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: Objectives Within a r and omised trial of neonatal vitamin A supplementation ( VAS ) in Guinea-Bissau , neonatal VAS did not affect overall  infant mortality . We conducted a post-hoc analysis to test the hypothesis that neonatal VAS primes the response to subsequent vitamin A. Methods All trial children were offered VAS after follow-up ended at 1 year of age ( FU-VAS ) . We compared mortality between 1 and 3 years of age according to initial r and omization to neonatal VAS or placebo in Cox-regression models ; we expected that children r and omized to neonatal VAS compared with those r and omized to placebo would have lower mortality after reception of FU-VAS . Results Of 4345 infants enrolled in the original trial , 3646 lived in the study area at 1 year of age and 2958 received FU-VAS .  Between 1 and 3 years of age , 112 children died . After FU-VAS , neonatal VAS was associated with lower mortality than placebo : Mortality Rate Ratio ( MRR ) = 0.54 ( 95%CI : 0.31–0.94 ) . The effect was more pronounced in girls ( MRR = 0.37 ( 0.16–0.89 ) ) than boys ( MRR = 0.73 ( 0.35–1.51 ) ) . The beneficial effect of neonatal VAS may have been particularly strong for girls who received both VAS in a campaign and FU-VAS ( MRR = 0.15 ( 0.03–0.67 ) ) . Among children who had not received FU-VAS , mortality in the second and third year of life did not differ according to reception of neonatal VAS or placebo . Hence , in the second and third year of life the effect of neonatal VAS versus placebo was different in girls who had or had not received FU-VAS ( p for homogeneity = 0.01 ) . Conclusions The present results suggest that neonatal VAS primes the response in girls such that they get a beneficial effect after a subsequent dose of VAS . Trial Registration Clinical trials.gov A r and omized , double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age ) and infants aged 1 - 6 months who received a large , oral dose of vitamin A ( 15,000 retinol equivalents ( RE ) ( 50,000 IU ) and 30,000 RE ( 100,000 IU ) , respectively ) or placebo ( 75 RE ( 250 IU ) and 150 RE ( 500 IU ) , respectively ) in oil . Infants ( vitamin A group , n = 1461 ; controls , n = 1379 ) were assessed for vomiting , loose stools , fever , and irritability during the 24 hours before and after dosing . Fontanelles were palpated 24 hours after dosing . Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE . Compared with controls the older infants who ingested 30,000 RE had a 1.6 % excess rate of vomiting ( 95 % confidence interval ( CI ) : 0.2 - 3.0 % ) and a 0.5 % excess rate ( 95 % CI : -0.1 to 1.1 % ) in the occurrence of bulging fontanelles . There were no other significant differences in the older infants . The controlled , periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants ; a 30,000 RE dose is associated with a minimum risk of transient , acute side-effects A placebo-controlled trial was carried out among 2067 Indonesian neonates to assess the safety of administering one oral 52-mumol ( 50,000 IU ) dose of vitamin A.  Infants were assessed for potential acute side-effects before and throughout 48 hours after the dose . The first 965 infants were examined by cranial ultrasound before and at 24 hours after dosing to rule out intracranial haemorrhage and determine the resistive index ( RI ) of the anterior cerebral artery using duplex Doppler . Groups were comparable at the baseline . A bulging fontanelle occurred in the control and vitamin A groups , respectively , among 2.7 % and 4.6 % of the infants at 24 hours , and 2.4 % and 4.5 % of the infants at 48 hours . The groups did not differ in any other sign or symptom assessed . No infant developed intracranial haemorrhage . Mean RI values were normal and not different between groups at baseline or at 24 hours . Mean RI fell during the 24 hours , as normally occurs ; the mean decrease was nearly identical in the two groups . A bulging fontanelle was not associated with increased rates of any sign or symptom or with an increase in RI . The 52-mumol dose of oral vitamin A may cause a small increase in intracranial volume in a small proportion of infants , but no increase in intracranial pressure . Acute side-effects following this intervention were rare and mild OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation .  MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality . Design R and omised placebo controlled trial . Setting B and i m Health Project ’s demographic surveillance system in Guinea-Bissau , covering approximately 90 000 inhabitants . Participants 4345 infants due to receive BCG . Intervention Infants were r and omised to 50 000 IU vitamin A or placebo and followed until age 12 months . Main outcome measure Mortality rate ratios . Results 174 children  died during follow-up ( mortality=47/1000 person-years ) . Vitamin A supplementation was not significantly associated with mortality ; the mortality rate ratio was 1.07 ( 95 % confidence interval 0.79 to 1.44 ) . The effect was 1.00 ( 0.65 to 1.56 ) during the first four months and 1.13 ( 0.75 to 1.68 ) from 4 to 12 months of age . The mortality rate ratio in boys was 0.84 ( 0.55 to 1.27 ) compared with 1.39 ( 0.90 to 2.14 ) in girls ( P for interaction=0.10 ) . An explorative analysis revealed a strong interaction between vitamin A and season of administration . Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting . Although little doubt exists that vitamin A supplementation reduces mortality in older children , a global recommendation of supplementation for all newborn infants may not contribute to better survival . Trial registration Clinical trials NCT00168597 Background Vitamin A supplementation of 6 - 59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality . There has been considerable interest in determining the benefits of neonatal vitamin A supplementation , but the results of existing trials are conflicting . A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation . Three trials were therefore initiated in Ghana , India and Tanzania to determine if vitamin A supplementation ( 50,000 IU ) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo . Methods / Design The trials are individually r and omized , double masked , and placebo controlled . The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania . The study participants are neonates who fulfil age eligibility , whose families are likely to stay in the study area for the next 6 months , who are able to feed orally , and whose parent(s ) provide informed written consent to participate in the study . Neonates r and omized to the intervention group receive 50,000 IU vitamin A and the ones r and omized to the control group receive placebo at the time of enrolment . Mortality and morbidity information are collected through periodic home visits by a study worker during infancy . The primary outcome of the study is mortality from supplementation to 6 months of age . The secondary outcome of the study is mortality from supplementation to 12 months of age . The three studies will be analysed independent of each other . Subgroup analysis will be carried out to determine the effect by birth weight , sex , and timing of DTP vaccine , socioeconomic groups and maternal large-dose vitamin A supplementation . Discussion The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates . Policy formulation will be based on the results of efficacy of the intervention from the ongoing r and omized controlled trials combined with results of previous studies .Trial Registration Ghana : Australian New Zeal and Clinical Trials Registry ( ANZCTR ) - ACTRN12610000582055 ; India : CLINICAL TRIALS.GOV - NCT01138449 ; Tanzania : Australian New Zeal and Clinical Trials Registry ( ANZCTR ) - ACTRN12610000636055 PURPOSE To assess the impact of vitamin A supplementation at 4-month intervals on the prevalence and incidence of xerophthalmia among preschool-age children . METHODS A stratified , r and om sample of 40 wards with 4766 children in Sarlahi district of Nepal was selected to participate in a r and omized , controlled , community trial . In the vitamin A group , at 4-month intervals , neonates received 50,000 IU , 1- to 11-month-old infants received 100,000 IU , and children 1 through 4 years of age received 200,000 IU . Children underwent eye examination before the intervention and 16 months later . RESULTS Before the intervention , 4318 children were examined for xerophthalmia .  The prevalence was 2.3 % in the  vitamin A group and 3.3 % in the placebo group . All children with xerophthalmia were treated with vitamin A at the time of the examination . Of those examined at baseline , 38 in the vitamin A group and 48 in the placebo group died in the 16 months after intervention . There were 1871 ( 84 % ) surviving children in the vitamin A group and 1711 ( 85 % ) in the placebo group examined at follow-up . After adjustment for the baseline prevalence of xerophthalmia , vitamin A reduced the prevalence at follow-up by 63 % ( 95 % confidence interval , 21 % to 83 % ) . The apparent incidence was 3.2/1000 per year in the vitamin A group and 9.2/1000 per year in the placebo group , an adjusted reduction of 62 % ( 95 % confidence interval , 0 % to 86 % ) . CONCLUSIONS Supplementation was effective at reducing the prevalence and incidence of xerophthalmia The effect of supplementing 11,918 infants < 1 mo and 1 - 5 mo of age with vitamin A ( 15,000 and 30,000 micrograms retinol equivalents or 50,000 and 100,000 IU , respectively ) or a placebo on subsequent 4-mo mortality was assessed in a r and omized , double-masked community trial in the rural plains of Nepal . There were 130 deaths ( 51.6/1000 child-y ) in the control group and 150 deaths ( 57.1/1000 child-y ) in the vitamin A group , yielding a relative risk of 1.11 ( 95 % CI : 0.86 , 1.42 ) , which is indic 
    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: Objectives Within a r and omised trial of neonatal vitamin A supplementation ( VAS ) in Guinea-Bissau , neonatal VAS did not affect overall  infant mortality . We conducted a post-hoc analysis to test the hypothesis that neonatal VAS primes the response to subsequent vitamin A. Methods All trial children were offered VAS after follow-up ended at 1 year of age ( FU-VAS ) . We compared mortality between 1 and 3 years of age according to initial r and omization to neonatal VAS or placebo in Cox-regression models ; we expected that children r and omized to neonatal VAS compared with those r and omized to placebo would have lower mortality after reception of FU-VAS . Results Of 4345 infants enrolled in the original trial , 3646 lived in the study area at 1 year of age and 2958 received FU-VAS .  Between 1 and 3 years of age , 112 children died . After FU-VAS , neonatal VAS was associated with lower mortality than placebo : Mortality Rate Ratio ( MRR ) = 0.54 ( 95%CI : 0.31–0.94 ) . The effect was more pronounced in girls ( MRR = 0.37 ( 0.16–0.89 ) ) than boys ( MRR = 0.73 ( 0.35–1.51 ) ) . The beneficial effect of neonatal VAS may have been particularly strong for girls who received both VAS in a campaign and FU-VAS ( MRR = 0.15 ( 0.03–0.67 ) ) . Among children who had not received FU-VAS , mortality in the second and third year of life did not differ according to reception of neonatal VAS or placebo . Hence , in the second and third year of life the effect of neonatal VAS versus placebo was different in girls who had or had not received FU-VAS ( p for homogeneity = 0.01 ) . Conclusions The present results suggest that neonatal VAS primes the response in girls such that they get a beneficial effect after a subsequent dose of VAS . Trial Registration Clinical trials.gov A r and omized , double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age ) and infants aged 1 - 6 months who received a large , oral dose of vitamin A ( 15,000 retinol equivalents ( RE ) ( 50,000 IU ) and 30,000 RE ( 100,000 IU ) , respectively ) or placebo ( 75 RE ( 250 IU ) and 150 RE ( 500 IU ) , respectively ) in oil . Infants ( vitamin A group , n = 1461 ; controls , n = 1379 ) were assessed for vomiting , loose stools , fever , and irritability during the 24 hours before and after dosing . Fontanelles were palpated 24 hours after dosing . Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE . Compared with controls the older infants who ingested 30,000 RE had a 1.6 % excess rate of vomiting ( 95 % confidence interval ( CI ) : 0.2 - 3.0 % ) and a 0.5 % excess rate ( 95 % CI : -0.1 to 1.1 % ) in the occurrence of bulging fontanelles . There were no other significant differences in the older infants . The controlled , periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants ; a 30,000 RE dose is associated with a minimum risk of transient , acute side-effects A placebo-controlled trial was carried out among 2067 Indonesian neonates to assess the safety of administering one oral 52-mumol ( 50,000 IU ) dose of vitamin A.  Infants were assessed for potential acute side-effects before and throughout 48 hours after the dose . The first 965 infants were examined by cranial ultrasound before and at 24 hours after dosing to rule out intracranial haemorrhage and determine the resistive index ( RI ) of the anterior cerebral artery using duplex Doppler . Groups were comparable at the baseline . A bulging fontanelle occurred in the control and vitamin A groups , respectively , among 2.7 % and 4.6 % of the infants at 24 hours , and 2.4 % and 4.5 % of the infants at 48 hours . The groups did not differ in any other sign or symptom assessed . No infant developed intracranial haemorrhage . Mean RI values were normal and not different between groups at baseline or at 24 hours . Mean RI fell during the 24 hours , as normally occurs ; the mean decrease was nearly identical in the two groups . A bulging fontanelle was not associated with increased rates of any sign or symptom or with an increase in RI . The 52-mumol dose of oral vitamin A may cause a small increase in intracranial volume in a small proportion of infants , but no increase in intracranial pressure . Acute side-effects following this intervention were rare and mild OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation .  MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality . Design R and omised placebo controlled trial . Setting B and i m Health Project ’s demographic surveillance system in Guinea-Bissau , covering approximately 90 000 inhabitants . Participants 4345 infants due to receive BCG . Intervention Infants were r and omised to 50 000 IU vitamin A or placebo and followed until age 12 months . Main outcome measure Mortality rate ratios . Results 174 children  died during follow-up ( mortality=47/1000 person-years ) . Vitamin A supplementation was not significantly associated with mortality ; the mortality rate ratio was 1.07 ( 95 % confidence interval 0.79 to 1.44 ) . The effect was 1.00 ( 0.65 to 1.56 ) during the first four months and 1.13 ( 0.75 to 1.68 ) from 4 to 12 months of age . The mortality rate ratio in boys was 0.84 ( 0.55 to 1.27 ) compared with 1.39 ( 0.90 to 2.14 ) in girls ( P for interaction=0.10 ) . An explorative analysis revealed a strong interaction between vitamin A and season of administration . Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting . Although little doubt exists that vitamin A supplementation reduces mortality in older children , a global recommendation of supplementation for all newborn infants may not contribute to better survival . Trial registration Clinical trials NCT00168597 Background Vitamin A supplementation of 6 - 59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality . There has been considerable interest in determining the benefits of neonatal vitamin A supplementation , but the results of existing trials are conflicting . A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation . Three trials were therefore initiated in Ghana , India and Tanzania to determine if vitamin A supplementation ( 50,000 IU ) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo . Methods / Design The trials are individually r and omized , double masked , and placebo controlled . The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania . The study participants are neonates who fulfil age eligibility , whose families are likely to stay in the study area for the next 6 months , who are able to feed orally , and whose parent(s ) provide informed written consent to participate in the study . Neonates r and omized to the intervention group receive 50,000 IU vitamin A and the ones r and omized to the control group receive placebo at the time of enrolment . Mortality and morbidity information are collected through periodic home visits by a study worker during infancy . The primary outcome of the study is mortality from supplementation to 6 months of age . The secondary outcome of the study is mortality from supplementation to 12 months of age . The three studies will be analysed independent of each other . Subgroup analysis will be carried out to determine the effect by birth weight , sex , and timing of DTP vaccine , socioeconomic groups and maternal large-dose vitamin A supplementation . Discussion The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates . Policy formulation will be based on the results of efficacy of the intervention from the ongoing r and omized controlled trials combined with results of previous studies .Trial Registration Ghana : Australian New Zeal and Clinical Trials Registry ( ANZCTR ) - ACTRN12610000582055 ; India : CLINICAL TRIALS.GOV - NCT01138449 ; Tanzania : Australian New Zeal and Clinical Trials Registry ( ANZCTR ) - ACTRN12610000636055 PURPOSE To assess the impact of vitamin A supplementation at 4-month intervals on the prevalence and incidence of xerophthalmia among preschool-age children . METHODS A stratified , r and om sample of 40 wards with 4766 children in Sarlahi district of Nepal was selected to participate in a r and omized , controlled , community trial . In the vitamin A group , at 4-month intervals , neonates received 50,000 IU , 1- to 11-month-old infants received 100,000 IU , and children 1 through 4 years of age received 200,000 IU . Children underwent eye examination before the intervention and 16 months later . RESULTS Before the intervention , 4318 children were examined for xerophthalmia .  The prevalence was 2.3 % in the  vitamin A group and 3.3 % in the placebo group . All children with xerophthalmia were treated with vitamin A at the time of the examination . Of those examined at baseline , 38 in the vitamin A group and 48 in the placebo group died in the 16 months after intervention . There were 1871 ( 84 % ) surviving children in the vitamin A group and 1711 ( 85 % ) in the placebo group examined at follow-up . After adjustment for the baseline prevalence of xerophthalmia , vitamin A reduced the prevalence at follow-up by 63 % ( 95 % confidence interval , 21 % to 83 % ) . The apparent incidence was 3.2/1000 per year in the vitamin A group and 9.2/1000 per year in the placebo group , an adjusted reduction of 62 % ( 95 % confidence interval , 0 % to 86 % ) . CONCLUSIONS Supplementation was effective at reducing the prevalence and incidence of xerophthalmia The effect of supplementing 11,918 infants < 1 mo and 1 - 5 mo of age with vitamin A ( 15,000 and 30,000 micrograms retinol equivalents or 50,000 and 100,000 IU , respectively ) or a placebo on subsequent 4-mo mortality was assessed in a r and omized , double-masked community trial in the rural plains of Nepal . There were 130 deaths ( 51.6/1000 child-y ) in the control group and 150 deaths ( 57.1/1000 child-y ) in the vitamin A group , yielding a relative risk of 1.11 ( 95 % CI : 0.86 , 1.42 ) , which is indic 
    Output:
    