UROGENITAL FISTULA: STUDIES ON EPIDEMIOLOGY AND TREATMENT OUTCOMES IN HIGH-INCOME AND LOW- AND MIDDLE-INCOME COUNTRIES Work submitted to Newcastle University for the degree of Doctor of Science in Medicine September 2018 Paul Hilton MB, BS (Newcastle University, 1974); MD (Newcastle University, 1981); FRCOG (Royal College of Obstetricians & Gynaecologists, 1996) Clinical Academic Office (Guest) and Institute of Health and Society (Affiliate) Newcastle University, Newcastle upon Tyne, United Kingdom ii Table of contents Table of contents ..................................................................................................................iii List of tables ......................................................................................................................... v List of figures ........................................................................................................................ v Declaration ..........................................................................................................................vii Abstract ............................................................................................................................... ix Dedication ............................................................................................................................ xi Acknowledgements ............................................................................................................ xiii Funding ...................................................................................................................................... xiv Abbreviations ..................................................................................................................... xv Conventions ...............................................................................................................................xvii Chapter 1: Background literature ........................................................................................... 1 Introduction ................................................................................................................................... 1 Categorisation of countries ....................................................................................................... 1 Quality of available evidence .................................................................................................... 5 Epidemiology of urogenital fistulas .............................................................................................. 6 Aetiology .................................................................................................................................. 6 Incidence and prevalence ......................................................................................................... 7 Risk of lower urinary tract fistula after hysterectomy .............................................................. 8 Risk of ureteric injury after hysterectomy ................................................................................ 9 Patterns of care for fistula ...........................................................................................................10 Obstetric fistula – in low- and middle-income countries ..........................................................10 Non-obstetric fistula – in high-income countries .....................................................................10 Outcomes of treatment for lower urinary tract fistula ................................................................ 12 Definition of cure ..................................................................................................................... 12 Classification of fistula and treatment outcome......................................................................16 Urinary tract function in association with fistula and fistula repair ......................................... 17 Treatment outcomes ...............................................................................................................18 Chapter 2: Group I publications ........................................................................................... 21 (Works upon which a candidate primarily bases his claim to have satisfied the standards for the award of the degree) Paper 1: The aetiology, treatment and outcome of urogenital fistulae managed in well- and low- resourced countries: a systematic review................................................................................... 25 Paper 2: Epidemiological and surgical aspects of urogenital fistulae: a review of 25 years’ experience in southeast Nigeria. ................................................................................................ 43 Paper 3: Urogenital fistula in the UK: a personal case series managed over 25 years................. 51 Paper 4: Urodynamic findings in patients with urogenital fistulae. ............................................ 63 Paper 5: Urinary symptoms and quality of life in women following urogenital fistula repair: a long-term follow-up study. ......................................................................................................... 69 Paper 6: The risk of vesicovaginal and urethrovaginal fistula after hysterectomy performed in the English National Health Service - a retrospective cohort study examining patterns of care between 2000 and 2008. ............................................................................................................ 77 Paper 7: The risk of ureteric injury associated with hysterectomy: a 10-year retrospective cohort study. .......................................................................................................................................... 87 iii Paper 8: Retrospective cohort study on patterns of care and outcomes of surgical treatment for lower urinary–genital tract fistula among English National Health Service hospitals between 2000 and 2009. .......................................................................................................................... 101 Chapter 3: Summary of main findings from included papers ........................................... 109 Chapter 4: Findings from the included studies set in context ........................................... 127 Chapter 5: Further commentary on emerging trends in the aetiology of urogenital fistula ........................................................................................................................................... 145 Recent trends in iatrogenic/surgical fistula ............................................................................... 145 Drivers for recent trends seen in iatrogenic fistulae in high-income countries ..................... 145 Recent trends in of ‘obstetric’ fistula ........................................................................................ 146 Drivers for recent trends seen in ‘obstetric’ fistula in low-income countries ........................ 147 Post-caesarean section fistula – traumatic or ischaemic? ...................................................... 149 References ......................................................................................................................... 153 Appendix A: Group II-a publications .................................................................................. 173 (Other works put forward as evidence of the scope of the candidate's contribution to the specific field of study in which the primary submissions lie - i.e. urogenital fistula) Appendix B: Group II-b publications .................................................................................. 181 (Other works put forward as evidence of the scope of the candidate's contribution to the broader field of study - i.e. urogynaecology) Appendix C: Candidate’s complete cohort of patients with urogenital fistulae referred and managed in UK ...................................................................................................................211 i.e. updated from included paper 3, to cover the period 1985 to 2015. iv List of tables Table 1: Matrix of classifications of well- and poorly-resourced countries .............................. 3 Table 2: (a) Summary of IUCD modified OCEBM systems for levels of evidence (above) and (b) grades of guideline recommendation (below). ...................................................................... 6 Table 3: Adapted WHO fistula classification (de Bernis, 2007; de Ridder et al., 2013) ............. 14 The categorical and continuous definitions of cure and scales of outcome are summarised overleaf (table 4). ................................................................................................................. 14 Table 4: Summary of outcome measures for fistula treatment ............................................. 15 Table 5: Waaldijk classification of obstetric fistula showing postoperative closure and incontinence rates in 1716 consecutive women undergoing early closure of type I & II fistulas (Waaldijk, 2009; de Ridder et al., 2012). ................................................................................ 17 Table 6: Group II-a publications listed by format ................................................................. 173 Table 7: Group II-b publications listed by format (above); total publications (below) ......... 181 List of figures Figure 1: World map of the Human Development Index by country, grouped by quartiles (based on 2015 and