title: Nebulized hypertonic-saline vs epinephrine for bronchiolitis; proof of concept study of cumulative sum (CUSUM) analysis.
abstract: OBJECTIVE
  To apply cumulative sum (CUSUM) to monitor a drug trial of nebulized hypertonic-saline in bronchiolitis. To test if monitoring with CUSUM control lines is practical and useful as a prompt to stop the drug trial early, if the study drug performs significantly worse than the comparator drug.
  
  
  METHODS
  Prospective, open label, controlled trial using standard therapy (epinephrine) and study drug (hypertonic-saline) sequentially in two groups of patients.
  
  
  METHODS
  Hospital offering tertiary-level pediatric care.
  
  
  METHODS
  Children, 2 months to 2 years, with first episode of bronchiolitis, excluding those with cardiac disease, immunodeficiency and critical illness at presentation.
  
  
  METHODS
  Nebulized epinephrine in first half of the bronchiolitis season (n = 35) and hypertonic saline subsequently (n = 29). Continuous monitoring of response to hypertonic-saline using CUSUM control charts developed with epinephrine-response data.
  
  
  METHODS
  Clinical score, tachycardia and total duration of hospital stay.
  
  
  RESULTS
  In the epinephrine group, the maximum CUSUM was +2.25 (SD 1.34) and minimum CUSUM was -2.26 (SD 1.34). CUSUM score with hypertonic saline group stayed above the zero line throughout the study. There was no statistical difference in the post-treatment clinical score at 24 hours between the treatment groups {Mean (SD) 3.516 (2.816): 3.552 (2.686); 95% CI:  -1.416 to  1.356}, heart rate {Mean (SD) 136 (44): 137(12); 95% CI:  -17.849 to 15.849) or duration of hospital stay (Mean (SD) 96.029 (111.41): 82.914 (65.940); 95% CI:  -33.888 to 60.128}.
  
  
  CONCLUSIONS
  The software we developed allows for drawing of control lines to monitor study drug performance. Hypertonic saline performed as well or better than nebulized epinephrine in bronchiolitis.
authors.affiliation: Department of Pediatrics and Neonatology, St Stephens Hospital, Delhi, India. drneeraj79@yahoo.co.in
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gupta
authors.forename: Ashish
authors.initials: A
authors.lastname: Puliyel
authors.forename: Ayush
authors.initials: A
authors.lastname: Manchanda
authors.forename: Jacob
authors.initials: J
authors.lastname: Puliyel
mesh_terms: D001988:Bronchiolitis / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D003627:Data Interpretation, Statistical; D004837:Epinephrine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009330:Nebulizers and Vaporizers; D011446:Prospective Studies; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*
chemical_list: D001993:Bronchodilator Agents; D012462:Saline Solution, Hypertonic; D004837:Epinephrine