***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 
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    Input: BACKGROUND Current classification of traumatic brain injury ( TBI ) is suboptimal , and management is based on weak evidence , with little attempt to personalize treatment . A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies . OBJECTIVE To improve characterization and classification of TBI and to identify best clinical care , using comparative effectiveness research approaches . METHODS This multicenter , longitudinal , prospect i ve , observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients , presenting within 24 hours of injury , with a clinical diagnosis of TBI and an indication for computed tomography .  Broader registry-level data collection in approximately 20,000 patients will assess generalizability . Cross sectional comprehensive outcome assessment s , including quality of life and neuropsychological testing , will be performed at 6 months . Longitudinal assessment s will continue up to 24 months post TBI in patient subsets . Advanced neuroimaging and genomic and biomarker data will be used to improve characterization , and analyses will include neuroinformatics approaches to address variations in process and clinical care . Results will be integrated with living systematic review s in a process of knowledge transfer . The study initiation was from October to December 2014 , and the recruitment period was for 18 to 24 months . EXPECTED OUTCOMES Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification , evidence to support treatment recommendations , and benchmarks for quality of care . Data and sample repositories will ensure opportunities for legacy research . DISCUSSION Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient population s by exploiting differences in biology , care , and outcome to support optimal personalized patient management To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury . In a large international r and omized trial patients were r and omly assigned to a target blood glucose ( BG ) range of either 4.5–6.0 mmol/L ( intensive control ) or < 10 mmol/L ( conventional control ) . Patients with traumatic brain injury ( TBI ) were identified at r and omization and data were collected to examine the extended Glasgow outcome score ( includes mortality ) at 24 months . Of the 6104 r and omized patients , 391 satisfied diagnostic criteria for TBI ; 203 ( 51.9 % ) were assigned to intensive and 188 ( 48.1 % ) to conventional control ; the primary outcome was available for 166 ( 81.8 % ) and 149 ( 79.3 % ) patients , respectively . The two groups had similar baseline characteristics . At 2 years 98 ( 58.7 % ) patients in the intensive group and 79 ( 53.0 % ) in the conventional group had a favorable neurological outcome ( odds ratio [ OR ] 1.26 , 95 % CI 0.81–1.97 ; P = 0.3 ) ; 35 patients ( 20.9 % ) in the intensive group and 34 ( 22.8 % ) in the conventional group had died ( OR 0.90 , 95 % CI 0.53–1.53 ; P = 0.7 ) ; moderate hypoglycemia ( BG 2.3–3.9 mmol/L ; 41–70 mg/dL ) occurred in 160/202 ( 79.2 % ) and 17/188 ( 9.0 % ) , respectively ( OR 38.3 , 95 % CI 21.0–70.1 ; P < 0.0001 ) ; severe hypoglycemia ( BG ≤ 2.2 mmol/L ; ≤40 mg/dL ) in 10 ( 4.9 % ) and 0 ( 0.0 % ) , respectively ( OR 20.5 95 % CI 1.2–351.6 , P = 0.003 ) . Although patients with traumatic brain injury r and omly assigned to intensive compared to conventional glucose control  experienced moderate and severe hypoglycemia more frequently , we found no significant difference in clinical ly important outcomes BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management . However , the appropriate caloric intake for critically ill patients remains ill defined . OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy ( IIT ) compared with that of conventional insulin therapy ( CIT ) on the outcomes of critically ill patients . DESIGN This study had a 2 × 2 factorial , r and omized , controlled design . Eligible patients were r and omly assigned to permissive underfeeding or target feeding groups ( caloric goal : 60 - 70 % compared with 90 - 100 % of calculated requirement , respectively ) with either IIT or CIT ( target blood glucose : 4.4 - 6.1 compared with 10 - 11.1 mmol/L , respectively ) . RESULTS Twenty-eight-day all-cause mortality was 18.3 % in the permissive underfeeding group compared with 23.3 % in the target feeding group ( relative risk : 0.79 ; 95 % CI : 0.48 , 1.29 ; P = 0.34 ) . Hospital mortality was lower in the permissive underfeeding group than in the target group ( 30.0 % compared with 42.5 % ; relative risk : 0.71 ; 95 % CI : 0.50 , 0.99 ; P = 0.04 ) . No significant differences in outcomes were observed between the IIT and CIT groups . CONCLUSION In critically ill patients , permissive underfeeding may be associated with lower mortality rates than target feeding . This trial was registered at controlled-trials.com as IS RCT N96294863 BACKGROUND The role of intensive insulin therapy in patients with severe sepsis is uncertain . Fluid resuscitation improves survival among patients with septic shock , but evidence is lacking to support the choice of either crystalloids or colloids . METHODS In a multicenter , two-by-two factorial trial , we r and omly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10 % pentastarch , a low-molecular-weight hydroxyethyl starch ( HES 200/0.5 ) , or modified Ringer 's lactate for fluid resuscitation . The rate of death at 28 days and the mean score for organ failure were co primary end points . RESULTS The trial was stopped early for safety reasons . Among 537 patients who could be evaluated , the mean morning blood glucose level was lower in the intensive-therapy group ( 112 mg per deciliter [ 6.2 mmol per liter ] ) than in the conventional-therapy group ( 151 mg per deciliter [ 8.4 mmol per liter ] , P<0.001 ) . However , at 28 days , there was no significant difference between the two groups in the rate of death or the mean score for organ failure . The rate of severe hypoglycemia ( glucose level , < or = 40 mg per deciliter [ 2.2 mmol per liter ] ) was higher in the intensive-therapy group than in the conventional-therapy group ( 17.0 % vs. 4.1 % , P<0.001 ) , as was the rate of serious adverse events ( 10.9 % vs. 5.2 % , P=0.01 ) . HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer 's lactate . CONCLUSIONS The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia . As used in this study , HES was harmful , and its toxicity increased with accumulating doses . ( Clinical Trials.gov number , NCT00135473 . Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction Hyperglycemia is a marker of poor prognosis in severe brain injuries . There is currently little data regarding the effects of intensive insulin therapy ( IIT ) on neurological recovery . Methods A sub-group analysis of the r and omized-controlled CGAO-REA study ( NCT01002482 ) in surgical intensive care units ( ICU ) of two university hospitals . Patients with severe brain injury , with an expected ICU length of stay ≥48 hours were included . Patients were r and omized between a conventional glucose management group ( blood glucose target between 5.5 and 9 mmol . L−1 ) and an IIT group ( blood glucose target between 4.4 and 6 mmol . L−1 ) . The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale . Results A total of 188 patients were included in this analysis . In total 98 ( 52 % ) patients were r and omized in the control group and 90 ( 48 % ) in the IIT group . The mean Glasgow coma score at baseline was 7 ( ±4 ) . Patients in the IIT group received more insulin ( 130 ( 68 to 251 ) IU versus 74 ( 13 to 165 ) IU in the control group , P = 0.01 ) , had a significantly lower morning blood glucose level ( 5.9 ( 5.1 to 6.7 ) mmol . L−1 versus 6.5 ( 5.6 to 7.2 ) mmol . L−1 , P < 0.001 ) in the first 5 days after ICU admission . The IIT group experienced more episodes of hypoglycemia ( P < 0.0001 ) . In the IIT group 24 ( 26.6 % ) patients had a favorable neurological outcome ( good recovery or moderate disability ) compared to 31 ( 31.6 % ) in the control group ( P = 0.4 ) . There were no differences in day-28 mortality . The occurrence of hypoglycemia did not influence the outcome . Conclusions In this sub-group analysis of a large multicenter r and omized trial , IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity Intensive insulin therapy ( IIT ) improves the outcome of prolonged critically ill patients , but concerns remain regarding potential harm and the optimal blood glucose level . These questions were addressed using the pooled data set of two r and omized controlled trials . Independent of parenteral glucose load , IIT reduced mortality from 23.6 to 20.4 % in the intention-to-treat group ( n = 2,748 ; P = 0.04 ) and from 37.9 to 30.1 % among long stayers ( n = 1,389 ; P = 0.002 ) , with no difference among short stayers ( 8.9 vs. 10.4 % ; n = 1,359 ; P = 0.4 ) . Compared with blood glucose of 110–150 mg/dl , mortality was higher with blood glucose > 150 mg/dl ( odds ratio 1.38 [ 95 % CI 1.10–1.75 ] ; P = 0.007 ) and lower with < 110 mg/dl ( 0.77 [ 0.61–0.96 ] ; P = 0.02 ) . Only patients with diabetes ( n = 407 ) showed no survival benefit of IIT . Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly < 110 mg/day , but this level carried the highest risk of hypoglycemia . Within 24 h of hypoglycemia , three patients in the conventional and one in the IIT group died ( P = 0.0004 ) without difference in hospital mortality . No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units ( ICUs ) . We conclude that IIT reduces mortality of all medical/surgical ICU patients , except those with a prior history of diabetes , and does not cause harm . A blood glucose target < 110 mg/day was most effective but also carried the highest risk of hypoglycemia Introduction Critically ill patients can develop hyperglycaemia even if they do not have diabetes . Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit ( ICU ) and decreases morbidity in patients in a medical ICU . The effect of this therapy on patients in a mixed medical/surgical ICU is unknown . Our goal was to assess whether the effect of intensive insulin therapy , compared with st and ard therapy , decreases morbidity and mortality in patients hospitalised in a mixed ICU . Methods This is a prospect i ve , r and omised , non-blinded , single-centre clinical trial in a medical/surgical ICU . Patients were r and omly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl ( 4.4 to 6.1 mmol/l ) or st and ard insulin therapy to maintain glucose levels between 180 and 200 mg/dl ( 10 and 11.1 mmol/l ) . The primary end point was mortality at 28 days . Results Over a period of 30 months , 504 patients were enrolled . The 28 
    Output:
    
Conclusions This meta- analysis of intensive glycaemic control shows no association with reduced mortality in TBI .
Intensive glucose control showed a borderline significant reduction in the risk of poor neurological outcome , but markedly increased the risk of hypoglycaemia .