title: Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study.
abstract: OBJECTIVE
  To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs).
  
  
  METHODS
  A European Union-based multicentre, retrospective nested case-control study.
  
  
  METHODS
  276 adult women treated for RUTIs starting from 2009 to 2013.
  
  
  METHODS
  Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry).
  
  
  METHODS
  The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented.
  
  
  RESULTS
  181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5.
  
  
  CONCLUSIONS
  Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time.
  
  
  BACKGROUND
  NCT02016118.
authors.affiliation: Centre for Research on Health and Social Care Management, Università Bocconi, Milan, Italy Evidence Synthesis & Modelling for Health Improvement, Institute of Health Research, University of Exeter Medical School, Exeter, UK.
authors.forename: Oriana
authors.initials: O
authors.lastname: Ciani
authors.affiliation: Diaconessenhuis, Maatschap, Urologie, Leiden, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Arendsen
authors.affiliation: Department of Urology, St. Cyril and Method University Hospital, Bratislava, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Romancik
authors.affiliation: Department of Urology, Fakultná nemocnica s poliklinikou, Prešov, Slovakia.
authors.forename: Richard
authors.initials: R
authors.lastname: Lunik
authors.affiliation: Department of Surgical and Biomedical Science, University of Perugia, Urology and Andrology Clinic, Perugia, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Costantini
authors.affiliation: Department of Surgical and Biomedical Science, University of Perugia, Urology and Andrology Clinic, Perugia, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Di Biase
authors.affiliation: Department of Urology, University of Catania, Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morgia
authors.affiliation: Department of Urology, University of Catania, Catania, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Fragalà
authors.affiliation: Department of Urology, Jessenius School of Medicine, University Hospital, Martin, Slovakia.
authors.forename: Tomaskin
authors.initials: T
authors.lastname: Roman
authors.affiliation: FNsP, Urologicka Klinika, Nové Zámky, Slovakia.
authors.forename: Marian
authors.initials: M
authors.lastname: Bernat
authors.affiliation: Department of Urology, Humanitas Clinical and Research Center, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Guazzoni
authors.affiliation: Centre for Research on Health and Social Care Management, Università Bocconi, Milan, Italy Department of Policy Analysis and Public Management, Università Bocconi, Milano, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tarricone
authors.affiliation: Department of Urology, Humanitas Clinical and Research Center, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Lazzeri
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002809:Chondroitin Sulfates / Q000008:administration & dosage*; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011788:Quality of Life; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy*
chemical_list: D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates
keywords: Antimicrobial Resistance; Hyaluronic acid; chondroitin sulphate