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: In Russia for prevention of influenza in children , aged from 3 to 14 years , the children 's live influenza vaccine ( LIV ) , based upon A/Leningrad/134/47/57(H2N2 ) master strain ( LIVI ) is used . The need for double immunization appears to be one out of the faulties of this preparation . The study was aim ed to comparing the safety , immunogenic activity and prevention of influenza by  LIV for adults ( LIVII ) ( A/Leningrad/134/17/57(H2N2 master strain ) and LIVI in children aged from 7 to 17 years under similar administration schedule . The safety , the preventive efficacy , humoral and secretory immunity were studied . In total 2486 persons , including 539 children , twice inoculated with LIVI , 971 persons once inoculated with LIVII , and 840 treated by placebo were obserbed . From the data of the clinical observations during 7 days after immunization both vaccines appeared to be low reactogenic . The LIVII advantages in induction of the humoral and secretory antibodies in comparison with children 's vaccine had been revealed . Both vaccines were highly efficacious , the efficiency of both preparations was more pronounced after serologic correction of the diagnosis . The results obtained permit to recommend the single immunization by the variant of LIV at the base on A/Leningrad/134/17/57/(H2N2 ) master strain for prevention of influenza in school children A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials To evaluate the efficacy of an intranasal , inactivated , virosomal subunit influenza vaccine for prevention of new episodes of acute otitis media ( AOM ) in children with recurrent AOM , 133 children aged 1 - 5 years were r and omized to receive the vaccine  ( n=67 ) or  no vaccination  ( n=66 ) . During a 6-month period , 24 ( 35.8 % ) vaccine recipients had 32 episodes of AOM ; 42 ( 63.6 % ) control subjects had 64 episodes . The overall efficacy of vaccination in preventing AOM was 43.7 % ( 95 % confidence interval , 18.6 - 61.1 ; P=.002 ) . Children vaccinated before influenza season had a significantly better outcome than did those vaccinated after the onset of influenza season . The cumulative duration of middle ear effusion was significantly less in vaccinated children than in control subjects . Data suggest that the intranasal virosomal influenza vaccine might be considered among the options for the prevention of AOM in children < 5 years old with recurrent AOM BACKGROUND Influenzavirus vaccine is used infrequently in healthy children , even though the rates of influenza in this group are high . We conducted a multicenter , double-blind , placebo-controlled trial of a live attenuated , cold-adapted , trivalent influenzavirus vaccine in children 15 to 71 months old . METHODS Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray , and 1314 were assigned to receive two doses approximately 60 days apart . The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time . The subjects were monitored with viral cultures for influenza during the subsequent influenza season . A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions . RESULTS The intranasal vaccine was accepted and well tolerated . Among children who were initially seronegative , antibody titers increased by a factor of four in 61 to 96 percent , depending on the influenza strain . Culture-positive influenza was significantly less common in the vaccine group ( 14 cases among 1070 subjects ) than the placebo group ( 95 cases among 532 subjects ) . The vaccine efficacy was 93 percent ( 95 percent confidence interval , 88 to 96 percent ) against culture-confirmed influenza . Both the one-dose regimen ( 89 percent efficacy ) and the two-dose regimen ( 94 percent efficacy ) were efficacious , and the vaccine was efficacious against both strains of influenza circulating in 1996 - 1997 , A(H3N2 ) and B. The vaccinated children had significantly fewer febrile illnesses , including 30 percent fewer episodes of febrile otitis media ( 95 percent confidence interval , 18 to 45 percent ; P<0.001 ) . CONCLUSIONS A live attenuated , cold-adapted influenzavirus vaccine was safe , immunogenic , and effective against influenza A(H3N2 ) and B in healthy children Reported is a study of live , cold-adapted ( CA ) reassortant mono- , di- , and trivalent influenza type A and B vaccines in a series of controlled clinical and epidemiological investigations involving nearly 130 000 children aged 3 - 15 years . The results of clinical , immunological , and morbidity investigations of the vaccinees and a control group over 6-months ' follow-up indicated that the vaccines were completely attenuated by the children . Transient febrile reactions occurred in < 1 % of the children after vaccination , including double seronegative individuals with low antibody titres . The type A reisolates examined were genetically stable . The reassortants did not suppress each other after simultaneous inoculation of children and stimulated antibody response to influenza virus strains A1 , A3 , and B. The incidence of influenza-like diseases was approximately 30 - 40 % lower among the vaccinated group than among the control group . The study demonstrates , for the first time , the efficacy of CA vaccine  against infections caused by influenza B virus Children aged 7 - 14 years in Novgorod , Russia , were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period . Schools were r and omly assigned as a whole to one of the preparations . In the first year , the vaccines were bivalent , containing types A ( H3N2 ) and A ( H1N1 ) components . In the second year , the vaccines also contained a type B component . In the first year , all viruses isolated were type A ( H3N2 ) ; in the second , about three-quarters of the isolates were type B and the rest type A ( H1N1 ) . During both years , the vaccines protected the vaccinated children . Where significant differences existed , the live attenuated vaccine was more protective than the inactivated . Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staff and unvaccinated children , suggesting that viral transmission had been reduced by the vaccine Three groups of children were immunized with an inactivated Port Chalmers ( H3ChN2Ch ) influenza vaccine ( group A ) , a neuraminidase-specific ( Heq1N2Ch ) influenza vaccine ( group B ) , or a placebo . Immunization induced seroconversion for H3Ch and N2Ch-specific antibody in group A and for N2Ch antibody in group B. The protective efficacies observed against naturally acquired illness with the Port Chalmers strain of influneza A virus were 68.7 % and 37.4 % in groups A and B , respectively , in comparison to the placebo group , and those against illness produced by the subsequent outbreak of the Victoria strain were 80.0 % and 72.7 % . These data support the role of neuraminidase-specific immunization in protection against influenza . Although the degree of protection after vaccination with the Heq1N2Ch vaccine was less than that provided by the biphasic H3ChN2Ch vaccine against the Port Chalmers strain , it appeared to be similar in the two vaccine study groups against the Victoria strain BACKGROUND Studies of  influenza vaccination in healthy children have not definitely answered the question of their efficacy . METHODS We have carried out a r and omized trial in a well selected population of healthy preschool children in Sardinia , Italy . During October 1995 , 344 children aged 1 to 6 years , were r and omly assigned to receive  influenza vaccine  ( n=177 ) or no treatment ( n=167 ) . Two doses of a trivalent subvirion vaccine , containing 15 mg of highly purified surface antigens from the component strains A/Johannesburg/33/94-like , A/Singapore/6/86-like and B/ Beijing/184/ 93-like were administered . Follow-up data were collected from December 1 , 1995 through April 30 , 1996 . RESULTS Seroconversion was documented in 17 out of 17 children . No specific systemic symptoms or severe local reactions were observed after vaccination . Influenza-like episodes , defined by the presence of fever and cough or sore throat that lasted at least 72 hours , occurred in 63 ( 37.7 % ) of unvaccinated children and in 22 ( 12.4 % ) of vaccinated ones . The corresponding reduction in disease incidence was 67 % ( 95 % CI : 0.59 - 0.74 ) . Three episodes of otitis were observed among children in the control group versus zero among vaccinated children ( p=0.07 ) . Mean duration of day care center absenteism was significantly reduced by vaccination ( 2.3 days in unvaccinated and 0.5 day in vaccinated children , p<0.001 ) CONCLUSIONS Influenza vaccine is safe and effective in healthy preschool children . However the favourable implication s of vaccination on disease rate in subsequent years have to be evaluated A placebo-controlled influenza vaccination trial was carried out on 374 children in the winter of 1967 - 68 . The children were r and omly vaccinated with 300 CCA of A2/Engl and /1/1966 , 300 CCA of A/equine 2/Miami/1963 , or with a placebo . During this winter an influenza outbreak occurred , caused by A2/Nederl and /1968 . The A2 vaccine yielded a protection rate of 58 % ( P = 0.02 ) and the A/equine 2 vaccine a rate of 19 % ( P = 0.33 ) . Serological data revealed that all influenza infections occurred in subjects who had a pre-epidemic  haemagglutination inhibition titre  below 150 . The antibody response against various human influenza A2 viruses and against the horse strain ( A/equine 2 ) is discussed CONTEXT Acute otitis media ( AOM ) frequently complicates influenza infection . Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years . OBJECTIVE To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children 's Hospital of Pittsburgh before the 1999 - 2000 ( 411 children ) and 2000 - 2001 ( 375 children ) respiratory seasons ( defined as December 1 through March 31 of the respective following year ) . Children received influenza vaccine or placebo in a 2:1 ratio . The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season . INTERVENTION Two doses ( 0.25 mL each ) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart . MAIN OUTCOME MEASURES Proportion of children who developed AOM , monthly occurrence rate of AOM , estimated proportion of time with middle ear effusion , and utilization of selected health care and related re sources . RESULTS Of the 66 children in the vaccine group from whom serum sample s were collected , seroconversion against strains in the vaccine formulations developed in 88.6 % to 96.8 % , depending on the specific strain . The efficacy of the vaccine against culture-confirmed influenza was 66 % ( 95 % confidence interval [ CI ] , 34%-82 % ) in 1999 - 2000 and -7 % ( 95 % CI , -247 % to 67 % ) in 2000 - 2001 ; however , influenza attack rates differed between these 2 periods ( in the placebo group , 15.9 % and 3.3 % , respectively ) . Compared with placebo , influenza vaccine 
    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: In Russia for prevention of influenza in children , aged from 3 to 14 years , the children 's live influenza vaccine ( LIV ) , based upon A/Leningrad/134/47/57(H2N2 ) master strain ( LIVI ) is used . The need for double immunization appears to be one out of the faulties of this preparation . The study was aim ed to comparing the safety , immunogenic activity and prevention of influenza by  LIV for adults ( LIVII ) ( A/Leningrad/134/17/57(H2N2 master strain ) and LIVI in children aged from 7 to 17 years under similar administration schedule . The safety , the preventive efficacy , humoral and secretory immunity were studied . In total 2486 persons , including 539 children , twice inoculated with LIVI , 971 persons once inoculated with LIVII , and 840 treated by placebo were obserbed . From the data of the clinical observations during 7 days after immunization both vaccines appeared to be low reactogenic . The LIVII advantages in induction of the humoral and secretory antibodies in comparison with children 's vaccine had been revealed . Both vaccines were highly efficacious , the efficiency of both preparations was more pronounced after serologic correction of the diagnosis . The results obtained permit to recommend the single immunization by the variant of LIV at the base on A/Leningrad/134/17/57/(H2N2 ) master strain for prevention of influenza in school children A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials To evaluate the efficacy of an intranasal , inactivated , virosomal subunit influenza vaccine for prevention of new episodes of acute otitis media ( AOM ) in children with recurrent AOM , 133 children aged 1 - 5 years were r and omized to receive the vaccine  ( n=67 ) or  no vaccination  ( n=66 ) . During a 6-month period , 24 ( 35.8 % ) vaccine recipients had 32 episodes of AOM ; 42 ( 63.6 % ) control subjects had 64 episodes . The overall efficacy of vaccination in preventing AOM was 43.7 % ( 95 % confidence interval , 18.6 - 61.1 ; P=.002 ) . Children vaccinated before influenza season had a significantly better outcome than did those vaccinated after the onset of influenza season . The cumulative duration of middle ear effusion was significantly less in vaccinated children than in control subjects . Data suggest that the intranasal virosomal influenza vaccine might be considered among the options for the prevention of AOM in children < 5 years old with recurrent AOM BACKGROUND Influenzavirus vaccine is used infrequently in healthy children , even though the rates of influenza in this group are high . We conducted a multicenter , double-blind , placebo-controlled trial of a live attenuated , cold-adapted , trivalent influenzavirus vaccine in children 15 to 71 months old . METHODS Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray , and 1314 were assigned to receive two doses approximately 60 days apart . The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time . The subjects were monitored with viral cultures for influenza during the subsequent influenza season . A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions . RESULTS The intranasal vaccine was accepted and well tolerated . Among children who were initially seronegative , antibody titers increased by a factor of four in 61 to 96 percent , depending on the influenza strain . Culture-positive influenza was significantly less common in the vaccine group ( 14 cases among 1070 subjects ) than the placebo group ( 95 cases among 532 subjects ) . The vaccine efficacy was 93 percent ( 95 percent confidence interval , 88 to 96 percent ) against culture-confirmed influenza . Both the one-dose regimen ( 89 percent efficacy ) and the two-dose regimen ( 94 percent efficacy ) were efficacious , and the vaccine was efficacious against both strains of influenza circulating in 1996 - 1997 , A(H3N2 ) and B. The vaccinated children had significantly fewer febrile illnesses , including 30 percent fewer episodes of febrile otitis media ( 95 percent confidence interval , 18 to 45 percent ; P<0.001 ) . CONCLUSIONS A live attenuated , cold-adapted influenzavirus vaccine was safe , immunogenic , and effective against influenza A(H3N2 ) and B in healthy children Reported is a study of live , cold-adapted ( CA ) reassortant mono- , di- , and trivalent influenza type A and B vaccines in a series of controlled clinical and epidemiological investigations involving nearly 130 000 children aged 3 - 15 years . The results of clinical , immunological , and morbidity investigations of the vaccinees and a control group over 6-months ' follow-up indicated that the vaccines were completely attenuated by the children . Transient febrile reactions occurred in < 1 % of the children after vaccination , including double seronegative individuals with low antibody titres . The type A reisolates examined were genetically stable . The reassortants did not suppress each other after simultaneous inoculation of children and stimulated antibody response to influenza virus strains A1 , A3 , and B. The incidence of influenza-like diseases was approximately 30 - 40 % lower among the vaccinated group than among the control group . The study demonstrates , for the first time , the efficacy of CA vaccine  against infections caused by influenza B virus Children aged 7 - 14 years in Novgorod , Russia , were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period . Schools were r and omly assigned as a whole to one of the preparations . In the first year , the vaccines were bivalent , containing types A ( H3N2 ) and A ( H1N1 ) components . In the second year , the vaccines also contained a type B component . In the first year , all viruses isolated were type A ( H3N2 ) ; in the second , about three-quarters of the isolates were type B and the rest type A ( H1N1 ) . During both years , the vaccines protected the vaccinated children . Where significant differences existed , the live attenuated vaccine was more protective than the inactivated . Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staff and unvaccinated children , suggesting that viral transmission had been reduced by the vaccine Three groups of children were immunized with an inactivated Port Chalmers ( H3ChN2Ch ) influenza vaccine ( group A ) , a neuraminidase-specific ( Heq1N2Ch ) influenza vaccine ( group B ) , or a placebo . Immunization induced seroconversion for H3Ch and N2Ch-specific antibody in group A and for N2Ch antibody in group B. The protective efficacies observed against naturally acquired illness with the Port Chalmers strain of influneza A virus were 68.7 % and 37.4 % in groups A and B , respectively , in comparison to the placebo group , and those against illness produced by the subsequent outbreak of the Victoria strain were 80.0 % and 72.7 % . These data support the role of neuraminidase-specific immunization in protection against influenza . Although the degree of protection after vaccination with the Heq1N2Ch vaccine was less than that provided by the biphasic H3ChN2Ch vaccine against the Port Chalmers strain , it appeared to be similar in the two vaccine study groups against the Victoria strain BACKGROUND Studies of  influenza vaccination in healthy children have not definitely answered the question of their efficacy . METHODS We have carried out a r and omized trial in a well selected population of healthy preschool children in Sardinia , Italy . During October 1995 , 344 children aged 1 to 6 years , were r and omly assigned to receive  influenza vaccine  ( n=177 ) or no treatment ( n=167 ) . Two doses of a trivalent subvirion vaccine , containing 15 mg of highly purified surface antigens from the component strains A/Johannesburg/33/94-like , A/Singapore/6/86-like and B/ Beijing/184/ 93-like were administered . Follow-up data were collected from December 1 , 1995 through April 30 , 1996 . RESULTS Seroconversion was documented in 17 out of 17 children . No specific systemic symptoms or severe local reactions were observed after vaccination . Influenza-like episodes , defined by the presence of fever and cough or sore throat that lasted at least 72 hours , occurred in 63 ( 37.7 % ) of unvaccinated children and in 22 ( 12.4 % ) of vaccinated ones . The corresponding reduction in disease incidence was 67 % ( 95 % CI : 0.59 - 0.74 ) . Three episodes of otitis were observed among children in the control group versus zero among vaccinated children ( p=0.07 ) . Mean duration of day care center absenteism was significantly reduced by vaccination ( 2.3 days in unvaccinated and 0.5 day in vaccinated children , p<0.001 ) CONCLUSIONS Influenza vaccine is safe and effective in healthy preschool children . However the favourable implication s of vaccination on disease rate in subsequent years have to be evaluated A placebo-controlled influenza vaccination trial was carried out on 374 children in the winter of 1967 - 68 . The children were r and omly vaccinated with 300 CCA of A2/Engl and /1/1966 , 300 CCA of A/equine 2/Miami/1963 , or with a placebo . During this winter an influenza outbreak occurred , caused by A2/Nederl and /1968 . The A2 vaccine yielded a protection rate of 58 % ( P = 0.02 ) and the A/equine 2 vaccine a rate of 19 % ( P = 0.33 ) . Serological data revealed that all influenza infections occurred in subjects who had a pre-epidemic  haemagglutination inhibition titre  below 150 . The antibody response against various human influenza A2 viruses and against the horse strain ( A/equine 2 ) is discussed CONTEXT Acute otitis media ( AOM ) frequently complicates influenza infection . Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years . OBJECTIVE To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children 's Hospital of Pittsburgh before the 1999 - 2000 ( 411 children ) and 2000 - 2001 ( 375 children ) respiratory seasons ( defined as December 1 through March 31 of the respective following year ) . Children received influenza vaccine or placebo in a 2:1 ratio . The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season . INTERVENTION Two doses ( 0.25 mL each ) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart . MAIN OUTCOME MEASURES Proportion of children who developed AOM , monthly occurrence rate of AOM , estimated proportion of time with middle ear effusion , and utilization of selected health care and related re sources . RESULTS Of the 66 children in the vaccine group from whom serum sample s were collected , seroconversion against strains in the vaccine formulations developed in 88.6 % to 96.8 % , depending on the specific strain . The efficacy of the vaccine against culture-confirmed influenza was 66 % ( 95 % confidence interval [ CI ] , 34%-82 % ) in 1999 - 2000 and -7 % ( 95 % CI , -247 % to 67 % ) in 2000 - 2001 ; however , influenza attack rates differed between these 2 periods ( in the placebo group , 15.9 % and 3.3 % , respectively ) . Compared with placebo , influenza vaccine 
    Output:
    