***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: During the National Neurotrauma Symposium 2010 , the DG Research of the European Commission and the National Institutes of Health/National Institute of Neurological Disorders and Stroke ( NIH/NINDS ) organized a workshop on  comparative effectiveness research  ( CER ) in traumatic brain injury ( TBI ) . This workshop review ed existing approaches to improve outcomes of TBI patients . It had two main outcomes : First , it initiated a process of re-orientation of clinical research in TBI . Second , it provided ideas for a potential collaboration between the European Commission and the NIH/NINDS to stimulate research in TBI . Advances in provision of care for TBI patients have result ed from observational studies , guideline development , and meta-analyses of individual patient data . In contrast , r and omized controlled trials have not led to any identifiable major advances . Rigorous protocol s and tightly selected population s constrain generalizability . The workshop addressed additional research approaches , summarized the greatest unmet needs , and highlighted priorities for future research . The collection of high- quality clinical data bases , associated with systems biology and CER , offers substantial opportunities . Systems biology aims to identify multiple factors contributing to a disease and addresses complex interactions . Effectiveness research aims to measure benefits and risks of systems of care and interventions in ordinary setting s and broader population s. These approaches have great potential for TBI research . Although not new , they still need to be introduced to and accepted by TBI research ers as instruments for clinical research . As with therapeutic targets in individual patient management , so it is with research tools : one size does not fit all Background Severe traumatic brain injury ( TBI ) has been increasing with greater incidence of injuries from traffic or sporting accidents . Although there are a number of animal models of TBI using progesterone for head injury , the effects of progesterone on neurologic outcome of acute TBI patients remain unclear . The aim of the present clinical study was to assess the longer-term efficacy of progesterone on the improvement in neurologic outcome of patients with acute severe TBI . Methods A total of 159 patients who arrived within 8 hours of injury with a Glasgow Coma Score ≤ 8 were enrolled in the study . A prospect i ve , r and omized , placebo-controlled trial of progesterone was conducted in the Neurotrauma Center of our teaching hospital . The patients were r and omized to receive either progesterone or placebo . The primary endpoint was the Glasgow Outcome Scale score 3 months after brain injury . Secondary efficacy endpoints included the modified Functional Independence Measure score and mortality . In a follow-up protocol at 6 months , the Glasgow Outcome Scale and the modified Functional Independence Measure scores were again determined . Results Of the 159 patients r and omized , 82 received progesterone and 77 received placebo .  The demographic characteristics , the mechanism of injury , and the time of treatment were compared for the two groups . After 3 months and 6 months of treatment , the dichotomized Glasgow Outcome Scale score analysis exhibited more favorable outcomes among the patients who were given progesterone compared with the control individuals ( P = 0.034 and P = 0.048 , respectively ) . The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up ( P < 0.05 and P < 0.01 ) . The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up ( P < 0.05 ) . The mean intracranial pressure values 72 hours and 7 days after injury were lower in the progesterone group than in the placebo group , but there was no statistical significance between the two groups ( P > 0.05 ) . Instances of complications and adverse events associated with the administration of progesterone were not found . Conclusion Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months . These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug . Trial Registration ACTRN12607000545460 Background : Pre clinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage ( ICH ) ; however , gonadal hormones have sex-specific effects . Therefore , an experimental model of ICH was used to assess recovery after progesterone administration in male and female rats . Methods : ICH was induced in male and female Wistar rats via stereotactic intrastriatal injection of clostridial collagenase ( 0.5 U ) . Animals were r and omized to receive vehicle or 8 mg/kg progesterone intraperitoneally at 2 h , then subcutaneously at 5 , 24 , 48 , and 72 h after injury . Outcomes included relevant physiology during the first 3 h , hemorrhage and edema evolution over the first 24 h , proinflammatory transcription factor and cytokine regulation at 24 h , rotarod latency and neuroseverity score over the first 7 days , and microglial activation/macrophage recruitment at 7 days after injury . Results : Rotarod latency ( p = 0.001 ) and neuroseverity score ( p = 0.01 ) were improved in progesterone-treated males , but worsened in progesterone-treated females ( p = 0.028 and p = 0.008 , respectively ) . Progesterone  decreased cerebral edema ( p = 0.04 ) , microglial activation/macrophage recruitment ( p < 0.001 ) , and proinflammatory transcription factor phosphorylated nuclear factor-κB p65 expression ( p = 0.0038 ) in males but not females , independent of tumor necrosis factor-α , interleukin-6 , and toll-like receptor-4 expression . Cerebral perfusion was increased in progesterone-treated males at 4 h ( p = 0.043 ) but not 24 h after injury . Hemorrhage volume , arterial blood gases , glucose , and systolic blood pressure were not affected . Conclusions : Progesterone administration improved early neurobehavioral recovery and decreased secondary neuroinflammation after ICH in male rats . Paradoxically , progesterone  worsened neurobehavioral recovery and did not modify neuroinflammation in female rats . Future work should isolate mechanisms of sex-specific progesterone effects after ICH BACKGROUND Traumatic brain injury ( TBI ) is a major cause of death and disability worldwide . Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI . METHODS We conducted a double-blind , multicenter clinical trial in which patients with severe , moderate-to-severe , or moderate acute TBI ( Glasgow Coma Scale score of 4 to 12 , on a scale from 3 to 15 , with lower scores indicating a lower level of consciousness ) were r and omly assigned to intravenous progesterone or placebo , with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours . Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome , as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury . Secondary outcomes included mortality and the Disability Rating Scale score . RESULTS A total of 882 of the planned sample of 1140 patients underwent r and omization before the trial was stopped for futility with respect to the primary outcome . The study groups were similar with regard to baseline characteristics ; the median age of the patients was 35 years , 73.7 % were men , 15.2 % were black , and the mean Injury Severity Score was 24.4 ( on a scale from 0 to 75 , with higher scores indicating greater severity ) . The most frequent mechanism of injury was a motor vehicle accident . There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome ( relative benefit of progesterone , 0.95 ; 95 % confidence interval [ CI ] , 0.85 to 1.06 ; P=0.35 ) . Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group ( relative risk , 3.03 ; CI , 1.96 to 4.66 ) . There were no significant differences in the other prespecified safety outcomes . CONCLUSIONS This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI . ( Funded by the National Institute of Neurological Disorders and Stroke and others ; PROTECT III Clinical Trials.gov number , NCT00822900 . ) Traumatic brain injury ( TBI ) is one of the leading causes of injury-related death . In the United States alone , an estimated 1.7 million people sustain a TBI each year , and approximately 5.3 million people live with a TBI-related disability . The direct medical costs and indirect costs such as lost productivity of TBIs totaled an estimated $ 76.5 billion in the U.S. in the year 2000 . Improving the limited treatment options for this condition remains challenging . However , recent reports from interdisciplinary working groups ( consisting primarily of neurologists , neurosurgeons , neuropsychologists , and biostatisticians ) have stated that to improve TBI treatment , important method ological lessons from the past must be taken into account in future clinical research . An evaluation of the neuroprotection intervention studies conducted over the last 30 years has indicated that a limited underst and ing of the underlying biological concepts and method ological design flaws are the major reasons for the failure of pharmacological agents to demonstrate efficacy . Cerebrolysin is a parenterally-administered neuro-peptide preparation that acts in a manner similar to endogenous neurotrophic factors . Cerebrolysin has a favorable adverse effect profile , and several meta-analyses have suggested that Cerebrolysin is beneficial as a dementia treatment . CAPTAIN is a r and omized , double-blind ,  placebo-controlled , multi-center , multinational trial of the effects of Cerebrolysin on neuroprotection and neurorecovery after TBI using a multidimensional ensemble of outcome scales . The CAPTAIN trial will be the first TBI trial with a ' true ' multidimensional approach based on full outcome scales , while avoiding prior weaknesses , such as loss of information through " dichotomization , " or unrealistic assumptions such as " normal distribution . OBJECTIVE Severe traumatic brain injury ( TBI ) has a major role in mortality rate among the other types of trauma . The aim of this clinical study was to assess the effect of progesterone on the improvement of neurologic outcome in patients with acute severe TBI . METHODS A total of 76 patients who had arrived within 8h of injury with a Glasgow Coma Score≤8 were enrolled in the study . In a r and omized style 38 received progesterone ( 1mg/kg per 12h for 5 days ) and 38 did not . RESULTS There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period ( 50 % vs. 21 % ) ; subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5 - 8 ( p=0.03 ) . CONCLUSION The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury , especially those with 5≤GCS≤8 , providing a potential benefit to the treatment of acute severe TBI patients . Considering this drug had no significant side effects , so progesterone could be used in patients with severe TBI as a neuro-protective drug Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale ( GOSE ) as the primary outcome for traumatic brain injury ( TBI ) trials . We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures . Using data from a r and omized trial , we created a " super " data set of 16,550 subjects from patients with complete data ( n=331 ) and then simulated multiple treatment effects across multiple outcome measures . Patients were sample d with replacement ( bootstrapping ) to generate 10,000 sample s for each treatment effect ( n=400 patients /group ) . The percentage of sample s where the null hypothesis was rejected estimates the power . All analytic techniques had appropriate rates of type I error ( ≤5 % ) . Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis . Analyzing GOSE using multivariate proportional odds regression or analyzing the four- outcome battery with regression-based adjustments had the highest power , assuming equal treatment effect across all components . Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses . We assumed an equal treatment effect for all measures . This may not be true in an actual clinical trial . Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials . The choice of primary outcome for future trials should be guided by power , the domain of brain function that an intervention is likely to impact , and the feasibility of collecting outcome data STUDY OBJECTIVE Laboratory evidence indicates that progesterone has potent neuroprotective effects . We conducted a pilot clinical trial to assess the safety and potential benefit of administering progesterone to patients with acute traumatic brain injury . METHODS This phase II , r and omized , double-blind , placebo-controlled trial was conducted at an urban Level I trauma center . One hundred adult trauma patients who arrived within 11 hours of injury 
    Output:
    
This up date d review did not find evidence that progesterone could reduce mortality or disability in patients with TBI .