human
***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: Background : The booster ( fourth ) dose of 7-valent pneumococcal conjugate vaccine ( PCV7 ) is recommended to be given at 12–15 months but in Canada it better fits the national schedule at 18 months , prompting this comparison of the safety and immunogenicity of booster immunization at 15 or 18 months . Methods : Children who had completed a study of primary PCV7 immunization ( with final serology at 7–8 months of age ) were enrolled at 12 months , bled and r and omly assigned to receive a PCV7 booster at age 15 or 18 months , with serologic testing before and 4 weeks afterward . Adverse events were documented for 3 days postbooster . Antibody concentrations were measured for the 7 pneumococcal serotypes and Haemophilus influenzae type b at 7–8 , 12 , 15 or 18 months and after boosting . Results : Three hundred thirty-one children were boosted , 167 at 15 months and 164 at 18 months . Pneumococcal geometric mean antibody concentrations declined by 15 months to 23.4 % of peak geometric mean concentrations at age 7–8 months and to 19.8 % by 18 months . Spontaneous increases in 1 or more antibody concentrations were noted in 195 subjects ( 61.7 % ) , most commonly with types 6B and 19F . Antibody responses to PCV7 were similarly brisk at 15 and 18 months . Mild injection-site redness and swelling were significantly more frequent at 15 than 18 months but no other differences in reactogenicity were observed . Conclusions : Residual antibody concentrations differed minimally between 15 and 18 months . Spontaneous antibody increases often occurred before boosting , possibly from colonization . PCV7 booster vaccination at 18 months appears to be safe and provides comparable immunogenicity to 15 months vaccination In developing countries , Haemophilus influenzae type b is a major cause of meningitis and pneumonia in the 1st year of life . The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine ( PRP-T ) were evaluated in two studies of Gambian infants . In the first study , 131 infants were recruited and r and omized into three groups to receive PRP-T at 1 and 3 months ( group A ) , PRP-T at 2 and 4 months ( group B ) or no PRP-T ( group C ) . The liquid form of PRP-T was used . The geometric mean titre ( GMT ) of anti-PRP antibody 1 month after the second dose was 0.26 microgram/ml in group A and 0.41 microgram/ml in group B. In the second study , 66 infants were given PRP-T in the lyophilized form at 2 , 3 and 4 months of age . The GMT 1 month after the first dose was 0.09 microgram/ml , after the second 0.74 microgram/ml and after the third 2.32 micrograms/ml . After the third dose , 72 % of children had antibody levels greater than 1.0 microgram/ml and 93 % greater than 0.15 microgram/ml . No serious side-effects were observed and the rate of adverse reactions was consistent with the concurrent administration of diphtheria-tetanus-pertussis ( DPT ) vaccine We report an enhanced prospect i ve survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H. influenzae type b ( Hib ) vaccination program .  During the prevaccination period the majority of cases of invasive H. influenzae were caused by type b ; most ( 89 % ) of these infections occurred in children < 5 years of age and the most common presentation was meningitis . Since the introduction of routine immunization of infants with conjugate Hib vaccine , there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children < 5 years of age . This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs . The number of infections caused by non-type b H. influenzae has shown a small but progressive increase over the same period , emphasizing the need for continued surveillance . There was no increase in the number of infections caused by other serotypes . Diagnostic category varied with both age and serotype but was not affected by vaccine introduction ; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed METHODS In an open r and omized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants . A pentavalent combination vaccine , including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria , tetanus , acellular pertussis ( pertussis toxoid and filamentous hemagglutinin ) and inactivated polio vaccine ( DTaP-IPV/Act-HIB ; Pasteur Mérieux Connaught , Lyon , France ) was administered to 236 Swedish infants either at 2 , 4 and 6 months or at 3 and 5 months , and a booster dose was administered 7 months after the last primary dose . Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits . Antibodies against the different vaccine components were analyzed after the primary series of vaccinations , before and after the booster injections . RESULTS There were no serious adverse reactions , and the rates of febrile events and local reactions were low in both groups . The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule , but there were no differences between the groups in proportions with protective antibody titers against diphtheria , tetanus , Hib and polio or in proportions with certain defined levels of pertussis antibodies . Prebooster results showed a similar pattern , with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3 . After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations , indicating effective priming from both primary series of vaccinations . Conclusion . The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied BACKGROUND AND METHODS Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants . We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex ( OMPC ) of Neisseria meningitidis serogroup B. We conducted a double-blind , placebo , controlled trial in Navajo infants , who are at high risk for systemic infections caused by H. influenzae type b. The infants were r and omly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age . RESULTS Of the infants in the trial , 2588 were assigned to receive the vaccine and 2602 to receive placebo .  The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group . Before the age of 18 months , there was 1 systemic H. influenzae type b infection in the vaccine group , as compared with 22 in the placebo group ( P less than 0.001 ; point estimate of efficacy , 95 percent ; 95 percent confidence interval , 72 to 99 percent ) . Of the 22 H. influenzae type b infections in the placebo group , 13 were meningitis . Among the children who received both doses , there was 1 H. influenzae type b infection in the vaccine group ( n = 2056 ) and 14 in the placebo group ( n = 2105 ) ( P less than 0.001 ; point estimate of efficacy , 93 percent ; 95 percent confidence interval , 53 to 98 percent ) . The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis . Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group ( P less than 0.005 ; point estimate of efficacy , 100 percent ; 95 percent confidence interval , 41 to 100 percent ) . CONCLUSIONS The H. influenzae type b OMPC vaccine , administered at 2 and 4 months of age , is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months . Protection begins after the first dose We r and omly assigned 150 newborn infants to receive diphtheria and tetanus toxoids ( DT ) or Hib oligosaccharide conjugate ( HbOC ) at birth to determine whether exposure to the Haemophilus influenzae type b ( Hib ) conjugate vaccines ' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate ( PRP-T ) at 2 , 4 , and 6 months of age . Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age . No serious adverse reactions were associated with neonatal vaccination . Administration of HbOC at birth did not lead to earlier or higher antibody levels . Newborn immunization with DT did not prime children for enhanced antibody responses . Moreover , Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age . Diphtheria antibody levels , but not tetanus antibody levels , were also lower in children immunized with DT at birth . We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease . Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines , and may lead to suppression of Hib and diphtheria antibody responses The efficacy of the HbOC conjugate Haemophilus influenzae type b vaccine was evaluated in a study population of 61 080 infants in the Northern California Kaiser Permanente Medical Care Program . Between February , 1988 , and June , 1990 , the HbOC vaccine was given as part of a three-dose series at 2 , 4 and 6 months of age to 20 800 infants . The study population included children with a well-care visit at a study center during the first 6 months of life . There were 25 cases of Haemophilus influenzae type b disease in the study population : 22 in unvaccinated children and 3 in children who received only one dose of HbOC vaccine .  The efficacy of the full three-dose series was evaluated by several methods : a primary analysis comparing fully vaccinated children with unvaccinated children from 7 to 18 months of age ; a stratified exact analysis adjusted for age and seasonality ; and a case-control analysis which further adjusted for known risk factors . The efficacy of three doses of vaccine was 100 % with the lower bound of the 95 % confidence interval for the three analyses at 68 , 71 , and 64 % , respectively . There were no cases of disease result ing from two doses of HbOC vaccine yielding an estimate of 100 % efficacy ( 95 % confidence interval , 47 to 100 ) for two doses of HbOC vaccine . However , for children who had received only one dose of HbOC vaccine , vaccine efficacy was estimated to be 26 % and the possibility that one dose of HbOC vaccine had no efficacy could not be excluded . An intent-to-treat analysis and supplementary analyses of possible sources of bias supported the conclusion that immunization with HbOC vaccine was effective in preventing H. influenzae type b disease in infancy Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants , but it was not clear 
    Output:
    
agent
***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: Background : The booster ( fourth ) dose of 7-valent pneumococcal conjugate vaccine ( PCV7 ) is recommended to be given at 12–15 months but in Canada it better fits the national schedule at 18 months , prompting this comparison of the safety and immunogenicity of booster immunization at 15 or 18 months . Methods : Children who had completed a study of primary PCV7 immunization ( with final serology at 7–8 months of age ) were enrolled at 12 months , bled and r and omly assigned to receive a PCV7 booster at age 15 or 18 months , with serologic testing before and 4 weeks afterward . Adverse events were documented for 3 days postbooster . Antibody concentrations were measured for the 7 pneumococcal serotypes and Haemophilus influenzae type b at 7–8 , 12 , 15 or 18 months and after boosting . Results : Three hundred thirty-one children were boosted , 167 at 15 months and 164 at 18 months . Pneumococcal geometric mean antibody concentrations declined by 15 months to 23.4 % of peak geometric mean concentrations at age 7–8 months and to 19.8 % by 18 months . Spontaneous increases in 1 or more antibody concentrations were noted in 195 subjects ( 61.7 % ) , most commonly with types 6B and 19F . Antibody responses to PCV7 were similarly brisk at 15 and 18 months . Mild injection-site redness and swelling were significantly more frequent at 15 than 18 months but no other differences in reactogenicity were observed . Conclusions : Residual antibody concentrations differed minimally between 15 and 18 months . Spontaneous antibody increases often occurred before boosting , possibly from colonization . PCV7 booster vaccination at 18 months appears to be safe and provides comparable immunogenicity to 15 months vaccination In developing countries , Haemophilus influenzae type b is a major cause of meningitis and pneumonia in the 1st year of life . The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine ( PRP-T ) were evaluated in two studies of Gambian infants . In the first study , 131 infants were recruited and r and omized into three groups to receive PRP-T at 1 and 3 months ( group A ) , PRP-T at 2 and 4 months ( group B ) or no PRP-T ( group C ) . The liquid form of PRP-T was used . The geometric mean titre ( GMT ) of anti-PRP antibody 1 month after the second dose was 0.26 microgram/ml in group A and 0.41 microgram/ml in group B. In the second study , 66 infants were given PRP-T in the lyophilized form at 2 , 3 and 4 months of age . The GMT 1 month after the first dose was 0.09 microgram/ml , after the second 0.74 microgram/ml and after the third 2.32 micrograms/ml . After the third dose , 72 % of children had antibody levels greater than 1.0 microgram/ml and 93 % greater than 0.15 microgram/ml . No serious side-effects were observed and the rate of adverse reactions was consistent with the concurrent administration of diphtheria-tetanus-pertussis ( DPT ) vaccine We report an enhanced prospect i ve survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H. influenzae type b ( Hib ) vaccination program .  During the prevaccination period the majority of cases of invasive H. influenzae were caused by type b ; most ( 89 % ) of these infections occurred in children < 5 years of age and the most common presentation was meningitis . Since the introduction of routine immunization of infants with conjugate Hib vaccine , there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children < 5 years of age . This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs . The number of infections caused by non-type b H. influenzae has shown a small but progressive increase over the same period , emphasizing the need for continued surveillance . There was no increase in the number of infections caused by other serotypes . Diagnostic category varied with both age and serotype but was not affected by vaccine introduction ; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed METHODS In an open r and omized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants . A pentavalent combination vaccine , including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria , tetanus , acellular pertussis ( pertussis toxoid and filamentous hemagglutinin ) and inactivated polio vaccine ( DTaP-IPV/Act-HIB ; Pasteur Mérieux Connaught , Lyon , France ) was administered to 236 Swedish infants either at 2 , 4 and 6 months or at 3 and 5 months , and a booster dose was administered 7 months after the last primary dose . Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits . Antibodies against the different vaccine components were analyzed after the primary series of vaccinations , before and after the booster injections . RESULTS There were no serious adverse reactions , and the rates of febrile events and local reactions were low in both groups . The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule , but there were no differences between the groups in proportions with protective antibody titers against diphtheria , tetanus , Hib and polio or in proportions with certain defined levels of pertussis antibodies . Prebooster results showed a similar pattern , with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3 . After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations , indicating effective priming from both primary series of vaccinations . Conclusion . The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied BACKGROUND AND METHODS Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants . We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex ( OMPC ) of Neisseria meningitidis serogroup B. We conducted a double-blind , placebo , controlled trial in Navajo infants , who are at high risk for systemic infections caused by H. influenzae type b. The infants were r and omly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age . RESULTS Of the infants in the trial , 2588 were assigned to receive the vaccine and 2602 to receive placebo .  The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group . Before the age of 18 months , there was 1 systemic H. influenzae type b infection in the vaccine group , as compared with 22 in the placebo group ( P less than 0.001 ; point estimate of efficacy , 95 percent ; 95 percent confidence interval , 72 to 99 percent ) . Of the 22 H. influenzae type b infections in the placebo group , 13 were meningitis . Among the children who received both doses , there was 1 H. influenzae type b infection in the vaccine group ( n = 2056 ) and 14 in the placebo group ( n = 2105 ) ( P less than 0.001 ; point estimate of efficacy , 93 percent ; 95 percent confidence interval , 53 to 98 percent ) . The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis . Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group ( P less than 0.005 ; point estimate of efficacy , 100 percent ; 95 percent confidence interval , 41 to 100 percent ) . CONCLUSIONS The H. influenzae type b OMPC vaccine , administered at 2 and 4 months of age , is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months . Protection begins after the first dose We r and omly assigned 150 newborn infants to receive diphtheria and tetanus toxoids ( DT ) or Hib oligosaccharide conjugate ( HbOC ) at birth to determine whether exposure to the Haemophilus influenzae type b ( Hib ) conjugate vaccines ' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate ( PRP-T ) at 2 , 4 , and 6 months of age . Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age . No serious adverse reactions were associated with neonatal vaccination . Administration of HbOC at birth did not lead to earlier or higher antibody levels . Newborn immunization with DT did not prime children for enhanced antibody responses . Moreover , Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age . Diphtheria antibody levels , but not tetanus antibody levels , were also lower in children immunized with DT at birth . We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease . Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines , and may lead to suppression of Hib and diphtheria antibody responses The efficacy of the HbOC conjugate Haemophilus influenzae type b vaccine was evaluated in a study population of 61 080 infants in the Northern California Kaiser Permanente Medical Care Program . Between February , 1988 , and June , 1990 , the HbOC vaccine was given as part of a three-dose series at 2 , 4 and 6 months of age to 20 800 infants . The study population included children with a well-care visit at a study center during the first 6 months of life . There were 25 cases of Haemophilus influenzae type b disease in the study population : 22 in unvaccinated children and 3 in children who received only one dose of HbOC vaccine .  The efficacy of the full three-dose series was evaluated by several methods : a primary analysis comparing fully vaccinated children with unvaccinated children from 7 to 18 months of age ; a stratified exact analysis adjusted for age and seasonality ; and a case-control analysis which further adjusted for known risk factors . The efficacy of three doses of vaccine was 100 % with the lower bound of the 95 % confidence interval for the three analyses at 68 , 71 , and 64 % , respectively . There were no cases of disease result ing from two doses of HbOC vaccine yielding an estimate of 100 % efficacy ( 95 % confidence interval , 47 to 100 ) for two doses of HbOC vaccine . However , for children who had received only one dose of HbOC vaccine , vaccine efficacy was estimated to be 26 % and the possibility that one dose of HbOC vaccine had no efficacy could not be excluded . An intent-to-treat analysis and supplementary analyses of possible sources of bias supported the conclusion that immunization with HbOC vaccine was effective in preventing H. influenzae type b disease in infancy Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants , but it was not clear 
    Output:
    