title: Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites.
  
  
  OBJECTIVE
  This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen.
  
  
  METHODS
  A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015.
  
  
  METHODS
  All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria.
  
  
  METHODS
  The interventions used were various doses of botulinum toxin.
  
  
  METHODS
  Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals.
  
  
  RESULTS
  There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined.
  
  
  CONCLUSIONS
  This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented.
  
  
  CONCLUSIONS
  Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.
authors: 1 Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand 2 Department of Surgery, The University of Auckland, Auckland, New Zealand.
authors: Jin Xin
authors: JX
authors: Lin
authors: Sanjeev
authors: S
authors: Krishna
authors: Bruce
authors: B
authors: Su'a
authors: Andrew G
authors: AG
authors: Hill
mesh_terms: D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000627:therapeutic use; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005401:Fissure in Ano / Q000188:drug therapy*; D006801:Humans; D007267:Injections; D009465:Neuromuscular Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A