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: Objective : To evaluate Bacille Calmette-Guérin ( BCG ) effects after clinical ly isolated syndromes ( CIS ) . Methods : In a double-blind , placebo-controlled trial , participants were r and omly assigned to receive BCG or placebo  and monitored monthly with brain MRI ( 6 scans ) . Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months . From month 18 onward , the patients took the disease-modifying therapies ( DMTs ) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months . Results : Of 82 r and omized subjects , 73 completed the study ( 33 vaccinated and 40 placebo ) . During the initial 6 months , the number of cumulative lesions was significantly lower in vaccinated people . The relative risks were 0.541 ( 95 % confidence interval [ CI ] 0.308–0.956 ; p = 0.03 ) for gadolinium-enhancing lesions ( the primary endpoint ) , 0.364 ( 95 % CI 0.207–0.639 ; p = 0.001 ) for new and enlarging T2-hyperintense lesions , and 0.149 ( 95 % CI 0.046–0.416 ; p = 0.001 ) for new T1-hypointense lesions . The number of total T1-hypointense lesions was lower in the BCG group at months 6 , 12 , and 18 : mean changes from baseline were −0.09 ± 0.72 vs 0.75 ± 1.81 ( p = 0.01 ) , 0.0 ± 0.83 vs 0.88 ± 2.21 ( p = 0.08 ) , and −0.21 ± 1.03 vs 1.00 ± 2.49 ( p = 0.02 ) . After 60 months , the cumulative probability of clinical ly definite multiple sclerosis was lower in the BCG + DMT arm ( hazard ratio = 0.52 , 95 % CI 0.27–0.99 ; p < 0.05 ) , and more vaccinated people remained DMT-free ( odds ratio = 0.20 , 95 % CI 0.04–0.93 ; p = 0.04 ) . Conclusions : Early BCG may benefit CIS and affect its long-term course . Classification of evidence : BCG , as compared to placebo , was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy ( Class I evidence ) Article abstract -We determined the effect of influenza vaccine in patients with relapsing/remitting MS . Considerable controversy surrounds the question of whether to administer influenza vaccines to MS patients . Prevention of a febrile viral illness is clearly desirable in MS , and previous studies suggest that immunization is safe . Despite this , many clinicians avoid vaccination because they fear precipitating an MS exacerbation . We conducted a multicenter , prospect i ve , r and omized , double-blind trial of influenza immunization in patients with relapsing/remitting MS . In the autumn of 1993 , 104 patients at five MS centers received either st and ard influenza vaccine or placebo .  Patients were followed for 6 months for evaluation of neurologic status and the occurrence of influenza . Influenza was operationally defined as fever > or = to 38 degrees C in the presence of coryza , cough , or sore throat at a time when the disease was present in the community . Attacks were defined in the st and ard manner , requiring objective change in the examination . Patients were examined at 4 weeks and 6 months after inoculation and were contacted by telephone at 1 week and 3 months . They were also examined at times of possible attacks but not when they were sick with flu-like illness . Three vaccine patients and two placebo patients experienced attacks within 28 days of vaccine ( no significant difference ) . Exacerbation rates in the first month for both groups were equal to or less than expected from published series . The two groups showed no difference in attack rate or disease progression over 6 months . Influenza immunization in MS patients is neither associated with an increased exacerbation rate in the postvaccination period nor a change in disease course over the subsequent 6 months . NEUROLOGY 1997;48 : 312 - Background : The risk of CNS inflammatory demyelination associated with hepatitis B ( HB ) vaccine is debated , with studies reporting conflicting findings . Methods : We conducted a population -based case-control study where the cases were children with a first episode of acute CNS inflammatory demyelination in France ( 1994–2003 ) . Each case was matched on age , sex , and geographic location to up to 12 controls , r and omly selected from the general population . Information on vaccinations was confirmed by a copy of the vaccination certificate . The odds ratios ( ORs ) of CNS inflammatory demyelination associated with HB vaccination were estimated using conditional logistic regression . Results : The rates of HB vaccination  in the 3 years before the index date were 24.4 % for the 349 cases and 27.3 % for their 2,941 matched controls . HB vaccination within this period was not associated with an increase in the rate of CNS inflammatory demyelination ( adjusted OR , 0.74 ; 0.54–1.02 ) , neither > 3 years nor as a function of the number of injections or br and type . When the analysis was restricted to subjects compliant with vaccination , HB vaccine exposure > 3 years before index date was associated with an increased trend ( 1.50 ; 0.93–2.43 ) , essentially from the Engerix B vaccine ( 1.74 ; 1.03–2.95 ) . The OR was particularly elevated for this br and in patients with confirmed multiple sclerosis ( 2.77 ; 1.23–6.24 ) . Conclusions : Hepatitis B vaccination does not generally increase the risk of CNS inflammatory demyelination in childhood . However , the Engerix B vaccine appears to increase this risk , particularly for confirmed multiple sclerosis , in the longer term . Our results require confirmation in future studies . ADEM = acute disseminated encephalomyelitis ; BCG = Bacille Calmette – Guèrin ; HB = hepatitis B ; MS = multiple sclerosis ; OR = odds ratio OBJECTIVE To investigate whether vaccination against hepatitis B ( HB ) increases the risk of incident multiple sclerosis ( MS ) in childhood in the short and long terms . DESIGN Case-control study . SETTING Population -based study conducted in France from January 1 , 1994 , to December 31 , 2003 . PARTICIPANTS The case patients had incident MS with onset before age 16 years . Each case was individually matched for age , sex , and geographic location ( current place of residence ) to 12 control participants r and omly selected from the general population of France . EXPOSURE Hepatitis B vaccine . MAIN OUTCOME MEASURE The risk of MS associated with HB vaccine exposure . RESULTS One hundred forty-three case patients with MS were matched to 1122 control participants . The rate of HB vaccination  in the 3 years before the index date was approximately 32 % for both cases and controls . Vaccination against HB within the 3-year study period was not associated with an increased rate of a first episode of MS ( adjusted odds ratio , 1.03 ; 95 % confidence interval , 0.62 - 1.69 ) . The rate was also not increased for  HB vaccination  within 6 months of the index date or at any time since birth or as a function of the number of injections or the br and of HB vaccine . CONCLUSION Vaccination against HB does not seem to increase the risk of a first episode of MS in childhood Background : A potential link between the recombinant hepatitis B vaccine and an increased risk of multiple sclerosis ( MS )  has been evaluated in several studies , but some of them have substantial method ologic limitations . Methods : The authors conducted a nested case-control study within the General Practice Research Data base ( GPRD ) in the United Kingdom . The authors identified patients who had a first MS diagnosis recorded in the GPRD between January 1993 and December 2000 . Cases were patients with a diagnosis of MS confirmed through examination of medical records , and with at least 3 years of continuous recording in the GPRD before their date of first symptoms ( index date ) . Up to 10 controls per case were r and omly selected , matched on age , sex , practice , and date of joining the practice . Information on receipt of immunizations was obtained from the computer records . Results : The analyses include 163 cases of MS and 1,604 controls . The OR of MS for vaccination within 3 years before the index date compared to no vaccination was 3.1 ( 95 % CI 1.5 , 6.3 ) . No increased risk of MS was associated with tetanus and influenza vaccinations . Conclusions : These findings are consistent with the hypothesis that immunization with the recombinant hepatitis B vaccine is associated with an increased risk of MS , and challenge the idea that the relation between hepatitis B vaccination and risk of MS is well understood Hepatitis B infection is one of the most important causes of acute and chronic liver disease . During the 1980s , genetically engineered hepatitis B vaccines ( HBVs ) were introduced in the United States . A large-series of serious autoimmune conditions have been reported following HBVs , despite the fact that HBVs have been reported to be “ generally well-tolerated . ” A case-control epidemiological study was conducted to evaluate serious autoimmune adverse events prospect ively reported to the vaccine adverse events reporting system ( VAERS ) data base following HBVs , in comparison to an age , sex , and vaccine year matched unexposed tetanus-containing vaccine ( TCV )  group for conditions that have been previously identified on an a priori basis from case-reports . Adults receiving HBV had significantly increased odds ratios ( OR ) for multiple sclerosis ( OR = 5.2 , p < 0.0003 , 95 % Confidence Interval ( CI ) = 1.9 ™ 20 ) , optic neuritis ( OR = 14 , p < 0.0002 , 95 % CI = 2.3 − 560 ) , vasculitis ( OR = 2.6 , p < 0.04 , 95 % CI = 1.03 ™ 8.7 ) , arthritis ( OR = 2.01 , p < 0.0003 , 95 % CI = 1.3 − 3.1 ) , alopecia ( OR = 7.2 , p < 0.0001 , 95 % CI = 3.2 − 20 ) , lupus erythematosus ( OR = 9.1 , p < 0.0001 , 95 % CI = 2.3 − 76 ) , rheumatoid arthritis ( OR = 18 , p < 0.0001 , 95 % CI = 3.1 − 740 ) , and thrombocytopenia ( OR = 2.3 , p < 0.04 , 95 % CI = 1.02 − 6.2 ) in comparison to the TCV group . Minimal confounding or systematic error was observed . Despite the negative findings of the present study regarding the rare serious adverse effects of HBVs , it is clear that HBV does , indeed , offer significant benefits , but it is also clear that chances of exposure to hepatitis B virus in adults is largely life-style dependent . Adults should make an informed consent decision , weighing the risks and benefits of HBV , as to whether or not to be immunized A double-blind , placebo-controlled study was conducted to evaluate the safety and efficacy of inactivated influenza virus vaccines in patients with multiple sclerosis . The vaccine used contained 200 chick cell-agglutinating ( CCA ) units of influenza A/New Jersey/76 and 200 CCA units of influenza A/Victoria/75 whole viruses ( Merrell-National Laboratories , Cincinnati , Ohio ) . The frequency of clinical relapses of multiple sclerosis was the same in the vaccine-treated ( four of 33 patients ) and placebo-treated ( four of 33 ) groups . An untreated control group had a slightly higher rate of relapses ( four of 22 ) . Toxic reactions to the vaccine were not a significant problem . The efficacy of the vaccination as measured by titers of hemagglutination-inhibiting antibody was comparable to that reported for the general population . However , patients with preexisting antibody were less responsive to the vaccine than normal controls studied previously . The patients who did not respond to the vaccine tended to be older and more disabled . There were no changes in titers of antibody to rubeola or rubella virus after vaccination or in relation to change in clinical course . It is concluded that the vaccine is safe and effective in patients with multiple sclerosis The aim of this study was to investigate a possible link between a single vaccination against tick-borne encephalitis ( TBE ) and the appearance of one or more new cerebral lesions in magnetic resonance imaging ( MRI ) and /or a clinical relapse of MS . Fifteen MS patients with documented history of MS relapses living in a TBE endemic area were matched with 15 patients selected from a patient data base containing 500 cases of MS . Three patients in each 
    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: Objective : To evaluate Bacille Calmette-Guérin ( BCG ) effects after clinical ly isolated syndromes ( CIS ) . Methods : In a double-blind , placebo-controlled trial , participants were r and omly assigned to receive BCG or placebo  and monitored monthly with brain MRI ( 6 scans ) . Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months . From month 18 onward , the patients took the disease-modifying therapies ( DMTs ) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months . Results : Of 82 r and omized subjects , 73 completed the study ( 33 vaccinated and 40 placebo ) . During the initial 6 months , the number of cumulative lesions was significantly lower in vaccinated people . The relative risks were 0.541 ( 95 % confidence interval [ CI ] 0.308–0.956 ; p = 0.03 ) for gadolinium-enhancing lesions ( the primary endpoint ) , 0.364 ( 95 % CI 0.207–0.639 ; p = 0.001 ) for new and enlarging T2-hyperintense lesions , and 0.149 ( 95 % CI 0.046–0.416 ; p = 0.001 ) for new T1-hypointense lesions . The number of total T1-hypointense lesions was lower in the BCG group at months 6 , 12 , and 18 : mean changes from baseline were −0.09 ± 0.72 vs 0.75 ± 1.81 ( p = 0.01 ) , 0.0 ± 0.83 vs 0.88 ± 2.21 ( p = 0.08 ) , and −0.21 ± 1.03 vs 1.00 ± 2.49 ( p = 0.02 ) . After 60 months , the cumulative probability of clinical ly definite multiple sclerosis was lower in the BCG + DMT arm ( hazard ratio = 0.52 , 95 % CI 0.27–0.99 ; p < 0.05 ) , and more vaccinated people remained DMT-free ( odds ratio = 0.20 , 95 % CI 0.04–0.93 ; p = 0.04 ) . Conclusions : Early BCG may benefit CIS and affect its long-term course . Classification of evidence : BCG , as compared to placebo , was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy ( Class I evidence ) Article abstract -We determined the effect of influenza vaccine in patients with relapsing/remitting MS . Considerable controversy surrounds the question of whether to administer influenza vaccines to MS patients . Prevention of a febrile viral illness is clearly desirable in MS , and previous studies suggest that immunization is safe . Despite this , many clinicians avoid vaccination because they fear precipitating an MS exacerbation . We conducted a multicenter , prospect i ve , r and omized , double-blind trial of influenza immunization in patients with relapsing/remitting MS . In the autumn of 1993 , 104 patients at five MS centers received either st and ard influenza vaccine or placebo .  Patients were followed for 6 months for evaluation of neurologic status and the occurrence of influenza . Influenza was operationally defined as fever > or = to 38 degrees C in the presence of coryza , cough , or sore throat at a time when the disease was present in the community . Attacks were defined in the st and ard manner , requiring objective change in the examination . Patients were examined at 4 weeks and 6 months after inoculation and were contacted by telephone at 1 week and 3 months . They were also examined at times of possible attacks but not when they were sick with flu-like illness . Three vaccine patients and two placebo patients experienced attacks within 28 days of vaccine ( no significant difference ) . Exacerbation rates in the first month for both groups were equal to or less than expected from published series . The two groups showed no difference in attack rate or disease progression over 6 months . Influenza immunization in MS patients is neither associated with an increased exacerbation rate in the postvaccination period nor a change in disease course over the subsequent 6 months . NEUROLOGY 1997;48 : 312 - Background : The risk of CNS inflammatory demyelination associated with hepatitis B ( HB ) vaccine is debated , with studies reporting conflicting findings . Methods : We conducted a population -based case-control study where the cases were children with a first episode of acute CNS inflammatory demyelination in France ( 1994–2003 ) . Each case was matched on age , sex , and geographic location to up to 12 controls , r and omly selected from the general population . Information on vaccinations was confirmed by a copy of the vaccination certificate . The odds ratios ( ORs ) of CNS inflammatory demyelination associated with HB vaccination were estimated using conditional logistic regression . Results : The rates of HB vaccination  in the 3 years before the index date were 24.4 % for the 349 cases and 27.3 % for their 2,941 matched controls . HB vaccination within this period was not associated with an increase in the rate of CNS inflammatory demyelination ( adjusted OR , 0.74 ; 0.54–1.02 ) , neither > 3 years nor as a function of the number of injections or br and type . When the analysis was restricted to subjects compliant with vaccination , HB vaccine exposure > 3 years before index date was associated with an increased trend ( 1.50 ; 0.93–2.43 ) , essentially from the Engerix B vaccine ( 1.74 ; 1.03–2.95 ) . The OR was particularly elevated for this br and in patients with confirmed multiple sclerosis ( 2.77 ; 1.23–6.24 ) . Conclusions : Hepatitis B vaccination does not generally increase the risk of CNS inflammatory demyelination in childhood . However , the Engerix B vaccine appears to increase this risk , particularly for confirmed multiple sclerosis , in the longer term . Our results require confirmation in future studies . ADEM = acute disseminated encephalomyelitis ; BCG = Bacille Calmette – Guèrin ; HB = hepatitis B ; MS = multiple sclerosis ; OR = odds ratio OBJECTIVE To investigate whether vaccination against hepatitis B ( HB ) increases the risk of incident multiple sclerosis ( MS ) in childhood in the short and long terms . DESIGN Case-control study . SETTING Population -based study conducted in France from January 1 , 1994 , to December 31 , 2003 . PARTICIPANTS The case patients had incident MS with onset before age 16 years . Each case was individually matched for age , sex , and geographic location ( current place of residence ) to 12 control participants r and omly selected from the general population of France . EXPOSURE Hepatitis B vaccine . MAIN OUTCOME MEASURE The risk of MS associated with HB vaccine exposure . RESULTS One hundred forty-three case patients with MS were matched to 1122 control participants . The rate of HB vaccination  in the 3 years before the index date was approximately 32 % for both cases and controls . Vaccination against HB within the 3-year study period was not associated with an increased rate of a first episode of MS ( adjusted odds ratio , 1.03 ; 95 % confidence interval , 0.62 - 1.69 ) . The rate was also not increased for  HB vaccination  within 6 months of the index date or at any time since birth or as a function of the number of injections or the br and of HB vaccine . CONCLUSION Vaccination against HB does not seem to increase the risk of a first episode of MS in childhood Background : A potential link between the recombinant hepatitis B vaccine and an increased risk of multiple sclerosis ( MS )  has been evaluated in several studies , but some of them have substantial method ologic limitations . Methods : The authors conducted a nested case-control study within the General Practice Research Data base ( GPRD ) in the United Kingdom . The authors identified patients who had a first MS diagnosis recorded in the GPRD between January 1993 and December 2000 . Cases were patients with a diagnosis of MS confirmed through examination of medical records , and with at least 3 years of continuous recording in the GPRD before their date of first symptoms ( index date ) . Up to 10 controls per case were r and omly selected , matched on age , sex , practice , and date of joining the practice . Information on receipt of immunizations was obtained from the computer records . Results : The analyses include 163 cases of MS and 1,604 controls . The OR of MS for vaccination within 3 years before the index date compared to no vaccination was 3.1 ( 95 % CI 1.5 , 6.3 ) . No increased risk of MS was associated with tetanus and influenza vaccinations . Conclusions : These findings are consistent with the hypothesis that immunization with the recombinant hepatitis B vaccine is associated with an increased risk of MS , and challenge the idea that the relation between hepatitis B vaccination and risk of MS is well understood Hepatitis B infection is one of the most important causes of acute and chronic liver disease . During the 1980s , genetically engineered hepatitis B vaccines ( HBVs ) were introduced in the United States . A large-series of serious autoimmune conditions have been reported following HBVs , despite the fact that HBVs have been reported to be “ generally well-tolerated . ” A case-control epidemiological study was conducted to evaluate serious autoimmune adverse events prospect ively reported to the vaccine adverse events reporting system ( VAERS ) data base following HBVs , in comparison to an age , sex , and vaccine year matched unexposed tetanus-containing vaccine ( TCV )  group for conditions that have been previously identified on an a priori basis from case-reports . Adults receiving HBV had significantly increased odds ratios ( OR ) for multiple sclerosis ( OR = 5.2 , p < 0.0003 , 95 % Confidence Interval ( CI ) = 1.9 ™ 20 ) , optic neuritis ( OR = 14 , p < 0.0002 , 95 % CI = 2.3 − 560 ) , vasculitis ( OR = 2.6 , p < 0.04 , 95 % CI = 1.03 ™ 8.7 ) , arthritis ( OR = 2.01 , p < 0.0003 , 95 % CI = 1.3 − 3.1 ) , alopecia ( OR = 7.2 , p < 0.0001 , 95 % CI = 3.2 − 20 ) , lupus erythematosus ( OR = 9.1 , p < 0.0001 , 95 % CI = 2.3 − 76 ) , rheumatoid arthritis ( OR = 18 , p < 0.0001 , 95 % CI = 3.1 − 740 ) , and thrombocytopenia ( OR = 2.3 , p < 0.04 , 95 % CI = 1.02 − 6.2 ) in comparison to the TCV group . Minimal confounding or systematic error was observed . Despite the negative findings of the present study regarding the rare serious adverse effects of HBVs , it is clear that HBV does , indeed , offer significant benefits , but it is also clear that chances of exposure to hepatitis B virus in adults is largely life-style dependent . Adults should make an informed consent decision , weighing the risks and benefits of HBV , as to whether or not to be immunized A double-blind , placebo-controlled study was conducted to evaluate the safety and efficacy of inactivated influenza virus vaccines in patients with multiple sclerosis . The vaccine used contained 200 chick cell-agglutinating ( CCA ) units of influenza A/New Jersey/76 and 200 CCA units of influenza A/Victoria/75 whole viruses ( Merrell-National Laboratories , Cincinnati , Ohio ) . The frequency of clinical relapses of multiple sclerosis was the same in the vaccine-treated ( four of 33 patients ) and placebo-treated ( four of 33 ) groups . An untreated control group had a slightly higher rate of relapses ( four of 22 ) . Toxic reactions to the vaccine were not a significant problem . The efficacy of the vaccination as measured by titers of hemagglutination-inhibiting antibody was comparable to that reported for the general population . However , patients with preexisting antibody were less responsive to the vaccine than normal controls studied previously . The patients who did not respond to the vaccine tended to be older and more disabled . There were no changes in titers of antibody to rubeola or rubella virus after vaccination or in relation to change in clinical course . It is concluded that the vaccine is safe and effective in patients with multiple sclerosis The aim of this study was to investigate a possible link between a single vaccination against tick-borne encephalitis ( TBE ) and the appearance of one or more new cerebral lesions in magnetic resonance imaging ( MRI ) and /or a clinical relapse of MS . Fifteen MS patients with documented history of MS relapses living in a TBE endemic area were matched with 15 patients selected from a patient data base containing 500 cases of MS . Three patients in each 
    Output:
    