title: Relative effectiveness of additive pain interventions during vaccination in infants.
abstract: BACKGROUND
  Vaccine injections can cause acute pain and distress in infants, which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. We sought to compare the effectiveness of additive pain interventions administered consistently during vaccine injections in the first year of life.
  
  
  METHODS
  We conducted a multicentre, longitudinal, double-blind, add-on, randomized controlled trial. Healthy infants were randomly assigned to 1 of 4 levels of pain management for all vaccine injections at 2, 4, 6 and 12 months: (i) placebo control; (ii) parent-directed video education about infant soothing; (iii) the video plus sucrose administered orally or (iv) the video plus sucrose plus liposomal lidocaine applied topically. All infants benefit from injection techniques that minimize pain. We used a double-dummy design; hence all parents watched a video (active psychological intervention or placebo) and all infants received oral solution (sucrose or placebo) and topical cream (lidocaine or placebo). We assessed infant distress during 3 phases - preinjection (baseline), vaccine injection (needle), and 1 minute postinjection (recovery) - using the Modified Behavioural Pain Scale (range 0-10). We compared scores between groups and across infant ages using a mixed-model repeated-measures analysis.
  
  
  RESULTS
  A total of 352 infants participated in the study, from Jan. 17, 2012, to Feb. 2, 2016. Demographics did not differ among intervention groups (p> 0.05). Baseline pain scores did not differ among intervention groups (p= 0.4), but did differ across ages (p< 0.001). Needle pain scores differed among groups (p= 0.003) and across ages (p< 0.001). The mean (± standard deviation) needle score was 6.3 (± 0.8) in the video-sucrose-lidocaine group compared with 6.7 (± 0.8) in each of the other groups. There were no other between-group differences. Recovery scores did not differ among groups (p= 0.98), but did differ across ages (p< 0.001).
  
  
  CONCLUSIONS
  Only liposomal lidocaine provided consistent analgesia within an additive pain intervention regimen during vaccinations in infants.Trial registration:ClinicalTrials.gov, no. NCT01503060.
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont. anna.taddio@utoronto.ca.
authors.forename: Anna
authors.initials: A
authors.lastname: Taddio
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Rebecca Pillai
authors.initials: RP
authors.lastname: Riddell
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Moshe
authors.initials: M
authors.lastname: Ipp
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Steven
authors.initials: S
authors.lastname: Moss
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tolkin
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Dave
authors.initials: D
authors.lastname: Malini
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Sharmeen
authors.initials: S
authors.lastname: Feerasta
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Preeya
authors.initials: P
authors.lastname: Govan
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Emma
authors.initials: E
authors.lastname: Fletcher
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Horace
authors.initials: H
authors.lastname: Wong
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Caitlin
authors.initials: C
authors.lastname: McNair
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Priyanjali
authors.initials: P
authors.lastname: Mithal
authors.affiliation: Leslie Dan Faculty of Pharmacy (Taddio, Fletcher, Wong, McNair, Mithal), University of Toronto; Child Health Evaluative Sciences (Taddio), The Hospital for Sick Children, Toronto, Ont.; Department of Psychology (Pillai Riddell), York University, North York, Ont.; Department of Psychiatry (Pillai Riddell) and Paediatrics (Ipp), University of Toronto, Toronto, Ont.; Pediatricians (Moss, Baker, Tolkin, Malini, Feerasta, Govan), North York, Ont.; Biostatistics and Data Analysis Unit (Stephens), The Hospital for Sick Children, Toronto, Ont.
authors.forename: Derek
authors.initials: D
authors.lastname: Stephens
mesh_terms: D059787:Acute Pain / Q000209:etiology / Q000517:prevention & control*; D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000627:therapeutic use*; D001296:Audiovisual Aids; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D007224:Infant Care / Q000379:methods; D007267:Injections / Q000009:adverse effects*; D008012:Lidocaine / Q000627:therapeutic use*; D008081:Liposomes; D008137:Longitudinal Studies; D008297:Male; D059408:Pain Management; D010147:Pain Measurement; D010290:Parents / Q000193:education*; D013395:Sucrose / Q000627:therapeutic use*; D013549:Sweetening Agents / Q000627:therapeutic use*; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000779:Anesthetics, Local; D008081:Liposomes; D013549:Sweetening Agents; D014612:Vaccines; D013395:Sucrose; D008012:Lidocaine