title: Comparing the effectiveness profile of pharmacological interventions used for orthodontic pain relief: an arm-based multilevel network meta-analysis of longitudinal data.
abstract: OBJECTIVE
  We compare the effectiveness profile of various analgesics used for orthodontic pain relief over a 1-week time period by conducting a longitudinal network meta-analysis (NMA).
  
  
  METHODS
  The MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were searched till 31st December 2015 to identify the relevant studies. Additional studies were identified by hand searching journals and reference lists. Unpublished literature was also searched.
  
  
  METHODS
  Eligible studies were randomized-controlled trials (RCTs) evaluating the effectiveness of pharmacological interventions for pain relief after placement of separator or initial aligning arch wire.
  
  
  METHODS
  Pain intensity data at 2, 6, 12, 24, 36, 48, 72, 96, and 168 hours was collected. In addition, data were also extracted for potential covariates (age, sex, and procedure). A covariate-adjusted arm-based multilevel random coefficient model was used for evidence synthesis.
  
  
  RESULTS
  Fifteen RCTs (1341 participants; male/females 595, 44.6%/746 55.4%; mean age 17.3 years, SD 4.1) were included. A total of 11 nodes (Acetaminophen, Aspirin, Etoricoxib, Flurbiprofen, Ibuprofen, Lumiracoxib, Meloxicam, Naproxen, Piroxicam, Placebo, and Control) were identified out of which five nodes (Placebo, Ibuprofen, Naproxen, Acetaminophen, and Aspirin) had subnodes (based on timing of administration). Compared to Control, Placebo, Flurbiprofen, Lumiracoxib, and Meloxicam were not significantly effective. Etoricoxib (most effective) and Piroxicam (second most effective) were effective over a long period which lasted up to 96 and 72 hours, respectively. Ibuprofen, Acetaminophen, Naproxen, and Aspirin were effective at 6, 12, and 24 hours. The effectiveness of these analgesics was significantly influenced by the timing of administration. Assessment of heterogeneity, transitivity, inconsistency, and publication bias revealed no major threat to the NMA derived estimates.
  
  
  CONCLUSIONS
  Compared to the Control, Placebo was least effective whereas Etoricoxib was the most effective analgesic in reducing orthodontic pain. Administration timing has significant influence on the effectiveness profile of analgesics routinely used for managing orthodontic pain.
authors.affiliation: Centre for Multilevel Modelling and Graduate School of Education, University of Bristol, Bristol, UK.
authors.forename: Satpal S
authors.initials: SS
authors.lastname: Sandhu
authors.affiliation: Biostatistics Unit, Institute of Crop Science, Fruwirthstrasse 23, 70599 Stuttgart, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Piepho
authors.affiliation: Private practice, Jalandhar, Punjab, India.
authors.forename: Harpreet S
authors.initials: HS
authors.lastname: Khehra
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D000077613:Etoricoxib / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use; D009971:Orthodontics, Corrective / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D059408:Pain Management / Q000379:methods; D016032:Randomized Controlled Trials as Topic
chemical_list: D000700:Analgesics; D000082:Acetaminophen; D007052:Ibuprofen; D000077613:Etoricoxib