of conventional ventilation ( 5.12 + /- 4.3 days ) . We employed lung volume recruitment strategy that consisted of incremental increases in mean airway pressure to achieve a PaO2 of > or = 60 torr ( > or = 8.0 kPa ) , with an FiO2 of < or = 0.6 . MEASUREMENTS AND MAIN RESULTS  High-frequency oscillator ventilator setting s ( FiO2 , mean airway pressure , pressure amplitude of oscillation [ delta P ] frequency ) and hemodynamic parameters ( cardiac output , oxygen delivery [ DO2 ] ) , mean systemic and pulmonary arterial pressures , and the oxygenation index ( oxygenation index = [ FiO2 x mean airway pressure x 100]/PaO2 ) were monitored during the transition to high-frequency oscillatory ventilation and throughout the course of the high-frequency protocol . Thirteen patients demonstrated improved gas exchange and an overall improvement in PaO2/FiO2 ratio ( p < .02 ) . Reductions in the oxygenation index ( p < .01 ) and FiO2 ( p < .02 ) at 12 , 24 , and 48 hrs after starting high-frequency oscillatory ventilation were observed . No significant compromise in cardiac output or DO2 was observed , despite a significant increase in mean airway pressure ( 31.2 + /- 10.3 to 34.0 + /- 6.7 cm H2O , p < .05 ) on high-frequency oscillatory ventilation . The overall survival rate at 30 days was 47 % . A greater number of pretreatment days on conventional ventilation ( p < .009 ) and an entry oxygenation index of > 47 ( sensitivity 100 % , specificity 100 % ) were associated with mortality . CONCLUSIONS High-frequency oscillatory ventilation is both safe and effective in adult patients with severe ARDS failing conventional ventilation . A lung volume recruitment strategy during high-frequency oscillatory ventilation produced improved gas exchange without a compromise in DO2 . These results are encouraging and support the need for a prospect i ve , r and omized trial of algorithm-controlled conventional ventilation vs. high-frequency oscillatory ventilation for adults with severe ARDS 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 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-Bu 
    Output:
    