title: Immediate 1-month efficacy of desmopressin and anticholinergic combination therapy versus desmopressin monotherapy in the treatment of pediatric enuresis: A meta-analysis.
abstract: BACKGROUND
  Several studies have proposed the combination of desmopressin and anticholinergic as a treatment regimen to address the pathophysiology of polyuria and bladder dysfunction in pediatric enuresis. However, the available literature is inconsistent with regards to the immediate 1-month efficiency of the combination therapy in the treatment for pediatric enuresis.
  
  
  OBJECTIVE
  The aim was to assess the immediate 1-month efficacy and safety of desmopressin and anticholinergic agent combination therapy versus desmopressin monotherapy in the treatment of pediatric enuresis using meta-analysis of randomized controlled trials (RCTs).
  
  
  METHODS
  Systematic literature acquisition was carried out on electronic medical databases up to April 2015. RCTs relevant to the topic were critically appraised. Dichotomous data of the 1-month post-treatment response rate (defined as ≥90% reduction of wet nights) were extracted for calculation of the risk ratio (RR) and 95% confidence interval (CI). The Mantel-Haenszel method with the random effects model was used to pool effect estimates. Inter-study heterogeneity and publication bias were assessed. Subgroup analysis was done for the desmopressin treatment-naive versus treatment-resistant groups: PROSPERO (CRD42015017922).
  
  
  RESULTS
  Four RCTs of good methodological quality without heterogeneity were included for meta-analysis. The pooled effect estimates showed that combination therapy was associated with a significantly better immediate 1-month response rate than desmopressin monotherapy. Subgroup analysis showed a greater immediate 1-month response rate among desmopressin-resistant patients than treatment-naive patients. No severe adverse events were noted among combination therapy treated groups.
  
  
  CONCLUSIONS
  The limitation of the current meta-analyses is the small sample size, albeit with high-quality studies pooled for effect estimation. Despite the limitation, the study results were able to consistently illustrate a large treatment effect of combination therapy among desmopressin treatment-resistant patients. It was consistent with the literature review of retrospective and non-comparative studies by Alloussi et al. (2011), who summarized a similar impressive treatment outcome. However, due to the low level of evidence available at the time of their study, only a grade B-C recommendation was given to combination therapy as an approach for second-line treatment. This study also summarized that combination therapy was well tolerated and similar to desmopressin monotherapy.
  
  
  CONCLUSIONS
  This study was able to summarize the immediate 1-month efficacy of combination therapy compared with desmopressin monotherapy in the treatment of pediatric enuresis. For both treatment-naive and desmopressin-resistant pediatric enuresis, combination therapy of desmopressin with an anticholinergic agent is well tolerated and resulted in a significantly better immediate 1-month response rate than desmopressin monotherapy.
authors.affiliation: Institute of Urology, St. Luke's Medical Center, NCR, Philippines; Division of Urology, Taipei Tzu Chi Hospital, New Taipei, Taiwan, ROC.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Chua
authors.affiliation: Institute of Urology, St. Luke's Medical Center, NCR, Philippines.
authors.forename: Jan Michael A
authors.initials: JM
authors.lastname: Silangcruz
authors.affiliation: Division of Urology, Taipei Tzu Chi Hospital, New Taipei, Taiwan, ROC; School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan, ROC.
authors.forename: Shang-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Division of Urology, Taipei Tzu Chi Hospital, New Taipei, Taiwan, ROC; School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan, ROC. Electronic address: ekim.auhc@gmail.com.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Yang
mesh_terms: D002648:Child; D002675:Child, Preschool; D018680:Cholinergic Antagonists / Q000008:administration & dosage*; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004775:Enuresis / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018680:Cholinergic Antagonists; D003894:Deamino Arginine Vasopressin
keywords: Cholinergic antagonists; Combination therapy; Desmopressin; Enuresis; Meta-analysis; Response rate