***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: OBJECTIVE Intravenous ibuprofen ( IBU ) has been found to be as effective as indomethacin for the treatment of patent ductus arteriosus ( PDA ) in preterm infants and has been associated with fewer adverse effects in comparative phase III studies . The dose regimen used ( 10 - 5 - 5 mg/kg/day ) was based on limited pharmacokinetic data and no phase II study was available to determine the optimal dose of IBU for this indication . The present study was design ed to determine the minimum effective dose regimen ( MEDR ) of IBU ( one course ) required to close ductus arteriosus in preterm infants . METHOD A double-blind dose-finding study was conducted using the continual re assessment method , a Bayesian sequential design . Two distinct target closure rates were initially chosen according to postmenstrual age ( PMA ) at birth : 80 % in infants with a PMA of 27 - 29 weeks , and 50 % in infants with a PMA < 27 weeks . Forty neonates ( 20 in each PMA group ) with PDA were treated between days 3 and 5 of life . Four different dose regimens were tested : loading doses of 5 , 10 , 15 or 20 mg/kg , followed by two doses ( 1/2 loading dose ) at 24-h intervals . Efficacy was evaluated by echocardiography 24 h after the third infusion . RESULTS In infants with a PMA of 27 - 29 weeks , the estimated MEDR was 10 - 5 - 5 mg/kg with a final estimated probability of success of 77 % ( 95 % credibility interval : 56 - 92 % ) . The 15 - 7.5 - 7.5 mg/kg dose regimen had a better estimated probability of success ( 88 % , 95 % credibility interval : 68 - 97 % ) , but result ed in more minor renal adverse effects . In contrast , in infants with a PMA < 27 weeks , the estimated MEDR was 20 - 10 - 10 mg/kg with an estimated probability of success of 54.8 % ( 95 % credibility interval : 22 - 84 % ) , whereas the conventional dose regimen result ed in a low estimated probability of success ( 30.6 % , 95 % credibility interval : 13 - 56 % ) . In these infants , compared with those with a PMA of 27 - 29 weeks , minor renal adverse effects were more frequent from the 10 - 5 - 5 mg/kg/day dose regimen and did not appear to be clearly dose related . CONCLUSION This study confirms that the currently recommended dose regimen ( 10 - 5 - 5 mg/kg ) of IBU is associated with a high closure rate ( 80 % ) and few adverse effects in premature infants with a PMA of 27 - 29 weeks . The failure rate was much higher below 27 weeks . A higher dose regimen ( 20 - 10 - 10 mg/kg ) might achieve a higher closure rate . However , tolerability and safety of this dose regimen should be assessed in a larger population before considering the use of these doses for ductus arteriosus closure Dexamethasone was compared with placebo in a double-blind , crossover , r and omised study of infants with severe bronchopulmonary dysplasia who had required mechanical ventilation for at least four weeks , despite treatment with diuretics , methylxanthines , bronchodilators , fluid restriction , nutritional supplementation , and ligation of the patent ductus arteriosus when indicated . Gestational age ranged from 27 to 33 weeks and birth weight from 800 to 1730 g. Patients received dexamethasone ( 0 . 5 mg/kg/day ) or normal saline for the first 3 days , then treatment was crossed over for the next 3 days . The study was terminated when sequential analysis showed that all six patients had improved during dexamethasone therapy . Significant improvements were seen in ventilator-determined respiratory rate , peak inspiratory pressure , fractional inspired oxygen concentration , and alveolar arterial oxygen gradients ( p less than 0 . 05 ) . Although dexamethasone hastened weaning from mechanical ventilation , infection occurred in a substantial proportion of patients Background — Complex neonatal cardiac surgery is associated with cerebral injury . In particular , aortic arch repair , requiring either deep hypothermic circulatory arrest ( DHCA ) or ante grade cerebral perfusion ( ACP ) , entails a high risk of perioperative injury . It is unknown whether ACP results in less cerebral injury than DHCA . Methods and Results — Thirty-seven neonates with an aortic arch obstruction presenting for univentricular or biventricular repair were r and omized to either  DHCA or ACP . Preoperatively and 1 week after surgery , magnetic resonance imaging was performed in 36 patients ( 1 patient died during the hospital stay ) . The presence of new postoperative cerebral injury was scored , and results were entered into a sequential analysis , which allows for immediate data analysis . After the 36th patient , it was clear that there was no difference between DHCA and ACP in terms of new cerebral injury . Preoperatively , 50 % of patients had evidence of cerebral injury . Postoperatively , 14 of 18 DHCA patients ( 78 % ) had new injury versus 13 of 18 ACP patients ( 72 % ) ( P=0.66 ) . White matter injury was the most common type of injury in both groups , but central infa rct ions occurred exclusively after ACP ( 0 vs 6/18 [ 33 % ] ; P=0.02 ) . Early motor and cognitive outcomes at 24 months were assessed and were similar between groups ( P=0.28 and P=0.25 , respectively ) . Additional analysis revealed lower postoperative arterial PCO2 as a risk factor for new white matter injury ( P=0.04 ) . Conclusions — In this group of neonates undergoing complex cardiac surgery , we were unable to demonstrate a difference in the incidence of perioperative cerebral injury after ACP compared with DHCA . Both techniques result ed in a high incidence of new white matter injury , with central infa rct ions occurring exclusively after ACP . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01032876 Two different ventilation techniques were compared in a seven-centre , r and omised trial with 181 preterm infants up to and including 32 completed weeks gestational age , who needed mechanical ventilation because of lung disease of any type . Technique A used a constant rate ( 60 cycles/min ) , inspiratory time ( IT ) ( 0.33s ) and inspiratory : expiratory ratio ( I∶E ) ( 1∶2 ) . The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure . Technique B used a lower rate ( 30 cycles/min ) with longer IT ( 1.0s ) . The I∶E ratio could be changed from 1∶1 to 2∶1 in case of hypoxaemia . Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients . A reduction of at least 20 % in extra-alveolar air leakage ( EAL ) or death prior to EAl was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis . The null hypothesis was rejected ( P=0.05 ) when the 22nd untied pair was completed . The largest reduction in EAL ( −55 % ) was observed in the subgroup 31–32 weeks of gestation and none in the most immature group ( < 28 weeks ) . We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency , ventilation at 60 cycles/min and short IT ( 0.33s ) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1s . We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants A r and omized trial was conducted of dexamethasone therapy in infants with bronchopulmonary dysplasia who were dependent on respirators and were not progressing clinical ly despite conventional treatment . Babies were admitted to the study if they had a roentgenogram and clinical diagnosis of bronchopulmonary dysplasia , were 2 to 6 weeks in age , weighed less than 1,500 g , had made no progress in weaning for the preceding five days , and were free of sepsis , patent ductus arteriosus , and congenital heart disease , and had had no intravenous fat for at least 24 hours . After parental consent was obtained , infants were r and omly assigned to control or treatment groups . The study hypothesis was that with steroid treatment , babies could be weaned from the respirator within 72 hours and would show a significant improvement in lung compliance within that time . Sequential analysis exceeded criterion ( P less than .05 ) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants . Pulmonary compliance improved by 64 % in the treated group and 5 % in the control group ( P less than .01 ) . No significant intergroup differences were noted in mortality , length of hospital stay , sepsis , hypertension , hyperglycemia , or electrolyte abnormalities . Study design permits the conclusion that dexamethasone can produce substantial short-term improvement in lung function , often permitting rapid weaning from the respirator , but long-term efficacy and safety must be demonstrated by further investigations BACKGROUND Hyperbilirubinemia in new-borns with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency is a serious clinical problem because of the severity and unpredictability of its course . An innovative approach to this problem is suggested by previous experience with Sn-mesoporphyrin ( SnMP ) , a potent inhibitor of bilirubin production , in moderating neonatal hyperbilirubinemia caused by ABO incompatibility , immaturity , and unspecified mechanisms . OBJECTIVE To compare the effectiveness of the preventive and therapeutic uses of SnMP in ameliorating the course of bilirubinemia of G6PD-deficient neonates . METHODS Neonates born at the Metera Maternity Hospital , Athens , Greece , and found to be G6PD-deficient by cord blood testing were stratified by sex and gestational age ( 210 - 265 days and > 265 days ) and r and omized in pairs to receive SnMP ( 6 micromol/kg birth weight , intramuscularly ) either on the first day of life ( preventive use ) or if and when the plasma bilirubin concentration ( PBC ) level reached an age-specific threshold level for intervention ( therapeutic use ) . In the case of failure of SnMP to control the rise of PBC levels , the protocol defined precisely the threshold PBC levels for switchover to phototherapy ( PT ) and , if necessary , exchange transfusion .  PBC was measured daily until a declining value was obtained and the case was closed . RESULTS A total of 86 G6PD-deficient neonates were r and omized : 42 in the preventive arm and 44 in the therapeutic arm . Of the latter , 20 ( 45 % ) reached PBC levels requiring therapeutic intervention and thus received SnMP . Regardless of the trial arm , none of the 86 neonates required PT , whereas in a previous study in the same population , 33 % of G6PD-deficient neonates required PT . In the intrapair sequential analysis , the favored arm was decided on the criterion of the age at closure of the case being shorter by at least 1 day . After plotting 30 untied pairs in the sequential analysis graph , the preventive use of SnMP proved to be the favored arm , and the trial was stopped . At this point , there were 2 unpaired neonates , 12 tied pairs , 22 pairs in which the preventive use of SnMP was favored and 8 pairs in which the therapeutic use of SnMP was favored . In the group analysis , infants in the preventive group , compared with those in the therapeutic group , had a lower maximum PBC level ( 8.2 + /- 3.1 and 10.9 + /- 2.8 mg/dL , respectively ) , which was reached at an earlier age ( 63.5 + /- 34.8 and 82.2 + /- 24.7 hours , respectively ) as well as a lower closing PBC level ( 7.2 + /- 2.9 and 9.6 + /- 2.5 mg/dL , respectively ) and an earlier age at closing ( 89.1 + /- 35.6 and 110.8 + /- 23.6 hours , respectively ) . Moreover , a PBC level of > /=8.0 mg/dL , a level at which jaundice is clearly visible , was not reached by 52 % of the neonates in the preventive arm and 16 % of the neonates in the therapeutic arm . CONCLUSIONS In G6PD-deficient neonates , a single dose of SnMP administered preventively or therapeutically entirely supplanted the need for PT to control hyperbilirubinemia . The preventive use of SnMP offers practical advantages in population s with a high enough prevalence of G6PD deficiency to justify cord blood screening ( 1 ) Phenobarbitone in a dose of 8 mg/kg per day was given in twice-daily intramus 
    Output:
    
They might potentially be able to reduce the number of patients in drug trials , although this is not always the case .