David Schnadower1, Robert E Sapien2, T Charles Casper3, Cheryl Vance4, Phillip I Tarr5, Karen J O'Connell6, Adam C Levine7, Cindy G Roskind8, Alexander J Rogers9, Seema R Bhatt1, Prashant Mahajan9, Elizabeth C Powell10, Cody S Olsen3, Marc H Gorelick11, J Michael Dean3, Stephen B Freedman12. 1. Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 2. Department of Emergency Medicine, University of New Mexico, Albuquerque, NM, USA. 3. Department of Pediatrics, University of Utah, Salt Lake City, UT, USA. 4. Departments of Emergency Medicine and Pediatrics, University of California, Davis, School of Medicine, Sacramento, CA, USA. 5. Division of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. 6. Division of Emergency Medicine, Children's National Health System, Department of Pediatrics and Emergency Medicine, The George Washington School of Medicine and Health Sciences, Washington, DC, USA. 7. Department of Emergency Medicine, Rhode Island Hospital/Hasbro Children's Hospital and Brown University, Providence, RI, USA. 8. Division of Emergency Medicine, Department of Pediatrics, Columbia University College of Physicians & Surgeons, New York, NY, USA. 9. Departments of Emergency Medicine and Pediatrics, University of Michigan, Ann Arbor, MI, USA. 10. Division of Emergency Medicine, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 11. Central Administration, Children's Minnesota, Minneapolis, MN, USA. 12. Sections of Pediatric Emergency Medicine and Gastroenterology, Department of Pediatrics, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Abstract
BACKGROUND: Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes. OBJECTIVES: We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered. METHODS: This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3-48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received. RESULTS: A total of 813 children (84%) were included in the analysis; 413 receivedplacebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05). CONCLUSIONS:LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE.This trial was registered at clinicaltrials.gov as NCT01773967.
RCT Entities:
BACKGROUND:Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes. OBJECTIVES: We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered. METHODS: This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3-48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received. RESULTS: A total of 813 children (84%) were included in the analysis; 413 received placebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05). CONCLUSIONS:LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE.This trial was registered at clinicaltrials.gov as NCT01773967.
Authors: Bryon W Petschow; Reinaldo Figueroa; Cheryl L Harris; Laura B Beck; Eckhard Ziegler; Barry Goldin Journal: J Clin Gastroenterol Date: 2005-10 Impact factor: 3.062
Authors: Stephen B Freedman; Sarah Williamson-Urquhart; Ken J Farion; Serge Gouin; Andrew R Willan; Naveen Poonai; Katrina Hurley; Philip M Sherman; Yaron Finkelstein; Bonita E Lee; Xiao-Li Pang; Linda Chui; David Schnadower; Jianling Xie; Marc Gorelick; Suzanne Schuh Journal: N Engl J Med Date: 2018-11-22 Impact factor: 91.245
Authors: Christa L Fischer Walker; Igor Rudan; Li Liu; Harish Nair; Evropi Theodoratou; Zulfiqar A Bhutta; Katherine L O'Brien; Harry Campbell; Robert E Black Journal: Lancet Date: 2013-04-12 Impact factor: 79.321