Dr Stephen Jeffery Groote Schuur Hospital Cape Town

Name: Dr Stephen Jeffery Groote Schuur Hospital Cape Town
Uploaded: 2017-08-23T17:16:16+00:00
Duration: PTM42S29
Channel: Barnaby Doyle
Description: Dr Stephen Jeffery Groote Schuur Hospital Cape Town

Dr Stephen Jeffery Groote Schuur Hospital Cape Town
Recent Advances in the Management of the Overactive Bladder Chairmen ladies and gentleman thank you for allowing me to give you an update on this topic. I will focus on Botulinum toxin since a lot has come out recently on its use in OAB. Dr Stephen Jeffery Groote Schuur Hospital Cape Town

Relative proportions of incontinence by age
Stress urinary incontinence (SUI) Total 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 85–89 90+ Mixed urinary incontinence (MUI) 80 60 40 20 Urge urinary incontinence (UUI) Percentage of incontinent women (%) KEY POINT: Urinary incontinence (UI) is a common condition in women, and its prevalence increases with age. Younger and middle aged women with UI are more likely to have stress UI (SUI) than urge UI (UUI) or mixed UI.1 In older women, mixed UI and UUI are proportionally more prevalent than SUI.1 ADDITIONAL INFORMATION: A Norwegian survey of 27,936 women aged 20 years found an overall prevalence of UI of 25%.1 While the lowest prevalence was found among the youngest age group and the highest prevalence among the oldest age group, a peak was also seen around middle age and the onset of the menopause (50–54 years).1 REFERENCE: Hannestad YS et al. J Clin Epidemiol 2000; 53: 1150–1157. Age (years) n=6876 Hannestad YS et al. J Clin Epidemiol 2000; 53: 1150–1157. Reproduced with permission from Professor David Castro-Diaz.

Why do patients stop taking antimuscarinic therapy?
International web survey 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Female ≤55 Years of Age 57 30 2 9 Female >55 Years of Age 47 39 8 4 Male 50 24 3 18 In Employment/Activity Working 50 31 7 9 Retired/Unemployment 50 30 4 14 OAB Dry 58 26 2 10 Pure UUI 61 24 3 10 Mixed UI 66 16 13 2 Insufficient efficacy Intolerable side effects Dosing convenience Other reasons This was an international quantitative web survey of practicing doctors, including urology/gynaecology specialists. Lack of efficacy is the major reason for failure of first-line antimuscarinic therapy Reference: Global Market Research Study (Yamanouchi Pharma Ltd, December 2003:n=736).

What Percentage of Urge Incontinent Patients achieve Long-Term Benefit From Drugs?
10 20 30 40 50 60 70 80 90 100 All Patients With DO and UI Cured/ Improved Responders Using Drugs >6 Months Urge Incontinent Patients (%) This slide shows that non-compliance is a problem with anticholinergics, even in those patients that experience an improvement of urge incontinence. Non-compliance is mainly due to muscarinic side effects. Kelleher et al. Br J Obstet Gyn. 1997;104:

Persistence on Specific Medications for OAB Based on Prescription Data
Percent Months Chui M, et al. Value in Health. 2004;7:366.

When Anticholinergics Fail
Sacroneuromadulation PTNS Acupuncture Physiotherapy Botox

Botulinum Toxin Introduction Options Neuromodulation
Augmentation / Ileocystoplasty Botulinum Toxin The options for these patients include neuromodulation. As we will hear from Mr drake later – these modalities are expensive, not readliy available and reqire an infrastructure. The other option is surgery in the form of aug/ cystplasty. These operations have a morbidity and in many cases – the patient is condemned to a life of voiding dysfunction. Over the last six years Botulinum Toxin has become an alternative in this group of patiets and many physicians will now place it here as a option before proceding to Neuromodulation or surgery or as an alternative.

Introduction 21st Century Penicillin for the Bladder ! Schurch 2000
21 Neurogenic Detrusor Overactivity (NDO) Botox u 17/19 achieved continence Bladder capacity increased 296ml to 480ml Reflex volume 215ml to 415 ml Brigitte Schurch’s group from Switzerland was the first to publish on the use of Botox in these patients. They looked at 21 NDO. They had previously done a dose finding study on 15 patients and that is how they came to the dose of units. Of the 19 patients 17 achieved total continence. There were remarkable URO findings with capacity increasing from 296 to 480 ml and reflex voume 215 to 415. These results have been repeated in many other studies since then and at a recent meeting in Schurch has been quoted as saying that Botox…………………… 21st Century Penicillin for the Bladder ! Schurch et al . J. Urol 2000; 164:

Introduction Clostridium botulinum Gram positive Anaerobic
1 g kills I million people Botulinum toxin comes from Clostridium botulinum. It is a Gram positive, anaerobic bacteria which is commonly found in the soil. Of note, 1 g of toxin can kill 1 million people.

Hence its potential as a biological weapon.

Introduction 1946 Purified botulinum toxin type A in a crystalline form (Schantz) 1960s Neuromuscular toxin (Schantz) 1980 Strabismus (Scott) Amongst those who have contributed to the science of botulinum toxin, credit must be given to Schantz who purified the toxin and enabled its mass production. Despite being an army officer, he advocated its use in medicine. Its first clinical use was in 1980 when it was used in strabismus.

Types 7 Subtypes A, B, C, D, E, F, G
Only A and B available commercially There are 7 subtypes However only and B are available commercially

Types Botulinum A Botulinum B Botox® (Allergan Inc.)
Dysport® (Ipsen Pharma) Botulinum B Neurobloc ® (Solstice Neurosciences Inc.) Many of us flippantly refer to Botulium products as Botox. However Botox is the Botulnum A product made by allergan. There is an alternative called Dysport and in fact more Dysport is used than Botox in tne UK. Botulinum B is marketed by Solstice. In OAB most of the studies have used Botulum A – B seems to have a shorter duration of action and is reserved for patients with resistance

Botulinum Toxin A Botox® Dysport ® MW (kDa) 900 Target protein SNAP 25
Units / vial 100 500 Price / vial ~£135 ~£173 Dose IDO ~200 units ~500 unit NDO ~300 units ~750 units Two commercial preparations of Botulinum toxin A anre Botox and Dysport and this summarises their charactistics. Essentially Botox is about 3x more potent than Dysport ie . You need three x more to kill a mouse than Botox.

Dosages Botox Dysport NDO 300u IDO 200u 500 to 1000u Fewer studies
There is a lot more evidence for Botox than for Dysport and most studies use 300 for NDO and 200 for IDO. Exact dosage for Dysport is less clear with dosages ranging from 500 to 1000.

Administration Rigid Flexible
With regard to administration, all that is required are a cystoscopy and an appropriate needle. You can use either a rigid or flexible cystoscope. Anaesthesia ranges from GA to sedation to simply local anaesthetic. Flexible

Administration The needle option also ranges from a simple needle that is through to a fine 26G olympus needle.

Administration Normal Saline Do not shake
. Most of us use normal saline to dilute the Botulinum because some reports suggest pain …. Also – when reconstititing the botox – do not shake it since it is suggested that it breaks the bonds.

Administration Trigone or not? Lucioni et al Karsenty et al
16 intratrigonal and 24 trigone sparing Similar results at 3 weeks & 6 months on UDI and SIIQ Karsenty et al VCU 1hr before 6 weeks N=10 No new cases of reflux with similar efficacy Most reports have avoided injecting the trigone because of the theoretical risk of reflux . However a styudy by Smith et al from the states specifically injected the trigone and no incidence of pyelonephritis. Lucioni et al Can J Urol 2006;13(5): Karsenty et al J Urol 2007; 177(3):1011-4

Contraindications Neuromuscular Disorders
Previous Failure of Botulinum Injections Bleeding Tendencies We tend to avoid giving it in patients with

Efficacy: NDO A large amount of data has emerged over the few years suggesting excellent efficaccy in NDO.

Efficacy: NDO Schurch 2005 BOTOX N=59 (NDO)
Double blind placebo controlled parallel group study Scurch et al reported again in NDO patients. This was a Schurch et al J Urol 2005; 174:

Efficacy: NDO Schurch 2005 BOTOX Dose F u Urodynamics
Incontinence episodes Dry QOL 300u (n=19) 200u placebo (n=21) 6 m Increase in MCC, RV Decrease in Max Det Pressure 50 % reduction for 200 and 300u 49% Mean I-QOL scoes improved (p<0.002) They gave patients either ………………. And up to 6 month FU there was a 50 % reduction in IE with 49% reporting being dry. Profound improvements in QOL Schurch et al J Urol 2005; 174:

Increase in Maximum Cystometric Capacity (MCC)
Mean increase in MCC from baseline (in ml) The urodynamic findings compared to placebo were remarkable at with highly significant increases in in MCC at 2 , 6 and 24 weeks compared to placebo. Schurch et al J Urol 2005; 174:

Efficacy: NDO Reitz 2004 Large European study 10 Centres N=231(NDO)
BOTOX Reitz 2004 Large European study 10 Centres N=231(NDO) 12 week and 24 week follow up The largest study reporting on Botox was by reitz et al who looked at 231 NDO patients with follow up at 12 and 24 weeks Reitz et al Eur Urol 2004; 45:

Efficacy: NDO Reitz et al 2005 Dose F u Urodynamics Dry Botox 300u 3m
& 9 m Increase in MCC, RV and compliance 3 m 9 m Again very high rates of patiets reporting dry with significant increses in urodynamic findings

Efficacy: NDO BOTOX Study N Dose FU Improved Dry Urodynamics Kuo 2005
24 BTX 200u 3m & 6m 70 % improved 25% Increased Reflex volume and MCC Klaphajone 2005 10 NDO BTX 300 9 70% Increased MCC, compliance, reflex volume, decrease in detrusor pressure Schulte-Baukloh 2006 16 MS Reduction in daily pad use from 1.75 to 1.08 (4 weeks) and 0.63 (3 months) Increased Reflex volume and MCC. Decreased Detrusor pressure Other studies reporting on Botox in NDO again with dry rates ranging from 25 with 200u to 70 with 300u. This study looked at pad use showing a reduction to 0.63 at 3 months