***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: AIM ( S ) Little is known about the pharmacokinetic ( PK ) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia . This study prospect ively evaluates and describes the population PK of gentamicin in these patients METHODS Demographic , clinical and laboratory data of patients included in a multicentre prospect i ve observational cohort study ( the ‘ PharmaCool Study ’ ) were collected . A non-linear mixed-effects regression analysis ( nonmem ® ) was performed to describe the population PK of gentamicin . The most optimal dosing regimen was evaluated based on simulations of the final model . RESULTS A total of 47 patients receiving gentamicin were included in the analysis . The PK were best described by an allometric two compartment model with gestational age ( GA ) as a covariate on clearance ( CL ) . During hypothermia the CL of a typical patient ( 3 kg , GA 40 weeks , 2 days post-natal age ( PNA ) ) was 0.06 l kg−1 h−1 ( inter-individual variability ( IIV ) 26.6 % ) and volume of distribution of the central compartment ( Vc ) was 0.46 l kg−1 ( IIV 40.8 % ) . CL was constant during hypothermia and rewarming , but increased by 29 % after reaching normothermia ( > 96 h PNA ) . CONCLUSIONS This study describes the PK of gentamicin in neonates undergoing controlled hypothermia . The 29 % higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred . Based on simulations we recommend an empiric dose of 5 mg kg−1 every 36 h or every 24 h for patients with GA 36–40 weeks and GA 42 weeks , respectively In an examination of the relationships among plasma aminoglycoside concentrations , the minimal inhibitory concentration ( MIC ) for the infecting organism , and therapeutic outcome , data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin , tobramycin , and amikacin .  Clinical response to therapy occurred in 188 ( 80 % ) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response ( P less than .00001 and P less than .0001 , respectively ) . A grade d dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy A prospect i ve case controlled study was conducted in the NICU of a tertiary level referral teaching hospital to determine the incidence of renal failure in asphyxiated neonates and to correlate severity and type of renal failure with Apgar score and hypoxic ischemic encephalopathy ( HIE ) grading of the neonates . Ninety-eight neonates were enrolled 70 asphyxiated babies and 28 healthy controls .  Renal functions were assessed using urinary output , urine microscopy , biochemical parameters and sonographic findings .  Babies having renal failure were managed on a protocol ised plan and followed up till 6 months of age to detect any residual impairment . Blood urea and serum creatinine were significantly higher in asphyxiated babies compared to the control group . Biochemical derangements correlated well with HIE staging and Apgar scores . There was no significant difference in urine output in the control and the study group as significant oliguria was seen in only 7 of the 70 asphyxiated babies and the output did not correlate with severity of asphyxia . Serum sodium level and fractional excretion of sodium showed significantly different values in the asphyxiated babies compared to control . Of the 70 asphyxiated babies 33 ( 47.1 % ) had renal failure , which was of the non-oliguric type in 78 % cases and oliguric type in 22 % cases . Sonographic abnormalities were seen more often in oliguric babies and was associated with a bad prognosis . Renal parameters normalized in all neonates by 6 months of age . Mortality was higher in babies with oliguric renal failure . We conclude that renal failure is a significant problem in asphyxiated neonates with majority of babies having nonoliguric failure . Severity of renal function abnormality correlates well with degree of asphyxia . Oliguria , hyponatremia and abnormal sonographic scan are bad prognostic signs in renal failure secondary to birth asphyxia Abstract Background and objective : Preterm and term newborn infants show wide interindividual variability ( IIV ) in pharmacokinetic parameters of gentamicin . More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concentration monitoring . This study was performed to characterize the population pharmacokinetics of gentamicin in preterm and term neonates and to identify and quantify relationships between patient characteristics and IIV . A secondary aim was to evaluate cystatin C as a marker for gentamicin clearance in this patient population . Methods : Data were collected in a prospect i ve study performed in the Neonatal Intensive Care Unit at the University Children ’s Hospital , Uppsala , Sweden . Population pharmacokinetic modelling was performed using nonlinear mixed-effects modelling ( NONMEM ) software . Bodyweight was included as the primary covariate according to an allometric power model . Other evaluated covariates were age ( postmenstrual age , gestational age [ GA ] , postnatal age [ PNA ] ) , markers for renal function ( serum creatinine , serum cystatin C ) and concomitant medication with cefuroxime , vancomycin or indometacin . Covariate-parameter relationships were explored using a stepwise covariate model building procedure . The predictive performance of the developed model was evaluated using an independent external data set for a similar patient population . Results : Sixty-one newborn infants ( GA range 23.3–42.1 weeks , PNA range 0–45 days ) were enrolled in the study . In total , 894  serum gentamicin sample s were included in the analysis . The concentration-time profile was described using a three-compartment model . Gentamicin clearance increased with the GA and PNA ( included in a nonlinear fashion ) . The GA was also identified as having a significant influence on the central volume of distribution , with a preterm neonate having a larger central volume of distribution per kilogram of bodyweight than a term neonate . Cystatin C and creatinine were not correlated with gentamicin clearance in this study population . The external data set was well predicted by the developed model . Conclusion : Bodyweight and age ( GA and PNA ) were found to be major factors contributing to IIV in gentamicin clearance in neonates . Based on these data , cystatin C and serum creatinine were not correlated with gentamicin clearance and therefore not likely to be predictive markers of renal function in this patient population . Based on predictions from the developed model , preterm neonates do not reach targeted peak and trough gentamicin concentrations after a st and ard dosage regimen of 4 mg/kg given once daily , suggesting a need for higher loading doses and prolonged dosing intervals in this patient population OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required OBJECTIVE To define the incidence of hearing impairment , document plasma gentamicin concentrations , and identify factors associated with permanent hearing impairment in infants subjected to therapeutic hypothermia for moderate or severe neonatal encephalopathy . STUDY DESIGN Data were collected prospect ively in a regional center providing therapeutic hypothermia . Cooled infants at ≥ 36 weeks gestation with moderate or severe neonatal encephalopathy were analyzed if a full data set was available ( n = 108 ) , including clinical variables and gentamicin trough levels . Infants with hearing impairment were identified , and survivors were followed up with neurodevelopmental evaluation at age 18 months . Stepwise logistic regression identified factors associated with hearing impairment . RESULTS Nine infants died , and among the survivors , 10.1 % developed a permanent hearing impairment . The trough gentamicin level was above the recommended cutoff of 2 mg/L in 37 % of the infants in the entire cohort and in 90 % of the infants with hearing impairment . Logistic regression analysis identified high trough gentamicin level , low cord pH , and hypoglycemia ( < 46.8 mg/dL ) in the first postnatal hour as significantly associated with hearing impairment . The need for inotropic support was close to significant ( P = .055 ) . CONCLUSION Hearing impairment was a common finding among cooled infants . Plasma gentamicin levels were commonly > 2 mg/L. Based on these findings , we propose changes in gentamicin dosing interval and trough level monitoring to minimize the risk of potentially toxic levels in cooled newborns Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospect i ve , r and omized , double-blind trial . One hundred forty-six patients received nine or more doses , had serial determinations of serum creatinine , and were evaluated for nephrotoxicity ; 91 were able to cooperate with audiometry and were evaluated for auditory toxicity .  Auditory toxicity developed in five of 47 ( 10 per cent ) given gentamicin and five of 44 ( 11 per cent ) given tobramycin .  Nephrotoxicity developed in 19 of 72 ( 26 per cent ) given gentamicin and nine of 74 ( 12 per cent ) given tobramycin ( P less than 0.025 ) . The severity of the nephrotoxicity was not different ; the mean increase in creatinine was 1.3 mg per 100 ml ( 114.9 mumol per liter ) in both groups . Both the tobramycin and gentamicin groups had a similar mean age , initial serum creatinine level , total dose , serum aminoglycoside level , and duration of therapy . We conclude that tobramycin causes nephrotoxicity less frequently than does gentamicin BACKGROUND Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain . METHODS We performed a r and omized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy . We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone . The primary outcome was death or severe disability at 18 months of age . Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes . RESULTS Of 325 infants enrolled , 163 underwent intensive care with cooling , and 162 underwent intensive care alone . In the cooled group , 42 infants died and 32 survived but had severe neurodevelopmental disability , whereas in the noncooled group , 44 infants died and 42 had severe disability ( relative risk for either outcome , 0.86 ; 95 % confidence interval [ CI ] , 0.68 to 1.07 ; P=0.17 ) . Infants in the cooled group had an increased rate of survival without neurologic abnormality ( relative risk , 1.57 ; 95 % CI , 1.16 to 2.12 ; P=0.003 ) . Among survivors , cooling result ed in reduced risks of cerebral palsy ( relative risk , 0.67 ; 95 % CI , 0.47 to 0.96 ; P=0.03 ) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II ( P=0.03 for each ) and the Gross Motor 
    Output:
    
WHAT IS NEW AND CONCLUSION Gentamicin clearance is decreased in neonates with HIE receiving hypothermia treatment compared to those not receiving hypothermia treatment .