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: The immunogenicity of plasma derived hepatitis B vaccine ( Hevac B ) was studied for active pre-exposure immunisation in 176 healthy volunteer adults and 162 r and omised children who had no hepatitis B virus markers . All subjects received three injections of 5 micrograms of hepatitis B vaccine intramuscularly at one month intervals . Seroconversion at 2 months after the third dose of vaccine was 96.30 percent in the children and 92.00 percent in the adults with mean anti-HBs titres of 800 mlU/ml and 353 mlU/ml respectively . The difference of anti-HBs levels between these two groups was statistically significant ( p less than 0.05 ) . Female adults had exhibited higher immune response to HB vaccine than male adults but there was no seroconversion difference between boys and girls . There were no serious local or systemic side effects of hepatitis B vaccination . It was concluded that active immunisation with plasma derived hepatitis B vaccine in non-immune children and adults is highly effective without any serious side effects or complications . The prevention of horizontal transmission of hepatitis B virus should be done by vaccination in children since they have a much better immune response to hepatitis B vaccine than adults The reactogenicity and immunogenicity of the administration of recombinant vaccine against hepatitis B simultaneously ( but at separate sites ) with diphtheria/tetanus/pertussis ( DTP ) and oral polio vaccines were examined . Six hundred and twenty-six children ( group I ) were given hepatitis B vaccine at 0 , 2 and 6 months of age ; the other vaccines were administered at 2 , 4 and 6 months of age . A control group of 731 children ( group II ) received only DTP and oral polio vaccines . The results showed that 93 % of the infants in group I had anti-HBs titres above the protective level ( > or = 10 mIU ml-1 ) after vaccination . There were no differences in the immune responses for DTP and polio between the two study groups . The vaccine efficacy against poliomyelitis was 96 % for serotype I , 100 % for serotype II and 97 - 98 % for serotype III . Of the infants in both groups , 97 % had antibodies against B. pertussis ; all children were positive for tetanus and diphtheria . There were no differences in the incidences of general reactions between groups . Local swelling and redness were reported following 4.2 and 4.4 % , respectively , of all injections of hepatitis B vaccine . These reactions were reported following 31 and 33 % , respectively , of all doses of DTP vaccine . It can be concluded that the simultaneous administration of hepatitis B vaccine with the DTP and polio vaccines is well-tolerated ; hepatitis B vaccine remained highly immunogenic and did not interfere with the immune response to the other antigens Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available To determine necessity and timing of booster of hepatitis B vaccine , we need to observe the duration of its protection . We report the results of a 15-year follow-up of a cohort of 649 children who participated a r and omized , double blind , placebo-controlled trial on a plasma-derived hepatitis B vaccine in 1982 . During the 15 years after vaccination , more vaccinated children had anti-HBs of 10 S/N ratios or over , compared with the controls , at all nine observations . At 15 years 50.0 % ( 26/52 ) of the participants studied in the vaccinated group and 33.3 % of the tested controls ( 18/54 ) retained anti-HBs levels of S/N ratios > or = 10 ( P < 0.09 ) . However , since 5 years after vaccination , median S/N ratios of anti-HBs among the vaccinated children with detectable anti-HBs were lower than those of the controls except that detected at 15 years . 16.7 % ( 9/54 ) of the tested children in the control group were HBsAg positive at 15 years after vaccination , in comparison with 1.9 % ( 1/52 ) of the tested children in the vaccinated ( P < 0.02 ) . 28 chronic HBsAg carriers were identified in the control cohort over the 15 years , whereas only 1 case was noted in the vaccinated group ( 8.2 % vs. 0.3 % , P < 0.00001 ) , corresponding to an efficacy of 96 % BACKGROUND / AIMS Treatment of hepatitis B virus carriers by vaccine containing hepatitis B surface antigen with Pre-S protein and HBsAg/ anti-HBs complex has been reported and these studies have constituted a new and promising concept for the treatment of HBV-carriers . The present communication , a placebo-controlled trial of vaccination in HBV-transgenic mice , was design ed to examine the impact of vaccination using a high dose of HBsAg for a duration of 12 months to achieve further insights about the dose , duration and effectiveness of vaccine therapy . Another aim of this study was to analyse the mechanism underlying the antiviral and immunomodulatory potentiality of vaccine therapy in HBV-transgenic mice . METHODS HBV-transgenic mice positive for HBV DNA , hepatitis B surface antigen and hepatitis B e antigen in sera received either HBV-vaccine containing HBsAg in complete Freund 's adjuvant ( CFA ) , intraperitoneally , once a month for 12 consecutive months ( vaccine recipients ) , or only CFA , intraperitoneally once in a month for 12 consecutive months ( placebo recipients ) . Thirty-two vaccine-recipient and 16 placebo-recipient HBV-transgenic mice were injected , checked and followed on a monthly basis for the entire duration of 12 months . RESULTS Of the 32 transgenic mice from the vaccine-recipient group , 25 became completely negative for HBsAg and 30 for HBeAg . Five mice developed anti-HBs in sera after the observation period of 12 months . Semiquantitative estimation of HBV DNA by polymerase chain reaction showed that vaccination result ed in a decrease of HBV DNA in sera . Placebo-recipient transgenic mice did not show any significant change in the titres of HBV markers after receiving 12 monthly injections of CFA . Interleukin-2 could be detected in sera from vaccine-recipient transgenic mice , but not in placebo-recipient transgenic mice . CONCLUSIONS Vaccination with a high dose of HBsAg in adjuvant over a long period had a significant antiviral as well as immunomodulatory potential in HBV-transgenic mice . This inspires optimism that vaccine alone or in combination with antiviral agents can be used successfully for the treatment of human HBV-carriers Hepatitis B is a serious disease of global significance . In developing countries , hepatitis B virus ( HBV ) infection and its sequelae rank among the public health problems of highest priority . Infants born to mothers who are chronic carriers of HBV are at particularly high risk of acquiring infection and becoming chronic HBV carriers . The efficacy of hepatitis B vaccine alone in preventing the transmission of HBV to infants born to HBV carrier mothers was determined in a double-blind placebo-controlled trial . Infants received plasma-derived vaccine at birth , 1 month , and 6 months of age . Of 180 infants born to hepatitis B surface antigen (HBsAg)-positive mothers , equal numbers received National Institute of Allergy and Infectious Disease ( NIAID ) vaccine , Beijing Institute of Vaccine and Serum ( BIVS ) vaccine , and placebo . The cumulative seroconversion to the vaccines at 1 year of age was 95 % and 75 % , respectively . Vaccine efficacy as measured by the prevention of HBsAg-positive events was 88 % for the NIAID vaccine and 51 % for the BIVS vaccine . Vaccine efficacy was similar among infants born to hepatitis Be antigen-positive mothers . Because of the low efficacy of the BIVS vaccine , an additional group of 28 infants was given vaccine and hepatitis B immune globulin at birth . The result ing efficacy was 83 % . The results of this trial indicate that hepatitis B vaccine alone can substantially reduce perinatally acquired HBV infection and the result ing chronic carrier state Yupik Eskimos of southwestern Alaska have the highest known prevalence of hepatitis B virus infection of any general population in the United States . Prospect i ve serological surveys of 1,280 seronegative Yupik Eskimos , performed between 1971 and 1976 , identified 189 ( 14.8 % ) who developed serological evidence of hepatitis B virus infection .  Twenty-six ( 13.8 % ) developed clinical hepatitis during the interval when seroconversion occurred . The proportion of patients with clinical ly apparent hepatitis increased with age ( P less than .01 ) , ranging from 9.5 % of infections in patients who were four years of age or less to 33.3 % of infections in patients who were 30 years of age or older . Twenty-five ( 13.3 % ) of the 188 individuals who were studied became chronic carriers of hepatitis B surface antigen . The risk of becoming a carrier was inversely related to the age of the patient at the time of infection ( P = .02 ) . Among patients who were four years of age or less when infected , 28.8 % became chronic carriers of hepatitis B , as compared with 7.7 % of those who were 30 years of age or older We assessed the efficacy of an inactivated hepatitis B vaccine in a placebo-controlled , r and omized , double-blind trial in 1083 homosexual men known to be at high risk for hepatitis B virus infection . The vaccine was found to be safe and the incidence of side effects was low . Within two months , 77 % of the vaccinated persons had high levels of antibody against the hepatitis B surface antigen . This rate increased to 96 % after the booster dose and remained essentially unchanged for the duration of the trial . For the first 18 months of follow-up , hepatitis B or sub clinical infection developed in only 1.4 to 3.4 % of the vaccine recipients as compared with 18 to 27 % of placebo recipients ( P < 0.0001 ) . The reduction of incidence in the vaccinees was as high as 92.3 % ; none of the vaccinees with a detectable immune response to the vaccine had clinical hepatitis B or asymptomatic antigenemia . A significant reduction of incidence was already seen within 75 days after r and omization ; this observation suggests that the vaccine may be efficacious even when given after exposure OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( 
    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: The immunogenicity of plasma derived hepatitis B vaccine ( Hevac B ) was studied for active pre-exposure immunisation in 176 healthy volunteer adults and 162 r and omised children who had no hepatitis B virus markers . All subjects received three injections of 5 micrograms of hepatitis B vaccine intramuscularly at one month intervals . Seroconversion at 2 months after the third dose of vaccine was 96.30 percent in the children and 92.00 percent in the adults with mean anti-HBs titres of 800 mlU/ml and 353 mlU/ml respectively . The difference of anti-HBs levels between these two groups was statistically significant ( p less than 0.05 ) . Female adults had exhibited higher immune response to HB vaccine than male adults but there was no seroconversion difference between boys and girls . There were no serious local or systemic side effects of hepatitis B vaccination . It was concluded that active immunisation with plasma derived hepatitis B vaccine in non-immune children and adults is highly effective without any serious side effects or complications . The prevention of horizontal transmission of hepatitis B virus should be done by vaccination in children since they have a much better immune response to hepatitis B vaccine than adults The reactogenicity and immunogenicity of the administration of recombinant vaccine against hepatitis B simultaneously ( but at separate sites ) with diphtheria/tetanus/pertussis ( DTP ) and oral polio vaccines were examined . Six hundred and twenty-six children ( group I ) were given hepatitis B vaccine at 0 , 2 and 6 months of age ; the other vaccines were administered at 2 , 4 and 6 months of age . A control group of 731 children ( group II ) received only DTP and oral polio vaccines . The results showed that 93 % of the infants in group I had anti-HBs titres above the protective level ( > or = 10 mIU ml-1 ) after vaccination . There were no differences in the immune responses for DTP and polio between the two study groups . The vaccine efficacy against poliomyelitis was 96 % for serotype I , 100 % for serotype II and 97 - 98 % for serotype III . Of the infants in both groups , 97 % had antibodies against B. pertussis ; all children were positive for tetanus and diphtheria . There were no differences in the incidences of general reactions between groups . Local swelling and redness were reported following 4.2 and 4.4 % , respectively , of all injections of hepatitis B vaccine . These reactions were reported following 31 and 33 % , respectively , of all doses of DTP vaccine . It can be concluded that the simultaneous administration of hepatitis B vaccine with the DTP and polio vaccines is well-tolerated ; hepatitis B vaccine remained highly immunogenic and did not interfere with the immune response to the other antigens Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available To determine necessity and timing of booster of hepatitis B vaccine , we need to observe the duration of its protection . We report the results of a 15-year follow-up of a cohort of 649 children who participated a r and omized , double blind , placebo-controlled trial on a plasma-derived hepatitis B vaccine in 1982 . During the 15 years after vaccination , more vaccinated children had anti-HBs of 10 S/N ratios or over , compared with the controls , at all nine observations . At 15 years 50.0 % ( 26/52 ) of the participants studied in the vaccinated group and 33.3 % of the tested controls ( 18/54 ) retained anti-HBs levels of S/N ratios > or = 10 ( P < 0.09 ) . However , since 5 years after vaccination , median S/N ratios of anti-HBs among the vaccinated children with detectable anti-HBs were lower than those of the controls except that detected at 15 years . 16.7 % ( 9/54 ) of the tested children in the control group were HBsAg positive at 15 years after vaccination , in comparison with 1.9 % ( 1/52 ) of the tested children in the vaccinated ( P < 0.02 ) . 28 chronic HBsAg carriers were identified in the control cohort over the 15 years , whereas only 1 case was noted in the vaccinated group ( 8.2 % vs. 0.3 % , P < 0.00001 ) , corresponding to an efficacy of 96 % BACKGROUND / AIMS Treatment of hepatitis B virus carriers by vaccine containing hepatitis B surface antigen with Pre-S protein and HBsAg/ anti-HBs complex has been reported and these studies have constituted a new and promising concept for the treatment of HBV-carriers . The present communication , a placebo-controlled trial of vaccination in HBV-transgenic mice , was design ed to examine the impact of vaccination using a high dose of HBsAg for a duration of 12 months to achieve further insights about the dose , duration and effectiveness of vaccine therapy . Another aim of this study was to analyse the mechanism underlying the antiviral and immunomodulatory potentiality of vaccine therapy in HBV-transgenic mice . METHODS HBV-transgenic mice positive for HBV DNA , hepatitis B surface antigen and hepatitis B e antigen in sera received either HBV-vaccine containing HBsAg in complete Freund 's adjuvant ( CFA ) , intraperitoneally , once a month for 12 consecutive months ( vaccine recipients ) , or only CFA , intraperitoneally once in a month for 12 consecutive months ( placebo recipients ) . Thirty-two vaccine-recipient and 16 placebo-recipient HBV-transgenic mice were injected , checked and followed on a monthly basis for the entire duration of 12 months . RESULTS Of the 32 transgenic mice from the vaccine-recipient group , 25 became completely negative for HBsAg and 30 for HBeAg . Five mice developed anti-HBs in sera after the observation period of 12 months . Semiquantitative estimation of HBV DNA by polymerase chain reaction showed that vaccination result ed in a decrease of HBV DNA in sera . Placebo-recipient transgenic mice did not show any significant change in the titres of HBV markers after receiving 12 monthly injections of CFA . Interleukin-2 could be detected in sera from vaccine-recipient transgenic mice , but not in placebo-recipient transgenic mice . CONCLUSIONS Vaccination with a high dose of HBsAg in adjuvant over a long period had a significant antiviral as well as immunomodulatory potential in HBV-transgenic mice . This inspires optimism that vaccine alone or in combination with antiviral agents can be used successfully for the treatment of human HBV-carriers Hepatitis B is a serious disease of global significance . In developing countries , hepatitis B virus ( HBV ) infection and its sequelae rank among the public health problems of highest priority . Infants born to mothers who are chronic carriers of HBV are at particularly high risk of acquiring infection and becoming chronic HBV carriers . The efficacy of hepatitis B vaccine alone in preventing the transmission of HBV to infants born to HBV carrier mothers was determined in a double-blind placebo-controlled trial . Infants received plasma-derived vaccine at birth , 1 month , and 6 months of age . Of 180 infants born to hepatitis B surface antigen (HBsAg)-positive mothers , equal numbers received National Institute of Allergy and Infectious Disease ( NIAID ) vaccine , Beijing Institute of Vaccine and Serum ( BIVS ) vaccine , and placebo . The cumulative seroconversion to the vaccines at 1 year of age was 95 % and 75 % , respectively . Vaccine efficacy as measured by the prevention of HBsAg-positive events was 88 % for the NIAID vaccine and 51 % for the BIVS vaccine . Vaccine efficacy was similar among infants born to hepatitis Be antigen-positive mothers . Because of the low efficacy of the BIVS vaccine , an additional group of 28 infants was given vaccine and hepatitis B immune globulin at birth . The result ing efficacy was 83 % . The results of this trial indicate that hepatitis B vaccine alone can substantially reduce perinatally acquired HBV infection and the result ing chronic carrier state Yupik Eskimos of southwestern Alaska have the highest known prevalence of hepatitis B virus infection of any general population in the United States . Prospect i ve serological surveys of 1,280 seronegative Yupik Eskimos , performed between 1971 and 1976 , identified 189 ( 14.8 % ) who developed serological evidence of hepatitis B virus infection .  Twenty-six ( 13.8 % ) developed clinical hepatitis during the interval when seroconversion occurred . The proportion of patients with clinical ly apparent hepatitis increased with age ( P less than .01 ) , ranging from 9.5 % of infections in patients who were four years of age or less to 33.3 % of infections in patients who were 30 years of age or older . Twenty-five ( 13.3 % ) of the 188 individuals who were studied became chronic carriers of hepatitis B surface antigen . The risk of becoming a carrier was inversely related to the age of the patient at the time of infection ( P = .02 ) . Among patients who were four years of age or less when infected , 28.8 % became chronic carriers of hepatitis B , as compared with 7.7 % of those who were 30 years of age or older We assessed the efficacy of an inactivated hepatitis B vaccine in a placebo-controlled , r and omized , double-blind trial in 1083 homosexual men known to be at high risk for hepatitis B virus infection . The vaccine was found to be safe and the incidence of side effects was low . Within two months , 77 % of the vaccinated persons had high levels of antibody against the hepatitis B surface antigen . This rate increased to 96 % after the booster dose and remained essentially unchanged for the duration of the trial . For the first 18 months of follow-up , hepatitis B or sub clinical infection developed in only 1.4 to 3.4 % of the vaccine recipients as compared with 18 to 27 % of placebo recipients ( P < 0.0001 ) . The reduction of incidence in the vaccinees was as high as 92.3 % ; none of the vaccinees with a detectable immune response to the vaccine had clinical hepatitis B or asymptomatic antigenemia . A significant reduction of incidence was already seen within 75 days after r and omization ; this observation suggests that the vaccine may be efficacious even when given after exposure OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( 
    Output:
    