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 present prospect i ve study was conducted from 2003–2005 , among all individuals 65 years and older in Uppsala County , a region with 300 000 inhabitants situated close to the Stockholm urban area . The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay ( LOHS ) even during periods of low influenza activity . The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons . Results In 2003 , the total study population was 41,059 , of which 12,907 ( 31 % ) received influenza vaccine  of these , 4,447 ( 11 % ) were administered the pneumococcal vaccine . In 2004 , 14,799 ( 34 % ) individuals received the influenza vaccine and 8,843 ( 21 % ) the pneumococcal vaccine and in 2005 16,926 ( 39 % ) individuals were given the influenza vaccine and 12,340 ( 28 % ) the pneumococcal vaccine . Our findings indicated that 35 % of the vaccinated cohort belonged to a medical risk category ( mainly those persons that received the pneumococcal vaccine ) . Data on hospitalisation and mortality during the 3-year period were obtained from the administrative data base of the Uppsala county council . During the influenza seasons , reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort ( below 80 years of age ) . For individuals who also had received the pneumococcal vaccine , a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia . Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine , despite that the pneumococcal vaccinated mainly belonged to a medical risk category . Reduction of death from all causes was observed during the influenza season of 2004 , in the 75–84-year old age group and in all age-groups during the influenza season 2005 . Conclusion The present study confirmed the additive effect of the two vaccines in the elderly , which was associated with a reduced risk in hospitalisation and a reduction in mean LOHS in seasons with low influenza activity Background . Highly pathogenic avian influenza H5N1 viruses remain a threat to human health , with potential to become p and emic agents . Methods . This phase III , placebo-controlled , observer-blinded study evaluated the immunogenicity , cross-reactivity , safety , and lot consistency of 2 doses of oil-in-water ( AS03A ) adjuvanted H5N1 A/Indonesia/05/2005 ( 3.75 μg hemagglutinin antigen ) prep and emic c and i date vaccine in 4561 adults aged 18–91 years . Results . Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for p and emic vaccines in all age strata 21 days after the second dose . At 6 months after the administration of the primary dose , serum antibody seroconversion rates continued to fulfill licensure criteria . Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004 . Consistency was demonstrated for 3 consecutive H5N1 vaccine lots . Temporary injection-site pain was more frequent with H5N1 vaccine than placebo ( 89.3 % and 70.7 % in the 18–64 and ≥65 years strata vs 22.2 % and 14.4 % in the placebo groups ) . Unsolicited adverse event frequency , including medically attended and serious events , was similar between groups through day 364 . Conclusions . In adults and elderly adults  , AS03A-adjuvanted H5N1 c and i date vaccine was highly immunogenic for A/Indonesia/05/2005 , with cross-reactivity against A/Vietnam/1194/2004 . Temporary injection site reactions were more frequent with H5N1 vaccine than placebo , although the H5N1 vaccine was well tolerated overall . Clinical Trials Registration . NCT00616928 Background and Purpose — Vascular death rates and hospitalizations for stroke are increased during influenza epidemics . Influenza vaccination may prevent stroke . We investigated whether influenza vaccination is associated independently with reduced odds of stroke and whether effects are confined to stroke subgroups and winter seasons and shared by other vaccinations . Methods — During 18 months , we performed st and ardized interviews assessing vaccination status , risk factors , health-related behavior , and socioeconomic factors in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack ( TIA ) and 370 age- and sex-matched control subjects selected r and omly from the population . Results —  Influenza vaccination  during the last vaccination campaign was less common in patients ( 19.2 % ) than control subjects ( 31.4 % ; P<0.0001 ) . After adjustment for vascular risk factors , education , health-related behavior and other factors ,  influenza vaccination  ( odds ratio [ OR ] , 0.46 ; 95 % CI , 0.28 to 0.77 ) but not other combined recent vaccinations ( OR , 0.80 ; 95 % CI , 0.42 to 1.43 ) were associated with reduced odds of stroke/TIA . Significant effects were found in men , older subjects ( > 65 years ) , subjects with previous vascular diseases , and regarding ischemic stroke ; nonsignificant trends existed in women , younger subjects , and regarding hemorrhagic stroke . In etiologic subgroups of cerebral ischemia , similar effects were found . No protective effects were found during summer months ; however , results also varied considerably between both winter seasons examined . Conclusions — These results support the hypothesis that influenza vaccination may be associated with reduced stroke risk . However , residual confounding can not be excluded , and interventional studies are required to evaluate the role of influenza vaccination in stroke prevention BACKGROUND Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications . This has led to the current interest in developing effective oral or intranasal preparations . OBJECTIVE This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults . It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant . METHODS This was a multicenter , Phase I , r and omized , open-label pilot study in which the primary end point was immunogenicity ( hemagglutination-inhibition [ HI ] antibody assay on days 1 and 29 ) . The secondary end point was the frequency of adverse events ( AEs ) . Subjects were assigned to 4 vaccination groups : groups AI , AII , and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used , and group B received intramuscular virosomal subunit vaccine . Assessment s of health status , hematology , biochemistry , body temperature , heart rate , blood pressure , and incidence of AEs were made on days 1 , 8 , and 29 , and serology was assessed on days 1 and 29 . RESULTS The study enrolled 88 subjects . All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered ( A/Singapore , A/Texas , A/Wuhan , B/Beijing ) , with no notable immunogenic differences between lots . After intranasal vaccination , geometric mean titers ( GMT ) increased 2.7-fold against A/Singapore ( group AI ) ; 1.8- and 3.1-fold against A/Texas ( groups AII and AIII , respectively ) ; 1.9- to 2.4-fold against A/Wuhan ; and 1.5- to 1.7-fold against B/Beijing . After intramuscular vaccination . GMT increased 11.3- , 6.3- , and 2.7-fold against A/Texas , A/Wuhan , and B/Beijing , respectively . Seroprotection ( HI antibody titers > or = 1:40 in > 70 % of those vaccinated ) was achieved against all strains in the group that received intramuscular vaccination , against A/Wuhan in all groups that received intranasal vaccination , and against A/Texas in group AII . Both vaccine formulations were well tolerated . Intranasal vaccination was associated with a low incidence ( < 20 % ) of nasal AEs . CONCLUSIONS Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated . The different batches of intranasal vaccine showed a similar immunogenic profile . Intranasal administration may be preferred to intramuscular administration by some patients The effects on anticoagulation of a purified trivalent sub-unit influenza vaccine and a 14-valent pneumococcal vaccine were investigated in a single-blind controlled study involving 69 well-stabilised warfarin recipients . There were no clinical ly or statistically significant alterations of anticoagulant control in vaccine recipients as compared with controls at 2 , 7 and 21 days after vaccination . On the basis of these data , concern about warfarin-vaccine interaction should not deter practitioners from immunising warfarin recipients against influenza or infection with Streptococcus pneumoniae AIMS To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease ( CAD ) . METHODS AND RESULTS R and omized , double-blind , placebo controlled study . We included 658 optimally treated CAD patients ; 477 men , mean age 59.9+/-10.3 years . Three hundred and twenty-five patients received the influenza vaccine  , and 333 patients  placebo . Median follow-up was 298 ( interquartile range 263 - 317 ) days . Primary endpoint was the cardiovascular death . Its estimated 12-month cumulative event rate was 0.63 % in the vaccine vs. 0.76 % in controls ( HR 1.06 95 % CI : 0.15 - 7.56 , P = 0.95 ) . There were two secondary composite endpoints : ( i ) the MACE ( cardiovascular death , myocardial infa rct ion , coronary revascularization ) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87 % , respectively ( HR 0.54;95 % CI : 0.24 - 1.21 , P = 0.13 ) . ( ii ) Coronary ischaemic event ( MACE or hospitalization for myocardial ischaemia ) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97 % in controls ( HR 0.54 ; 95 % CI : 0.29 - 0.99 , P = 0.047 ) . CONCLUSION In optimally treated CAD patients  influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events . Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality . ( Clinical Trials.gov : NCT 00371098 ) Background —Numerous studies have suggested that microbial agents may promote atherosclerosis . A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infa rct ion ( MI ) . We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease ( CHD ) . Methods and Results —A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998 . Patients who experienced new MI were included in the case group , and those who did not experience new MI or unstable angina were assigned to the control group . Data were collected by structured review of patients ’ charts and through a subsequent telephone survey . Adjusted for history of influenza vaccination in previous years , multivariate logistic regression revealed risk of MI to be associated with current hypertension ( OR 4.96 , 95 % CI 2.06 to 11.96 , P < 0.0001 ) , hypercholesterolemia ( OR 4.08 , 95 % CI 1.67 to 9.99 , P = 0.002 ) , smoking ( OR 3.75 , 95 % CI 1.76 to 7.98 , P = 0.001 ) , and  influenza vaccination  ( OR 0.33 , 95 % CI 0.13 to 0.82 , P = 0.017 ) . Despite significant association in univariate analysis , multivitamin therapy and physical exercise were not associated with risk of reinfa rct ion in multivariate analysis . Conclusions —In this study in patients with chronic CHD , vaccination against influenza 
    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 present prospect i ve study was conducted from 2003–2005 , among all individuals 65 years and older in Uppsala County , a region with 300 000 inhabitants situated close to the Stockholm urban area . The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay ( LOHS ) even during periods of low influenza activity . The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons . Results In 2003 , the total study population was 41,059 , of which 12,907 ( 31 % ) received influenza vaccine  of these , 4,447 ( 11 % ) were administered the pneumococcal vaccine . In 2004 , 14,799 ( 34 % ) individuals received the influenza vaccine and 8,843 ( 21 % ) the pneumococcal vaccine and in 2005 16,926 ( 39 % ) individuals were given the influenza vaccine and 12,340 ( 28 % ) the pneumococcal vaccine . Our findings indicated that 35 % of the vaccinated cohort belonged to a medical risk category ( mainly those persons that received the pneumococcal vaccine ) . Data on hospitalisation and mortality during the 3-year period were obtained from the administrative data base of the Uppsala county council . During the influenza seasons , reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort ( below 80 years of age ) . For individuals who also had received the pneumococcal vaccine , a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia . Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine , despite that the pneumococcal vaccinated mainly belonged to a medical risk category . Reduction of death from all causes was observed during the influenza season of 2004 , in the 75–84-year old age group and in all age-groups during the influenza season 2005 . Conclusion The present study confirmed the additive effect of the two vaccines in the elderly , which was associated with a reduced risk in hospitalisation and a reduction in mean LOHS in seasons with low influenza activity Background . Highly pathogenic avian influenza H5N1 viruses remain a threat to human health , with potential to become p and emic agents . Methods . This phase III , placebo-controlled , observer-blinded study evaluated the immunogenicity , cross-reactivity , safety , and lot consistency of 2 doses of oil-in-water ( AS03A ) adjuvanted H5N1 A/Indonesia/05/2005 ( 3.75 μg hemagglutinin antigen ) prep and emic c and i date vaccine in 4561 adults aged 18–91 years . Results . Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for p and emic vaccines in all age strata 21 days after the second dose . At 6 months after the administration of the primary dose , serum antibody seroconversion rates continued to fulfill licensure criteria . Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004 . Consistency was demonstrated for 3 consecutive H5N1 vaccine lots . Temporary injection-site pain was more frequent with H5N1 vaccine than placebo ( 89.3 % and 70.7 % in the 18–64 and ≥65 years strata vs 22.2 % and 14.4 % in the placebo groups ) . Unsolicited adverse event frequency , including medically attended and serious events , was similar between groups through day 364 . Conclusions . In adults and elderly adults  , AS03A-adjuvanted H5N1 c and i date vaccine was highly immunogenic for A/Indonesia/05/2005 , with cross-reactivity against A/Vietnam/1194/2004 . Temporary injection site reactions were more frequent with H5N1 vaccine than placebo , although the H5N1 vaccine was well tolerated overall . Clinical Trials Registration . NCT00616928 Background and Purpose — Vascular death rates and hospitalizations for stroke are increased during influenza epidemics . Influenza vaccination may prevent stroke . We investigated whether influenza vaccination is associated independently with reduced odds of stroke and whether effects are confined to stroke subgroups and winter seasons and shared by other vaccinations . Methods — During 18 months , we performed st and ardized interviews assessing vaccination status , risk factors , health-related behavior , and socioeconomic factors in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack ( TIA ) and 370 age- and sex-matched control subjects selected r and omly from the population . Results —  Influenza vaccination  during the last vaccination campaign was less common in patients ( 19.2 % ) than control subjects ( 31.4 % ; P<0.0001 ) . After adjustment for vascular risk factors , education , health-related behavior and other factors ,  influenza vaccination  ( odds ratio [ OR ] , 0.46 ; 95 % CI , 0.28 to 0.77 ) but not other combined recent vaccinations ( OR , 0.80 ; 95 % CI , 0.42 to 1.43 ) were associated with reduced odds of stroke/TIA . Significant effects were found in men , older subjects ( > 65 years ) , subjects with previous vascular diseases , and regarding ischemic stroke ; nonsignificant trends existed in women , younger subjects , and regarding hemorrhagic stroke . In etiologic subgroups of cerebral ischemia , similar effects were found . No protective effects were found during summer months ; however , results also varied considerably between both winter seasons examined . Conclusions — These results support the hypothesis that influenza vaccination may be associated with reduced stroke risk . However , residual confounding can not be excluded , and interventional studies are required to evaluate the role of influenza vaccination in stroke prevention BACKGROUND Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications . This has led to the current interest in developing effective oral or intranasal preparations . OBJECTIVE This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults . It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant . METHODS This was a multicenter , Phase I , r and omized , open-label pilot study in which the primary end point was immunogenicity ( hemagglutination-inhibition [ HI ] antibody assay on days 1 and 29 ) . The secondary end point was the frequency of adverse events ( AEs ) . Subjects were assigned to 4 vaccination groups : groups AI , AII , and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used , and group B received intramuscular virosomal subunit vaccine . Assessment s of health status , hematology , biochemistry , body temperature , heart rate , blood pressure , and incidence of AEs were made on days 1 , 8 , and 29 , and serology was assessed on days 1 and 29 . RESULTS The study enrolled 88 subjects . All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered ( A/Singapore , A/Texas , A/Wuhan , B/Beijing ) , with no notable immunogenic differences between lots . After intranasal vaccination , geometric mean titers ( GMT ) increased 2.7-fold against A/Singapore ( group AI ) ; 1.8- and 3.1-fold against A/Texas ( groups AII and AIII , respectively ) ; 1.9- to 2.4-fold against A/Wuhan ; and 1.5- to 1.7-fold against B/Beijing . After intramuscular vaccination . GMT increased 11.3- , 6.3- , and 2.7-fold against A/Texas , A/Wuhan , and B/Beijing , respectively . Seroprotection ( HI antibody titers > or = 1:40 in > 70 % of those vaccinated ) was achieved against all strains in the group that received intramuscular vaccination , against A/Wuhan in all groups that received intranasal vaccination , and against A/Texas in group AII . Both vaccine formulations were well tolerated . Intranasal vaccination was associated with a low incidence ( < 20 % ) of nasal AEs . CONCLUSIONS Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated . The different batches of intranasal vaccine showed a similar immunogenic profile . Intranasal administration may be preferred to intramuscular administration by some patients The effects on anticoagulation of a purified trivalent sub-unit influenza vaccine and a 14-valent pneumococcal vaccine were investigated in a single-blind controlled study involving 69 well-stabilised warfarin recipients . There were no clinical ly or statistically significant alterations of anticoagulant control in vaccine recipients as compared with controls at 2 , 7 and 21 days after vaccination . On the basis of these data , concern about warfarin-vaccine interaction should not deter practitioners from immunising warfarin recipients against influenza or infection with Streptococcus pneumoniae AIMS To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease ( CAD ) . METHODS AND RESULTS R and omized , double-blind , placebo controlled study . We included 658 optimally treated CAD patients ; 477 men , mean age 59.9+/-10.3 years . Three hundred and twenty-five patients received the influenza vaccine  , and 333 patients  placebo . Median follow-up was 298 ( interquartile range 263 - 317 ) days . Primary endpoint was the cardiovascular death . Its estimated 12-month cumulative event rate was 0.63 % in the vaccine vs. 0.76 % in controls ( HR 1.06 95 % CI : 0.15 - 7.56 , P = 0.95 ) . There were two secondary composite endpoints : ( i ) the MACE ( cardiovascular death , myocardial infa rct ion , coronary revascularization ) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87 % , respectively ( HR 0.54;95 % CI : 0.24 - 1.21 , P = 0.13 ) . ( ii ) Coronary ischaemic event ( MACE or hospitalization for myocardial ischaemia ) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97 % in controls ( HR 0.54 ; 95 % CI : 0.29 - 0.99 , P = 0.047 ) . CONCLUSION In optimally treated CAD patients  influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events . Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality . ( Clinical Trials.gov : NCT 00371098 ) Background —Numerous studies have suggested that microbial agents may promote atherosclerosis . A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infa rct ion ( MI ) . We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease ( CHD ) . Methods and Results —A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998 . Patients who experienced new MI were included in the case group , and those who did not experience new MI or unstable angina were assigned to the control group . Data were collected by structured review of patients ’ charts and through a subsequent telephone survey . Adjusted for history of influenza vaccination in previous years , multivariate logistic regression revealed risk of MI to be associated with current hypertension ( OR 4.96 , 95 % CI 2.06 to 11.96 , P < 0.0001 ) , hypercholesterolemia ( OR 4.08 , 95 % CI 1.67 to 9.99 , P = 0.002 ) , smoking ( OR 3.75 , 95 % CI 1.76 to 7.98 , P = 0.001 ) , and  influenza vaccination  ( OR 0.33 , 95 % CI 0.13 to 0.82 , P = 0.017 ) . Despite significant association in univariate analysis , multivitamin therapy and physical exercise were not associated with risk of reinfa rct ion in multivariate analysis . Conclusions —In this study in patients with chronic CHD , vaccination against influenza 
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