***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: We examined the in vivo immune response of infants to natural respiratory syncytial virus ( RSV ) infection through analysis of cytokine levels in nasal lavage fluid and stimulated peripheral blood mononuclear cells . Eighty-eight babies with at least one parent with atopy and asthma were prospect ively studied through their first winter . Twenty-eight infants had an upper respiratory tract infection where RSV was detected , of whom nine developed signs of acute bronchiolitis .  Nasal lavage specimens were assayed for interferon-gamma , interleukin (IL)-4 , IL-10 , and IL-12 and the RSV load determined by quantitative polymerase chain reaction . Messenger RNA ( mRNA ) was extracted from stimulated peripheral blood mononuclear cells and interferon-gamma , IL-4 , IL-12 , and IL-18 mRNA levels determined by polymerase chain reaction . Cytokine profiles were analyzed in relation to clinical outcome . The IL-4/interferon-gamma ratio for infants with acute bronchiolitis was elevated in nasal lavage fluid on both Days 1 - 2 ( p = 0.014 ) and Days 5 - 7 ( p = 0.001 ) of the illness compared with infants with upper respiratory tract infection alone . Those with acute bronchiolitis demonstrated a higher IL-10/IL-12 ratio ( p = 0.0015 ) on Days 1 - 2 . IL-18 mRNA levels were reduced ( p = 0.019 ) and the IL-4/interferon-gamma ratio elevated ( p = 0.01 ) in stimulated peripheral blood mononuclear cells from infants with acute bronchiolitis . There was no difference in initial RSV load . These data strongly implicate excess type 2 and /or deficient type 1 immune responses in the pathogenesis of RSV bronchiolitis BACKGROUND Bronchiolitis caused by respiratory syncytial virus ( RSV ) is an important cause of morbidity in ex-premature infants . In a r and omised placebo controlled trial monoclonal antibody prophylaxis showed a 55 % reduction in relative risk of hospital admission for these high risk infants , against a background incidence of 10.6 admissions per 100 high risk infants . AIMS To follow a cohort of high risk infants in order to assess hospitalisation rate from RSV and the potential impact of prophylaxis for these patients in a UK local health authority . METHODS A cohort of high risk infants from a local health authority were followed over the 1998/99 and 1999/2000 RSV seasons . The high risk population was defined as infants who , at the beginning of the seasons studied , were : ( 1 ) under 6 months old and born prior to 36 weeks gestation with no domiciliary oxygen requirement ; or ( 2 ) under 24 months of age and discharged home in supplemental oxygen . All admissions with bronchiolitis during the season were identified . RESULTS A total of 370 high risk infants were identified for the 1998/99 season and 286 for the following year . Over the two years there were 68 admissions . Significantly more admissions occurred from group 2 infants . RSV was identified in 27 cases ( four admissions per hundred high risk infants ) . Prophylaxis may have saved up to £ 195 134 in hospital costs over the two years , but would have cost £ 1.1 million in drug acquisition costs . CONCLUSIONS Careful consideration of risk factors is needed when selecting infants for RSV prophylaxis BACKGROUND Respiratory syncytial virus ( RSV ) is the most common cause of lower respiratory tract infection in infants .  MEDI-493 ( palivizumab ) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication . OBJECTIVE To describe the safety , tolerance , immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia . DESIGN Phase I/II multicenter , r and omized , double blind , placebo-controlled , dose escalation trial . PATIENT POPULATION Infants born prematurely ( < or = 35 weeks of gestation ) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 24 months of age were eligible for study participation . STUDY AGENTS : Participants received 3 , 10 or 15 mg/kg MEDI-493 or 0.9 % saline intravenously every 30 days for up to five doses . RESULTS MEDI-493 was safe and well-tolerated and did not induce a specific anti-MEDI-493 response . The mean half-life of 20 days was comparable with that of other immunoglobulin G preparations . Mean trough serum concentrations 30 days after Infusion 1 were 6.8 , 36.1 and 60.6 microg/ml for the 3- , 10- and 15-mg/kg dose groups , respectively . After Infusion 2 the trough concentrations were 11.9 , 45.2 and 70.7 microg/ml . After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 ( 46 to 72 microg/ml and 88 to 96 microg/ml , respectively ) . CONCLUSIONS MEDI-493 was safe and well-tolerated in this high risk pediatric population . Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease . Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients BACKGROUND Respiratory syncytial virus ( RSV ) is the leading cause of lower respiratory disease in infants and children .  MEDI-493 ( palivizumab , Synagis ) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV , and it is highly active in vitro against RSV A and B strains . OBJECTIVE To describe the safety , tolerance , immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing . DESIGN A Phase I/II multicenter , open label , escalating dose clinical trial . PATIENT POPULATION AND DOSING REGIMEN : Children ( n=65 ) born prematurely at < or = 35 weeks of gestation who were < or = 6 months of age ( n=41 ) and children with bronchopulmonary dysplasia who were < or = 24 months of age ( n=24 ) were enrolled . From 1 to 5 monthly injections were given at doses of 5 mg/kg ( n=11 ) , 10 mg/kg ( n=6 ) and 15 mg/kg ( n=48 ) . Serum was collected before administration of each dose , 30 days after the last dose , and 2 , 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay . RESULTS The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies . Mean serum MEDI-493 concentrations were 91.1 microg/ml ( range , 52.3 to 174.0 ) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml ( range , 13.5 to 132.0 ) at 30 days . Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml . These concentrations were similar to previously published trough concentrations after i.v . administration . MEDI-493 injections were well-tolerated . Only three children had adverse events judged to be possibly related to MEDI-493 . Ten children had transient , low titer anti-MEDI-493 binding titers ( 1:10 to 1:40 ) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations . Two patients in the 5-mg/kg dose group were hospitalized for RSV ; no RSV hospitalizations were found in the higher dose groups . CONCLUSIONS MEDI-493 was safe and well-tolerated . Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml ( the value associated with 99 % reduction of pulmonary RSV in the cotton rat model ) . These concentrations were similar to those previously reported with i.v . administration of MEDI-493 Objective . To provide information on the use and outcomes of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus ( RSV ) infection . Design . Observational , prospect i ve , longitudinal , multicenter study . Setting . Eighteen hospitals and pediatric clinics located in six provinces across Canada . Patients . Infants enrolled in the palivizumab Special Access Programme of Canada ’s Therapeutic Products Programme throughout the 1999 to 2000 RSV season . Most were premature infants born at ≤32 weeks of gestation and /or had bronchopulmonary dysplasia . Methods and main outcome measures . Neonatal and demographic data were recorded for each subject . The parent/caregiver was contacted on a monthly basis until the end of the RSV season to obtain information on palivizumab utilization and compliance as well as incidence and severity of respiratory infections . Results . There were 444 evaluable subjects who each received 1 to 7 injections of palivizumab for a total of 1702 doses from September 1999 to April 2000 . Most subjects received 5 injections with high compliance . Prophylaxis was discontinued in 2 % of children . There were 116 clinical events or hospitalizations involving respiratory tract infections reported in 91 children . Eighty-six of these were managed in an outpatient setting , and 30 required hospitalization . The estimated incidence of hospitalization for RSV-positive lower respiratory tract infections ( LRTIs ) was 2.4 % . Hospitalization for RSV LRTI occurred more often in children with bronchopulmonary dysplasia ( 6.0 % ) than in those with prematurity only ( 1.6 % ) . Conclusions . This study demonstrates that prophylaxis with palivizumab during the RSV season was associated with a low rate of hospitalization for RSV-positive LRTIs  . Palivizumab was well-tolerated , and compliance was high . The findings confirm the results of the major r and omized clinical trial of palivizumab and demonstrate the safety and effectiveness of RSV prophylaxis An Exp and ed Access Study was conducted to collect additional safety data on palivizumab .  Preterm infants with or without bronchopulmonary dysplasia received palivizumab every 30 days during the respiratory syncytial virus season . Adverse events were low ( 6.9 % ) in the 565 subjects . Serious adverse events included hospitalization and 1 case of respiratory syncytial virus bronchiolitis not requiring hospitalization . This study reaffirms the safety and tolerability of palivizumab 
    Output:
    
None of the United Kingdom cost studies showed economic benefit for palivizumab prophylaxis .
New treatments are rarely cost effective , and , in the absence of a comprehensive economic assessment , continued use for high risk infants may appear justified