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 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 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 was negatively associated with the development of new MI during the same influenza season . However , to address causal inference , examination of prospect i ve data sets will be needed Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes , and cardiovascular mortality increases abruptly during influenza epidemics , with little evidence of a lag period . In a population -based case-control study , the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest ( PCA ) , a major contributor to cardiovascular mortality in the community . Cases of PCA ( n = 342 ) without prior heart disease or life-threatening comorbidity that occurred in King County , Washington , were identified from paramedic incident reports from October 1988 to July 1994 . Demographically similar controls ( n = 549 ) were identified from the community by using r and om digit dialing . Spouses of subjects were interviewed to assess treatment with  influenza vaccine  during the previous year and other risk factors . After adjustment for demographic , clinical , and behavioral risk factors , influenza vaccination was associated with a reduced risk of PCA ( odds ratio = 0.51 , 95 percent confidence interval : 0.33 , 0.79 ) . The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of  influenza vaccination and total mortality , further studies are needed to determine whether the observed association reflects protection or selection Background —Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season . In addition , the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001.We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infa rct ion patients and in subjects undergoing planned percutaneous coronary angioplasty . Methods and Results —We included 200 myocardial infa rct ion patients admitted in the first 72 hours and 101 planned angioplasty/stent ( PCI ) patients without unstable coronary artery disease , prior bypass surgery , angioplasty , or tissue necrosis , in a prospect i ve , multicenter log during the winter season . Infa rct patients received a st and ard therapy and were then r and omly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group . Similarly , PCI patients were allocated to either vaccination or control groups . Combined end points ( death , reinfa rct ion , and rehospitalization for ischemia ) were assessed at 6 months ’ follow-up . The first primary outcome , cardiovascular death , occurred in 2 % of the patients in the vaccine group compared with 8 % in the control group ( relative risk with vaccine as compared with controls , 0.25 ; 95 % CI 0.07 to 0.86;P = 0.01 ) . The triple composite end point occurred in 11 % of the patients in the vaccine group compared with 23 % in controls ( P = 0.009 ) . Conclusions —Influenza vaccination may reduce the risk of death and ischemic events in patients suffering from infa rct ion and those recovering from angioplasty during flu season . This response could be related to a humoral immune response with positive consequences during flu seasons An open , r and omised study was performed to determine whether two doses of influenza vaccine were more effective than one to elicit an immune response in 70 patients with haematological malignancies . The responses were not improved by two doses compared with one ( influenza A virus serotypes H1/N1 18 % vs. 22 % and H3/N2 26 % vs. 14 % ; influenza B 25 % vs. 22 % ) . The results were similar in patients with ongoing and discontinued therapy . Patients treated with monoclonal antibodies for lymphoma had very poor responses . We conclude that two doses of influenza vaccine do not improve the antibody response in patients with haematological malignancies CONTEXT Influenza virus is a major cause of illness , disruption to daily life , and increased use of health care in all age groups . OBJECTIVE To assess the safety and effectiveness of intranasally administered trivalent , live , attenuated influenza virus ( LAIV ) vaccine for reducing illness , absenteeism , and health care use among healthy , working adults . DESIGN R and omized , double-blind , placebo-controlled trial conducted from September 1997 through March 1998 . SETTING Thirteen centers across the United States . PARTICIPANTS A total of 4561 healthy , working adults aged 18 to 64 years recruited through health insurance plans , at work sites , and from the general population . INTERVENTION Participants were r and omized 2:1 to receive intranasally administered trivalent LAIV vaccine ( n = 3041 ) or placebo ( n = 1520 ) in the fall of 1997 . MAIN OUTCOME MEASURES Episodes of febrile illness , severe febrile illness , febrile upper respiratory tract illness , work loss , and health care use during the peak and total influenza outbreak periods , and adverse events . RESULTS Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods ( 13.2 % for vaccine vs 14.6 % for placebo ; P=.19 ) . However , vaccination significantly reduced the numbers of severe febrile illnesses ( 18.8 % reduction ; 95 % confidence interval [ CI ] , 7.4%-28.8 % ) and febrile upper respiratory tract illnesses ( 23.6 % reduction ; 95 % CI , 12.7%-33.2 % ) . Vaccination also led to fewer days of illness across all illness syndromes ( 22.9 % reduction for febrile illnesses ; 27.3 % reduction for severe febrile illnesses ) , fewer days of work lost ( 17.9 % reduction for severe febrile illnesses ; 28.4 % reduction for febrile upper respiratory tract illnesses ) , and fewer days with health care provider visits ( 24.8 % reduction for severe febrile illnesses ; 40.9 % reduction for febrile upper respiratory tract illnesses ) . Use of prescription antibiotics 
    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 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 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 was negatively associated with the development of new MI during the same influenza season . However , to address causal inference , examination of prospect i ve data sets will be needed Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes , and cardiovascular mortality increases abruptly during influenza epidemics , with little evidence of a lag period . In a population -based case-control study , the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest ( PCA ) , a major contributor to cardiovascular mortality in the community . Cases of PCA ( n = 342 ) without prior heart disease or life-threatening comorbidity that occurred in King County , Washington , were identified from paramedic incident reports from October 1988 to July 1994 . Demographically similar controls ( n = 549 ) were identified from the community by using r and om digit dialing . Spouses of subjects were interviewed to assess treatment with  influenza vaccine  during the previous year and other risk factors . After adjustment for demographic , clinical , and behavioral risk factors , influenza vaccination was associated with a reduced risk of PCA ( odds ratio = 0.51 , 95 percent confidence interval : 0.33 , 0.79 ) . The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of  influenza vaccination and total mortality , further studies are needed to determine whether the observed association reflects protection or selection Background —Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season . In addition , the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001.We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infa rct ion patients and in subjects undergoing planned percutaneous coronary angioplasty . Methods and Results —We included 200 myocardial infa rct ion patients admitted in the first 72 hours and 101 planned angioplasty/stent ( PCI ) patients without unstable coronary artery disease , prior bypass surgery , angioplasty , or tissue necrosis , in a prospect i ve , multicenter log during the winter season . Infa rct patients received a st and ard therapy and were then r and omly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group . Similarly , PCI patients were allocated to either vaccination or control groups . Combined end points ( death , reinfa rct ion , and rehospitalization for ischemia ) were assessed at 6 months ’ follow-up . The first primary outcome , cardiovascular death , occurred in 2 % of the patients in the vaccine group compared with 8 % in the control group ( relative risk with vaccine as compared with controls , 0.25 ; 95 % CI 0.07 to 0.86;P = 0.01 ) . The triple composite end point occurred in 11 % of the patients in the vaccine group compared with 23 % in controls ( P = 0.009 ) . Conclusions —Influenza vaccination may reduce the risk of death and ischemic events in patients suffering from infa rct ion and those recovering from angioplasty during flu season . This response could be related to a humoral immune response with positive consequences during flu seasons An open , r and omised study was performed to determine whether two doses of influenza vaccine were more effective than one to elicit an immune response in 70 patients with haematological malignancies . The responses were not improved by two doses compared with one ( influenza A virus serotypes H1/N1 18 % vs. 22 % and H3/N2 26 % vs. 14 % ; influenza B 25 % vs. 22 % ) . The results were similar in patients with ongoing and discontinued therapy . Patients treated with monoclonal antibodies for lymphoma had very poor responses . We conclude that two doses of influenza vaccine do not improve the antibody response in patients with haematological malignancies CONTEXT Influenza virus is a major cause of illness , disruption to daily life , and increased use of health care in all age groups . OBJECTIVE To assess the safety and effectiveness of intranasally administered trivalent , live , attenuated influenza virus ( LAIV ) vaccine for reducing illness , absenteeism , and health care use among healthy , working adults . DESIGN R and omized , double-blind , placebo-controlled trial conducted from September 1997 through March 1998 . SETTING Thirteen centers across the United States . PARTICIPANTS A total of 4561 healthy , working adults aged 18 to 64 years recruited through health insurance plans , at work sites , and from the general population . INTERVENTION Participants were r and omized 2:1 to receive intranasally administered trivalent LAIV vaccine ( n = 3041 ) or placebo ( n = 1520 ) in the fall of 1997 . MAIN OUTCOME MEASURES Episodes of febrile illness , severe febrile illness , febrile upper respiratory tract illness , work loss , and health care use during the peak and total influenza outbreak periods , and adverse events . RESULTS Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods ( 13.2 % for vaccine vs 14.6 % for placebo ; P=.19 ) . However , vaccination significantly reduced the numbers of severe febrile illnesses ( 18.8 % reduction ; 95 % confidence interval [ CI ] , 7.4%-28.8 % ) and febrile upper respiratory tract illnesses ( 23.6 % reduction ; 95 % CI , 12.7%-33.2 % ) . Vaccination also led to fewer days of illness across all illness syndromes ( 22.9 % reduction for febrile illnesses ; 27.3 % reduction for severe febrile illnesses ) , fewer days of work lost ( 17.9 % reduction for severe febrile illnesses ; 28.4 % reduction for febrile upper respiratory tract illnesses ) , and fewer days with health care provider visits ( 24.8 % reduction for severe febrile illnesses ; 40.9 % reduction for febrile upper respiratory tract illnesses ) . Use of prescription antibiotics 
    Output:
    