***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 The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury . We aim ed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury . METHODS The National Acute Brain Injury Study : Hypothermia II ( NABIS : H II ) was a r and omised , multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada . Patients with non-penetrating brain injury who were 16 - 45 years old and were not responsive to instructions were r and omly assigned ( 1:1 ) by a r and om number generator to hypothermia or normothermia . Patients r and omly assigned to hypothermia were cooled to 35 ° C until their trauma assessment was completed . Patients who had none of a second set of exclusion criteria were either cooled to 33 ° C for 48 h and then gradually rewarmed or treated at normothermia , depending upon their initial treatment assignment . Investigators who assessed the outcome measures were masked to treatment allocation . The primary outcome was the Glasgow outcome scale score at 6 months . Analysis was by modified intention to treat . This trial is registered with Clinical Trials.gov , NCT00178711 . FINDINGS Enrolment occurred from December , 2005 , to June , 2009 , when the trial was terminated for futility . Follow-up was from June , 2006 , to December , 2009 . 232 patients were initially r and omised a mean of 1·6 h ( SD 0·5 ) after injury : 119 to hypothermia and 113 to normothermia . 97 patients ( 52 in the hypothermia group and 45 in the normothermia group ) did not meet any of the second set of exclusion criteria . The mean time to 35 ° C for the 52 patients in the hypothermia group was 2·6 h ( SD 1·2 ) and to 33 ° C was 4·4 h ( 1·5 ) . Outcome was poor ( severe disability , vegetative state , or death ) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group ( relative risk [ RR ] 1·08 , 95 % CI 0·76 - 1·53 ; p=0·67 ) . 12 patients in the hypothermia group died compared with eight in the normothermia group ( RR 1·30 , 95 % CI 0·58 - 2·52 ; p=0·52 ) . INTERPRETATION This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury Objectives : Therapeutic hypothermia has been of topical interest for many years and with the publication of two international , multicenter r and omized controlled trials , the evidence base now needs updating . The aim of this systematic review of r and omized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality , poor outcomes , and new pneumonia . Data Sources : The following data bases were search ed from January 1 , 2011 , to January 26 , 2018 : Cochrane Central Register of Controlled Trial , MEDLINE , PubMed , and EMBASE . Study Selection : Only foreign articles published in the English language were included . Only articles that were r and omized controlled trials investigating adult traumatic brain injury sustained following an acute , closed head injury were included . Two authors independently assessed at each stage . Data Extraction : Quality was assessed using the Cochrane Collaboration ’s tool for assessing the risk of bias . All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95 % CIs . p value of less than 0.05 was considered statistically significant . All statistical analyses were conducted using RevMan 5 ( Cochrane Collaboration , Version 5.3 , Copenhagen : The Nordic Cochrane Centre , The Cochrane Collaboration , 2014 ) . Data Synthesis : Twenty-two studies with 2,346 patients are included . R and omized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group ( risk ratio , 1.37 ; 95 % CI , 1.04–1.79 ; p = 0.02 ) , whereas r and omized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group ( risk ratio , 0.70 ; 95 % CI , 0.60–0.82 ; p < 0.00001 ) . Conclusions : Overall , this review is in-keeping with the conclusions published by the most recent r and omized controlled trials . High- quality studies show no significant difference in mortality , poor outcomes , or new pneumonia . In addition , this review shows a place for fever control in the management of traumatic brain injury BACKGROUND Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies , but the results were not definitive . To study this issue , we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury . METHODS The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were r and omly assigned to be treated with hypothermia ( body temperature , 33 degrees C ) , which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling , or normothermia . All patients otherwise received st and ard treatment . The primary outcome measure was functional status six months after the injury . RESULTS The mean age of the patients and the type and severity of injury in the two treatment groups were similar . The mean ( + /-SD ) time from injury to r and omization was 4.3+/-1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group , and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours . The outcome was poor ( defined as severe disability , a vegetative state , or death ) in 57 percent of the patients in both groups . Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group ( P=0.79 ) . The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group . Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group . CONCLUSIONS Treatment with hypothermia , with the body temperature reaching 33 degrees C within eight hours after injury , is not effective in improving outcomes in patients with severe brain injury Background Clinical trials in traumatic brain injury ( TBI ) are challenging . Previous trials of complex interventions were conducted in high-income countries , reported long lead times for site setup and low screened-to-recruitment rates . In this report we evaluate the internal pilot phase of an international , multicentre TBI trial of a complex intervention to assess : design and implementation of an online case report form ; feasibility of recruitment ( sites and patients ) ; feasibility and effectiveness of delivery of the protocol . Methods All aspects of the pilot phase of the trial were conducted as for the main trial . The pilot phase had oversight by independent Steering and Data Monitoring committees . Results Forty sites across 12 countries gained ethical approval . Thirty seven of 40 sites were initiated for recruitment . Of these , 29 had screened patients and 21 r and omized at least one patient . Lead times to ethics approval ( 6.8 weeks ) , hospital approval ( 18 weeks ) , interest to set up ( 61 weeks ) , set up to screening ( 11 weeks ) , and set up to r and omization ( 31.6 weeks ) are comparable with other international trials . Sixteen per cent of screened patients were eligible . We found 88 % compliance rate with trial protocol . Conclusion The pilot data demonstrated good feasibility for this large international multicentre r and omized controlled trial of hypothermia to control intracranial pressure . The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered . Trial registration Current Controlled Trials : IS RCT N34555414 BACKGROUND In patients with traumatic brain injury , hypothermia can reduce intracranial hypertension . The benefit of hypothermia on functional outcome is unclear . METHODS We r and omly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments ( including mechanical ventilation and sedation management ) to st and ard care ( control group ) or hypothermia ( 32 to 35 ° C ) plus st and ard care .  In the control group , stage 2 treatments ( e.g. , osmotherapy ) were added as needed to control intracranial pressure . In the hypothermia group , stage 2 treatments were added only if hypothermia failed to control intracranial pressure . In both groups , stage 3 treatments ( barbiturates and decompressive craniectomy ) were used if all stage 2 treatments failed to control intracranial pressure . The primary outcome was the score on the Extended Glasgow Outcome Scale ( GOS-E ; range , 1 to 8 , with lower scores indicating a worse functional outcome ) at 6 months . The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio ( with an odds ratio < 1.0 favoring hypothermia ) . RESULTS We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014 , at which time recruitment was suspended owing to safety concerns . Stage 3 treatments were required to control intracranial pressure in 54 % of the patients in the control group and in 44 % of the patients in the hypothermia group . The adjusted common odds ratio for the GOS-E score was 1.53 ( 95 % confidence interval , 1.02 to 2.30 ; P=0.04 ) , indicating a worse outcome in the hypothermia group than in the control group . A favorable outcome ( GOS-E score of 5 to 8 , indicating moderate disability or good recovery ) occurred in 26 % of the patients in the hypothermia group and in 37 % of the patients in the control group ( P=0.03 ) . CONCLUSIONS In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury  , therapeutic hypothermia plus st and ard care to reduce intracranial pressure did not result in outcomes better than those with st and ard care alone . ( Funded by the National Institute for Health Research Health Technology Assessment program ; Current Controlled Trials number , IS RCT N34555414 . ) Traumatic brain injury ( TBI ) is a significant cause of disability and death and a huge economic burden throughout the world . Much of the morbidity associated with TBI is attributed to secondary brain injuries result ing in hypoxia and ischemia after the initial trauma . Intracranial hypertension and decreased partial brain oxygen tension ( PbtO2 ) are targeted as potentially avoidable causes of morbidity . Therapeutic hypothermia ( TH ) may be an effective intervention to reduce intracranial pressure ( ICP ) , but could also affect cerebral blood flow ( CBF ) . This is a retrospective analysis of prospect ively collected data from 17 patients admitted to the Western General Hospital , Edinburgh . Patients with an ICP > 20 mmHg refractory to initial therapy were r and omized to st and ard care or st and ard care and TH ( intervention group ) titrated between 32 ° C and 35 ° C to reduce ICP . ICP and PbtO2 were measured using the Licox system and core temperature was recorded through rectal thermometer . Data were analyzed at the hour before cooling , the first hour at target temperature , 2 consecutive hours at target temperature , and after 6 hours of hypothermia . There was a mean decrease in ICP of 4.3±1.6 mmHg ( p<0.04 ) from 15.7 to 11.4 mmHg , from precooling to the first epoch of hypothermia in the intervention group ( n=9 ) that was not seen in the control group ( n=8 ) . A decrease in ICP was maintained throughout all time periods . There was a mean decrease in PbtO2 of 7.8±3.1 mmHg ( p<0.05 ) from 30.2 to 22.4 mmHg , from precooling to stable hypothermia , which was not seen in the control group . This research supports others in demonstrating a decrease in ICP with temperature , which could facilitate a reduction in the use of hyperosmolar agents or other stage II interventions . The decrease in PbtO2 is not below the suggested treatment threshold of 20 mmHg , but might indicate a decrease in CBF Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients , and asphyxic newborns , recent r and omized controlled trials ( RCTs ) have equally shown good neurological outcome between targeted temperature management at 33 ° C versus 36 ° C , and have not shown consistent benefits in patients with traumatic brain injury ( TBI ) . We aim ed to determine the effect of therapeutic hypothermia , while avoiding some limitations of earlier studies , which included patient selection based on Glasgow coma scale ( GCS ) , delayed initiation of cooling , short duration of cooling , inter-center variation in patient care , and relatively rapid rewarming . We conducted a multicenter RCT in patients with severe TBI ( GCS 4 - 8 ) . Patients were r and omly assigned ( 2:1 allocation ratio ) to either therapeutic hypothermia ( 32 - 34 ° C , n 
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Even more compelling was the report that when these studies were stratified according to risk of bias , data from the higher- quality studies showed that hypothermia was effective when delivered immediately or soon after injury .