***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 and Purpose — Hypothermia improves outcome in resuscitated patients and newborns with hypoxic brain injury . We studied the safety and feasibility of mild hypothermia in awake patients with stroke after intravenous thrombolysis . Methods — Patients were r and omized 1:1 to mild hypothermia ( 35 ° C ) or to st and ard stroke unit care within 6 hours of symptom onset .  Hypothermia was induced with a surface-cooling device and cold saline infusions . Active cooling was restrained gradually after 12 hours at < 35.5 ° C . The primary outcome measure was the number of patients with < 36 ° C body temperature for > 80 % of the 12-hour cooling period . Results — We included 36 patients with a median of National Institutes of Health Stroke Scale score of 9 one hour after thrombolysis . Fifteen of 18 ( 83 % ) patients achieved the primary end point . Sixteen ( 89 % ) patients reached < 35.5 ° C in a median time of 10 hours ( range , 7–16 hours ) from symptom onset , spent 10.5 hours ( 1–17 hours ) in hypothermia , and were back to normothermia in 23 hours ( 15–29 hours ) . Few serious adverse events were more common in the hypothermia group . At 3 months , 7 patients ( 39 % ) in both groups had good outcome ( modified Ranking Scale , 0–2 ) , whereas poor outcome ( modified Ranking Scale , 4–6 ) was twice as common in the normothermia group ( 44 % versus 22 % ) . Conclusions — Mild hypothermia with a surface-cooling device in an acute stroke unit is safe and feasible in thrombolyzed , spontaneously breathing patients with stroke , despite the adverse events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00987922 A promising treatment or equipoise between existing therapies needs to be tested in a scientifically valid and timely manner . Once the research question , design , and sample size of a clinical trial are determined , time becomes brain even more so : thous and s of patient lives are being affected by delays in bringing effective treatments to clinical wards . Time also becomes money for sponsors . A future therapy will cost more the longer it takes to provide an answer . A large company would rather spend money on a fast negative trial than a very slow positive trial . Although patent ‘ life ’ and other factors also play a role here , a quick solution , whether negative or positive , is always preferred . For a small start-up company , a slow recruitment in clinical trials may be a ‘ kiss of death ’ . Inasmuch as academics would prefer to test every hypothesis out there in a clinical trial , we are also dependent on innovation and industry to test new proprietary treatments . Given that incidence of stroke events is lower than myocardial infa rct ion , our field has limited re sources . This means that every patient counts , not only as a unique human being to us as clinicians but also to our scientific community as an invaluable participant in research processes . To a scientist , this simply implies that not every research question can be answered . A clinician will add that not every question we have could or should be answered in a r and omized trial . Nevertheless , we commit our careers to a challenging field of development of new treatments . We think , search , struggle , design , and argue about treatment options , priorities , and multi-task in ever-changing clinical research environment . One obstacle that does impede our progress is slow recruitment into clinical trials that we , as clinician-scientists , already committed our centres to participation . There are several major reasons why recruitment is slow in r and omized clinical trials : the patient pool , the eligibility criteria , the attractiveness of a trial , and adequacy of the network of clinical sites may influence patient enrolment ( 1 ) . In a study of clinical trials in immune-deficient patients , early enrolment offered strong evidence on the feasibility of a trial and was indicative of its future pace of recruitment . In stroke , the Interventional Management of Stroke trial ( 2 ) , for example , took off at an unprecedented pace , but the subsequent phases nevertheless experienced slow-downs due to various reasons . The reasons that can slow down recruitment in stroke trials are as follows ( although the list is by no means complete ) : competing trials ; slow start ( insufficient site recruitment , unforeseen obstacles , etc ) ; more complex protocol s ; trial fatigue by investigators ; patients less willing to participate ; excessive ( though necessary or often unavoidable ) and lengthy regulatory work ; and regulatory issues with drugs and devices , their combinations , and evolving technologies . Investigators , who timely execute clinical trials , such as the recently conducted neuro-protection trial of NXY-059 ( 3 ) , identified some solutions : find new population s , particularly in Asia , Latin America , and Eastern Europe ; keep protocol s as simple as possible ; create incentives for investigators ( not necessarily financial but adequate academic recognition ) ; and public education about the need for translational research to the benefit of communities . Trials with recruitment ahead of time have often been exceptionally well funded . Although slow trials are usually less well funded , it would be nice to have solutions other than reimbursement . Recently , top recruiters in a major stroke prevention trial were asked to give a formula of their success . It turned out to be no secret and was summarized in one word : ‘ commitment ’ ( C. Estol , personal communication ) . These high-recruiting centres are well thought after by industry as well as government funding agencies . We need to train more clinical investigators and exp and the network of research stroke centres worldwide Background and Purpose — Induced hypothermia is a promising neuroprotective therapy . We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke . Methods — Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke ( ICTuS-L ) was a r and omized , multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke . Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours . Patients presenting within 3 hours of symptom onset received st and ard dose intravenous alteplase and were r and omized to undergo 24 hours of endovascular cooling to 33 ° C followed by 12 hours of controlled rewarming or normothermia treatment .  Patients presenting between 3 and 6 hours were r and omized twice : to receive tissue plasminogen activator or not and to receive hypothermia or not . Results – In total , 59 patients were enrolled . One patient was enrolled but not treated when pneumonia was discovered just before treatment . All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator . Overall , 28 patients r and omized to receive hypothermia ( HY ) and 30 to  normothermia  ( NT ) . Baseline demographics and risk factors were similar between groups . Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0 ; 32 ( 55 % ) were male . Cooling was achieved in all patients except 2 in whom there were technical difficulties . The median time to target temperature after catheter placement was 67 minutes ( Quartile 1 57.3 to Quartile 3 99.4 ) . At 3 months , 18 % of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24 % in the normothermia groups ( nonsignificant ) . Symptomatic intracranial hemorrhage occurred in 4 patients ( 68 ) ; all were treated with tissue plasminogen activator <3 hours ( 1 received hypothermia ) . Six patients in the hypothermia and 5 in the normothermia groups died within 90 days ( nonsignificant ) . Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups ( P=0.001 ) . The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score ( P=0.32 ) . Conclusion — This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis . Pneumonia was more frequent after hypothermia , but further studies are needed to determine its effect on patient outcome and whether it can be prevented . A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke Background and Purpose — The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed . Methods — We performed a r and omized controlled trial with screening , consent , r and omization , and treatment performed by paramedics prior to hospitalization . Patients with probable ultra-acute stroke ( < 4 hours ) and systolic blood pressure ( SBP ) > 140 mm Hg were r and omized to transdermal glyceryl trinitrate ( GTN ; 5 mg/24 hours ) or none ( blinding under gauze dressing ) for 7 days with the first dose given by paramedics . The primary outcome was SBP at 2 hours . Results — Of a planned 80 patients , 41 ( 25 GTN , 16 no GTN ) were enrolled > 22 months with median age [ interquartile range ] 79 [ 16 ] years ; men 22 ( 54 % ) ; SBP 168 [ 46 ] ; final diagnosis : stroke 33 ( 80 % ) and transient ischemic attack 3 ( 7 % ) .  Time to r and omization was 55 [ 75 ] minutes . After treatment with GTN versus no GTN , SBP at 2 hours was 153 [ 31 ] versus 174 [ 27 ] mm Hg , respectively , with difference −18 [ 30 ] mm Hg ( P=0.030 ) . GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [ 3 ] point ( P=0.040 ) . The rates of death , 4 ( 16 % ) versus 6 ( 38 % ; P=0.15 ) , and serious adverse events , 14 ( 56 % ) versus 10 ( 63 % ; P=0.75 ) , did not differ between GTN and no GTN . Conclusions — Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial . GTN  reduces SBP at 2 hours and seems to be safe in ultra-acute stroke . A larger trial is needed to assess whether GTN improves functional outcome . Clinical Trial Registration — URL : http://www.controlled-trials.com/IS RCT N66434824/66434824 . Unique identifier : 66434824 Successful implementation of a r and omized clinical trial ( RCT ) for neuro-vascular emergencies such as cerebral infa rct ion , intracerebral hemorrhage , or subarachnoid hemorrhage is extraordinarily challenging . Besides establishing an accurate , hyper-expedited diagnosis among many mimics in a person with acute neurological deficits , informed consent must be obtained from this vulnerable group of patients who may be unable to convey their own wishes , grasp the gravity of their situation , or give a complete history or examination . We review the influences , barriers , and factors investigators encounter when providing established and putative stroke therapies , and focus on informed consent , the most important research protector of human subjects , as the rate-limiting step for enrollment into acute stroke RCTs . The informed consent process has received relatively little attention in the stroke literature , but is especially important for stroke victims with acute cognitive , aural , lingual , motor , or visual impairments .  Consent by a surrogate may not accurately reflect the patient ’s wishes . Further , confusion about trial methodology , negative opinions of placebo-controlled studies , and therapeutic misconception by patients or surrogates may impede trial enrollment and requires further study . Exception from informed consent offers an opportunity that is rarely if ever utilized for stroke RCTs . Ultimately , advancing the knowledge base and treatment paradigms for acute stroke is essential but autonomy , beneficence ( non-malfeasance ) , and justice must also be carefully interwoven into any well- design ed RCT BACKGROUND In patients with ischemic stroke , endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy . However , comparison of the clinical efficacy of the two approaches is needed . METHODS We r and omly assigned 362 patients with acute ischemic stroke , within 4.5 hours after onset , to  endovascular therapy ( intraarterial thrombolysis with recombinant tissue plasminogen activator [ t-PA ] , mechanical clot disruption or retrieval , or a combination of these approaches ) or intravenous t-PA . Treatments were to be given as soon as possible after r and omization . The primary outcome was survival free of disability ( defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6 , with 0 indicating no symptoms , 1 no clinical ly significant disability despite symptoms , and 6 death ) at 3 months . RESULTS A total of 181 patients were assigned to receive endovascular therapy , and 181 intravenous t-PA .  The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA ( P<0.001 ) . At 3 months , 55 patients in the endovascular-therapy group ( 30.4 % 
    Output:
    
Alternatives to written informed consent in acute stroke trials may enable trial design s that would not be feasible otherwise .
However , we did not find evidence that , within traditional trial design s , such alternatives are associated with faster recruitment