***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury , but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth . This study reports a multicenter , r and omized , controlled , pilot trial of moderate systemic hypothermia ( 33 degrees C ) vs normothermia ( 37 degrees C ) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event . The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers , and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vinel and tests between normothermic and hypothermic groups . Thirty-two hypothermic and 33 normothermic neonates were enrolled . The entry criteria selected a severely affected group of neonates , with 77 % Sarnat stage III . Ten  hypothermia ( 10/32 , 31 % ) and 14 normothermia ( 14/33 , 42 % ) patients expired . Controlling for treatment group , outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers ( odds ratio 10.7 , 95 % confidence interval 1.3 - 90 ) . Severely abnormal motor scores ( Psychomotor Development Index < 70 ) were recorded in 64 % of normothermia patients and in 24 % of hypothermia patients . The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group ( 52 % ) than the normothermia group ( 84 % ) ( P = 0.019 ) . Although these results need to be vali date d in a large clinical trial , this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality .  Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials OBJECTIVE To assess the safety of selective head cooling in birth-asphyxiated term newborn infants while maintaining the rectal temperature at 35.0 degrees C or 34.5 degrees C. METHODS Twenty-six term infants with Apgar < or=6 at 5 minutes or cord/first arterial pH < 7.1 , plus evidence of encephalopathy , were studied . After parental consent had been obtained , 13 infants received selective head cooling with the rectal temperature maintained at 35.0 degrees C in 6 infants and at 34.5 degrees C in 7 infants . The remaining 13 infants were normothermic . Cooling was achieved by circulating water at 10 degrees C through a cap placed around the head . Rectal , fontanelle , and nasopharyngeal temperatures were monitored . RESULTS One cooled infant died 2 days after rewarming , and 3 control infants died . Seizures occurred in 9 (69%)of 13 cooled infants and 5 ( 38 % ) of 13 control infants . Respiratory support within the first 72 hours of life was required in 10 of 13 infants in both the cooled and control groups . Three cooled infants and 1 control infant received nitric oxide for persistent pulmonary hypertension . During the same interval , 6 of the cooled infants and 4 of the control infants had episodes in which their blood pressure fell to < 40 mm Hg ; in 2 infants in each group , the lowest blood pressure was below 35 mm Hg . No requirement for volume expansion or increased inotropic support was seen in any infant during stepwise rewarming . All of the cooled infants demonstrated a fall in heart rate during cooling , but the rate was < 80/min in only 2 cases and no infant had a rate < 70/min . No infant demonstrated an abnormal rhythm or was clinical ly compromised by the change in heart rate . One infant cooled to a rectal temperature of 34.5 degrees C had a prolonged QT interval of 570 ms associated with a heart rate of 85/min on electrocardiogram aged 34 hours . This returned to normal after rewarming . Platelet counts below 150 x 10(9)/L , hypoglycemia below 2.6 mmol/L , and highest creatinine were not statistically different between cooled and control infants . Positive precooling blood cultures were found in 1 cooled and 1 control infant . The mean cap water input temperature used during cooling was 10 + /- 1 degrees C. During active cooling , the mean difference between rectal and nasopharyngeal temperature was 1.4 degrees C in the infants who were not receiving respiratory support , but this gradient could not be measured in those who were receiving respiratory support that involved delivery of warmed gases to the nasopharynx . CONCLUSIONS This study suggests that selective head cooling combined with mild systemic hypothermia of 34.4 degrees C or 35.0 degrees C is a stable , well-tolerated method of reducing cerebral temperature in term newborn infants after perinatal asphyxia OBJECTIVE . The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy . METHODS . A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings , assigned r and omly to head cooling  for 72 hours , starting within 6 hours after birth ( with the rectal temperature maintained at 34.5 ± 0.5 ° C ) , or conventional care , were studied . Death or severe disability at 18 months of age was assessed in a multicenter , r and omized , controlled study ( the CoolCap trial ) . RESULTS . Treatment , lower encephalopathy grade , lower birth weight , greater amplitude-integrated electroencephalographic amplitude , absence of seizures , and higher Apgar score , but not gender or gestational age , were associated significantly with better outcomes . In a multivariate analysis , each of the individually predictive factors except for Apgar score remained predictive . There was a significant interaction between treatment and birth weight , categorized as ≥25th or < 25th percentile for term , such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling . For larger infants , the number needed to treat was 3.8 . Pyrexia ( ≥38 ° C ) in control infants was associated with adverse outcomes . Although there was a small correlation with birth weight , the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy . CONCLUSIONS . Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy . The protective effect of hypothermia was greater in larger infants Hypoxic-ischemic encephalopathy ( HIE ) remains one of the most important neurologic complications in the newborn . Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage . Furthermore , recent data have suggested that platelet-activating factor ( PAF ) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury . The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia . In addition , we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid ( CSF ) after hypoxic-ischemic brain injury . The group of asphyxiated infants ( Group 1 ) consisted of 21 full-term ( gestational age > 37 weeks ) . These infants were r and omized and divided into either a st and ard therapy group ( Group 1a ; n=10 ) or cooling group ( Group 1b ; n=11 ) . Head cooling combined with minimal hypothermia ( rectal temperature 36.5 - 36 degrees C ) was started as soon as practicable after birth . The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h . The control group ( Group 2 ) consisted of seven full-term infants and none of these infants showed any sign of asphyxia . To measure PAF concentration in CSF , CSF with lumbar puncture was collected into tubes immediately before the cooling ( 1 - 3h after birth ) and again after 36h . We had no evidence of severe adverse events related to hypothermia . In Group 1a , two infants died after 72h of life ; however , all newborn infants in Group 1b survived . Convulsion required treatment in three infants of st and ard therapy group ( 1a ) ; none of the infants in Group 1b had clinical seizure activity . Abnormal EEG patterns were found in four infants of Group 1a ; no EEG abnormalities were noted in Group 1b ( P<0.05 ) . On admission ( before cooling ) , PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control ( P<0.001 ) . Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups ( Group 1a vs. 1b ) ( P>0.05 ) . Obtained PAF level in CSF after 36h , showed a profound decline in cooling group of infants compared to Group 1a infants ( P<0.01 ) . In conclusion , the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging . Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants School performance testing was completed at 8 years of age on 145 children who had had neonatal encephalopathy associated with birth asphyxia as term infants and on a comparison peer group of 155 children . The prospect ively identified clinical categories of encephalopathy for the neonates were 56 mild ( hyperalertness , hyperexcitability ) , 84 moderate ( lethargy , hypotonia , suppressed primitive reflexes ) , and 5 severe ( stupor , flaccidity , absent primitive reflexes ) . The mortality rate to 8 years of age was 13 % . The incidence of impairment , which included cerebral palsy , blindness , cognitive delay , convulsive disorder , and severe hearing loss , was 16 % among those assessed at 8 years ( 75 % of survivors ) . Intellectual , visual-motor integration , and receptive vocabulary scores , as well as reading , spelling , and arithmetic grade levels for those with moderate or severe encephalopathy , were significantly below ( p less than 0.01 ) those in the mild encephalopathy or peer comparison groups . Predictors of reading performance for the study group included category of encephalopathy , birth weight for gestational age , native language , and mother 's educational level ( multiple R = 0.58 ) . Nonimpaired survivors of moderate encephalopathy were more likely to be more than one grade level delayed than were children from the peer group ( reading 35 % vs 15 % , spelling 18 % vs 8 % , arithmetic 20 % vs 12 % , p less than 0.01 ) . Thus children who had moderate and severe neonatal encephalopathy are at risk for physical and mental impairment and reduced school performance . Children with mild encephalopathy had school performance scores similar to those of their peers BACKGROUND Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia . We did a multicentre r and omised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy . METHODS 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroence 
    Output:
    
Conclusion In general , therapeutic hypothermia seems to have a beneficial effect on the outcome of term neonates with moderate to severe hypoxic ischemic encephalopathy .