***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: Abstract Objective : To evaluate the effect of simultaneous zinc and vitamin A supplementation on  diarrhoea and acute lower respiratory infections in children . Study design : R and omised double blind placebo controlled trial . Setting : Urban slums of Dhaka , Bangladesh . Participants and methods : 800 children aged 12 - 35 months were r and omly assigned to one of four intervention groups : 20 mg zinc once daily for 14 days ; 200 000 IU vitamin A , single dose on day 14 ; both zinc and vitamin A ; placebo . The children were followed up once a week for six months , and morbidity information was collected . Results : The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group . Zinc and vitamin A interaction had a rate ratio ( 95 % confidence interval ) of 0.79 ( 0.66 to 0.94 ) for the prevalence of persistent diarrhoea and 0.80 ( 0.67 to 0.95 ) for dysentery . Incidence ( 1.62 ; 1.16 to 2.25 ) and prevalence ( 2.07 ; 1.76 to 2.44 ) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group . The interaction term had rate ratios of 0.75 ( 0.46 to 1.20 ) for incidence and 0.58 ( 0.46 to 0.73 ) for prevalence of acute lower respiratory infection . Conclusions : Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery . Zinc was associated with a significant increase in acute lower respiratory infection , but this adverse effect was reduced by the interaction between zinc and vitamin A. What is already known on this topic Trials of vitamin A supplementation have failed to show a beneficial effect on morbidity in children Experimental studies have shown that , in the presence of zinc deficiency , vitamin A supplementation fails to reverse vitamin A deficiency Coexistence of deficiencies of zinc and vitamin A could be a reason for the failure of vitamin A supplementation , but data in humans are limited What this paper adds Combined zinc and vitamin A supplementation is more effective in reducing persistent diarrhoea and dysentery than either vitamin A or zinc alone Zinc alone increased respiratory illnesses , but interaction between zinc and vitamin A reduced this adverse There is uncertainty over whether vitamin A supplementation reduces morbidity among children with sub clinical deficiency of the vitamin . Hence a double-blind , placebo-controlled trial of the effect of vitamin A supplementation on  childhood morbidity  was conducted among 11,124 children aged 6 - 83 months in the northwest of Haiti . After a r and om start , children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart . 2 to 8 weeks after each administration of the vitamin A and placebo capsules , indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families . The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed , including diarrhoea ( rate ratio [ RR ] = 1.09 , 95 % confidence interval 1.05 - 1.14 ) , rhinitis ( RR = 1.02 , 95 % confidence interval 1.00 - 1.04 ) , cold/flu symptoms ( RR = 1.04 , 95 % confidence interval 1.01 - 1.06 ) , cough ( RR = 1.07 , 95 % confidence interval 1.03 - 1.11 ) , and rapid breathing ( RR = 1.18 , 95 % confidence interval 1.09 - 1.27 ) . The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation 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 BACKGROUND R and omized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the st and ard treatment of pneumonia . OBJECTIVE We evaluated the effect of a moderate dose of vitamin A as an adjunct to st and ard antimicrobial treatment on the duration of respiratory signs in children with pneumonia . DESIGN Children , aged 2 - 59 mo , with pneumonia and weight-for-age < 50th percentile who had been admitted to the Baca Ortíz Children 's Hospital in Quito , Ecuador , were r and omly assigned to receive 50,000 IU ( aged 2 - 12 mo ) or 100,000 IU ( aged > 12 - 59 mo ) vitamin A or a placebo . RESULTS Of the 287 children enrolled , 145 received vitamin A and 142 received placebo . No overall differences were observed between the 2 groups in the duration of signs of pneumonia . Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time ( in h ) to remission of respiratory signs ( beta = -3.57 , SE = 1.09 , P = 0.001 ) . Duration of clinical signs was less in children with basal serum retinol concentrations > 200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo ( 69.9 + /- 49.9 h compared with 131.3 + /- 143.9 h ; P = 0.049 ) . CONCLUSIONS Overall , we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged < 5 y. However , a beneficial effect was seen in children with high basal serum retinol concentrations Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction Vitamin A supplementation of population s of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality , but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated . We conducted an individually r and omized , placebo-controlled , double-masked trial among 1,407 Indonesian preschool-age children , to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses . Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers . High dose vitamin A supplements increased the incidence of acute respiratory illnesses ( ARI ) by 8 % , and acute lower respiratory illnesses ( ALRI ) by 39 % . These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status ( rate ratio 1.83 , 95 % confidence interval 1.257 - 2.669 ) . In contrast , vitamin A tended to be protective of ALRI in chronically malnourished children ( rate ratio 0.71 , 95 % confidence interval 0.375 - 1.331 ) . There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease ( rate ratio 1.06 , 95 % confidence interval 0.920 - 1.225 ) . However , we found a significant interaction between supplementation and age : vitamin A increased the incidence of diarrhea in children < 30 mo of age , but tended to reduce the incidence in older children . The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting population s of preschool-age children for vitamin A supplementation BACKGROUND The relative-dose-response ( RDR ) test is used to identify subjects with marginal liver vitamin A stores , but its use has not been evaluated during episodes of infection . OBJECTIVE The objective was to assess , with the RDR test , the vitamin A status of children recovering from pneumonia . DESIGN As part of a double-blind , placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima , Peru , we examined the association of treatment group , nutritional status , severity of disease , and induction of the acute phase response [ on the basis of serum C-reactive protein ( CRP ) ] on serum retinol and the RDR test . RESULTS Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery . Serum CRP had a significant , inverse association with retinol at both admission and discharge . Serum retinol and CRP concentrations never differed significantly between the treatment groups . Among subjects with CRP > or = 10 mg/L , 21 % in the vitamin A group and 20 % in the placebo groups ( P = 0.83 ) had a positive RDR test result . Among subjects with CRP < 10 mg/L , 56 % in the placebo group but only 6 % in the vitamin A group had positive RDR test results ( P = 0.002 ) . CONCLUSION The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were < 10 mg/L but not when CRP concentrations were higher Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries . We carried out a r and omized , double-blind , placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease .  Six hundred eighty-seven children were r and omly assigned to receive either placebo or vitamin A [ 200 000 IU ( 60 mg retinol equivalents ) for children > 1 y of age and 100000 IU ( 30 mg retinol equivalents ) for infants ] on the day of admission and another dose on the following day . Of the 346 children in the vitamin A group , 13 died in the hospital , compared with 8 of 341 children in the placebo group ; the relative mortality was 1.63 ( 95 % CI : 0.67 , 3.97 ; P = 0.28 ) . The mean number of days of hospitalization was the same in both groups ( 4.2 d ) . There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age , sex , breast-feeding status , nutritional status at baseline , or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital . There were also no differences in the mean number of days of fever , rapid respiratory rate , or hypoxia , whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline . Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting . The effect of daily , low doses has never been assessed . We investigated the effect of a single high 
    Output:
    
Disease severity after supplementary high-dose vitamin A was significantly worse in children who received vitamin A compared with placebo .
The evidence did not suggest a significant reduction with vitamin A adjunctive treatment in mortality , measures of morbidity , nor an effect on the clinical course of pneumonia in children with non-measles pneumonia .