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 recommended vaccination schedule for the pneumococcal conjugate vaccine ( PCV ) includes 4 immunizations , according to the national programs in the United States and some European countries . Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses . Aims : The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life ( a 2 + 1 dose schedule ) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b ( Hib ) vaccine . Methods : A total of 101 healthy Swedish infants were enrolled in an open , nonr and omized , multicenter study . PCV was administered concomitantly with ( at separate sites ) a diphtheria-tetanus toxoids-acellular pertussis vaccine , inactivated polio vaccine and Hib conjugate vaccine combination at 3 , 5 and 12 months of age . IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum sample s taken at 3 , 6 , 12 and 13 months were determined with enzyme immunoassays . Local and systemic reactions were monitored for 3 days after each immunization , and serious adverse reactions were monitored for the whole study period . Results : Two doses of PCV induced satisfactory antibody responses , with the exception of serotypes 6B and 23F . The third dose evoked strong responses for all serotypes , which suggests good immunologic priming with the primary series of 2 doses . The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children . The PCV was well tolerated . Conclusion : The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule . The results suggest that the implementation of a 2 + 1 dose schedule for PCV should be considered AIM In a prospect i ve controlled study in young children with a history of recurrent acute otitis media , we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine ( PCV ) given once or twice , followed by a 23-valent polysaccharide booster vaccination . METHODS Salivary IgA and IgG antibody concentrations to vaccine serotype 6B , 14 , 18C and 19F were measured by enzyme immunoassay in 38 sample s of children vaccinated with PCV and 45 control sample s. In the PCV  group , 12 sample s were taken prior to vaccination , 12 sample s 4 weeks after the polysaccharide booster ( 8 months after the first conjugate vaccination ) and 14 sample s 7 months after the last vaccination ( 14 months after the first conjugate vaccination ) . In the control group 15 children were sample d at each of these three time points . RESULTS We observed an increase in salivary IgG antibody concentrations against serotype 6B , 14 , and 18C 14 months after the primary vaccination in children vaccinated with PCV twice , although this was significant for serotype 14 only . There was no increase in salivary IgG antibody in children vaccinate with PCV once nor in control children . IgA antibody titers increased significantly after 8 and after 14 months in both the pneumococcal vaccine recipients and the controls . However , the observed increase in mean antibody titers was significantly higher in control children compared to the PCV group . CONCLUSION We suggest that repeated pneumococcal conjugate vaccination is necessary to induce an increase in salivary IgG antibodies and effectuate clearance of S. pneumoniae from the nasopharyngeal mucosa of children with recurrent acute otitis media . We hypothesize that the increase in salivary IgA is caused by the local boosting of the mucosal immune response by carriage and recurrent infections , which occurs less often in the PCV group compared to the control children Here we show , in a double-blind , r and omized , placebo-controlled trial in 37,107 fully immunized infants in Soweto , South Africa , that a 9-valent pneumococcal conjugate vaccine , PncCV , prevents 31 % ( 95 % confidence interval = 15–43 % ) of pneumonias associated with any of seven respiratory viruses in children in hospital . These data suggest that the pneumococcus has a major role in the development of pneumonia associated with these viruses and that viruses contribute to the pathogenesis of bacterial pneumonia . NOTE : In the version of this article originally published online , the species name was misspelled Streptococcus pnemoniae in the title of the article . The name should be Streptococcus pneumoniae . This error has been corrected for the HTML and print versions of the article In the clinical research er 's perfect world every patient entered into a r and omised controlled clinical trial ( RCT ) would satisfy all entry criteria , would complete their allocated treatment as described in the protocol , and would contribute data records which were complete in all respects . In practice it is doubtful if this ideal is ever achieved , and hence strategies have been developed for the analysis of RCTs which seek to protect their inferential basis from consequent biases . Such a strategy is ' intention to treat ' ( ITT ) which is frequently advocated as the preferred approach to analysis . This is particularly so for major trials design ed to establish definitively the efficacy and safety of a new medication or medical procedure . Indeed ITT has been endorsed in regulatory guidelines in Europe and the USA ( Nordic Council on Medicines , 1989 ; Food & Drug Administration , 1988 ) . But is ITT always the preferred approach ? Can it always be satisfactorily applied ? Is it a well-defined and well understood concept ? The subject of ITT regularly arouses debate and controversy . In particular the idea that a patient who has been r and omised to treatment A , but actually receives treatment B , should be assigned to the group who received A for analysis purpose s is totally incomprehensible to some . This controversy is fuelled by the fact that there are a large number of clinical trials , particularly in the early phases of research , for which ITT would indeed be inappropriate . Further fuel is added by the different attitudes to ITT in different research environments it is a constant concern in the later phases of drug regulation , for example , whereas research workers in the Medical Research Council generally show greater flexibility , probably because they are less concerned with satisfying conservative regulatory requirements . It has even been argued that ITT encourages sloppiness ' Whatever we do , give the treatment or not , it is OK since the analysis is by ITT ! ' . ITT came to prominence in connection with long-term RCTs with mortality as their major end-point . Peto and co-workers laid out the general principles for the design and analysis of such studies in their comprehensive and highly influential publications in this journal ( Peto et al. , 1976 , 1977 ) . They did not use the term ' intention to treat ' but did advocate that ' even patients who do not get the proper treatment must not be withdrawn from the analysis ' . Their guidance is detailed : the various ways in which patients may fail to complete the study as per protocol are all discussed , together with the possibility that the patients who so fail may differ in characteristics , or numbers , from treatment arm to treatment arm . Such differences are the source of the bias which ITT attempts to avoid any analysis which omits patients is open to bias because it no longer compares the groups as r and omised . However , although Peto and coworkers do recommend that all properly r and omised patients should be included in the analysis regardless of protocol deviation , they do leave open the possibility for some inappropriately r and omised patients to be excluded , and thus stop short of espousing the inclusion of all r and omised patients Children who had been r and omized to receive one dose of either heptavalent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine ( PCV ) or 23-valent pneumococcal polysaccharide vaccine ( PN23 ) at 12 , 15 , or 18 months of age were subsequently r and omized to receive a booster injection of either PCV or PN23 12 months later . For those children who received a priming dose of PCV ( N=75 ) compared to PN23 ( N=48 ) at 12 , 15 , or 18 months of age , higher serum antibody concentrations were achieved 1 month following a booster injection of either PCV or PN23 for all serotypes tested ( p<0.001 ) . Within the group of children receiving a priming dose of PCV , those children who received a booster dose of PN23 developed higher serum antibody concentrations for four of the seven serotypes tested and similar opsonic antibody titers to serotype 6B , yet more frequent erythema ( p=0.030 ) and pain or soreness ( p=0.024 ) at the injection site compared to those boosted with PCV . In conclusion , a single dose of PCV at 12 - 18 months of age primed for responses to booster doses of either PCV or PN23 12 months later . For those children who received a priming dose of PCV , boosting with PN23 result ed in more frequent injection site pain and erythema than boosting with PCV , yet higher antibody concentrations for most of the serotypes tested BACKGROUND Pneumococcal conjugate vaccine prevents recurrent acute otitis media ( AOM ) in infants immunised at 2 , 4 , 6 , and 12 - 15 months of age . We aim ed to find out whether this vaccine also prevents AOM in older children who have had previous episodes of AOM . METHODS In this double-blind , r and omised study , we enrolled 383 patients aged 1 - 7 years who had had two or more episodes of AOM in the year before entry . R and omisation was stratified in four groups according to age ( 12 - 24 months vs 25 - 84 months ) and the number of previous AOM episodes ( two or three episodes vs four or more episodes ) . Children received either 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine , or hepatitis A or B vaccines . They were followed up for 18 months for recurrence of AOM . We also cultured sample s of middle-ear fluid and nasopharyngeal swabs to assess association of pneumococcal serotypes with AOM after vaccination . FINDINGS We noted no reduction of AOM episodes in the pneumococcal vaccine group compared with controls ( intention-to-treat analysis : rate ratio 1.25 , 95 % CI 0.99 - 1.57 ) . Although nasopharyngeal carriage of pneumococci of serotypes included in the conjugate-vaccine was greatly reduced after pneumococcal vaccinations , immediate and complete replacement by non-vaccine pneumococcal serotypes took place . INTERPRETATION These data do not lend support to the use of pneumococcal conjugate vaccine to prevent otitis media in previously unvaccinated toddlers and children with a history of recurrent AOM Background : The 7-valent pneumococcal ( 7vPn ) conjugate vaccine is licensed for primary and booster vaccination according to the same immunization schedules as routinely recommended diphtheria-tetanus-pertussis-based childhood vaccines and can be coadministered during the same vaccination visit . Methods : An open , r and omized study evaluated the immunogenicity and safety of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b ( DTPa-HBV-IPV/Hib ) vaccine and a 7vPn conjugate vaccine when coadministered at 2 , 3 and 4 months and 12–23 months of age , compared with the administration of the hexavalent DTPa-HBV-IPV/Hib vaccine given alone . Serum antibody titers were measured before and 1 month after the primary course and before and 1 month after the booster dose . Solicited local and general adverse events were recorded for 4 days and unsolicited adverse events were recorded for 30 days after each vaccine dose . Results : A total of 345 subjects were enrolled for primary vaccination with the hexavalent vaccine  ( 170 without and 175 with the  7vPn vaccine coadministered ) and 266 returned for booster vaccination ( 122 without and 144 with coadministration of the 7vPn vaccine ) . After primary vaccination , antibody responses against the common antigens were similar in both groups , with seroprotection rates of 93.6–100 % and with similar antibody decay before booster vaccination . The fourth dose induced a vigorous booster response , with seroprotection/vaccine response rates of 96.8–100 % . Response to the 7vPn primary and booster vaccination was within previously reported ranges . Differences in reactogenicity result ed from higher incidences of symptoms after concomitant vaccination . Rectal temperature > 39.5 ° C was observed after 1.2 % of the coadministered vaccine doses during primary vaccination and after 2.8 % of the booster vaccine doses . Conclusion : Coadministration of the DTPa-HBV-IPV/Hib and 7vPn vaccines at separate injection sites during the same vaccination visit was effective and safe A group-r and omized , double-masked , phase III trial of a Streptococcus pneumoniae conjugate vaccine is being conducted in American Indian population s 
    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 recommended vaccination schedule for the pneumococcal conjugate vaccine ( PCV ) includes 4 immunizations , according to the national programs in the United States and some European countries . Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses . Aims : The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life ( a 2 + 1 dose schedule ) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b ( Hib ) vaccine . Methods : A total of 101 healthy Swedish infants were enrolled in an open , nonr and omized , multicenter study . PCV was administered concomitantly with ( at separate sites ) a diphtheria-tetanus toxoids-acellular pertussis vaccine , inactivated polio vaccine and Hib conjugate vaccine combination at 3 , 5 and 12 months of age . IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum sample s taken at 3 , 6 , 12 and 13 months were determined with enzyme immunoassays . Local and systemic reactions were monitored for 3 days after each immunization , and serious adverse reactions were monitored for the whole study period . Results : Two doses of PCV induced satisfactory antibody responses , with the exception of serotypes 6B and 23F . The third dose evoked strong responses for all serotypes , which suggests good immunologic priming with the primary series of 2 doses . The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children . The PCV was well tolerated . Conclusion : The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule . The results suggest that the implementation of a 2 + 1 dose schedule for PCV should be considered AIM In a prospect i ve controlled study in young children with a history of recurrent acute otitis media , we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine ( PCV ) given once or twice , followed by a 23-valent polysaccharide booster vaccination . METHODS Salivary IgA and IgG antibody concentrations to vaccine serotype 6B , 14 , 18C and 19F were measured by enzyme immunoassay in 38 sample s of children vaccinated with PCV and 45 control sample s. In the PCV  group , 12 sample s were taken prior to vaccination , 12 sample s 4 weeks after the polysaccharide booster ( 8 months after the first conjugate vaccination ) and 14 sample s 7 months after the last vaccination ( 14 months after the first conjugate vaccination ) . In the control group 15 children were sample d at each of these three time points . RESULTS We observed an increase in salivary IgG antibody concentrations against serotype 6B , 14 , and 18C 14 months after the primary vaccination in children vaccinated with PCV twice , although this was significant for serotype 14 only . There was no increase in salivary IgG antibody in children vaccinate with PCV once nor in control children . IgA antibody titers increased significantly after 8 and after 14 months in both the pneumococcal vaccine recipients and the controls . However , the observed increase in mean antibody titers was significantly higher in control children compared to the PCV group . CONCLUSION We suggest that repeated pneumococcal conjugate vaccination is necessary to induce an increase in salivary IgG antibodies and effectuate clearance of S. pneumoniae from the nasopharyngeal mucosa of children with recurrent acute otitis media . We hypothesize that the increase in salivary IgA is caused by the local boosting of the mucosal immune response by carriage and recurrent infections , which occurs less often in the PCV group compared to the control children Here we show , in a double-blind , r and omized , placebo-controlled trial in 37,107 fully immunized infants in Soweto , South Africa , that a 9-valent pneumococcal conjugate vaccine , PncCV , prevents 31 % ( 95 % confidence interval = 15–43 % ) of pneumonias associated with any of seven respiratory viruses in children in hospital . These data suggest that the pneumococcus has a major role in the development of pneumonia associated with these viruses and that viruses contribute to the pathogenesis of bacterial pneumonia . NOTE : In the version of this article originally published online , the species name was misspelled Streptococcus pnemoniae in the title of the article . The name should be Streptococcus pneumoniae . This error has been corrected for the HTML and print versions of the article In the clinical research er 's perfect world every patient entered into a r and omised controlled clinical trial ( RCT ) would satisfy all entry criteria , would complete their allocated treatment as described in the protocol , and would contribute data records which were complete in all respects . In practice it is doubtful if this ideal is ever achieved , and hence strategies have been developed for the analysis of RCTs which seek to protect their inferential basis from consequent biases . Such a strategy is ' intention to treat ' ( ITT ) which is frequently advocated as the preferred approach to analysis . This is particularly so for major trials design ed to establish definitively the efficacy and safety of a new medication or medical procedure . Indeed ITT has been endorsed in regulatory guidelines in Europe and the USA ( Nordic Council on Medicines , 1989 ; Food & Drug Administration , 1988 ) . But is ITT always the preferred approach ? Can it always be satisfactorily applied ? Is it a well-defined and well understood concept ? The subject of ITT regularly arouses debate and controversy . In particular the idea that a patient who has been r and omised to treatment A , but actually receives treatment B , should be assigned to the group who received A for analysis purpose s is totally incomprehensible to some . This controversy is fuelled by the fact that there are a large number of clinical trials , particularly in the early phases of research , for which ITT would indeed be inappropriate . Further fuel is added by the different attitudes to ITT in different research environments it is a constant concern in the later phases of drug regulation , for example , whereas research workers in the Medical Research Council generally show greater flexibility , probably because they are less concerned with satisfying conservative regulatory requirements . It has even been argued that ITT encourages sloppiness ' Whatever we do , give the treatment or not , it is OK since the analysis is by ITT ! ' . ITT came to prominence in connection with long-term RCTs with mortality as their major end-point . Peto and co-workers laid out the general principles for the design and analysis of such studies in their comprehensive and highly influential publications in this journal ( Peto et al. , 1976 , 1977 ) . They did not use the term ' intention to treat ' but did advocate that ' even patients who do not get the proper treatment must not be withdrawn from the analysis ' . Their guidance is detailed : the various ways in which patients may fail to complete the study as per protocol are all discussed , together with the possibility that the patients who so fail may differ in characteristics , or numbers , from treatment arm to treatment arm . Such differences are the source of the bias which ITT attempts to avoid any analysis which omits patients is open to bias because it no longer compares the groups as r and omised . However , although Peto and coworkers do recommend that all properly r and omised patients should be included in the analysis regardless of protocol deviation , they do leave open the possibility for some inappropriately r and omised patients to be excluded , and thus stop short of espousing the inclusion of all r and omised patients Children who had been r and omized to receive one dose of either heptavalent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine ( PCV ) or 23-valent pneumococcal polysaccharide vaccine ( PN23 ) at 12 , 15 , or 18 months of age were subsequently r and omized to receive a booster injection of either PCV or PN23 12 months later . For those children who received a priming dose of PCV ( N=75 ) compared to PN23 ( N=48 ) at 12 , 15 , or 18 months of age , higher serum antibody concentrations were achieved 1 month following a booster injection of either PCV or PN23 for all serotypes tested ( p<0.001 ) . Within the group of children receiving a priming dose of PCV , those children who received a booster dose of PN23 developed higher serum antibody concentrations for four of the seven serotypes tested and similar opsonic antibody titers to serotype 6B , yet more frequent erythema ( p=0.030 ) and pain or soreness ( p=0.024 ) at the injection site compared to those boosted with PCV . In conclusion , a single dose of PCV at 12 - 18 months of age primed for responses to booster doses of either PCV or PN23 12 months later . For those children who received a priming dose of PCV , boosting with PN23 result ed in more frequent injection site pain and erythema than boosting with PCV , yet higher antibody concentrations for most of the serotypes tested BACKGROUND Pneumococcal conjugate vaccine prevents recurrent acute otitis media ( AOM ) in infants immunised at 2 , 4 , 6 , and 12 - 15 months of age . We aim ed to find out whether this vaccine also prevents AOM in older children who have had previous episodes of AOM . METHODS In this double-blind , r and omised study , we enrolled 383 patients aged 1 - 7 years who had had two or more episodes of AOM in the year before entry . R and omisation was stratified in four groups according to age ( 12 - 24 months vs 25 - 84 months ) and the number of previous AOM episodes ( two or three episodes vs four or more episodes ) . Children received either 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine , or hepatitis A or B vaccines . They were followed up for 18 months for recurrence of AOM . We also cultured sample s of middle-ear fluid and nasopharyngeal swabs to assess association of pneumococcal serotypes with AOM after vaccination . FINDINGS We noted no reduction of AOM episodes in the pneumococcal vaccine group compared with controls ( intention-to-treat analysis : rate ratio 1.25 , 95 % CI 0.99 - 1.57 ) . Although nasopharyngeal carriage of pneumococci of serotypes included in the conjugate-vaccine was greatly reduced after pneumococcal vaccinations , immediate and complete replacement by non-vaccine pneumococcal serotypes took place . INTERPRETATION These data do not lend support to the use of pneumococcal conjugate vaccine to prevent otitis media in previously unvaccinated toddlers and children with a history of recurrent AOM Background : The 7-valent pneumococcal ( 7vPn ) conjugate vaccine is licensed for primary and booster vaccination according to the same immunization schedules as routinely recommended diphtheria-tetanus-pertussis-based childhood vaccines and can be coadministered during the same vaccination visit . Methods : An open , r and omized study evaluated the immunogenicity and safety of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b ( DTPa-HBV-IPV/Hib ) vaccine and a 7vPn conjugate vaccine when coadministered at 2 , 3 and 4 months and 12–23 months of age , compared with the administration of the hexavalent DTPa-HBV-IPV/Hib vaccine given alone . Serum antibody titers were measured before and 1 month after the primary course and before and 1 month after the booster dose . Solicited local and general adverse events were recorded for 4 days and unsolicited adverse events were recorded for 30 days after each vaccine dose . Results : A total of 345 subjects were enrolled for primary vaccination with the hexavalent vaccine  ( 170 without and 175 with the  7vPn vaccine coadministered ) and 266 returned for booster vaccination ( 122 without and 144 with coadministration of the 7vPn vaccine ) . After primary vaccination , antibody responses against the common antigens were similar in both groups , with seroprotection rates of 93.6–100 % and with similar antibody decay before booster vaccination . The fourth dose induced a vigorous booster response , with seroprotection/vaccine response rates of 96.8–100 % . Response to the 7vPn primary and booster vaccination was within previously reported ranges . Differences in reactogenicity result ed from higher incidences of symptoms after concomitant vaccination . Rectal temperature > 39.5 ° C was observed after 1.2 % of the coadministered vaccine doses during primary vaccination and after 2.8 % of the booster vaccine doses . Conclusion : Coadministration of the DTPa-HBV-IPV/Hib and 7vPn vaccines at separate injection sites during the same vaccination visit was effective and safe A group-r and omized , double-masked , phase III trial of a Streptococcus pneumoniae conjugate vaccine is being conducted in American Indian population s 
    Output:
    