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: Protein induced by vitamin K absence ( PIVKA-II ) has been used for the evaluation of vitamin K deficiency in the newborn . Differing PIVKA-II detection rates in various studies on hemorrhagic disease of the newborn have not been explained satisfactorily . In this study we investigated the PIVKA-II values of 44 healthy breastfed infants , of whom 29 received vitamin K1 either orally ( N = 13 ) or intramuscularly ( n = 16 ) , and the remaining 15 constituted the  control group .  PIVKA-II was detected in 15.3 percent ( 2/13 ) of the oral and 25 percent of the ( 4/16 ) intramuscular group on the third day of life . The detection rate was 93.3 percent ( 14/15 ) in the control group . However , at the one-month follow-up , there were no PIVKA-II positive infants . In conclusion , PIVKA-II positivity among breastfed Turkish infants on the third day of life was high compared to that in other studies , perhaps due to a delay in enzyme maturation related to racial , environmental and nutritional factors PIVKA-II ( protein induced by vitamin K absence or antagonist-II ) was measured in two groups of newborns , one group being given 5 mg vitamin K at birth and the other untreated . The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group . When vitamin K was administered to newborn babies whose normotest levels were less than 30 % , it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K , as monitored by the normotest . Thus PIVKA-II levels might be more useful than a coagulation test , since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity . The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding Abstract There is consensus that  late vitamin K deficiency bleeding ( VKDB )  should be prevented by vitamin K prophylaxis . One single dose of 1 mg vitamin K1 is effective if given i.m . or s.c . , but not if given orally . Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established . Different oral dose schedules are presently used in different countries . In Australia , Germany , The Netherl and s and Switzerl and active surveillance data on late VKDB were collected in a similar manner and failure rates compared . Identical case definitions were used . There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries : ( 1 ) daily supplementation of low dose vitamin K ( 25 μg ) for breast-fed infants ( The Netherl and s ) ; ( 2 ) 3 × 1 mg orally [ Australia ( January 1993 – March 1994 ) and Germany ( December 1992 – December 1994 ) ] ; ( 3 ) 1 mg vitamin K i.m . ( Australia since March 1994 ) ; and ( 4 ) 2 × 2 mg vitamin K ( new mixed micellar preparation ) ( Switzerl and ) . The respective failure rates per 100,000 live births ( including cases given all recommended doses and those given incomplete prophylaxis ) were for strategy : ( 1 ) 0.2 ( 0–1.3 ) in The Netherl and s ; ( 2 ) 2.3 ( 95 % CI 1.6–3.4 ) in Germany and 2.5 ( 1.1–4.8 ) in Australia ( oral prophylaxis ) ; ( 3 ) Australia ( i.m . prophylaxis ) 0 ( 0–0.9 ) ; and ( 4 ) 3.6 ( 0.7–10.6 ) in Switzerl and . The failure rates for complete prophylaxis only were : strategy ( 1 ) 0 ( 0–0.7 ) in The Netherl and s ; ( 2 ) 1.8 ( 1.1–2.8 ) in Germany and 1.5 ( 0.5–3.6 ) in Australia ; ( 3 ) Australia ( i.m . ) 0 ( 0–0.9 ) ; and ( 4 ) 1.2 ( 0–6.5 ) in Switzerl and . Conclusions The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m . vitamin K prophylaxis . A daily low oral dose of 25 μg vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis . The effectiveness of the “ mixed-micellar ” preparation of vitamin K1 needs further study OBJECTIVE To compare a new oral preparation of vitamin K1 ( Konakion MM ) containing lecithin and glycocholic acid with a st and ard intramuscular ( IM ) preparation during the first 8 weeks of life in exclusively breast fed infants . METHODS Infants were r and omised at birth to the IM group ( 1 mg vitamin K )  or the oral group  ( 2 mg given at birth and repeated at 7 and 30 days of life ) . Prothrombin time ( INR ) , plasma vitamin K1 , and PIVKA II ( undercarboxylated prothrombin ) were monitored at 14 , 30 , and 56 days of age . RESULTS Seventy nine infants were r and omised to the oral group and 77 to the IM group . Sixty seven infants in each group completed eight weeks of the study . Prothrombin times did not differ between the two groups . Mean ( SD ) plasma vitamin K1values ( in ng/ml ) decreased in both groups over time , but were higher in the oral group at 14 and 56 days : 2.0 ( 1.6 ) v 1.3 ( 1.1 ) at 14 days ; 0.5 ( 0.3 ) v 0.5 ( 0.7 ) at 30 days ; and 0.5 ( 0.8 ) v 0.2 ( 0.2 ) at 56 days of life . PIVKA II was raised ( ⩾ 0.1 AU/ml ) in cord blood in 47 % of the infants . By 14 days , only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood . At 30 days , there were no raised PIVKA II values . At 56 days , there were no raised PIVKA II values in the oral group , although three infants in the IM group had raised values . CONCLUSIONS Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured . Through the first 8 weeks of life , multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation ABSTRACT . In a r and omized study of 300 infants , the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection . The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint . Prothrombin ( antigen ) and PIVKA II ( acarboxyprothrombin ) were also measured . All infants were observed for events of bleeding until discharge from the hospital , normally on the fifth day . No significant differences between the groups in any of the biochemical markers were observed . The 95 % confidence limits of the differences were very narrow for all factors . No cases of bleeding were observed . We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn The plasma disposition of a new mixed-micellar preparation ( KONAKION MM , Roche ) of phylloquinone ( vitamin K1 ) has been studied in 25 healthy , fully breast-fed , newborn babies , r and omized to receive a single dose of either 1.5 mg i.m . ( 11 babies ) or 3 mg p.o . ( 14 babies ) . Venous blood sample s were collected at 25 h , 4 days , and 24 days . After p.o . administration , the median plasma phylloquinone concentration increased to 89 ng/ml after 24 h , then decreased to 51 ng/ml after 4 days ; the respective concentrations after i.m . injection were 146 ng/ml and 34 ng/ml . The higher plasma phylloquinone level in the i.m . group after 24 h was not statistically significant compared with that of the p.o . group , but the reversed higher concentration in the p.o . group after 4 days was significant ( p < 0.01 ) . After 24 days the median plasma phylloquinone had decreased to 0.44 ng/ml ( range 0.19 - 1.44 ) and 1.05 ng/ml ( range 0.37 - 1.87 ) in the p.o . and i.m . groups , respectively . There was a significant difference between these plasma concentrations ( p < 0.01 ) . They were within or above the reference adult fasting range ( 0.17 - 0.68 ng/ml ) . The narrow range of plasma concentrations at 24 h and 4 days suggests a greater consistency of absorption from this micellar preparation than from other emulsion-based preparations . Further studies are required to assess the long-term protection of a single oral dose against late hemorrhagic disease of the newborn . Until such time , breast-fed babies given this preparation orally should receive ( an ) additional dose(s ) Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost , pain , anxiety to parents and risk of transmission of infection . Oral route is a better alternative . Oral absorption of vitamin K has been shown to be equally good using special oral preparations . However , this preparation is not available in India . A prospect i ve study was carried out on 51 full term , healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K ( menadione sodium bisulphite ) could be as effective . Fourteen babies received 1 mg vitamin K intramuscularly , 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth .  PIVKA-II levels were measured in cord blood and at 72 - 78 hours of age in all babies as a marker of vitamin K deficiency . The overall PIVKA-II prevalence in cord blood was 64.7 % . At 72 - 78 hours , PIVKA-II was present in 50 % of babies in IM group , 58.3 % of babies in oral group and in 76.9 % of babies in ' no vitamin K ' group ( p > 0.05 ) . The PIVKA-II levels decreased or did not change at 72 - 78 hours in 91.6 % of babies in oral group versus 92.8 % of babies in IM group ( p > 0.05 ) . On the other h and , PIVKA-II levels increased in 30.7 % of babies who did not receive vitamin K as against in 7.8 % of babies receiving vitamin K in either form ( p < 0.05 ) . Hence , vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K ( menadione sodium bisulphite ) given orally to term healthy babies is effective in preventing vitamin K deficiency state A r and omised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1 , proteins induced by vitamin K absence ( PIVKA-II ) , and clotting factors . Two groups of about 165 healthy breast fed infants who received at r and om 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age . Although  vitamin K1 concentrations were statistically significantly higher in the intramuscular group , blood coagulability , activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups . At 2 weeks of age  vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable . At 3 months  vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5 % of infants . Therefore , a repeated oral prophylaxis will be necessary to completely prevent ( biochemical ) vitamin K deficiency beyond the age of 1 month The study was design ed to know the effect of oral vitamin K ( VK ) treatment , on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II ( PIVCA II ) on full term infants . Seventy healthy newborns were studied and each was r and omly placed in one of two groups : Group A , newborns that received  human milk and milk formula ( mixed feeding ) and group B , newborns that were exclusively breast fed . These groups were also divided in two subgroups : I received 2 mg of VK1 orally and II ( control ) did not receive VK .  Clotting activity of the coagulation factors and P 
    Output:
    
agent
One dose of vitamin K reduced clinical bleeding at 1 - 7 days , including bleeding after circumcision , and improved biochemical indices of coagulation status .
There was no evidence of a difference between the oral and intramuscular route in effects on biochemical indices of coagulation status .
REVIEW ER 'S CONCLUSIONS A single dose ( 1.0 mg ) of intramuscular vitamin K after birth is effective in the prevention of classic HDN .
Either intramuscular or oral ( 1.0 mg ) vitamin K prophylaxis improves biochemical indices of coagulation status at 1 - 7 days .
Neither intramuscular nor oral vitamin K has been tested in r and omized trials with respect to effect on late HDN .
Oral vitamin K , either single or multiple dose , has not been tested in r and omized trials for its effect on either classic or late HDN
***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: Protein induced by vitamin K absence ( PIVKA-II ) has been used for the evaluation of vitamin K deficiency in the newborn . Differing PIVKA-II detection rates in various studies on hemorrhagic disease of the newborn have not been explained satisfactorily . In this study we investigated the PIVKA-II values of 44 healthy breastfed infants , of whom 29 received vitamin K1 either orally ( N = 13 ) or intramuscularly ( n = 16 ) , and the remaining 15 constituted the  control group .  PIVKA-II was detected in 15.3 percent ( 2/13 ) of the oral and 25 percent of the ( 4/16 ) intramuscular group on the third day of life . The detection rate was 93.3 percent ( 14/15 ) in the control group . However , at the one-month follow-up , there were no PIVKA-II positive infants . In conclusion , PIVKA-II positivity among breastfed Turkish infants on the third day of life was high compared to that in other studies , perhaps due to a delay in enzyme maturation related to racial , environmental and nutritional factors PIVKA-II ( protein induced by vitamin K absence or antagonist-II ) was measured in two groups of newborns , one group being given 5 mg vitamin K at birth and the other untreated . The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group . When vitamin K was administered to newborn babies whose normotest levels were less than 30 % , it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K , as monitored by the normotest . Thus PIVKA-II levels might be more useful than a coagulation test , since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity . The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding Abstract There is consensus that  late vitamin K deficiency bleeding ( VKDB )  should be prevented by vitamin K prophylaxis . One single dose of 1 mg vitamin K1 is effective if given i.m . or s.c . , but not if given orally . Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established . Different oral dose schedules are presently used in different countries . In Australia , Germany , The Netherl and s and Switzerl and active surveillance data on late VKDB were collected in a similar manner and failure rates compared . Identical case definitions were used . There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries : ( 1 ) daily supplementation of low dose vitamin K ( 25 μg ) for breast-fed infants ( The Netherl and s ) ; ( 2 ) 3 × 1 mg orally [ Australia ( January 1993 – March 1994 ) and Germany ( December 1992 – December 1994 ) ] ; ( 3 ) 1 mg vitamin K i.m . ( Australia since March 1994 ) ; and ( 4 ) 2 × 2 mg vitamin K ( new mixed micellar preparation ) ( Switzerl and ) . The respective failure rates per 100,000 live births ( including cases given all recommended doses and those given incomplete prophylaxis ) were for strategy : ( 1 ) 0.2 ( 0–1.3 ) in The Netherl and s ; ( 2 ) 2.3 ( 95 % CI 1.6–3.4 ) in Germany and 2.5 ( 1.1–4.8 ) in Australia ( oral prophylaxis ) ; ( 3 ) Australia ( i.m . prophylaxis ) 0 ( 0–0.9 ) ; and ( 4 ) 3.6 ( 0.7–10.6 ) in Switzerl and . The failure rates for complete prophylaxis only were : strategy ( 1 ) 0 ( 0–0.7 ) in The Netherl and s ; ( 2 ) 1.8 ( 1.1–2.8 ) in Germany and 1.5 ( 0.5–3.6 ) in Australia ; ( 3 ) Australia ( i.m . ) 0 ( 0–0.9 ) ; and ( 4 ) 1.2 ( 0–6.5 ) in Switzerl and . Conclusions The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m . vitamin K prophylaxis . A daily low oral dose of 25 μg vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis . The effectiveness of the “ mixed-micellar ” preparation of vitamin K1 needs further study OBJECTIVE To compare a new oral preparation of vitamin K1 ( Konakion MM ) containing lecithin and glycocholic acid with a st and ard intramuscular ( IM ) preparation during the first 8 weeks of life in exclusively breast fed infants . METHODS Infants were r and omised at birth to the IM group ( 1 mg vitamin K )  or the oral group  ( 2 mg given at birth and repeated at 7 and 30 days of life ) . Prothrombin time ( INR ) , plasma vitamin K1 , and PIVKA II ( undercarboxylated prothrombin ) were monitored at 14 , 30 , and 56 days of age . RESULTS Seventy nine infants were r and omised to the oral group and 77 to the IM group . Sixty seven infants in each group completed eight weeks of the study . Prothrombin times did not differ between the two groups . Mean ( SD ) plasma vitamin K1values ( in ng/ml ) decreased in both groups over time , but were higher in the oral group at 14 and 56 days : 2.0 ( 1.6 ) v 1.3 ( 1.1 ) at 14 days ; 0.5 ( 0.3 ) v 0.5 ( 0.7 ) at 30 days ; and 0.5 ( 0.8 ) v 0.2 ( 0.2 ) at 56 days of life . PIVKA II was raised ( ⩾ 0.1 AU/ml ) in cord blood in 47 % of the infants . By 14 days , only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood . At 30 days , there were no raised PIVKA II values . At 56 days , there were no raised PIVKA II values in the oral group , although three infants in the IM group had raised values . CONCLUSIONS Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured . Through the first 8 weeks of life , multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation ABSTRACT . In a r and omized study of 300 infants , the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection . The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint . Prothrombin ( antigen ) and PIVKA II ( acarboxyprothrombin ) were also measured . All infants were observed for events of bleeding until discharge from the hospital , normally on the fifth day . No significant differences between the groups in any of the biochemical markers were observed . The 95 % confidence limits of the differences were very narrow for all factors . No cases of bleeding were observed . We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn The plasma disposition of a new mixed-micellar preparation ( KONAKION MM , Roche ) of phylloquinone ( vitamin K1 ) has been studied in 25 healthy , fully breast-fed , newborn babies , r and omized to receive a single dose of either 1.5 mg i.m . ( 11 babies ) or 3 mg p.o . ( 14 babies ) . Venous blood sample s were collected at 25 h , 4 days , and 24 days . After p.o . administration , the median plasma phylloquinone concentration increased to 89 ng/ml after 24 h , then decreased to 51 ng/ml after 4 days ; the respective concentrations after i.m . injection were 146 ng/ml and 34 ng/ml . The higher plasma phylloquinone level in the i.m . group after 24 h was not statistically significant compared with that of the p.o . group , but the reversed higher concentration in the p.o . group after 4 days was significant ( p < 0.01 ) . After 24 days the median plasma phylloquinone had decreased to 0.44 ng/ml ( range 0.19 - 1.44 ) and 1.05 ng/ml ( range 0.37 - 1.87 ) in the p.o . and i.m . groups , respectively . There was a significant difference between these plasma concentrations ( p < 0.01 ) . They were within or above the reference adult fasting range ( 0.17 - 0.68 ng/ml ) . The narrow range of plasma concentrations at 24 h and 4 days suggests a greater consistency of absorption from this micellar preparation than from other emulsion-based preparations . Further studies are required to assess the long-term protection of a single oral dose against late hemorrhagic disease of the newborn . Until such time , breast-fed babies given this preparation orally should receive ( an ) additional dose(s ) Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost , pain , anxiety to parents and risk of transmission of infection . Oral route is a better alternative . Oral absorption of vitamin K has been shown to be equally good using special oral preparations . However , this preparation is not available in India . A prospect i ve study was carried out on 51 full term , healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K ( menadione sodium bisulphite ) could be as effective . Fourteen babies received 1 mg vitamin K intramuscularly , 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth .  PIVKA-II levels were measured in cord blood and at 72 - 78 hours of age in all babies as a marker of vitamin K deficiency . The overall PIVKA-II prevalence in cord blood was 64.7 % . At 72 - 78 hours , PIVKA-II was present in 50 % of babies in IM group , 58.3 % of babies in oral group and in 76.9 % of babies in ' no vitamin K ' group ( p > 0.05 ) . The PIVKA-II levels decreased or did not change at 72 - 78 hours in 91.6 % of babies in oral group versus 92.8 % of babies in IM group ( p > 0.05 ) . On the other h and , PIVKA-II levels increased in 30.7 % of babies who did not receive vitamin K as against in 7.8 % of babies receiving vitamin K in either form ( p < 0.05 ) . Hence , vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K ( menadione sodium bisulphite ) given orally to term healthy babies is effective in preventing vitamin K deficiency state A r and omised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1 , proteins induced by vitamin K absence ( PIVKA-II ) , and clotting factors . Two groups of about 165 healthy breast fed infants who received at r and om 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age . Although  vitamin K1 concentrations were statistically significantly higher in the intramuscular group , blood coagulability , activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups . At 2 weeks of age  vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable . At 3 months  vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5 % of infants . Therefore , a repeated oral prophylaxis will be necessary to completely prevent ( biochemical ) vitamin K deficiency beyond the age of 1 month The study was design ed to know the effect of oral vitamin K ( VK ) treatment , on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II ( PIVCA II ) on full term infants . Seventy healthy newborns were studied and each was r and omly placed in one of two groups : Group A , newborns that received  human milk and milk formula ( mixed feeding ) and group B , newborns that were exclusively breast fed . These groups were also divided in two subgroups : I received 2 mg of VK1 orally and II ( control ) did not receive VK .  Clotting activity of the coagulation factors and P 
    Output:
    