Ganesh Thiagamoorthy

The efficacy and tolerability of mirabegron, a β3 adrenoceptor agonist, in patients with symptoms of overactive bladder

Mirabegron, is the only β-3 adrenoreceptor (AR) agonist available for the treatment of overactive bladder (OAB). To assess the efficacy and tolerability of this novel drug therapy, two phase II and six phase III Astellas-sponsored trials have been conducted with over 10,500 adults with OAB recruited. Of these, seven were randomized, double blind, 12-week placebo controlled studies and the other was for 12 months and not placebo controlled. The evidence described would suggest that mirabegron is as efficacious as most antimuscarinics, including tolterodine extended release (ER) 4 mg, compared with placebo with regard to objective measures such as reduction in number of voids per 24 hours, mean volume per void, mean number of episodes of general urinary incontinence, urgency urinary incontinence and urgency per 24 hours; and subjective measures such as severity of urgency, patient perception of bladder condition and validated continence quality of life questionnaires. Regarding tolerability, these data would suggest that patients taking mirabegron suffer a similar rate of adverse effects as those taking placebo alone, whereas the rate in those taking antimuscarinics is greater. Thus mirabegron presents a safe and effective alternative treatment to antimuscarinics for patients with OAB symptoms. Patients who may particularly benefit from mirabegron include those who are unsuitable for antimuscarinics or who have previously struggled with antimuscarinic side effects.

Current and future pharmacotherapy for treating overactive bladder

ABSTRACT Introduction: Drugs which prevent acetylcholine mediated involuntary detrusor contractions are the mainstay of overactive bladder(OAB) treatment but there are now several alternative therapeutic options available. Areas covered: Current and future drug therapies for OAB are highlighted. These include novel antimuscarinic molecules (imidafenacin and tarafenacin); novel combination therapies with β3-adrenoceptor agonists or muscarinic agonists (tolenix) and a novel vaginal delivery method for oxybutynin. β3-adrenoceptor agonists(β3-AR) have been shown to be efficiacious in the management of OAB. The evidence supporting the first licensed β3-AR agonist, mirabegron, is assessed, as well as other putative β3-AR agonists in development such as solabegron, ritobegron, aryloxypropanolamine, TRK-380, and CL 316,243. The role of vaginal oestrogen is highlighted followed by a detailed analysis of botulinum-A toxin. Expert opinion: Anticholinergics were the first OAB drug therapy on the market and have the largest dataset available. Despite obvious limitations, these are still first line medical therapy. There are a number of new OAB therapies under investigation and we await their contribution to the management armamentarium. Other novel drugs have been licenced and these are now vying for pole position in the treatment algorithm. One must exercise caution however until the long term effects of any new medicines are known.

Is there an association between aspects of the metabolic syndrome and overactive bladder? A prospective cohort study in women with lower urinary tract symptoms

OBJECTIVE The aim of our study was to determine whether there is a link between aspects of the metabolic syndrome (MetS) and overactive bladder (OAB) in women with lower urinary tract symptoms (LUTS). STUDY DESIGN A single-centre prospective study. We evaluated a cohort of consecutive women with LUTS attending a tertiary referral urodynamic clinic from October 2012 to January 2015. Obesity, diabetes, hypertension and dyslipidaemia were used as markers of MetS. OAB and detrusor overactivity (DO) were defined according to the International Urogynaecological Association/International Continence Society terminology. RESULTS Eight hundred and forty women were enrolled. Three hundred and eight (36.6%) had normal weight, 260 (31%) were overweight and 272 (32.4%) obese. We identified 168 women (20%) with hypertension, 64 (7.6%) with diabetes mellitus, and 98 (11.7%) with dyslipidaemia. Seven hundred and four (83.8%) women were diagnosed symptomatically with OAB and 305 (36.3%) were diagnosed urodynamically with DO. Obesity (p<0.001) was the only independent predictor for OAB (OR 1.09, 95% CI 1.05-1.13) and DO (OR 1.06, 95% CI 1.03-1.08), respectively. CONCLUSION Our study demonstrates a correlation between obesity and OAB/DO in female patients. However, other components of MetS do not appear to be associated with either OAB and DO. Weight reduction should be strongly recommended in women with OAB.

Anticholinergic prescription: are healthcare professionals the real burden?

Introduction and hypothesisAnticholinergic medication is the medical treatment for overactive bladder (OAB). These drugs can act on the central nervous system and can lead to cognitive decline, dementia, and potentially death. Patients taking drugs with anticholinergic effects increase their anticholinergic burden—defined as the cumulative effect of taking one or more drugs that can have adverse effects. When prescribing anticholinergic medication for the elderly, we must choose the right drug. We aimed to discover the level of understanding on this subject and its application to real clinical practice amongst our healthcare professionals (HCPs).MethodsAn 18-point questionnaire was distributed to urogynaecologists, general gynaecologists, urologists, geriatricians, general practitioners (GPs), and nurse specialists to assess knowledge on the subject.ResultsA total of 96 HCPs completed the questionnaire. The nurse specialists had the highest score in identifying that oxybutynin was the drug most likely to cross the blood–brain barrier (BBB). The urogynaecologists had the highest score in identifying that trospium chloride was least likely to cross the BBB, whereas the GPs had the lowest score. Solifenacin was the most popular anticholinergic drug prescribed in the elderly without dementia. Trospium chloride was the most popular drug prescribed in the elderly with dementia.ConclusionsWe have found that knowledge is lacking amongst all our HCPs, but especially amongst our first-line doctors, our GPs. Education is key in developing knowledge and safe prescribing, to improve the care we give to our patients.

Management of prolapse in older women

Pelvic organ prolapse (POP) is a common problem affecting 37% of women over the age of 80. Review by a specialist with the aid of a validated quality of life questionnaire will help assess bother, as well as the frequency and severity of urinary, bowel and sexual symptoms. Pelvic examination should be carried out to assess the extent of any prolapse and the compartments affected. The main aim of the treatment is to improve the woman’s quality of life. Treatment options may be conservative with lifestyle modifications and pelvic floor muscle therapy, use of a pessary or surgery. Treatment has previously been incorrectly limited in the elderly with the misconception that surgery should be avoided. Her current state of health and expectations are most important. Regardless of age, each patient should be assessed individually with a holistic multi-compartment approach and the risk benefit ratios of every treatment considered.

Pelvic Organ Prolapse in the Older Woman

Pelvic organ prolapse (POP) is a common problem affecting 37 % of women over the age of 80 (Morley, Clin Obstet Gynecol 39(4):959–69, 1996). There are several factors involved in the aetiopathogenesis. As the life expectancy increases, management of prolapse in this age group assumes greater significance. The management of POP in the older woman essentially follows the same principles in that this largely depends on the extent of bother it causes the woman. This chapter provides a comprehensive review of these options, expectant, conservative and surgical.

Laparoscopic mesh repair of a labial hernia

To present a narrated video designed to demonstrate the steps involved in a laparoscopic mesh repair of a labial hernia.

Combined Laparoscopic, Vesicoscopic, and Vaginal Repair of a Vesicovaginal Fistula

STUDY OBJECTIVE To demonstrate a combined laparoscopic, vesicoscopic, and vaginal approach to repair of a complex vesicovaginal fistula. DESIGN Technical video demonstrating a combined laparoscopic, vesicoscopic, and vaginal approach for repairing a vesicovaginal fistula (Canadian Task Force classification level III). SETTING Urogynecology and Urology Departments of a tertiary referral center for urogynecology. INTERVENTIONS A 38-year-old woman presented with a vesicovaginal fistula secondary to a previous total abdominal hysterectomy. An initial attempt to repair the fistula vaginally was unsuccessful owing to infection and comorbidities. After counseling, the patient agreed to a combined laparoscopic, vesicoscopic, and vaginal repair of her vesicovaginal fistula. CONCLUSION The incidence of vesicovaginal fistula following a total abdominal hysterectomy for benign causes is 1 in 540 [1]. Management of this complication can be challenging, and success rates vary. Initially, laparoscopy was performed, which allowed mobilization of the omentum to provide an interposition patch between the bladder and vagina after repair of the fistula. The fistula tract was then identified vesicoscopically and excised. Once the tract was closed and the patch secured, a vaginal approach was adopted to excise the remaining fistula tract as well as scar tissue. Interrupted closure of the vagina was performed in multiple layers to reduce the risk of recurrence. We have used vesicoscopy since 2007 for a variety of female urogynecologic problems, including bladder diverticula, ureteric stenosis, vesicoureteric reflux, foreign body removal, and vesicovaginal fistula repair [2]. This combined multidisciplinary approach offers a minimally invasive option for the repair of complex vesicovaginal fistulae, and should be considered in selected complex cases.

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 Kings 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.