***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: BACKGROUND Upper-gastrointestinal haemorrhage is a frequent reason for hospital admission . Although most risk scoring systems for this disorder incorporate endoscopic findings , the Glasgow-Blatchford bleeding score ( GBS ) is based on simple clinical and laboratory variables ; a score of 0 identifies low-risk patients who might be suitable for outpatient management . We aim ed to evaluate the GBS then assess the effect of a protocol based on this score for non-admission of low-risk individuals . METHODS Our study was undertaken at four hospitals in the UK . We calculated GBS and admission ( pre-endoscopy ) and full ( post-endoscopy ) Rockall scores  for consecutive patients presenting with upper-gastrointestinal haemorrhage . With receiver-operating characteristic ( ROC ) curves , we compared the ability of these scores to predict either need for clinical intervention or death . We then prospect ively assessed at two hospitals the introduction of GBS scoring to avoid admission of low-risk patients . FINDINGS Of 676 people presenting with upper-gastrointestinal haemorrhage , we identified 105 ( 16 % ) who scored 0 on the GBS . For prediction of need for intervention or death , GBS ( area under ROC curve 0.90 [ 95 % CI 0.88 - 0.93 ] ) was superior to full Rockall score ( 0.81 [ 0.77 - 0.84 ] ) , which in turn was better than the admission Rockall score ( 0.70 [ 0.65 - 0.75 ] ) . When introduced into clinical practice , 123 patients ( 22 % ) with upper-gastrointestinal haemorrhage were classified as low risk , of whom 84 ( 68 % ) were managed as out patients without adverse events . The proportion of individuals with this condition admitted to hospital also fell ( 96 % to 71 % , p<0.00001 ) . INTERPRETATION The GBS identifies many patients presenting to general hospitals with upper-gastrointestinal haemorrhage who can be managed safely as out patients . This score reduces admissions for this condition , allowing more appropriate use of in-patient re sources Background Hemorrhagic shock is responsible for one third of trauma related deaths . We hypothesized that intraoperative hypotensive resuscitation would improve survival for patients undergoing operative control of hemorrhage following penetrating trauma . Methods Between July 1 , 2007 , and March 28 , 2013 , penetrating trauma patients aged 14 years to 45 years with a systolic blood pressure of 90 mm Hg or lower requiring laparotomy or thoracotomy for control of hemorrhage were r and omized 1:1 based on a target minimum mean arterial pressure ( MAP ) of 50 mm Hg ( experimental arm , LMAP ) or 65 mm Hg ( control arm , HMAP ) . Patients were followed up 30 days postoperatively . The primary outcome of mortality ; secondary outcomes including stroke , myocardial infa rct ion , renal failure , coagulopathy , and infection ; and other clinical data were analyzed between study arms using univariate and Kaplan-Meier analyses . Results The trial enrolled 168 patients ( 86 LMAP , 82 HMAP patients ) before early termination , in part because of clinical equipoise and futility . Injuries result ed from gunshot wounds ( 76 % ) and stab wounds ( 24 % ) ; 90 % of the patients were male , and the median age was 31 years . Baseline vitals , laboratory results , and injury severity were similar between groups . Intraoperative MAP was 65.5 ± 11.6 mm Hg in the LMAP group and 69.1 ± 13.8 mm Hg in the HMAP group ( p = 0.07 ) . No significant survival advantage existed for the LMAP group at 30 days ( p = 0.48 ) or 24 hours ( p = 0.27 ) . Secondary outcomes were similar for the LMAP and HMAP groups : acute myocardial infa rct ion ( 1 % vs. 2 % ) , stroke ( 0 % vs. 3 % ) , any renal failure ( 15 % vs. 12 % ) , coagulopathy ( 28 % vs. 29 % ) , and infection ( 59 % vs. 58 % ) ( p > 0.05 for all ) . Acute renal injury occurred less often in the LMAP than in HMAP group ( 13 % vs. 30 % , p = 0.01 ) . Conclusion This study was unable to demonstrate that hypotensive resuscitation at a target MAP of 50 mm Hg could significantly improve 30-day mortality . Further study is necessary to fully realize the benefits of hypotensive resuscitation . LEVEL OF EVIDENCE Therapeutic study , level II BACKGROUND Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures . The optimum means of VKA reversal has not been established in comparative clinical trials . We compared the efficacy and safety of four-factor prothrombin complex concentrate ( 4F-PCC ) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures . METHODS In a multicentre , open-label , phase 3b r and omised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure . We r and omly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC ( Beriplex/Kcentra/Confidex ; CSL Behring , Marburg , Germany ) or plasma , with dosing based on international normalised ratio ( INR ) and weight . The primary endpoint was effective haemostasis , and the co- primary endpoint was rapid INR reduction ( ≤1·3 at 0·5 h after infusion end ) . The analyses were intended to evaluate , in a hierarchical fashion , first non-inferiority ( lower limit 95 % CI greater than -10 % for group difference ) for both endpoints , then superiority ( lower limit 95 % CI > 0 % ) if non-inferiority was achieved . Adverse events and serious adverse events were reported to days 10 and 45 , respectively . This trial is registered at Clinical Trials.gov , number NCT00803101 . FINDINGS 181 patients were r and omised ( 4F-PCC n=90 ; plasma n=91 ) . The intention-to-treat efficacy population comprised 168 patients ( 4F-PCC , n=87 ; plasma , n=81 ) . Effective haemostasis was achieved in 78 ( 90 % ) patients in the 4F-PCC group compared with 61 ( 75 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 14·3 % , 95 % CI 2·8 - 25·8 ) . Rapid INR reduction was achieved in 48 ( 55 % ) patients in the 4F-PCC group compared with eight ( 10 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 45·3 % , 95 % CI 31·9 - 56·4 ) . The safety profile of 4F-PCC was generally similar to that of plasma ; 49 ( 56 % ) patients receiving 4F-PCC had adverse events compared with 53 ( 60 % ) patients receiving plasma . Adverse events of interest were thromboembolic adverse events ( six [ 7 % ] patients receiving 4F-PCC vs seven [ 8 % ] patients receiving plasma ) , fluid overload or similar cardiac events ( three [ 3 % ] patients vs 11 [ 13 % ] patients ) , and late bleeding events ( three [ 3 % ] patients vs four [ 5 % ] patients ) . INTERPRETATION 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures . FUNDING CSL Behring BACKGROUND Concurrent therapy with a proton-pump inhibitor is a st and ard treatment for patients receiving aspirin who are at risk for ulcer . Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin . We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients . METHODS We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding . After the ulcers had healed , we r and omly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months . The end point was recurrent ulcer bleeding . RESULTS We enrolled 320 patients ( 161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole ) .  Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole . The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent ( 95 percent confidence interval , 4.1 to 13.1 percent ) among patients who received clopidogrel and 0.7 percent ( 95 percent confidence interval , 0 to 2.0 percent ) among those who received aspirin plus esomeprazole ( difference , 7.9 percentage points ; 95 percent confidence interval for the difference , 3.4 to 12.4 ; P=0.001 ) . CONCLUSIONS Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment , aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding . Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults , but it is not known which results in better clinical outcomes . METHODS In a pragmatic , cluster‐r and omized , multiple‐crossover trial conducted in five intensive care units at an academic center , we assigned 15,802 adults to receive saline ( 0.9 % sodium chloride ) or balanced crystalloids ( lactated Ringer 's solution or Plasma‐Lyte A ) according to the r and omization of the unit to which they were admitted . The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction ( defined as an elevation of the creatinine level to ≥200 % of baseline ) — all censored at hospital discharge or 30 days , whichever occurred first . RESULTS Among the 7942 patients in the balanced‐crystalloids group , 1139 ( 14.3 % ) had a major adverse kidney event , as compared with 1211 of 7860 patients ( 15.4 % ) in the saline group ( marginal odds ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.84 to 0.99 ; conditional odds ratio , 0.90 ; 95 % CI , 0.82 to 0.99 ; P=0.04 ) . In‐hospital mortality at 30 days was 10.3 % in the balanced‐crystalloids group and 11.1 % in the saline group ( P=0.06 ) . The incidence of new renal‐replacement therapy was 2.5 % and 2.9 % , respectively ( P=0.08 ) , and the incidence of persistent renal dysfunction was 6.4 % and 6.6 % , respectively ( P=0.60 ) . CONCLUSIONS Among critically ill adults , the use of balanced crystalloids for intravenous fluid administration result ed in a lower rate of the composite outcome of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction than the use of saline . ( Funded by the V and erbilt Institute for Clinical and Translational Research and others ; SMART‐MED and SMART‐SURG Clinical Trials.gov numbers , NCT02444988 and NCT02547779 . BACKGROUND 
    Output:
    
The goals of fluid resuscitation are to restore end-organ