title: Effect of a Probiotic Infant Formula on Infections in Child Care Centers: Comparison of Two Probiotic Agents Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study A patient-oriented, double-blind, cluster-randomized, placebo-controlled, clinical trial Viral Epidemiology and Severity of Respiratory Infections in Infants in 2009: A Prospective Study Efficacy of a synbiotic supplementation in the prevention of common winter diseases in children: a randomized, double-blind, placebo-controlled pilot study Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers - Randomized, double blind, placebo-controlled study. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in early childhood The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial Role of short-term use of L. acidophilus DDS-1 and B. lactis UABLA-12 in acute respiratory infections in children: a randomized controlled trial Applying psychological theories to evidence-based clinical practice: Identifying factors predictive of managing upper respiratory tract infections without antibiotics Specific probiotics in reducing the risk of acute infections in infancy--a randomised, double-blind, placebo-controlled study. Lactobacillus GG in the Prevention of Nosocomial Gastrointestinal and Respiratory Tract Infections Probiotic Effects on Cold and Influenza-Like Symptom Incidence and Duration in Children Effects of Consumption of a Fermented Dairy Product Containing the Probiotic Lactobacillus casei DN-114 001 on Common Respiratory and Gastrointestinal Infections in Shift Workers in a Randomized Controlled Trial Effect of recolonisation with “interfering” α streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial Randomized controlled trial of probiotics to reduce common cold in schoolchildren. Probiotics and Prebiotics in Preventing Episodes of Acute Otitis Media in High-risk Children: A Randomized, Double-blind, Placebo-controlled Study Bifidobacterium animalis subsp. lactis fails to prevent common infections in hospitalized children: a randomized, double-blind, placebo-controlled study. Human Milk Probiotic Lactobacillus fermentum CECT5716 Reduces the Incidence of Gastrointestinal and Upper Respiratory Tract Infections in Infants Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy. A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome. Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media Economic impact of community-acquired and nosocomial lower respiratory tract infections in young children in Germany Fermented Milk Containing Bifidobacterium lactis DN-173 010 in Childhood Constipation: A Randomized, Double-Blind, Controlled Trial Screening of Probiotic Activities of Forty-Seven Strains of Lactobacillus spp. by In Vitro Techniques and Evaluation of the Colonization Ability of Five Selected Strains in Humans Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial
abstract: Objective . To investigate the effect of 2 different species of probiotics in preventing infections in infants attending child care centers . Methods . A double-blind , placebo-controlled , r and omized trial was conducted from December 1 , 2000 , to September 30 , 2002 , at 14 child care centers in the Beer-Sheva area of Israel in healthy term infants 4 to 10 months old . Infants were assigned r and omly to formula supplemented with Bifidobacterium lactis ( BB-12 ) , Lactobacillus reuteri ( American Type Culture Collection 55730 ) , or no probiotics . Duration of feeding , including follow-up , for each participant was 12 weeks . All infants were fed only the assigned formula and were not breastfed due to parental decision before recruitment to the study . Probiotic or prebiotic food products or supplements were not allowed . Main outcome measures were number of days and number of episodes with fever ( > 38 ° C ) and number of days and number of episodes with diarrhea or respiratory illness . Results . Participants ( n = 201 ) were similar regarding gestational age , birth weight , gender , and previous breastfeeding . The controls ( n = 60 ) , compared with those fed B lactis ( n = 73 ) or L reuteri ( n = 68 ) , had significantly more febrile episodes ( mean [ 95 % confidence interval ] : 0.41 [ 0.28–0.54 ] vs 0.27 [ 0.17–0.37 ] vs 0.11 [ 0.04–0.18 ] , respectively ) . The controls also had more diarrhea episodes ( 0.31 [ 0.22–0.40 ] vs 0.13 [ 0.05–0.21 ] vs 0.02 [ 0.01–0.05 ] , respectively ) and episodes of longer duration ( 0.59 [ 0.34–0.84 ] vs 0.37 [ 0.08–0.66 ] vs 0.15 [ 0.12–0.18 ] days , respectively ) . The L reuteri group , compared with BB-12 or controls , had a significant decrease of number of days with fever , clinic visits , child care absences , and antibiotic prescriptions . Rate and duration of respiratory illnesses did not differ significantly between groups . Conclusions . Child care infants fed a formula supplemented with L reuteri or B lactis had fewer and shorter episodes of diarrhea , with no effect on respiratory illnesses . These effects were more prominent with L reuteri , which was also the only supplement to improve additional morbidity parameters Background : To evaluate whether a fermented dairy drink containing the probiotic strain Lactobacillus casei DN-114 001 could reduce the incidence of common infectious diseases ( CIDs ) and the change of behavior because of illness in children . Subjects/ Methods : We conducted a double-blinded , r and omized , placebo-controlled allocation concealment clinical trial in the Washington , DC metropolitan area . Participants were 638 children 3–6 years old in daycare/schools . The intervention was a fermented dairy drink containing a specific probiotic strain or matching placebo with no live cultures for 90 consecutive days . Two primary outcomes were assessed : incidence of CIDs and change of behavior because of illness ( both assessed by parental report ) . Results : The rate of change of behavior because of illness was similar among active and control groups . However , the incidence rate for CIDs in the active group ( 0.0782 ) is 19 % lower than that of the control group ( 0.0986 ) ( incidence rate ratio=0.81 , 95 % CI : 0.65 , 099 ) P=0.046 . Conclusions : Daily intake of a fermented dairy drink containing the probiotic strain L. casei DN-114 001 showed some promise in reducing overall incidence of illness , but was primarily driven by gastrointestinal infections and there were no differences in change of behavior Background : Viral respiratory infections are common in infants and can be severe . The new p and emic influenza virus H1N1v2009 was feared to cause particularly severe outcomes . Objective : This study aim ed at evaluating the impact of H1N1v2009 on the viral epidemiology , the clinical presentation and the severity of respiratory infections in infants . Patients and Methods : This prospect i ve epidemiologic study included all infants < 2 years of age , both in patients and out patients , presenting with respiratory symptoms , from November 2009 through April 2010 , at the pediatric emergency department of the University Hospital of Caen , France .  A nasal swab was taken for viral detection and analyzed by immunofluorescence and , if negative , polymerase chain reaction . Severe respiratory infection was defined by a score of respiratory severity . Results : One thous and twenty-one infectious episodes with a respiratory sample met inclusion criteria . Eight hundred thirty-four sample s ( 81.7 % ) were positive . The viruses with the highest incidence were the respiratory syncytial virus ( 34.2 % ) , the rhinoviruses ( 23.9 % ) , the coronaviruses ( 9.3 % ) and H1N1v2009 ( 7.7 % ) . Of all infections , 28.6 % were severe and more frequent in infants with risk factors . H1N1v2009 infections had a low risk of severe respiratory disease ( odds ratios = 0.15 ) and hospitalization ( odds ratios = 0.40 ) compared with the other viruses . Respiratory syncytial virus infections had a high risk of respiratory severity ( odds ratios = 7.85 ) and were responsible for 71.4 % of admissions to the intensive care unit . Conclusion : Despite the modest impact of H1N1v2009 observed in this study , further surveillance is needed to detect virological factors that may increase its severity Background and aims : The purpose of this study was to investigate the efficacy of a synbiotic supplementation in reducing common winter diseases  in children . Methods : A r and omized , double-blind , placebo-controlled , multicentre study was conducted in young school-age children ( 3—7 years old ) during a winter period . Participants were otherwise healthy children who suffered from at least three episodes of ear , nose and throat ( ENT ) , respiratory tract or gastrointestinal illness during the previous winter . They were supplemented daily with either a synbiotic preparation ( Lactobacillus helveticus R0052 , Bifidobacterium infantis R0033 , Bifidobacterium bifidum R0071 , and fructooligosaccharide ) or a matched placebo for 3 months . Over this period , all emergent health episodes of any type were recorded by parents in a diary . They were checked by investigators at regular monthly visits . The main study outcome was the percentage of children free of any episode during the study course . Results : We r and omized 135 children ( mean age : 4.1±1.0 years ) to the synbiotic group ( n = 62 ) or placebo ( n = 73 ) group . At least one illness episode was reported in 32 children in the synbiotic group and 50 in the placebo group ( 51.6 % versus 68.5 % ) . This corresponded to a significant 25 % relative risk reduction ( 95 % CI 0.6—44.3 % ; p = 0.045 ) . This difference was due to a decrease in the number of children who suffered from at least one ENT , respiratory tract or gastrointestinal disorder ( 50.0 % with synbiotic versus 67.1 % with placebo ; p = 0.044 ) . At least one sickness school day loss was noted in 25.8 % of children with the synbiotic as compared with 42.5 % with placebo ( p = 0.043 ) . No treatment related side effects were detected in either group . Conclusions : This study suggests that a 3-month supplementation with this synbiotic preparation  can decrease the risk of occurrence of common infectious diseases in children and limits the risk of school day loss BACKGROUND & AIMS The aim of our study was to investigate the role of Bifidobacterium animalis subsp . lactis ( BB-12 ( ® ) ) in the prevention of common ( gastrointestinal and respiratory ) infections in healthy children who attend day care centers . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in 210 children who attend day care centers . They were r and omly allocated to receive placebo ( Placebo group , n = 106 ) or BB-12 ( ® ) at a dose of 10(9 ) colony-forming units ( CFU ) ( Intervention group , n = 104 ) during the 3-month intervention period . RESULTS Intention to treat analysis was used . There were overall 99 infections in Placebo group and 97 in Intervention group ( incidence rate ratio = 1.0014 , p = 0.992 , Poisson regression model ) . Overall 65 children ( 61.3 % ) in Placebo group and 67 ( 64.4 % ) in Intervention group had common infections ( p = 0.642 ) . Mean number of infections per child was 0.93 ( range 0 - 3 ) in Placebo group and 0.93 ( range 0 - 3 ) in Intervention group ( p = 0.898 ) . There was no difference in secondary ( duration of symptoms , number of children with gastrointestinal and respiratory tract infections , absence from day care center due to infections , use of antibiotics ) and exploratory ( type of gastrointestinal and respiratory tract infection ) endpoints between groups . CONCLUSION Results of performed study show that BB-12 ( ® ) has no effect on the prevention of gastrointestinal and respiratory tract infections in healthy children who attend day care centers Background : Specific probiotic bacteria have proven to be effective in the prevention and treatment of infectious diseases in early life in at-risk population s. The impact of administration of Bifidobacterium animalis subsp . lactis BB-12 ( BB-12 ) on the risk of acute infectious diseases was studied in healthy children . Methods : In this double-blind , placebo-controlled study , 109 1-mo-old infants were assigned r and omly to a probiotic group receiving a BB-12–containing tablet ( n = 55 ) or a placebo ( n = 54 ) . Test tablets were administered to the infants twice a day ( daily dose of BB-12 10 billion colony-forming units ) until the age of 2 y with a novel slow-release pacifier or a spoon . Breastfeeding habits , pacifier use , dietary habits , medications , and all signs and symptoms of acute infections were registered in diaries by parents and in question naires by trained professionals . Results : The infants receiving BB-12 were reported to have experienced fewer respiratory tract infections ( RTIs ; 87 vs. 100 % ; risk ratio : 0.87 ; 95 % confidence interval : 0.76 , 1.00 ; P = 0.033 ) than the controls . No significant differences between the groups were observed in reported gastrointestinal symptoms , otitis media , or fever . The baseline characteristics of the two groups were similar , as was the duration of breastfeeding . Conclusion : Administration of BB-12 in early childhood may reduce RTIs 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 Abstract Objective : To examine whether long term consumption of a probiotic milk could reduce  gastrointestinal and respiratory infections in children in day care centres . Design : R and omised , double blind , placebo controlled study over seven months . Setting : 18 day care centres in Helsinki , Finl and . Participants : 571 healthy children aged 1 - 6 years : 282 ( mean ( SD ) age 4.6 ( 1.5 ) years ) in the intervention group and 289 ( mean ( SD ) age 4.4 ( 1.5 ) years ) in the control group . Intervention : Milk with or without Lactobacillus GG . Average daily consumption of milk in both groups was 260 ml . Main outcome measures : Number of days with respiratory and gastrointestinal symptoms , absences from day care because of illness , respiratory tract infections diagnosed by a doctor , and course of antibiotics . Results : Children in the Lactobacillus group had fewer days of absence from day care because of illness ( 4.9 ( 95 % confidence interval 4.4 to 5.5 ) v 5.8 ( 5.3 to 6.4 ) days , 16 % difference , P=0.03 ; age adjusted 5.1 ( 4.6 to 5.6 ) v 5.7 ( 5.2 to 6.3 ) days , 11 % difference , P=0.09 ) . There was also a relative reduction of 17 % in the number of children suffering from respiratory infections with complications and lower respiratory tract infections ( unadjusted absolute % reduction −8.6 ( −17.2 to −0.1 ) , P=0.05 ; age adjusted odds ratio 0.75 ( 0.52 to 1.09 ) , P=0.13 ) and a 19 % relative reduction in antibiotic treatments for respiratory infection ( unadjusted absolute % reduction −9.6 ( −18.2 to −1.0 ) , P=0.03 ; adjusted odds ratio 0.72 ( 0.50 to 1.03 ) , P=0.08 ) in the Lactobacillus group . Conclusions : Lactobacillus GG may reduce respiratory infections and their severity among children in day care . The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction . What is already known on this topic Children attending day care centres are at high risk of respiratory and gastrointestinal infection The successful prevention of respiratory infections could be extremely useful for families and for society in general Short term use of probiotic bacteria has been shown to reduce the severity of rotavirus diarrhoea and the incidence of diarrhoea associated with the use of antibiotics What this study adds In a double blind , r and omised , long term study milk containing Lactobacillus GG slightly reduced the incidence of respiratory infections and antibiotic treatment in Background / Objectives : Evidence suggests that the long-term consumption of probiotics may help in reducing the incidence of or modifying  acute respiratory infection ( ARI ) . We assessed the role of the short-term use of probiotics in ARI in children . Subjects/ Methods : This was a r and omized , double-blind , controlled study that enrolled 315 children with 90 dropouts . On the first day of appearance of a sick household member , otherwise healthy children of both sexes aged 3–12 years were allocated to receive Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABLA-12 ( Up4-Junior ) in a dose of 5 billion colony-forming units daily with 50 mg of fructooligosaccharide ( the probiotic group ) or rice maltodexrin ( the control group ) . Test supplementation and follow-up lasted for 2 weeks or until the end of the secondary ARI in a child . The primary outcome measure was the incidence of ARI . Time to resolution and the severity of ARI served the secondary outcome measures . Results : In all , 64 of 113 children in the probiotic group ( 57 % ) and 73 of 112 children in the control group ( 65 % ) developed ARI ( P=0.261 ) . Time to resolution of the secondary ARI was shorter in the probiotic group ( 5.0 ( interquartile range ( IQR ) : 4.0–6.0 ) vs 7.0 ( IQR : 6.0–8.0 ) days , P<0.001 ) . The median severity of ARI was 240 ( IQR : 163–350 ) score-days in the probiotic vs 525 ( IQR : 364–736 ) score-days in the control group ( P<0.001 ) . Conclusions : The short-term use of probiotics does not reduce the incidence , but shortens ARI in preschool and elementary school children Background Psychological models can be used to underst and and predict behaviour in a wide range of setting s. However , they have not been consistently applied to health professional behaviours , and the contribution of differing theories is not clear . The aim of this study was to explore the usefulness of a range of psychological theories to predict health professional behaviour relating to management of upper respiratory tract infections ( URTIs ) without antibiotics . Methods Psychological measures were collected by postal question naire survey from a r and om sample of general practitioners ( GPs ) in Scotl and . The outcome measures were clinical behaviour ( using antibiotic prescription rates as a proxy indicator ) ,  behavioural simulation ( scenario-based decisions to managing URTI with or without antibiotics ) and behavioural intention ( general intention to managing URTI without antibiotics ) . Explanatory variables were the constructs within the following theories : Theory of Planned Behaviour ( TPB ) , Social Cognitive Theory ( SCT ) , Common Sense Self-Regulation Model ( CS-SRM ) , Operant Learning Theory ( OLT ) , Implementation Intention ( II ) , Stage Model ( SM ) , and knowledge ( a non-theoretical construct ) . For each outcome measure , multiple regression analysis was used to examine the predictive value of each theoretical model individually . Following this ' theory level ' analysis , a ' cross theory ' analysis was conducted to investigate the combined predictive value of all significant individual constructs across theories . Results All theories were tested , but only significant results are presented . When predicting behaviour , at the theory level , OLT explained 6 % of the variance and , in a cross theory analysis , OLT ' evidence of habitual behaviour ' also explained 6 % . When predicting  behavioural simulation  , at the theory level , the proportion of variance explained was : TPB , 31 % ; SCT , 26 % ; II , 6 % ; OLT , 24 % . GPs who reported having already decided to change their management to try to avoid the use of antibiotics made significantly fewer scenario-based decisions to prescribe . In the cross theory analysis , perceived behavioural control ( TPB ) , evidence of habitual behaviour ( OLT ) , CS-SRM cause ( chance/bad luck ) , and intention entered the equation , together explaining 36 % of the variance . When predicting intention , at the theory level , the proportion of variance explained was : TPB , 30 % ; SCT , 29 % ; CS-SRM 27 % ; OLT , 43 % . GPs who reported that they had already decided to change their management to try to avoid the use of antibiotics had a significantly higher intention to manage URTIs without prescribing antibiotics . In the cross theory analysis , OLT evidence of habitual behaviour , TPB attitudes , risk perception , CS-SRM control by doctor , TPB perceived behavioural control and CS-SRM control by treatment entered the equation , together explaining 49 % of the variance in intention . Conclusion The study provides evidence that psychological models can be useful in underst and ing and predicting clinical behaviour . Taking a theory-based approach enables the creation of a replicable methodology for identifying factors that predict clinical behaviour . However , a number of conceptual and method ological challenges remain A r and omised , double-blind , placebo-controlled study was conducted to determine whether probiotics might be effective in reducing the risk of infections in infancy . Infants requiring formula before the age of 2 months were recruited from community well-baby clinics . Infant formula supplemented with the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 or placebo was administered daily until the age of 12 months . Incidence of early infections ( before the age of 7 months ) and incidence of recurrent ( three or more ) infections during the first year of life were recorded as the main outcome measures of the study . During the first 7 months of life , seven out of thirty-two ( 22 % ) infants receiving probiotics and twenty out of forty ( 50 % ) infants receiving placebo experienced acute otitis media ( risk ratio ( RR ) 0.44 ( 95 % CI 0.21 , 0.90 ) ; P = 0.014 ) and antibiotics were prescribed for ten out of thirty-two ( 31 % ) infants receiving probiotics and twenty-four out of forty ( 60 % ) infants receiving placebo ( RR 0.52 ( 95 % CI 0.29 , 0.92 ) ; P = 0.015 ) . During the first year of life , nine out of thirty-two ( 28 % ) infants receiving probiotics and twenty-two out of forty ( 55 % ) infants receiving placebo encountered recurrent respiratory infections ( RR 0.51 ( 95 % CI 0.27 , 0.95 ) ; P = 0.022 ) . These data suggest that probiotics may offer a safe means of reducing the risk of early acute otitis media and antibiotic use and the risk of recurrent respiratory infections during the first year of life . Further clinical trials are warranted OBJECTIVE : The incidence of nosocomial infections , predominantly gastrointestinal and respiratory , in children in developed countries is high , ranging from 5 % to 44 % . There is no effective strategy for preventing these infections . The objective of our study was to investigate the role of Lactobacillus GG ( LGG ) in preventing nosocomial gastrointestinal and respiratory tract infections at a pediatric hospital . METHODS : We conducted a r and omized , double-blind , placebo-controlled trial of 742 hospitalized children . They were r and omly allocated to receive for their hospitalization LGG at a dose of 109 colony-forming units in 100 mL of a fermented milk product ( LGG group , n = 376 ) or placebo that was the same postpasteurized fermented milk product without LGG ( placebo group , n = 366 ) . RESULTS : In the LGG group , compared with the placebo group , we found a significantly reduced risk for gastrointestinal infections ( relative risk [ RR ] : 0.40 [ 95 % confidence interval ( CI ) : 0.25–0.70 ] ; number needed to treat : 15 [ 95 % CI : 9–34 ) ] , respiratory tract infections ( RR : 0.38 [ 95 % CI : 0.18–0.85 ] ; number needed to treat : 30 [ 95 % CI : 16–159 ] ) , vomiting episodes ( RR : 0.5 [ 95 % CI : 0.3–0.9 ] ) , diarrheal episodes ( RR : 0.24 [ 95 % CI : 0.10–0.50 ] ) , episodes of gastrointestinal infections that lasted > 2 days ( RR : 0.40 [ 95 % CI : 0.25–0.70 ] ) , and episodes of respiratory tract infections that lasted > 3 days ( RR : 0.4 [ 95 % CI : 0.2–0.9 ] ) . Groups did not differ in hospitalization duration ( P = .1 ) . CONCLUSIONS : LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities OBJECTIVE : Probiotic consumption effects on cold and influenza-like symptom incidence and duration were evaluated in healthy children during the winter season . METHODS : In this double-blind , placebo-controlled study , 326 eligible children ( 3–5 years of age ) were assigned r and omly to receive placebo ( N = 104 ) , Lactobacillus acidophilus NCFM ( N = 110 ) , or L acidophilus NCFM in combination with Bifidobacterium animalis subsp lactis Bi-07 ( N = 112 ) . Children were treated twice daily for 6 months . RESULTS : Relative to the placebo group , single and combination probiotics  reduced fever incidence by 53.0 % ( P = .0085 ) and 72.7 % ( P = .0009 ) , coughing incidence by 41.4 % ( P = .027 ) and 62.1 % ( P = .005 ) , and rhinorrhea incidence by 28.2 % ( P = .68 ) and 58.8 % ( P = .03 ) , respectively . Fever , coughing , and rhinorrhea duration was decreased significantly , relative to placebo , by 32 % ( single strain ; P = .0023 ) and 48 % ( strain combination ; P < .001 ) . Antibiotic use incidence was reduced , relative to placebo , by 68.4 % ( single strain ; P = .0002 ) and 84.2 % ( strain combination ; P < .0001 ) . Subjects receiving probiotic products had significant reductions in days absent from group child care , by 31.8 % ( single strain ; P = .002 ) and 27.7 % ( strain combination ; P < .001 ) , compared with subjects receiving placebo treatment . CONCLUSION : Daily dietary probiotic supplementation for 6 months was a safe effective way to reduce fever , rhinorrhea , and cough incidence and duration and antibiotic prescription incidence , as well as the number of missed school days attributable to illness , for children 3 to 5 years of age Objective : The risk of infection may be increased in people under stress such as shift workers . This study examined the effect of a fermented dairy product containing the probiotic Lactobacillus casei DN-114 001 ( verum ) on the incidence of respiratory and gastrointestinal common infectious diseases ( CIDs ) and on immune functions in healthy shift workers . Methods : The study was single-center , r and omized , double-blind , and controlled . Volunteers  received 200 g/day of verum ( n = 500 ) or control product ( n = 500 ) for 3 months ; 1-month follow-up was carried out . Results : The cumulated number of CIDs ( primary outcome ) was not significantly different between groups . Because the Poisson distribution of the primary parameter did not fully fit the observed data , a post hoc categorical analysis was applied and showed a significantly lower cumulated number of CIDs in the verum group during the product consumption phase ( odds ratio [ OR ] = 0.75 , 95 % confidence interval [ CI ] 0.59–0.95 , p = 0.017 ) . Verum also reduced the proportion of volunteers experiencing at least 1 CID ( 43 % vs. 51 % , p = 0.005 ) , increased the time to the first occurrence of CID ( p = 0.017 ) in the whole population , and reduced the cumulated number of CIDs in the subgroup of smokers ( p = 0.033 ) . In the course of CID , cumulated duration of fever was lower in the verum group ( in the whole study phase ) ( p = 0.022 ) , and an increase in leukocyte , neutrophil , and natural killer ( NK ) cell counts and activity ( p = 0.047 to p < 0.001 ) was observed compared with control group . Verum was safe and well tolerated . Conclusion : The results indicate that daily consumption of a fermented dairy product containing Lactobacillus casei DN-114 001 could reduce the risk of common infections in stressed individuals such as shift workers Abstract Objective : To study the effect of recolonisation with α streptococci with the ability to inhibit the growth of otopathogens ( “ interfering ” activity ) on the recurrence of acute otitis media in susceptible children and the effect on the frequency of secretory otitis media . Design : Double blind , r and omised , placebo controlled study . Setting : Ear , nose , and throat clinic with three doctors . Participants : 130 children prone to otitis media aged between 6 months and 6 years , 108 of whom were eligible and followed for 3 months . Main outcome measures : Recurrence of otitis media during follow up and a normal tympanic membrane at the last valid visit . Interventions : Children with no recurrences during the last month received phenoxymethylpenicillin ( n=22 ) , and those with a recurrence within 1 month received amoxicillin clavulanic acid ( n=86 ) , both twice daily for 10 days . These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days . At day 60 the same spray was started for another 10 days . Results : At 3 months 22 children ( 42 % ) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 ( 22 % ) of those given placebo . This difference was shown separately for recurrences of both acute otitis media and secretory otitis media . Conclusions : Selected bacteria with the ability to inhibit the growth of common otopathogens can be used to protect against recurrent acute otitis media and secretory otitis media in children Background / Objectives : To determine whether long-term daily consumption of milk containing probiotic Lactobacillus rhamnosus GG ( GG ) decreases respiratory illness in children . Subjects/ Methods : A r and omized , double-blind , placebo-controlled trial was conducted with 523 children aged 2–6 years attending day care centers in Finl and . Subjects received either normal milk or the same milk with GG on three daily meals for 28 weeks . Daily recording of childrens ’ symptoms was done by parents . Primary outcome data from 501 subjects were available for analysis , and data from 128 subjects were analyzed as completed cases in terms of recovery of GG in fecal sample s. Results : Number of days with at least one respiratory symptom in all subjects was 5.03/month ( 95 % confidence interval ( CI ) : 4.92–5.15 ) in the GG group and 5.17/month ( 95 % CI : 5.05–5.29 ) in the placebo group incidence rate ratio ( IRR ) 0.97 ; 95 % CI : 0.94–1.00 ; P=0.098 ) . In the completed cases , the figures were 4.71 days/month ( 95 % CI : 4.52–4.90 ) in the GG group and 5.67 days/month ( 95 % CI : 5.40–5.94 ) in the placebo group ( IRR 0.83 ; 95 % CI : 0.78–0.88 ; P<0.001 ) . Conclusions : Consumption of GG reduced the occurence of respiratory illness in children attending day care centers in the completed cases subgroup , but not in the total population . Thus , future clinical trials are warranted to clarify the association between fecal recovery of a probiotic and the symptom prevalence BACKGROUND The common cold is responsible for the largest proportion of school and work absenteeism and causes a huge economic burden . None of the current interventions is greatly effective for prevention . Our aim was to assess the efficacy of a two-strain combination probiotic for prevention of common cold symptoms in healthy schoolchildren . METHODS A double-blind r and omized controlled trial was performed during the winter season in a public school of central Thail and . Children , aged 8 - 13 years , were r and omized to receive either a two-strain combination probiotic ( Lactobacillus acidophilus and Bifidobacterium bifidum ) or placebo given twice a day for 3 months . The primary outcome was any symptom of cold during the 3-month study period while vomiting , diarrhea , use of antibiotics , school absence due to any cause , school absence due to cold and duration of all symptoms were secondary outcomes . RESULTS Of the 40 children in each group , 31 ( 77 % ) in the probiotic group , compared to 38 ( 95 % ) in the placebo group ( P= 0.048 ) , developed at least one symptom of cold . Children in the probiotics group had significantly lower risk of fever , cough , rhinorrhea , school absence and school absence related to common cold compared to children in the placebo group . There was no impact on diarrhea and vomiting . CONCLUSION A two-strain probiotic combination given twice a day for 3 months was able to reduce the symptoms of the common cold and school absenteeism in schoolchildren Background : Several studies have suggested that probiotics ( proB ) and /or prebiotics ( preB ) could reduce the burden of infection in infants and toddlers . We aim ed to determine whether follow-up formula supplemented with proB and preB could reduce the risk of acute otitis media ( AOM ) . Methods : In this double-blind , placebo-controlled trial from November 2007 to April 2009 , 37 pediatricians in France enrolled children 7 to 13 months of age with high risk of AOM who were r and omly assigned to receive  follow-up formula supplemented with proB ( Streptococcus thermophilus NCC 2496 , Streptococcus salivarius DSM 13084 , Lactobacillus rhamnosus LPR CGMCC 1.3724 ) and preB ( Raftilose/Raftiline ) or follow-up formula alone ( placebo ) . During 12 months , the 2 groups were compared for number of AOM episodes diagnosed ( primary outcome ) and secondary outcomes by the Poisson model ( incidence rate ratio [ IRR ] ) or logistic regression ( odds ratio ; and 95 % confidence interval [ 95 % CI ] ) after adjustment on covariates of interest . Results : We enrolled 224 children ( 112 in each group ) . All children were vaccinated ( 4 doses ) with the 7-valent pneumococcal conjugate vaccine ; demographic characteristics were similar in the 2 groups . In total , 486 AOM episodes were reported , 249 and 237 in the treatment and control groups , respectively . The treatment and control groups did not differ in incidence of AOM ( IRR 1.0 , 95 % CI : 0.8–1.2 ) , lower respiratory tract infections ( IRR 0.9 , 0.7–1.2 ) or number of antibiotic treatment courses ( IRR = 1.0 , 95 % CI : 0.8–1.2 ) . Treatment was not associated with recurrent AOM ( odds ratio 1.0 , 95 % CI : 0.5–1.7 ) . With regard to gastrointestinal disorders , both formulas were well tolerated . Conclusion : The proB and preB included in follow-up formula given to children at 7 to 13 months of age did not reduce the risk of AOM , recurrent AOM , antibiotic use or lower respiratory tract infections at 1 year BACKGROUND The incidence of nosocomial infections in children in developed countries is still high , ranging from 8 % to 30 % , and st and ard preventive measures , such as increased hygiene , are not sufficiently efficacious . One of the potential strategies for their prevention is the use of probiotics . OBJECTIVE The aim of the study was to investigate the role of Bifidobacterium animalis subsp . lactis in preventing nosocomial infections in the acute hospital setting . DESIGN We conducted a r and omized , double-blind , placebo-controlled trial in 727 hospitalized children ( aged 1 - 18 y ) . The children were r and omly allocated to receive placebo ( placebo group , n = 365 ) or B. animalis subsp . lactis at a dose of 10(9 ) colony-forming units/d ( intervention group , n = 362 ) once daily for the entire duration of the hospital stay . Nosocomial infections were defined as infections that occurred > 48 h after hospital admission and that were not present or incubating at the time of admission . RESULTS Analysis was performed on an intention-to-treat basis . There was no difference in the study primary outcome or incidence of common nosocomial gastrointestinal and respiratory tract infections between groups ( 22 vs. 29 infections , respectively ; incidence rate ratio = 0.76 ; 95 % CI : 0.41 , 1.36 ; P = 0.32 ) . No difference was found for the duration of common nosocomial infections [ mean ( range ) : 3.58 ( 1 - 7 ) vs. 3.79 ( 1 - 8 ) d , in placebo vs. intervention group ; P = 0.74 ] . There was also no difference between the intervention and placebo groups for any of the other secondary outcomes ( incidence of gastrointestinal and respiratory tract infections separately , duration of gastrointestinal and respiratory infections , and duration of hospitalization ) and exploratory outcomes ( gastrointestinal and respiratory symptoms , severity of gastrointestinal and respiratory tract infections , and the use of antibiotics ) . CONCLUSIONS The results of this study show that the use of B. animalis subsp . lactis failed to prevent nosocomial infections in an acute- setting pediatric hospital in children who were > 1 y of age . However , it should be taken into account that the overall incidence of nosocomial infections was lower than expected . This trial was registered at clinical trials.gov as NCT01702766 Objectives : The aim of the study was to examine the effects of a follow-on formula containing Lactobacillus fermentum CECT5716 ( L fermentum ) on the incidence of infections in infants between the ages of 6 and 12 months . Patients and Methods : A r and omized double-blinded controlled study including infants at the age of 6 months was conducted . Infants were assigned r and omly to either follow-on formula supplemented with L fermentum plus galactooligosaccharide ( experimental group , EG ) , or the same formula supplemented with only galactooligosaccharide ( control group , CG ) . The main outcome was the incidence of infections for the 6-month duration of the study . Results : The EG showed a significant 46 % reduction in the incidence rate ( IR ) of gastrointestinal infections ( EG : 0.196 ± 0.51 , CG : 0.363 ± 0.53 , IR ratio 0.54 , 95 % confidence interval [ CI ] 0.307–0.950 , P = 0.032 ) , 27 % reduction in the incidence of upper respiratory tract infections ( EG : 0.969 ± 0.96 , CG : 1.330 ± 1.23 , IR ratio 0.729 , 95 % CI 0.46–1.38 , P = 0.026 ) , and 30 % reduction in the total number of infections ( EG : 1.464 ± 1.15 , CG : 2.077 ± 1.59 , IR ratio 0.70 , 95 % CI 0.46–1.38 , P = 0.003 ) , at the end of the study period compared with CG . Conclusions : Administration of a follow-on formula with L fermentum CECT5716 may be useful for the prevention of community-acquired gastrointestinal and upper respiratory infections OBJECTIVE Two r and omized controlled clinical trials have shown that Lactobacillus ( L ) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea . This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea . METHODS This was a multicenter , r and omized , single-blinded , case control clinical trial in children with acute watery diarrhea . A total of 64 children who presented at outpatient clinics were enrolled .  The probiotic group received 1 × 10(8)CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution ( ORS ) and the second group was treated with ORS only . The primary endpoint was the duration of diarrhea ( in hours ) . The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention . Adverse events were also recorded . RESULTS The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group ( approximately 15h , 60.4±24.5h [ 95 % CI : 51.0 - 69.7h ] vs. 74.3±15.3h [ 95 % CI : 68.7 - 79.9h ] , p<0.05 ) . The percentage of children with diarrhea was lower in the L. reuteri group ( 13/29 ; 44.8 % ) after 48h than the control group ( 27/31 ; 87 % ; RR : 0.51 ; 95 % CI : 0.34 - 0.79 , p<0.01 ) . From the 72nd hour of intervention onwards , there was no difference between the two groups in the percentage of children with diarrhea . No adverse effects related to L. reuteri were noted . CONCLUSION L. reuteri DSM 17938 is effective , safe , and well-tolerated in outpatient children with acute infectious diarrhea The impact of controlled administration of Bifidobacterium animalis subsp . lactis BB-12 ( BB-12 ) on the risk of acute infectious diseases was studied in healthy newborn infants . In this double-blind , placebo-controlled study , 109 newborn 1-month-old infants were assigned r and omly to a probiotic group receiving a BB-12-containing tablet ( n 55 ) or to a control group receiving a control tablet ( n 54 ) . Test tablets were administered to the infants twice a day ( daily dose of BB-12 10 billion colony-forming units ) from the age of 1 - 2 months to 8 months with a novel slow-release pacifier or a spoon . Breastfeeding habits , pacifier use , dietary habits , medications and all signs and symptoms of acute infections were registered . At the age of 8 months , faecal sample s were collected for BB-12 determination ( quantitative PCR method ) . The baseline characteristics of the two groups were similar , as was the duration of exclusive breastfeeding . BB-12 was recovered ( detection limit log 5 ) in the faeces of 62 % of the infants receiving the BB-12 tablet . The daily duration of pacifier sucking was not associated with the occurrence of acute otitis media . No significant differences between the groups were observed in reported gastrointestinal symptoms , otitis media or use of antibiotics . However , the infants receiving BB-12 were reported to have experienced fewer respiratory infections ( 65 v. 94 % ; risk ratio 0·69 ; 95 % CI 0·53 , 0·89 ; P = 0·014 ) than the control infants . Controlled administration of BB-12 in early childhood may reduce respiratory infections BACKGROUND We aim ed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae  in a r and omized double-blind placebo-controlled clinical trial . METHODS Overall , 179 adults with irritable bowel syndrome ( Rome III criteria ) were r and omized to receive once daily 500 mg of Saccharomyces cerevisiae , delivered by one capsule ( n = 86 , F : 84 % , age : 42.5 ± 12.5 ) , or placebo ( n = 93 , F : 88 % , age : 45.4 ± 14 ) for 8 weeks followed by a 3-week washout period . After a 2-week run-in period , cardinal symptoms ( abdominal pain/discomfort , bloating/distension , bowel movement difficulty ) and changes in stool frequency and consistency were recorded daily and assessed each week . A safety assessment was carried out throughout the study . RESULTS The proportion of responders , defined by an improvement of abdominal pain/discomfort , was significantly higher ( p = 0.04 ) in the treated group than the placebo group ( 63 % vs 47 % , OR = 1.88 , 95 % , CI : 0.99 - 3.57 ) in the last 4 weeks of treatment . A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms . Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency . CONCLUSION Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification . Thus , Saccharomyces cerevisiae may be a new promising c and i date for improving abdominal pain in subjects with irritable bowel syndrome Objective : Secretory otitis media ( SOM ) is characterised by persistent fluid in the middle ear cavity , but the cause is unknown . We investigated the clinical , bacteriological and immunological effects of treatment with probiotic bacteria on SOM . Design : In this double-blind pilot/preliminary study , 60 children with long-st and ing SOM ( median 6 months ) who were scheduled for insertion of tympanostomy tubes  were r and omised to nasal spray treatment with Streptococcus sanguinis , Lactobacillus rhamnosus or placebo for 10 days before surgery .  Clinical evaluation was carried out after 10 days of treatment . Middle ear fluid ( MEF ) was collected during surgery for quantification of cytokines and detection of bacteria by culture and polymerase chain reaction ( PCR ) . Nasopharyngeal swabs were obtained before treatment and at surgery . Results : Complete or significant clinical recovery occurred in 7/19 patients treated with S sanguinis compared to 1/17 patients in the placebo group ( p<0.05 ) . In the L rhamnosus treatment group , 3/18 patients were cured or much better ( p = 0.60 compared with placebo ) . Spray treatment did not alter the composition of the nasopharyngeal flora or the cytokine pattern observed in the nasopharynx or MEF , except for a higher level of IL-8 found in the nasopharynx of L rhamnosus treated children . Conclusions : This study shows that spray treatment with S sanguinis may be effective against SOM . The mechanism for the effect remains to be investigated Data on the economic burden of lower respiratory tract infections ( LRTI ) in young children are lacking in Germany . The objective of the cost-of-illness study was to estimate the economic impact of community-acquired LRTI and nosocomial LRTI as well as of infections due to respiratory syncytial virus ( RSV ) , parainfluenza viruses ( PIV ) and influenza viruses ( IV ) . The economic analysis is part of the PRI.DE study , a prospect i ve , multi-centre , population -based epidemiological study on the impact of LRTI in children aged 0 to 36 months in Germany . The analysis includes children with community-acquired infections ( 1329 cases treated as out patients , 2039 cases treated as in patients ) and nosocomial infections ( 90 cases ) .  Medical services consumed were generated by chart abstract ion and parental expenses data by telephone interviews within four weeks after physician visit or hospitalisation . Costs were evaluated from following perspectives : third party payer , parent and society . Total costs for outpatient treatment are € 123 per LRTI case . Stratified by virus type , total costs per case are € 163 ( RSV ) , € 100 ( PIV ) and € 223 ( IV ) . Total costs per hospitalised LRTI case amount to € 2579 . Stratified by virus type , total costs per case are € 2772 ( RSV ) , € 2374 ( PIV ) and € 2597 ( IV ) . Total costs per nosocomial case are € 2814 . Economic burden due to LRTI is € 213 million annually . It is concluded that treatment of LRTI in children up to age three causes a considerable economic burden in Germany . Presented results are the first data describing the economic burden of LRTI in young children assessed by means of the incidence data for Germany . This cost-of-illness study provides basic data for further decision-making , focusing on the economic assessment of preventive strategies for RSV , PIV and IV infections BACKGROUND : Constipation is a frustrating symptom affecting 3 % of children worldwide . A fermented dairy product containing Bifidobacterium lactis strain DN-173 010 was effective in increasing stool frequency in constipated women . Our aim was to assess the effects of this product in constipated children . METHODS : In this prospect i ve r and omized , double-blind , controlled trial , 159 constipated children ( defecation frequency < 3 times per week ) were r and omly allocated to receive either a fermented dairy product that contains B lactis DN-173 010 ( n = 79 ) or a control product ( n = 80 ) twice a day for 3 weeks . The primary endpoint was the change in stool frequency from baseline to after 3 weeks of product consumption . Analyses were by intention to treat . RESULTS : Eleven children did not return to any follow-up visit ( 5 in the probiotic group , 6 in the control group ) and were therefore excluded from the final analysis . Thus , 74 children in each group were analyzed . The change in stool frequency from baseline to after 3 weeks of product consumption increased in both groups , but the difference was not statistically significant ( 2.9 ± 3.2 in probiotic group versus 2.6 ± 2.6 in control group , P = .35 ) . There were no serious adverse events . CONCLUSIONS : In constipated children , the fermented dairy product containing B lactis strain DN-173 010 did increase stool frequency , but this increase was comparable in the control group . There is currently not sufficient evidence to recommend fermented dairy products containing B lactis strain DN-173 010 in this category of patients . Future studies should focus on whether a longer period of probiotic products is more effective in children who have a short history of constipation ABSTRACT The probiotic potential of 47 selected strains ofLactobacillus spp . was investigated . The strains were examined for resistance to pH 2.5 and 0.3 % oxgall , adhesion to Caco-2 cells , and antimicrobial activities against enteric pathogenic bacteria in model systems . From the results obtained in vitro , five strains , Lactobacillus rhamnosus 19070 - 2 , L. reuteri DSM 12246 , L. rhamnosus LGG , L. delbrueckii subsp.lactis CHCC 2329 , and L. casei subsp.alactus CHCC 3137 , were selected for in vivo studies . The daily consumption by 12 healthy volunteers of two doses of 1010 freeze-dried bacteria of the selected strains for 18 days was followed by a washout period of 17 days . Fecal sample s were taken at days 0 and 18 and during the washout period at days 5 and 11.Lactobacillus isolates were initially identified by API 50CHL and internal transcribed spacer PCR , and their identities were confirmed by restriction enzyme analysis in combination with pulsed-field gel electrophoresis . Among the tested strains , L. rhamnosus 19070 - 2 , L. reuteri DSM 12246 , and L. rhamnosus LGG were identified most frequently in fecal sample s ; they were found in 10 , 8 , and 7 of the 12 sample s tested during the intervention period , respectively , whereas reisolations were less frequent in the washout period . The bacteria were reisolated in concentrations from 105 to 108 cells/g of feces . Survival and reisolation of the bacteria in vivo appeared to be linked to pH tolerance , adhesion , and antimicrobial properties in vitro BACKGROUND & AIMS The aim of our study was to investigate the role of Lactobacillus GG ( LGG ) in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in 281 children who attend day care centers . They were r and omly allocated to receive LGG at a dose of 10(9 ) colony-forming units in 100ml of a fermented milk product ( LGG group , n=139 ) or placebo that was the same post-pasteurized fermented milk product without LGG ( placebo group , n=142 ) during the 3-month intervention period . RESULTS Compared to the placebo group , children in the LGG group had a significantly reduced risk of upper respiratory tract infections ( RR 0.66 , 95 % CI 0.52 to 0.82 , NNT 5 , 95 % CI 4 to 10 ) , a reduced risk of respiratory tract infections lasting longer than 3 days ( RR 0.57 , 95 % CI 0.41 to 0.78 , NNT 5 , 95 % CI 4 to 11 ) , and a significantly lower number of days with respiratory symptoms ( p<0.001 ) . There was no risk reduction in regard to lower respiratory tract infections ( RR 0.82 , 95 % CI 0.24 to 2.76 ) . Compared with the placebo group , children in the LGG group had no significant reduction in the risk of gastrointestinal infections ( RR 0.63 , 95 % CI 0.38 to 1.06 ) , vomiting episodes ( RR 0.60 , 95 % CI 0.29 to 1.24 ) , and diarrheal episodes ( RR 0.63 , 95 % CI 0.35 to 1.11 ) as well as no reduction in the number of days with gastrointestinal symptoms ( p=0.063 ) . CONCLUSION LGG administration can be recommended as a valid measure for decreasing the risk of upper respiratory tract infections in children attending day care centers OBJECTIVE : To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota . STUDY DESIGN : Fifty exclusively breastfed colicky infants , diagnosed according to modified Wessel 's criteria , were r and omly assigned to receive either L reuteri DSM 17 938 ( 108 colony-forming units ) or placebo daily for 21 days . Parental question naires monitored daily crying time and adverse effects . Stool sample s were collected for microbiologic analysis . RESULTS : Forty-six infants ( L reuteri group : 25 ; placebo group : 21 ) completed the trial . Daily crying times in minutes/day ( median [ interquartile range ] ) were 370 ( 120 ) vs 300 ( 150 ) ( P = .127 ) on day 0 and 35.0 ( 85 ) vs 90.0 ( 148 ) ( P = .022 ) on day 21 , in the L reuteri and placebo groups , respectively . Responders ( 50 % reduction in crying time from baseline ) were significantly higher in the L reuteri group versus placebo group on days 7 ( 20 vs 8 ; P = .006 ) , 14 ( 24 vs 13 ; P = .007 ) , and 21 ( 24 vs 15 ; P = .036 ) . During the study , there was a significant increase in fecal lactobacilli ( P = .002 ) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only ( P = .001 ) . There were no differences in weight gain , stooling frequency , or incidence of constipation or regurgitation between groups , and no adverse events related to the supplementation were observed . CONCLUSION : L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe . Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement
target: Conclusion : Based on the available data and taking into account the safety profile of RCTs , probiotic consumption appears to be a feasible way to decrease the incidence of RTIs in children
background: Background : Respiratory tract infections ( RTIs ) represent one of the main health problems in children .
  Probiotics are viable bacteria that colonize the intestine and affect the host intestinal microbial balance .
  Accumulating evidence suggests that probiotic consumption may decrease the incidence of or modify RTIs .
  The authors systematic ally review ed data from r and omized controlled trials ( RCTs ) to investigate the effect of probiotic consumption on  RTIs in children .