Anal incontinence following obstetric anal sphincter injury: Is there a difference between subtypes? A systematic review.

AIMS: Obstetric anal sphincter injury (OASI) is associated with long-term anal incontinence (AI). We aimed to address the following questions: (a) are women with major OASI (grade 3c and 4) at higher risk of developing AI when compared to women with minor OASI (grade 3a and 3b)? (b) is a fourth-degree tear more likely to cause AI over a third-degree tear? METHODS: A systematic literature search from inception until September 2022. We considered prospective and retrospective cohort studies, cross-sectional and case-control studies without language restrictions. The quality was assessed by the Newcastle-Ottawa Scale and the Joanna Briggs Institute critical appraisal checklist. Risk ratios (RRs) were calculated to measure the effect of different grades of OASI. RESULTS: Out of 22 studies, 8 were prospective cohort, 8 were retrospective cohort, and 6 were cross-sectional studies. Length of follow-up ranged from 1 month to 23 years, with the majority of the reports (n = 16) analysing data within 12-months postpartum. Third-degree tears evaluated were 6454 versus 764 fourth-degree tears. The risk of bias was low in 3, medium in 14 and high in 5 studies, respectively. Prospective studies showed that major tears are associated with a twofold risk of AI for major tears versus minor tears, while retrospective studies consistently showed a risk of fecal incontinence (FI) which was two- to fourfold higher. Prospective studies showed a trend toward worsening AI symptoms for fourth-degree tears, but this failed to reach statistical significance. Cross-sectional studies with long-term (≥5 years) follow-up showed that women with fourth-degree tear were more likely to develop AI, with an RR ranging from 1.4 to 2.2. Out of 3, 2 retrospective studies showed similar findings, but the follow-up was significantly shorter (≤1 year). Contrasting results were noted for FI rates, as only 5 out of 10 studies supported an association between fourth-degree tear and FI. CONCLUSIONS: Most studies investigate bowel symptoms within few months from delivery. Data heterogeneity hindered a meaningful synthesis. Prospective cohort studies with adequate power and long-term follow-up should be performed to evaluate the risk of AI for each OASI subtype.

Changing surgical trends for female stress urinary incontinence in England.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) surgery has significantly evolved with the introduction of synthetic midurethral slings (MUS). However, following reports from the US Food and Drug Administration and European Commission, the use of vaginal meshes in urogynaecology has been largely scrutinised. We analysed trends in female SUI surgery in England from 2000 to 2017. METHODS: The Hospital Episode Statistics database was retrieved from the Health and Social Care Information Centre website. Specific four-character codes of the evolving OPCS-4 coding system were used to quantify SUI operations. RESULTS: We analysed 180,773 admissions from 2000 to 2017. A steep rise in MUS use was noted until 2008-2009, followed by a consistent drop, with a nadir of 6383 procedures in 2016-2017. Removal of MUS has become increasingly popular, with a peak of 591 in 2012-2013. Numbers for traditional continence operations remained low. Colposuspensions markedly decreased to 189 in 2012-2013, with a slight positive trend only in the last few years, while autologous sling use costantly dropped from 262 to 124 throughout the study period. Admissions for urethral bulking agents increased from 650 to 1324 in the last 2 years. CONCLUSIONS: MUS represents the most commonly performed procedure for SUI, despite an obvious reduction in the last 8 years. Urethral bulking agents are becoming more popular, while the numbers of colposuspensions and autologous slings are still low. Training programmes should take into account current shifts in surgical practice.

Trends in prolapse surgery in England.

INTRODUCTION AND HYPOTHESIS: Women have a lifetime risk of undergoing pelvic organ prolapse (POP) surgery of 11-19%. Traditional native tissue repairs are associated with reoperation rates of approximately 11% after 20 years. Surgery with mesh augmentation was introduced to improve anatomic outcomes. However, the use of synthetic meshes in urogynaecological procedures has been scrutinised by the US Food and Drug Administration (FDA) and by the European Commission (SCENIHR). We aimed to review trends in pelvic organ prolapse (POP) surgery in England. METHODS: Data were collected from the national hospital episode statistics database. Procedure and interventions-4 character tables were used to quantify POP operations. Annual reports from 2005 to 2016 were considered. RESULTS: The total number of POP procedures increased from 2005, reaching a peak in 2014 (N = 29,228). With regard to vaginal prolapse, native tissue repairs represented more than 90% of the procedures, whereas surgical meshes were considered in a few selected cases. The number of sacrospinous ligament fixations (SSLFs) grew more than 3 times over the years, whereas sacrocolpopexy remained stable. To treat vault prolapse, transvaginal surgical meshes have been progressively abandoned. We also noted a steady increase in uterine-sparing, and obliterative procedures. CONCLUSIONS: Following FDA and SCENIHR warnings, a positive trend for meshes has only been seen in uterine-sparing surgery. Native tissue repairs constitute the vast majority of POP operations. SSLFs have been increasingly performed to achieve apical support. Urogynaecologists' training should take into account shifts in surgical practice.

Therapies in early development for the treatment of urinary tract inflammation.

INTRODUCTION: Urinary tract inflammation is a very common clinical condition. It is caused by several pathogens and antibiotic treatment is the mainstay of therapy. Increasing antimicrobial resistance and high recurrence rates represent a challenge. Consequently, there is an unmet need for new therapeutic options. AREAS COVERED: The authors discuss the rationale of emerging management strategies and current experimentation. Furthermore, they focus on both acute and recurrent urinary tract infections (UTIs) and examine a range of therapeutics, including new antibiotics, vaccines, mannosides, hyaluronic acid, probiotics, immunomodulant agents and novel compounds derived from nanotechnology. EXPERT OPINION: Basic science studies have elucidated the pathogenesis of UTIs and built up the ground for the development of new therapies. Evidence is mainly derived from animal studies on murine models of bacterial cystitis. However, clinical trials are scanty and cannot provide us with robust evidence. Hetereogeneity and virulence of uropathogens pose a threat that scientists and clinicians are struggling to overcome.

Novel targeted bladder drug-delivery systems: a review.

The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

Is there a link between preoperative fluoroscopic cough stress testing and synthetic midurethral tape outcome?

OBJECTIVES: The primary aim of our study was to assess the utility of fluoroscopic cough stress testing as a predictor of synthetic midurethral tape (MUT) outcome. The secondary aim was to examine whether baseline demographics, clinical symptoms and urodynamic variables could predict MUT success. STUDY DESIGN: We carried out a retrospective study including women with stress urinary incontinence (SUI) who underwent retropubic MUT in a tertiary referral urogynaecology unit. We excluded cases where concurrent pelvic organ prolapse surgery was performed. Patients were subdivided into groups based on the pre-operative fluoroscopic cough stress testing, using Blaivas and Versi classifications. Subjective outcome was evaluated at 6 weeks based on self-reported SUI in the symptom domain of the King's Health Questionnaire. Logistic regression models were used to identify predictors of treatment success. RESULTS: 143 patients were included in the study. Blaivas and Versi classifications were not useful in predicting subjective success (p=0.44 and p=0.40, respectively). Baseline demographics, clinical and other urodynamic variables failed to predict subjective outcome. CONCLUSIONS: Fluoroscopic cough stress testing is not a useful predictor of MUT outcome. No preoperative variables have been found to predict MUT success.

Phase II drugs that target cholinergic receptors for the treatment of overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is a term used to describe the symptom syndrome of urgency, with or without urgency incontinence, usually associated with frequency and nocturia. Antimuscarinics are the most widely prescribed class of drugs for OAB, although their systemic adverse effects limit their use in clinical practice as compliance. This has led to developments in the field. AREAS COVERED: In this review, the authors describe Phase II drugs that target cholinergic receptors. First, the authors present the new antimuscarinics (tarafenacin and afacifenacin). This is followed by reports on a combination drug (tolenix) containing a muscarinic antagonist (tolterodine) associated with a muscarinic agonist (pilocarpine). Further, the authors discuss the trials of well-known drugs in either new combination therapy (solifenacin and mirabegron) or with new routes of delivery (oxybutynin vaginal ring). Finally, the authors examine the option of targeting nicotinic acetylcholine receptors (dexmecamylamine). EXPERT OPINION: Different strategies have been adopted to improve the efficacy and tolerability of therapeutics for OAB. Nicotinic receptors represent a novel therapeutic target; however, it is unlikely that antimuscarinic agents will be replaced as standard first-line therapy in the near future.

Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne and pattern alopecia, often characterised by ovulation disorders (usually manifested as oligo- or amenorrhea). In addition, 30-40% of women with PCOS have impaired glucose tolerance, and a defect in the insulin signalling pathway seems to be implicated in the pathogenesis of insulin resistance. For this reason, insulin-lowering medications represent novel approach in women with PCOS. The aim of this study was to evaluate the effects of myo-inositol (MYO), an isoform of inositol, belonging to the vitamin B complex, in the treatment of cutaneous disorders like hirsutism and acne. METHODS: Fifty patients with PCOS were enrolled in the study. BMI, LH, FSH, insulin, HOMA index, androstenedione, testosterone, free testosterone, hirsutism and acne were evaluated at the baseline and after receiving MYO therapy for 6 months. RESULTS: After 3 months of MYO administration, plasma LH, testosterone, free testosterone, insulin and HOMA index resulted significantly reduced; no significant changes were observed in plasma FSH and androstenedione levels. Both hirsutism and acne decreased after 6 months of therapy. DISCUSSION: MYO administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.