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: A cohort of 1,749 newborns from the municipality of Odense , born during 1995 at the Odense University Hospital , were followed up prospect ively for the development of cow 's milk protein allergy/intolerance ( CMPA/I ) during the first year of life . Once a diagnosis of CMPA/I was confirmed , a milk-free diet was continued until a new milk challenge had shown development of tolerance . All infants with CMPA/I were rechallenged at 12 months of age and , in the event of continued clinical sensitivity to cow 's milk protein , controlled rechallenges were performed every 6 months up to 3 years of age ; and thereafter every 12 months until the age of 15 years . From the same birth cohort , 276 infants were r and omly selected at birth for prospect i ve non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood . St and ardized question naires on atopic heredity , environmental factors and presence of atopic symptoms were answered at 0 , 6 , 12 and 18 months and at 5 , 10 and 15 years of age . Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months , 5 , 10 and 15 years of age . Skin prick test and specific sIgE ( Pharmacia CAP ) testing were performed at 18 months , 5 , 10 and 15 years of age against a panel of inhalant allergens ( birch , grass , mugwort , dog , cat , horse , Dermatophagoidespteronyssinus , Dermatophagoides farinae , alternaria and cladosporium herbarum ) . Furthermore , lung function measurements were performed in children when 10 and 15 years of age . Based on controlled milk elimination and challenge procedures , the diagnosis of CMPA/I was confirmed in 39 out of 117 infants , with symptoms suggestive of CMPA/I , thus result ing in a 1-year incidence of CMPA/I of 2.2 % . The overall prognosis of CMPA/I was good , with a total recovery of 56 % at 1 year , 77 % at 2 years , 87 % at 3 years , 92 % at 5 and 10 years and 97 % at 15 years of age . In children younger than 10 years of age , 41 % developed asthma and 31 % rhinoconjunctivitis . Children with non-IgE-mediated CMPI had a good prognosis , whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA , development of other food allergies , asthma and rhinoconjunctivitis . During early infancy , recurrent wheezing was the most prevalent disease ( 20 % ) , followed by atopic dermatitis ( 14 % ) and food allergy ( 7 % ) at 18 months of age . Physician diagnosed asthma increased from 2 % at 1.5 years of age to 9 % at 10 years of age .  Rhinoconjunctivitis  increased from < 1 % at 1.5 years of age to 9 % at 10 years of age . Overall , the current prevalence of any atopic disease was 20 % at 1.5 years of age , declining to 14 % at 5 years of age and followed by an increase to 25 % at 10 years of age . Sensitization to inhalant and /or food allergens ( specific IgE of > or = class 2 ; CAP RAST ) showed a low rate of sensitization among asymptomatics ( 3 % , 10 % and 12 % ) compared with higher rates of sensitization of 8 % , 39 % and 30 % among symptomatic atopics at 1.5 , 5 and 10 years of age respectively . The highest rate of sensitization ( 53 % ) was found among children with current asthma at 10 years of age Background Prebiotics and probiotics ( synbiotics ) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula ( AAF ) for infants with cow ’s milk allergy ( CMA ) . Methods This multicenter , double-blind , r and omized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group ( ER/CC ) in feces from infants with suspected non-IgE-mediated CMA . Feces from age-matched healthy breastfed infants were used as reference ( healthy breastfed reference ( HBR ) ) for primary outcomes . The CMA subjects were r and omized and received test or control formula for 8 weeks . Test formula was a hypoallergenic , nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V . Control formula was AAF without synbiotics . Results A total of 35 ( test ) and 36 ( control ) subjects were r and omized ; HBR included 51 infants . At week 8 , the median percentage of bifidobacteria was higher in the test group than in the control group ( 35.4 % vs. 9.7 % , respectively ; P<0.001 ) , whereas ER/CC was lower ( 9.5 % vs. 24.2 % , respectively ; P<0.001 ) . HBR levels of bifidobacteria and ER/CC were 55 % and 6.5 % , respectively . Conclusion AAF including specific synbiotics , which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group , improves the fecal microbiota of infants with suspected non-IgE-mediated CMA Background Allergy to cow ’s milk protein ( CMP ) may cause gastrointestinal ( GI ) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood . Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow ’s milk protein allergy ( CMPA ) . Patients and methods We prospect ively recruited infants and young children ( n = 57 ; median age 8.7 months ) with gastrointestinal complaints suspected of CMPA . The diagnosis of CMPA was made using the double-blind , placebo-controlled food challenge . Serum and stool sample s were collected during CMP-free diet and after both placebo and active challenges . We analyzed the stool sample s for calprotectin , human β-defensin 2 and IgA. In serum , we analyzed the levels of β-lactoglobulin and α-casein specific IgA , and IgG antibodies ( total IgG and subclasses IgG1 and IgG4 ) . Control group included children with e.g. dermatological or pulmonary problems , consuming normal diets .  Results Fecal calprotectin levels were higher in the challenge positive group ( n = 18 ) than in the negative ( n = 37 ) , with respective geometric means 55 μg/g [ 95 % confidence interval 38–81 ] and 29 [ 24–36 ] μg/g ( p = 0.0039 ) , during cow ’s milk free diet . There were no significant inter-group differences in the fecal β-defensin and IgA levels . The CMP specific IgG and IgA were not elevated in patients with CMPA , but the levels of β-lactoglobulin-IgG4 ( p = 0.0118 ) and α-casein-IgG4 ( p = 0.0044 ) , and total α-casein-IgG ( p = 0.0054 ) and -IgA ( p = 0.0050 ) in all patient sample s ( regardless of CMPA diagnosis ) were significantly lower compared to the control group using dairy products . Conclusions Despite cow ’s milk elimination in children intolerant to cow ’s milk there might be ongoing low- grade inflammation in the gut mucosa . CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA . The observed frequency of impaired CMP specific total IgA , IgG and IgG4 production in patients following cow ’s milk free diet warrants further studies Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Large , prospect i ve population -based studies on clinical course , development of tolerance , and risk for other atopy in children with cow 's milk allergy ( CMA ) are lacking . OBJECTIVE We investigated the development of tolerance and the risk for asthma , rhinoconjunctivitis , atopic dermatitis , and sensitization in children with CMA followed to school age . METHODS We followed 118 children with CMA until recovery and repeatedly measured their sensitization to cow 's milk ( CM ) . At age 8.6 years , 94 allergic subjects and 80 control subjects from the same cohort were studied for atopic diseases and sensitization . In addition , the parents of 12 allergic subjects and 26 control children returned a question naire on atopy , respectively . RESULTS IgE-mediated CMA was detected in 86 ( 73 % ) children ; at age 8.6 years , 13 ( 15 % ) had persistent CMA . All children with IgE-negative CMA were tolerant by age 5.0 years ( P < .0001 ) . Risk factors for persistent CMA at age 2.0 years were sensitization to CM at age 1.6 years ( odds ratio , 6.3 ; 95 % CI , 2.6 - 15.2 ) , urticaria at diagnostic challenge ( odds ratio , 3.3 ; 95 % CI , 1.4 - 7.8 ) , CM exposure at the maternity hospital ( odds ratio , 3.2 ; 95 % CI , 1.4 - 7.8 ) , and early sensitization to egg ( odds ratio , 2.8 ; 95 % CI , 1.2 - 6.6 ) . By age 8.6 years , children with IgE-positive CMA more frequently had asthma ( 31 % vs 13 % , P < or = .01 ) , rhinoconjunctivitis ( 66 % vs 21 % , P < or = .001 ) , atopic eczema ( 81 % vs 26 % , P < or = .001 ) , and sensitization to any allergen ( 88 % vs 39 % , P < or = .001 ) than control subjects . CMA and family history of atopy were independent risk factors for atopic diseases , and CMA was also a risk factor for sensitization to inhalant allergens . CONCLUSION IgE-mediated CMA often persists to school age and is a risk factor for other atopy ; non-IgE-mediated CMA , by contrast , is a benign infantile condition OBJECTIVES To determine the benefits of Lactobacillus rhamnosus GG ( LGG ) in an extensively hydrolyzed casein formula ( EHCF ) in improving hematochezia and fecal calprotectin over EHCF alone . STUDY DESIGN Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group . We also compared fecal calprotectin and hematochezia on 26 formula-fed infants r and omly assigned to EHCF with LGG ( Nutramigen LGG ) ( EHCF + LGG ) or without ( Nutramigen ) ( EHCF - LGG )  and on 4 breastfed infants whose mothers eliminated dairy . RESULTS Fecal calprotectin in those with hematochezia was significantly higher than in comparisons ( mean + /- SD 325.89 + /- 152.31 vs 131.97 + /- 37.98 microg/g stool , t = 6.79 , P < .0001 ) . At 4 weeks , fecal calprotectin decreased to 50 % of baseline but was still significantly higher than in comparisons ( 157.5 + /- 149.13 vs 93.72 + /- 36.65 microg/g , P = .03 ) . Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG ( -214.5 + /- 107.93 vs -112.7 + /- 105.27 microg/g , t = 2.43 , P = .02 ) . At 4 weeks , none of the EHCF + LGG had blood in stools , and 5/14 on EHCF - LGG did ( P = .002 ) . CONCLUSION Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis . EHCF + LGG result ed in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone Objective : Cow`s milk protein allergy usually occurs in infants within the first months of life . It can affect several organs , but gastrointestinal symptoms are the most clinical symptoms observed . The most effective treatment is restricting the cow ` s milk protein in mother and infant`s diet . Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora . Methods : Thirty two breastfed infants with cow`s milk protein allergy 
    Output:
    
agent
Conclusion : Limited low- quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA .
CMPA is associated with significant socioeconomic burden.• Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.What is New:• This first systematic review of r and omized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP  in children at 36 months of age .
However , the evidence is low quality and influenced by data from one large study .• Probiotic supplementation was not associated with earlier resolution of hematochezia
***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: A cohort of 1,749 newborns from the municipality of Odense , born during 1995 at the Odense University Hospital , were followed up prospect ively for the development of cow 's milk protein allergy/intolerance ( CMPA/I ) during the first year of life . Once a diagnosis of CMPA/I was confirmed , a milk-free diet was continued until a new milk challenge had shown development of tolerance . All infants with CMPA/I were rechallenged at 12 months of age and , in the event of continued clinical sensitivity to cow 's milk protein , controlled rechallenges were performed every 6 months up to 3 years of age ; and thereafter every 12 months until the age of 15 years . From the same birth cohort , 276 infants were r and omly selected at birth for prospect i ve non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood . St and ardized question naires on atopic heredity , environmental factors and presence of atopic symptoms were answered at 0 , 6 , 12 and 18 months and at 5 , 10 and 15 years of age . Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months , 5 , 10 and 15 years of age . Skin prick test and specific sIgE ( Pharmacia CAP ) testing were performed at 18 months , 5 , 10 and 15 years of age against a panel of inhalant allergens ( birch , grass , mugwort , dog , cat , horse , Dermatophagoidespteronyssinus , Dermatophagoides farinae , alternaria and cladosporium herbarum ) . Furthermore , lung function measurements were performed in children when 10 and 15 years of age . Based on controlled milk elimination and challenge procedures , the diagnosis of CMPA/I was confirmed in 39 out of 117 infants , with symptoms suggestive of CMPA/I , thus result ing in a 1-year incidence of CMPA/I of 2.2 % . The overall prognosis of CMPA/I was good , with a total recovery of 56 % at 1 year , 77 % at 2 years , 87 % at 3 years , 92 % at 5 and 10 years and 97 % at 15 years of age . In children younger than 10 years of age , 41 % developed asthma and 31 % rhinoconjunctivitis . Children with non-IgE-mediated CMPI had a good prognosis , whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA , development of other food allergies , asthma and rhinoconjunctivitis . During early infancy , recurrent wheezing was the most prevalent disease ( 20 % ) , followed by atopic dermatitis ( 14 % ) and food allergy ( 7 % ) at 18 months of age . Physician diagnosed asthma increased from 2 % at 1.5 years of age to 9 % at 10 years of age .  Rhinoconjunctivitis  increased from < 1 % at 1.5 years of age to 9 % at 10 years of age . Overall , the current prevalence of any atopic disease was 20 % at 1.5 years of age , declining to 14 % at 5 years of age and followed by an increase to 25 % at 10 years of age . Sensitization to inhalant and /or food allergens ( specific IgE of > or = class 2 ; CAP RAST ) showed a low rate of sensitization among asymptomatics ( 3 % , 10 % and 12 % ) compared with higher rates of sensitization of 8 % , 39 % and 30 % among symptomatic atopics at 1.5 , 5 and 10 years of age respectively . The highest rate of sensitization ( 53 % ) was found among children with current asthma at 10 years of age Background Prebiotics and probiotics ( synbiotics ) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula ( AAF ) for infants with cow ’s milk allergy ( CMA ) . Methods This multicenter , double-blind , r and omized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group ( ER/CC ) in feces from infants with suspected non-IgE-mediated CMA . Feces from age-matched healthy breastfed infants were used as reference ( healthy breastfed reference ( HBR ) ) for primary outcomes . The CMA subjects were r and omized and received test or control formula for 8 weeks . Test formula was a hypoallergenic , nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V . Control formula was AAF without synbiotics . Results A total of 35 ( test ) and 36 ( control ) subjects were r and omized ; HBR included 51 infants . At week 8 , the median percentage of bifidobacteria was higher in the test group than in the control group ( 35.4 % vs. 9.7 % , respectively ; P<0.001 ) , whereas ER/CC was lower ( 9.5 % vs. 24.2 % , respectively ; P<0.001 ) . HBR levels of bifidobacteria and ER/CC were 55 % and 6.5 % , respectively . Conclusion AAF including specific synbiotics , which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group , improves the fecal microbiota of infants with suspected non-IgE-mediated CMA Background Allergy to cow ’s milk protein ( CMP ) may cause gastrointestinal ( GI ) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood . Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow ’s milk protein allergy ( CMPA ) . Patients and methods We prospect ively recruited infants and young children ( n = 57 ; median age 8.7 months ) with gastrointestinal complaints suspected of CMPA . The diagnosis of CMPA was made using the double-blind , placebo-controlled food challenge . Serum and stool sample s were collected during CMP-free diet and after both placebo and active challenges . We analyzed the stool sample s for calprotectin , human β-defensin 2 and IgA. In serum , we analyzed the levels of β-lactoglobulin and α-casein specific IgA , and IgG antibodies ( total IgG and subclasses IgG1 and IgG4 ) . Control group included children with e.g. dermatological or pulmonary problems , consuming normal diets .  Results Fecal calprotectin levels were higher in the challenge positive group ( n = 18 ) than in the negative ( n = 37 ) , with respective geometric means 55 μg/g [ 95 % confidence interval 38–81 ] and 29 [ 24–36 ] μg/g ( p = 0.0039 ) , during cow ’s milk free diet . There were no significant inter-group differences in the fecal β-defensin and IgA levels . The CMP specific IgG and IgA were not elevated in patients with CMPA , but the levels of β-lactoglobulin-IgG4 ( p = 0.0118 ) and α-casein-IgG4 ( p = 0.0044 ) , and total α-casein-IgG ( p = 0.0054 ) and -IgA ( p = 0.0050 ) in all patient sample s ( regardless of CMPA diagnosis ) were significantly lower compared to the control group using dairy products . Conclusions Despite cow ’s milk elimination in children intolerant to cow ’s milk there might be ongoing low- grade inflammation in the gut mucosa . CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA . The observed frequency of impaired CMP specific total IgA , IgG and IgG4 production in patients following cow ’s milk free diet warrants further studies Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Large , prospect i ve population -based studies on clinical course , development of tolerance , and risk for other atopy in children with cow 's milk allergy ( CMA ) are lacking . OBJECTIVE We investigated the development of tolerance and the risk for asthma , rhinoconjunctivitis , atopic dermatitis , and sensitization in children with CMA followed to school age . METHODS We followed 118 children with CMA until recovery and repeatedly measured their sensitization to cow 's milk ( CM ) . At age 8.6 years , 94 allergic subjects and 80 control subjects from the same cohort were studied for atopic diseases and sensitization . In addition , the parents of 12 allergic subjects and 26 control children returned a question naire on atopy , respectively . RESULTS IgE-mediated CMA was detected in 86 ( 73 % ) children ; at age 8.6 years , 13 ( 15 % ) had persistent CMA . All children with IgE-negative CMA were tolerant by age 5.0 years ( P < .0001 ) . Risk factors for persistent CMA at age 2.0 years were sensitization to CM at age 1.6 years ( odds ratio , 6.3 ; 95 % CI , 2.6 - 15.2 ) , urticaria at diagnostic challenge ( odds ratio , 3.3 ; 95 % CI , 1.4 - 7.8 ) , CM exposure at the maternity hospital ( odds ratio , 3.2 ; 95 % CI , 1.4 - 7.8 ) , and early sensitization to egg ( odds ratio , 2.8 ; 95 % CI , 1.2 - 6.6 ) . By age 8.6 years , children with IgE-positive CMA more frequently had asthma ( 31 % vs 13 % , P < or = .01 ) , rhinoconjunctivitis ( 66 % vs 21 % , P < or = .001 ) , atopic eczema ( 81 % vs 26 % , P < or = .001 ) , and sensitization to any allergen ( 88 % vs 39 % , P < or = .001 ) than control subjects . CMA and family history of atopy were independent risk factors for atopic diseases , and CMA was also a risk factor for sensitization to inhalant allergens . CONCLUSION IgE-mediated CMA often persists to school age and is a risk factor for other atopy ; non-IgE-mediated CMA , by contrast , is a benign infantile condition OBJECTIVES To determine the benefits of Lactobacillus rhamnosus GG ( LGG ) in an extensively hydrolyzed casein formula ( EHCF ) in improving hematochezia and fecal calprotectin over EHCF alone . STUDY DESIGN Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group . We also compared fecal calprotectin and hematochezia on 26 formula-fed infants r and omly assigned to EHCF with LGG ( Nutramigen LGG ) ( EHCF + LGG ) or without ( Nutramigen ) ( EHCF - LGG )  and on 4 breastfed infants whose mothers eliminated dairy . RESULTS Fecal calprotectin in those with hematochezia was significantly higher than in comparisons ( mean + /- SD 325.89 + /- 152.31 vs 131.97 + /- 37.98 microg/g stool , t = 6.79 , P < .0001 ) . At 4 weeks , fecal calprotectin decreased to 50 % of baseline but was still significantly higher than in comparisons ( 157.5 + /- 149.13 vs 93.72 + /- 36.65 microg/g , P = .03 ) . Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG ( -214.5 + /- 107.93 vs -112.7 + /- 105.27 microg/g , t = 2.43 , P = .02 ) . At 4 weeks , none of the EHCF + LGG had blood in stools , and 5/14 on EHCF - LGG did ( P = .002 ) . CONCLUSION Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis . EHCF + LGG result ed in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone Objective : Cow`s milk protein allergy usually occurs in infants within the first months of life . It can affect several organs , but gastrointestinal symptoms are the most clinical symptoms observed . The most effective treatment is restricting the cow ` s milk protein in mother and infant`s diet . Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora . Methods : Thirty two breastfed infants with cow`s milk protein allergy 
    Output:
    