Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children

New England Journal of Medicine

Volumn 379, Issue 21, 2018, Pages 2002-2014

  Schnadower, David ^a,b,k   Tarr, Phillip I ^c   Casper, T Charles ^d,e   Gorelick, Marc H ^f   Dean, J Michael ^d,e   O'Connell, Karen J ^g   Mahajan, Prashant ^h,i   Levine, Adam C ^j   Bhatt, Seema R ^k   Roskind, Cindy G ^l   Powell, Elizabeth C ^m   Rogers, Alexander J ⁱ   Vance, Cheryl ⁿ   Sapien, Robert E ^o   Olsen, Cody S ^d,e   Metheney, Melissa ^d,e   Dickey, Viani P ^b   Hall‑Moore, Carla ^c   Freedman, Stephen B ^p  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^b Department of Pediatrics   (United States)

^c Division of Gastroenterology   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^f UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^g CHILDREN'S NATIONAL MEDICAL CENTER   (United States)

^h WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ UNIVERSITY OF MICHIGAN   (United States)

^j BROWN UNIVERSITY   (United States)

^k UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^l College of Physicians and Surgeons ^*  (United States)

^m NORTHWESTERN UNIVERSITY   (United States)

ⁿ UNIVERSITY OF CALIFORNIA   (United States)

^o UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

^p UNIVERSITY OF CALGARY   (Canada)

more..

Author keywords

[No Author keywords available]

Indexed keywords

PLACEBO; PROBIOTIC AGENT;

ABSENTEEISM; ACUTE GASTROENTERITIS; ARTICLE; CHILD; CONTROLLED STUDY; DAY CARE; DIARRHEA; DIGESTIVE SYSTEM DISEASE ASSESSMENT; DISEASE DURATION; DISEASE SEVERITY; DISEASE TRANSMISSION; DOUBLE BLIND PROCEDURE; EMERGENCY WARD; FEMALE; FOLLOW UP; HOUSEHOLD; HUMAN; INFANT; LACTOBACILLUS RHAMNOSUS; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PATIENT COMPLIANCE; PRESCHOOL CHILD; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TREATMENT OUTCOME; UNITED STATES; VESIKARI SCALE; VOMITING; WHEEZING; ACUTE DISEASE; CLINICAL TRIAL; COMPARATIVE STUDY; COMPLICATION; GASTROENTERITIS; TREATMENT FAILURE;

ACUTE DISEASE; CHILD, PRESCHOOL; DIARRHEA; DOUBLE-BLIND METHOD; FEMALE; GASTROENTERITIS; HUMANS; INFANT; LACTOBACILLUS RHAMNOSUS; MALE; PROBIOTICS; PROSPECTIVE STUDIES; TREATMENT FAILURE; VOMITING;

EID: 85056965619     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1802598     Document Type: Article

References (46)

1. World Health Organization. Diarrhoeal disease fact sheet. May 2017 (http://www.who.int/mediacentre/factsheets/fs330/en/).
2. Freedman SB, Steiner MJ, Chan KJ. Oral ondansetron administration in emergency departments to children with gastroenteritis: an economic analysis. PLoS Med 2010;7(10):e1000350.
3. Freedman SB, Pasichnyk D, Black KJ, et al. Gastroenteritis therapies in developed countries: systematic review and meta-analysis. PLoS One 2015;10(6):e0128754.
4. Feizizadeh S, Salehi-Abargouei A, Akbari V. Efficacy and safety of Saccharo-myces boulardii for acute diarrhea. Pediatrics 2014;134(1):e176-e191.
5. Szajewska H, Skórka A, Ruszczyński M, Gieruszczak-Białek D. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children - updated analysis of randomised controlled trials. Aliment Pharmacol Ther 2013;38:467-76.
6. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev 2010;11:CD003048.
7. Reid G. Probiotics: definition, scope and mechanisms of action. Best Pract Res Clin Gastroenterol 2016;30:17-25.
8. Lomax AR, Calder PC. Probiotics, immune function, infection and inflammation: a review of the evidence from studies conducted in humans. Curr Pharm Des 2009;15:1428-518.
9. Szajewska H, Guarino A, Hojsak I, et al. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr 2014;58:531-9.
10. Guarino A, Ashkenazi S, Gendrel D, Lo Vecchio A, Shamir R, Szajewska H. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/ European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr 2014;59:132-52.
11. Vandenplas Y, De Greef E, Hauser B, Devreker T, Veereman-Wauters G. Probiotics and prebiotics in pediatric diarrheal disorders. Expert Opin Pharmacother 2013; 14:397-409.
12. Guarino A, Lo Vecchio A, Canani RB. Probiotics as prevention and treatment for diarrhea. Curr Opin Gastroenterol 2009; 25:18-23.
13. Schnadower D, Finkelstein Y, Freedman SB. Ondansetron and probiotics in the management of pediatric acute gastroenteritis in developed countries. Curr Opin Gastroenterol 2015;31:1-6.
14. Nixon AF, Cunningham SJ, Cohen HW, Crain EF. The effect of Lactobacillus GG on acute diarrheal illness in the pediatric emergency department. Pediatr Emerg Care 2012;28:1048-51.
15. MarketsandMarkets. U.S. digestive health enzymes, prebiotics and probiotics market (2010-2015). 2017 (http://www.marketsandmarkets.com/Market-Reports/ digestive-health-225.html).
16. Global Market Insights. Probiotics market size to exceed USD 64 billion by 2023. May 10, 2016 (http://www.prnewswire.com/news-releases/probiotics-market-size -to-exceed-usd-64-billion-by-2023-global -market-insights-inc-578769201.html).
17. Schnadower D, Tarr PI, Casper TC, et al. Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol. BMJ Open 2017;7(9):e018115.
18. Lo Vecchio A, Vandenplas Y, Benninga M, et al. An international consensus report on a new algorithm for the management of infant diarrhoea. Acta Paediatr 2016;105(8):e384-e389.
19. Pediatric Emergency Care Applied Research Network home page. 2017 (http://pecarn.org/index.html).
20. Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2015;12:CD004827.
21. Goldfarb DM, Steenhoff AP, Pernica JM, et al. Evaluation of anatomically designed flocked rectal swabs for molecular detection of enteric pathogens in children admitted to hospital with severe gastroenteritis in Botswana. J Clin Microbiol 2014;52:3922-7.
22. Freedman SB, Xie J, Nettel-Aguirre A, et al. Enteropathogen detection in children with diarrhoea, or vomiting, or both, comparing rectal flocked swabs with stool specimens: an outpatient cohort study. Lancet Gastroenterol Hepatol 2017; 2:662-9.
23. Mengelle C, Mansuy JM, Prere MF, et al. Simultaneous detection of gastrointestinal pathogens with a multiplex Luminex-based molecular assay in stool samples from diarrhoeic patients. Clin Microbiol Infect 2013;19:E458-E465.
24. Claas EC, Burnham CA, Mazzulli T, Templeton K, Topin F. Performance of the xTAG gastrointestinal pathogen panel, a multiplex molecular assay for simultaneous detection of bacterial, viral, and parasitic causes of infectious gastroenteritis. J Microbiol Biotechnol 2013;23:1041-5.
25. Schnadower D, Tarr PI, Gorelick MH, et al. Validation of the modified Vesikari score in children with gastroenteritis in 5 US emergency departments. J Pediatr Gastroenterol Nutr 2013;57:514-9.
26. Freedman SB, Eltorky M, Gorelick M. Evaluation of a gastroenteritis severity score for use in outpatient settings. Pediatrics 2010;125(6):e1278-e1285.
27. Alpern ER, Henretig FM. Fever. In: Fleisher GR, Ludwig S, eds. Textbook of pediatric emergency medicine. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2010:266-75.
28. Bhatt DL, Mehta C. Adaptive designs for clinical trials. N Engl J Med 2016;375: 65-74.
29. Nagelkerke N, Fidler V, Bernsen R, Borgdorff M. Estimating treatment effects in randomized clinical trials in the presence of non-compliance. Stat Med 2000; 19:1849-64.
30. Lewis JA, Machin D. Intention to treat - who should use ITT? Br J Cancer 1993; 68:647-50.
31. Raghunathan TE, Lepkowski JM, Van Hoewyk J, Solenberger P. A multivariate technique for multiply imputing missing values using a sequence of regression models. Surv Methodol 2001;27:85-95.
32. Rubin DB. Multiple imputation for nonresponse in surveys. New York: John Wiley, 1987.
33. Holm S. A simple sequentially rejec-tive multiple test procedure. Scand J Stat 1979;6:65-70.
34. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c332.
35. Hill C, Scott K, Klaenhammer TR, Quigley E, Sanders ME. Probiotic nomenclature matters. Gut Microbes 2016;7:1-2.
36. Sanders MML, Bush S. “Lactobacillus sporogenes” is not a Lactobacillus probiotic. ASM News 2001;68:385-6.
37. Meurer WJ, Lewis RJ, Berry DA. Adaptive clinical trials: a partial remedy for the therapeutic misconception? JAMA 2012; 307:2377-8.
38. Rosenblum M, Van der Laan MJ. Optimizing randomized trial designs to distinguish which subpopulations benefit from treatment. Biometrika 2011;98: 845-60.
39. LeLorier J, Grégoire G, Benhaddad A, Lapierre J, Derderian F. Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med 1997;337:536-42.
40. Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multi-centre trial. Lancet 2013;382:1249-57.
41. Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet 2016;387:649-60.
42. Little P, Stuart B, Wingrove Z, et al. Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial. CMAJ 2017;189:E1543-E1550.
43. Suez J, Zmora N, Zilberman-Schapira G, et al. Post-antibiotic gut mucosal micro-biome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 2018;174:1406-23.
44. Zmora N, Zilberman-Schapira G, Suez J, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and micro-biome features. Cell 2018;174:1388-405.
45. Cohen PA. Probiotic safety - no guarantees. JAMA Intern Med 2018 Sep-tember 17 (Epub ahead of print).
46. Denno DM, Shaikh N, Stapp JR, et al. Diarrhea etiology in a pediatric emergency department: a case control study. Clin Infect Dis 2012;55:897-904.