***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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    ***EXAMPLES*** 
    Input: Background Early rapid fluid resuscitation ( boluses ) in African children with severe febrileillnesses increases the 48-hour mortality by 3.3 % compared with controls ( nobolus ) . We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment , hemodynamic changes over the first hour , and on different modes of death , according to terminal clinical events . We hypothesizethat boluses may cause excess deaths from neurological or respiratory eventsrelating to fluid overload . Methods Pre-defined presentation syndromes ( PS ; severe acidosis or severe shock , respiratory , neurological ) and predominant terminal clinical events(cardiovascular collapse , respiratory , neurological ) were described by r and omizedarm ( bolus versus control  ) in 3,141 severely ill febrile children with shockenrolled in the Fluid Expansion as Supportive Therapy ( FEAST ) trial . L and markanalyses were used to compare early mortality in treatment groups , conditional onchanges in shock and hypoxia parameters . Competing risks methods were used toestimate cumulative incidence curves and sub-hazard ratios to compare treatmentgroups in terms of terminal clinical events . Results Of 2,396 out of 3,141 ( 76 % ) classifiable participants , 1,647 ( 69 % ) had a severemetabolic acidosis or severe shock PS , 625 ( 26 % ) had a respiratory PS and 976(41 % ) had a neurological PS , either alone or in combination . Mortality wasgreatest among children fulfilling criteria for all three PS ( 28 % bolus , 21%control ) and lowest for lone respiratory ( 2 % bolus , 5 % control ) or neurological(3 % bolus , 0 % control ) presentations . Excess mortality in bolus arms versuscontrol was apparent for all three PS , including all their component features . Byone hour , shock had resolved ( responders ) more frequently in bolus versus controlgroups ( 43 % versus 32 % , P < 0.001 ) , but excess mortality with boluseswas evident in responders ( relative risk 1.98 , 95 % confidence interval 0.94 to4.17 , P = 0.06 ) and ' non-responders ' ( relative risk 1.67 , 95 % confidenceinterval 1.23 to 2.28 , P = 0.001 ) , with no evidence of heterogeneity(P = 0.68 ) . The major difference between bolus and control arms wasthe higher proportion of cardiogenic or shock terminal clinical events in bolusarms ( n = 123 ; 4.6 % versus 2.6 % , P = 0.008 ) rather than respiratory ( n = 61 ; 2.2 % versus 1.3 % , P = 0.09 ) or neurological ( n = 63 , 2.1 % versus1.8 % , P = 0.6 ) terminal clinical events . Conclusions Excess mortality from boluses occurred in all subgroups of children . Contrary toexpectation , cardiovascular collapse rather than fluid overload appeared tocontribute most to excess deaths with rapid fluid resuscitation . These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and are- appraisal of the rate , composition and volume of resuscitation fluids . Trial registration IS RCT BACKGROUND New antimicrobials or adjunctive treatments have not substantially reduced mortality from acute childhood bacterial meningitis .  Paracetamol seems to have beneficial effects in bacteraemic adults and some experts recommend initial slow β-lactam infusion . We investigated whether these treatments had benefits in children with bacterial meningitis . METHODS We did a prospect i ve , double-blind , single-centre study with a two-by-two factorial design in Lu and a , Angola . 723 participants aged 2 months to 13 years were r and omly assigned two 12 h intravenous infusions , without loading doses , of 125 mg/kg bodyweight cefotaxime ( total dose 250 mg/kg ) given over 24 h , or 250 mg/kg bodyweight cefotaxime given as four boluses , one every 6 h over 24 h. Patients also received oral paracetamol at an initial dose of 30 mg/kg then 20 mg/kg every 6 h for 48 h or placebo . Two primary endpoints , death or severe neurological sequelae and deafness , were analysed by intention to treat . The study was registered as IS RCT N62824827 . FINDINGS 183 patients were assigned cefotaxime infusion plus paracetamol and 180 patients to each of the other three treatment groups . Causative agents were identified in 63 % of cases and were mostly Haemophilus influenzae type b , Streptococcus pneumoniae , or Neisseria meningitidis . Death or severe neurological sequelae were seen in 340 ( 47 % ) of 723 children and deafness in 45 ( 12 % ) of 374 tested , both distributed similarly across treatment groups . In a predefined subgroup analysis of death or any sequelae , by causative agent , a benefit was seen in favour of infusion over bolus in children with pneumococcal meningitis  ( infusion plus placebo , odds ratio 0·18 , 95 % CI 0·03 - 0·90 , p=0·04 ) . A similar effect was seen for children receiving cefotaxime infusion plus paracetamol , but the difference was not significant ( OR 0·22 , 95 % CI 0·04 - 1·09 , p=0·06 ) . A post-hoc analysis suggested that cefotaxime infusion plus paracetamol  lowered mortality at least during the first 3 days , irrespective of cause . INTERPRETATION Although no tested regimen improved the final outcomes of these very ill children , studies of longer courses of β-lactam infusion plus paracetamol seem warranted . FUNDING The Päivikki and Sakari Sohlberg , the Sigrid Jusélius , and the Paediatric Research Foundations , and the daily newspaper Helsingin Sanomat A prospect i ve study of bacterial meningitis in children was initiated two years ago . Serum sodium concentrations below 135 MEQ/liter were noted on admission in 72 of 124 ( 58.1 % ) of patients enrolled in the study protocol . Low initial serum sodium concentration and prolonged depression in serum sodium despite fluid restriction correlated significanly ( P less than 0.001 to 0.01 ) with the presence of neurologic sequelae of the disease . Inappropriate secretion of antidiuretic hormone as the cause of these electrolyte changes could be inferred by indirect measurement of serum and urine solute and volume data and was specifically documented , in patients enrolled most recently , by specific radioimmunoassay of antidiuretic hormone Introduction Early administration of antibiotics for sepsis , and of fluid boluses and vasoactive agents for septic shock , is recommended . Evidence for this in children is limited . Methods The Alberta Sepsis Network prospect ively enrolled eligible children admitted to the Pediatric Intensive Care Unit ( PICU ) with sepsis from 04/2012 - 10/2014 . Demographics , severity of illness , and outcomes variables were prospect ively entered into the ASN data base after deferred consent . Timing of interventions were determined by retrospective chart review using a study manual and case-report-form . We aim ed to determine the association of intervention timing and outcome in children with sepsis . Univariate ( t-test and Fisher ’s Exact ) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay ( LOS ) and ventilation days . Results Seventy-nine children , age median 60 ( IQR 22–133 ) months , 40 ( 51 % ) female , 39 ( 49 % ) with severe underlying co-morbidity , 44 ( 56 % ) with septic shock , and median PRISM-III 10.5 [ IQR 6.0 - 17.0 ] were enrolled . Most patients presented in an ED :  36 ( 46 % ) at an outlying hospital ED , and 21 ( 27 % ) at the Children ’s Hospital ED . Most infections were pneumonia with/without empyema ( 42 , 53 % ) , meningitis ( 11 , 14 % ) , or bacteremia ( 10 , 13 % ) . The time from presentation to acceptable antibiotic administration was a median of 115.0 [ IQR 59.0 - 323.0 ] minutes ; 20 ( 25 % ) of patients received their antibiotics in the first hour from presentation . Independent predictors of PICU LOS were PRISM-III , and severe underlying co-morbidity , but not time to antibiotics . In the septic shock subgroup , the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS ( effect size 0.22 days ; 95 % CI 0.5 , 0.38 ; per ml/kg ) . Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity . In the septic shock subgroup , volume of fluid boluses in the first 2 hours was independently associated with more ventilator days ( effect size 0.09 days ; 95 % CI 0.02 , 0.15 ; per ml/kg ) . Conclusion Higher volume of early fluid boluses in children with sepsis and septic shock was independently associated with longer PICU LOS and ventilator days . More study on the benefits and harms of fluid bolus therapy in children are needed Abstract Objective : To describe important sequelae occurring among a cohort of children aged 5 years who had had meningitis during the first year of life and who had been identified by a prospect i ve national study of meningitis in infancy in Engl and and Wales between 1985 and 1987 . Design : Follow up question naires asking about the children 's health and development were sent to general practitioners and parents of the children and to parents of matched controls . The organism that caused the infection and age at infection were also recorded . Setting : Engl and and Wales . Participants : General practitioners and parents of children who had had meningitis before the age of 1 year and of matched controls . Main outcome measures : The prevalence of health and developmental problems and overall disability among children who had had meningitis compared with controls . Results : Altogether , 1584 of 1717 ( 92.2 % ) children who had had meningitis and 1391 of 1485 ( 93.6 % ) controls were successfully followed up . Among children who survived to age 5 years 247 of 1584 ( 15.6 % ) had a disability ; there was a 10-fold increase in the risk of severe or moderate disability at 5 years of age among children who had had meningitis ( relative risk 10.3 , 95 % confidence interval 6.7 to 16.0 , P<0.001 ) . There was considerable variation in the rates of severe or moderate disability in children infected with different organisms . Conclusion : The long term consequences of having meningitis during the first year of life are significant : 32 of 1717 ( 1.8 % ) children died within five years . Not only did almost a fifth of children with meningitis have a permanent , severe or moderately severe disability , but subtle deficits were also more prevalent . What is already known on this topic Meningitis in infancy is associated with important long term consequences There is considerable variation in outcome depending on which organism caused the infection What this study adds This follow up study of 1717 children who had meningitis in infancy found that they had a 10-fold increase in risk of severe or moderate disabilities at age 5 years compared with children in the control group The outcome of having meningitis was associated with the age at infection , and children who had meningitis in the neonatal period were more likely to have health and development problems than those older than 1 month Subtle deficits , such as middle ear disease and visual and behavioural problems , were more prevalent among children who had had meningitis in We hypothesized that plasma arginine vasopressin ( AVP ) concentrations in children with meningitis are appropriate for the children 's degree of hypovolemia , even though the concentrations were higher than expected for the serum osmolality . A r and omized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours . Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours . Nineteen children , 2 months to 17 years of age , were studied ; 13 had bacterial meningitis ( 12 with Haemophilus influenzae type b ) . Ten children ( seven with bacterial meningitis ) received a mean of 1.42 times the calculated maintenance fluid requirements , and nine ( six with bacterial meningitis ) were restricted to a mean of 0.65 times maintenance . Children in the maintenance group also received significantly more sodium ( mean = 6.3 mEq/kg/24 hr ) than children in the fluid-restricted group ( mean = 2.0 mEq/kg/24 hr ) . The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun . The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction ( p = 0.005 ) , and the change in AVP concentration correlated with the amount of sodium given ( p less than 0.02 ) 
    Output:
    
There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis