Tag Archive for: overactive bladder

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Editorial: Should we start with low-dose anti-cholinergics when alpha-blockers alone fail?

Kim et al. [1] asked the question whether we should start by treating men who have persistent storage LUTS despite α-blocker monotherapy, with a low-dose anti-cholinergic as opposed to the standard dose (given the potentially increased risk of side-effects such as acute urinary retention and high discontinuation rates with the standard dose). It is a valid question, for we know that discontinuation rates with standard doses of anti-cholinergics can be as high as 50% in the first 3 months due to a combination of ineffectiveness and side-effects [2]. However, the problem lies in the multifactorial nature of the causes of storage vs voiding LUTS, and the difficulty in assessing and distinguishing them accurately with our current tools.

The authors have conducted a randomised controlled trial of 2 mg vs 4 mg tolterodine added to the participants’ on-going α-blocker regime and selected reduction in total IPSS as their primary outcome measure. They have also assessed IPSS sub-scores, 3-day bladder diary variables, and the Patient Perception of Bladder Condition (PPBC) and Overactive Bladder (OAB-q) questionnaires, as secondary outcomes. As would be expected of a peer-reviewed publication the trial has been seemingly well conducted and fairly well reported. Recruitment met the requirement set by the power calculation based on a clinically significant difference of a 4-point drop in total IPSS, and the authors concluded that 2 mg tolterodine is not inferior to the 4 mg dose in achieving a significant reduction in total IPSS at 12 weeks. They also report no difference in patient perception of treatment benefit or satisfaction at this time point.

These results are interesting, especially considering some of the details of the study. First of all, patients were not on the same α-blocker at baseline; the most common was tamsulosin (62.8%), but alfuzosin, doxazosin, and others were also being used. This in itself may not be a problem because all patients continued on the same α-blocker through the study, and in fact this better represents real-world practice. However, the mean (sd) duration of α-blocker therapy at baseline was 9.1 (19.9) months. We know that α-blocker therapy can improve IPSS by up to 30–40% [3], but the pertinent question for this study is whether these patients had achieved this level of improvement initially then stabilised and improved no further, or whether they had no improvement at all? It could conceivably make a difference to participants approach to the IPSS if they were previously familiar with it and, more importantly, aware of their results. The Hawthorne effect, also known as the observer effect, and the related Heisenberg uncertainty principle, are factors that we must necessarily encounter in clinical trials but we sometimes fail to account for.

Another aspect of the study that warrants consideration is the choice of primary outcome itself. This is a particular bug-bear of mine and indeed has been commented on by many authors including in the European Association of Urology (EAU) guideline on urinary incontinence in relation to anti-muscarinics [4]. Outcomes that lend themselves to easier power calculations and statistically significant results have almost evolved to be ‘un’-naturally selected for the purpose of clinical trial primary outcome measures. Drug trials are especially notorious for this. Here again, the choice of the total IPSS to assess whether an anti-muscarinic will help improve persistent storage LUTS is a case in point. Not least because it renders the significance of all the secondary outcomes dependant on the same power calculation. It is no doubt convenient, but is it appropriate? It is easy to point the finger at trialists for this, but the business-like, ‘bottom-line’ nature of medical publishing and research today is equally, if not more, to blame.

Finally, I would like to call the reader’s attention to the difference in baseline urgency and urgency urinary incontinence (UUI) episodes. The author’s state there was no statistically significant difference, but one might argue that when assessing improvement in storage LUTS, a group with a mean (sd) baseline number of UUI episodes of 3.9 (8.6) may perceive improvement quite differently compared with a group with a baseline of 1.6 (1.1). This has borne out in the difference in the bladder diary outcome of UUI/24 h; significant improvement in the first group (who were wetter at baseline and got 4 mg tolterodine) but no difference in the latter group (comparatively drier and got 2 mg tolterodine). But almost paradoxically this does not seem to have made a difference to the patient-reported outcome measures. One possible explanation for this could be the relatively few patients who were incontinent at baseline.Overall this paper gives us a lot of food for thought. The direct result – should we indeed start men with persistent storage LUTS on low-dose anti-cholinergics rather than standard dose, and then titrate upwards? But it also challenges us to consider whether we simply accept researcher’s and sponsor’s decisions on outcome measures. What do you think? Do we simply sit back and accept what is put before us because statistics scares us a little? Or, as researchers and consumers of medical literature, do we struggle to make the hard choices, risk our results being rejected by the top journals, and stand up for good science?

Conflicts of Interest

The author has received a travel grant to attend an international conference from Ferring pharmaceuticals.

 

Arjun K. Nambiar
Clinical Research Registrar
Department of Urology, Morriston Hospital, Abertawe Bro Morgannwg (ABM) University Local Health Board, Swansea, SA6 6NL, UK

 

References

 

1 Kim TH, Jung W, Suh YS, Yook S, Sung HH, Lee KS. Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an a-blocker in men with lower urinary tract symptoms (LUTS) and overactive bladder: a randomized controlled trial. BJU Int 2015; 117:  307–15
2 Lucas MG, Bedretdinova D, Berghmanset LC et al. Guidelines on Urinary Incontinence, Section 4.2.4. In: EAU Guidelines, edition presented at the 30th EAU Annual Congress, Madrid 2015. ISBN 978-90-79754-80-9. Available at: https://uroweb.org/wp-content/uploads/17-Urinary-Incontinence_LR.pdf. Accessed September 2015
3 Gravas S, Bach T, Bachmann A et al. Guidelines on Non-Neurogenic Male LUTS Including Benign Prostatic Obstruction, Section 3C.2. In: EAU Guidelines, edition presented at the 30th EAU Annual Congress, Madrid 2015. ISBN 978-90-79754-80-9. Available at: https://uroweb.org/wp-content/uploads/11-Male-LUTS_LR.pdf. Accessed September 2015
4 Lucas MG, Bedretdinova D, Berghmanset LC et al. Guidelines on Urinary Incontinence, Section 4.2.1. In: EAU Guidelines, edition presented at the 30th EAU Annual Congress, Madrid 2015. ISBN 978-90-79754-80-9. Available at: https://uroweb.org/wp-content/uploads/17- Urinary-Incontinence_LR.pdf. Accessed September 2015

 

Video: Tolterodine combined with an alpha-blocker in men with LUTS and OAB

Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an α-blocker in men with lower urinary tract symptoms (LUTS) and overactive bladder: a randomized controlled trial

Tae Heon Kim*, Wonho Jung†, Yoon Seok Suh*, Soonhyun Yook‡, Hyun Hwan Sung*
and Kyu-Sung Lee*‡
*Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, †Department of Urology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, and ‡Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea Tae Heon Kim and Wonho Jung contributed equally to this work.

 

Objective
To evaluate the efficacy and safety of low-dose (2 mg) tolterodine extended release (ER) with an a-blocker compared with standard-dose (4 mg) tolterodine ER with an α-blocker for the treatment of men with residual storage symptoms after α-blocker monotherapy.
Patients and Methods
The study was a 12-week, single-blind, randomized, parallel group, non-inferiority trial that included men with residual storage symptoms despite receiving at least 4 weeks of α-blocker
treatment. Inclusion criteria were total International Prostate Symptom Score (IPSS) ≥12, IPSS quality-of-life item score ≥3, and ≥8 micturitions and ≥2 urgency episodes per 24 h. The primary outcome was change in the total IPSS score from baseline. Bladder diary variables, patient-reported
outcomes and safety were also assessed.
Results
Patients were randomly assigned to addition of either 2 mg tolterodine ER (n = 47) or 4 mg tolterodine ER (n = 48) to α-blocker therapy for 12 weeks. Patients in both treatment groups had a significant improvement in total IPSS score (5.5 and 6.3, respectively), micturition per 24 h (1.3 and
1.7, respectively) and nocturia per night (0.4 and 0.4, respectively). Changes in IPSS, bladder diary variables, and patient-reported outcomes were not significantly different between the treatment groups. All interventions were well tolerated by patients.
Conclusions
These results suggest that 12 weeks of low-dose tolterodine ER add-on therapy is similar to standard-dose tolterodine ER add-on therapy in terms of efficacy and safety for patients experiencing residual storage symptoms after receiving α-blocker monotherapy.

Conjoint USANZ and UGSA Guidelines on the management of adult non-neurogenic overactive bladder

Guidelines

Abstract

Due to the myriad of treatment options available and the potential increase in the number of patients afflicted with overactive bladder (OAB) who will require treatment, the Female Urology Special Advisory Group (FUSAG) of the Urological Society of Australia and New Zealand (USANZ), in conjunction with the Urogynaecological Society of Australasia (UGSA), see the need to move forward and set up management guidelines for physicians who may encounter or have a special interest in the treatment of this condition. These guidelines, by utilising and recommending evidence-based data, will hopefully assist in the diagnosis, clinical assessment, and optimisation of treatment efficacy. They are divided into three sections: Diagnosis and Clinical Assessment, Conservative Management, and Surgical Management. These guidelines will also bring Australia and New Zealand in line with other regions of the world where guidelines have been established, such as the American Urological Association, European Association of Urology, International Consultation on Incontinence, and the National Institute for Health and Care Excellence guidelines of the UK.

Article of the Month: Safety and efficacy of mirabegron as add-on therapy in patients with solifenacin-treated OAB (MILAI study)

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Prof. Osamu Yamaguchi discussing his paper. 

If you only have time to read one article this week, it should be this one.

Safety and efficacy of mirabegron as add-on therapy in patients with overactive bladder treated with solifenacin: a postmarketing, open-label study in Japan (MILAI study)

Osamu Yamaguchi, Hidehiro Kakizaki*, Yukio Homma, Yasuhiko Igawa, Masayuki Takeda§, Osamu Nishizawa, Momokazu Gotoh**, Masaki Yoshida††, Osamu Yokoyama‡‡, Narihito Seki§§, Akira Okitsu¶¶, Takuya Hamada¶¶, Akiko Kobayashi¶¶ and Kentarou Kuroishi¶¶

 

Division of Bioengineering and LUTD Research, School of Engineering, Nihon University, Koriyama, *Department of Urology, Asahikawa Medical University, Asahikawa, Department of Urology, University of Tokyo Graduate School of Medicine, Tokyo, ‡Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, §Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, ¶Department of Urology, Shinshu University, Matsumoto, **Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, ††Department of Urology, National Centre for Geriatrics and Gerontology, Obu, ‡‡Department of Urology, University of Fukui Faculty of Medical Sciences, Fukui, §§Department of Urology, Kyushu
Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, and ¶¶Astellas Pharma Inc., Tokyo, Japan

 

OBJECTIVE

To examine the safety and efficacy of mirabegron as ‘add-on’ therapy to solifenacin in patients with overactive bladder (OAB).

PATIENTS AND METHODS

This multicentre, open-label, phase IV study enrolled patients aged ≥20 years with OAB, as determined by an OAB symptom score (OABSS) total of ≥3 points and an OABSS Question 3 score of ≥2 points, who were being treated with solifenacin at a stable dose of 2.5 or 5 mg once daily for at least 4 weeks. Study duration was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting eligibility criteria continued to receive solifenacin (2.5 or 5 mg once daily) and additional mirabegron (25 mg once daily) for 16 weeks. After 8 weeks of treatment, the mirabegron dose could be increased to 50 mg if the patient’s symptom improvement was not sufficient, if he/she was agreeable to the dose increase, and the investigator judged that there were no safety concerns. Safety assessments included adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram, QT corrected for heart rate using Fridericia’s correction (QTcF) interval and post-void residual (PVR) volume. Efficacy endpoints were changes from baseline in OABSS total score, OAB questionnaire short form (OAB-q SF) score (symptom bother and total health-related quality of life [HRQL] score), mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of urinary incontinence (UI) episodes/24 h, mean number of urgency UI episodes/24 h, mean volume voided/micturition, and mean number of nocturia episodes/night. Patients were instructed to complete the OABSS sheets at weeks −2, 0, 8 and 16 (or at discontinuation), OAB-q SF sheets at weeks 0, 8 and 16 (or at discontinuation) and patient voiding diaries at weeks 0, 4, 8, 12 and 16 (or at discontinuation).

RESULTS

Overall incidence of drug-related treatment-emergent AEs (TEAEs) was 23.3%. Almost all TEAEs were mild or moderate. The most common TEAE was constipation, with similar incidence in the groups receiving a dose increase to that observed in the groups maintained on the original dose. Changes in PVR volume, QTcF interval, pulse rate and blood pressure were not considered to be clinically significant and there were no reports of urinary retention. Significant improvement was seen for changes in efficacy endpoints from baseline to end of treatment (EOT) in all groups (patients receiving solifenacin 2.5 or 5 mg + mirabegron 25 or 50 mg).

CONCLUSIONS

Add-on therapy with mirabegron 25 mg once daily for 16 weeks, with an optional dose increase to 50 mg at week 8, was well tolerated in patients with OAB treated with solifenacin 2.5 mg or 5 mg once daily. There were significant improvements from baseline to EOT in OAB symptoms with combination therapy with mirabegron and solifenacin. Add-on therapy with mirabegron and an antimuscarinic agent, such as solifenacin, may provide an attractive therapeutic option.

 

Editorial: Combining solifenacin and mirabegron for OAB management

Overactive bladder (OAB) is one of the most frequent LUTS in both sexes, and is associated with significant bother and impact on quality of life [1]. In many cases, no underlying cause is found and OAB is stated as being ‘idiopathic’. Until recently, the first-line management of idiopathic OAB has been based on the use of antimuscarinics, solifenacin being one of the most prescribed drugs; however, the long-term adherence to antimuscarinics has been shown to be rather low because of lack of efficacy, treatment switch or adverse events, or for mixed reasons [2].

A few years ago, β3-adrenergics were successfully introduced as an alternative to antimuscarinics for OAB management. The efficacy of β3-adrenergics has been shown and they are associated with a new safety profile that differs from that of antimuscarinics [3]. Mirabegron, the most widely used β3-adrenergic drug, has thus gained popularity in clinical practice. Given that β3-adrenergics and anticholinergics have a distinct mechanism of action, the combination of both drugs has been seen as a possible option and has been tested through a huge randomized controlled trial [4].

In the present issue of BJUI, Yamaguchi et al. [5] report the results of the MILAI study, an open-label phase IV trial assessing the effects of mirabegron as an add-on therapy in patients treated for OAB with solifenacin. They found that the addition of mirabegron to solifenacin generated only mild to moderate adverse events, and led to promising efficacy results; however, this study, which the authors call a preliminary study, raises a number of questions that remain completely unanswered.

First, even if seen as fluctuant, idiopathic OAB is considered to be a chronic disease. Long-term results must be seen as a critical issue in the field, and there is no guarantee that the short-term data presented in the MILAI study will stand the test of time in terms of efficacy and adherence.

Second, the study raises an important question about the optimum use of mirabegron in idiopathic OAB. Should it be a first-line option, a secondary option after antimuscarinics (available for treatment switch), or an add-on therapy, as it is presented in the present trial? There might be some room for each of these pathways depending on the patient history and characteristics, and the results obtained under antimuscarinics. From that point of view, the MILAI study is probably too weak to identify factors associated with failure of the combination therapy. Further studies should better detail patient inclusion criteria (because ‘failure’ of antimuscarinics is a heterogeneous concept), as well as characteristics of non-responders. In the present study, these two points are not detailed, and the study provides only a global statistically significant improvement, paving the way for additional research. A better understanding of the mechanism of action of the treatment combination would be of great value to move forward and enable better patient selection.

Finally, one of the upcoming challenges will be to integrate mirabegron as an add-on therapy in the world of male LUTS, including benign prostatic obstruction, where β3-adrenergics probably have an important role to play. As underlined by the authors, several studies are on the way, and their results (in a male population) are urgently awaited.

After having been successfully introduced in most countries in the western world, the new life of mirabegron has begun (including post-marketing studies, extensions of market authorizations, potentially new indications, combination therapy). The future will tell us whether this success story will continue.

Jean-Nicolas Cornu 
Department of Urology, Tenon Hospital, Hopitaux Universitaires Paris-EST, Assistance publique Hopitaux de Paris, Universite Pierre et Marie Curie Paris 6, Paris, France

 

References

 

Video: Safety and efficacy of mirabegron as ‘add-on’ therapy in patients with OAB treated with solifenacin

Safety and efficacy of mirabegron as add-on therapy in patients with overactive bladder treated with solifenacin: a postmarketing, open-label study in Japan (MILAI study)

Osamu Yamaguchi, Hidehiro Kakizaki*, Yukio Homma, Yasuhiko Igawa, Masayuki Takeda§, Osamu Nishizawa, Momokazu Gotoh**, Masaki Yoshida††, Osamu Yokoyama‡‡, Narihito Seki§§, Akira Okitsu¶¶, Takuya Hamada¶¶, Akiko Kobayashi¶¶ and Kentarou Kuroishi¶¶

 

Division of Bioengineering and LUTD Research, School of Engineering, Nihon University, Koriyama, *Department of Urology, Asahikawa Medical University, Asahikawa, Department of Urology, University of Tokyo Graduate School of Medicine, Tokyo, ‡Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, §Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, ¶Department of Urology, Shinshu University, Matsumoto, **Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, ††Department of Urology, National Centre for Geriatrics and Gerontology, Obu, ‡‡Department of Urology, University of Fukui Faculty of Medical Sciences, Fukui, §§Department of Urology, Kyushu
Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, and ¶¶Astellas Pharma Inc., Tokyo, Japan

 

OBJECTIVE

To examine the safety and efficacy of mirabegron as ‘add-on’ therapy to solifenacin in patients with overactive bladder (OAB).

PATIENTS AND METHODS

This multicentre, open-label, phase IV study enrolled patients aged ≥20 years with OAB, as determined by an OAB symptom score (OABSS) total of ≥3 points and an OABSS Question 3 score of ≥2 points, who were being treated with solifenacin at a stable dose of 2.5 or 5 mg once daily for at least 4 weeks. Study duration was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting eligibility criteria continued to receive solifenacin (2.5 or 5 mg once daily) and additional mirabegron (25 mg once daily) for 16 weeks. After 8 weeks of treatment, the mirabegron dose could be increased to 50 mg if the patient’s symptom improvement was not sufficient, if he/she was agreeable to the dose increase, and the investigator judged that there were no safety concerns. Safety assessments included adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram, QT corrected for heart rate using Fridericia’s correction (QTcF) interval and post-void residual (PVR) volume. Efficacy endpoints were changes from baseline in OABSS total score, OAB questionnaire short form (OAB-q SF) score (symptom bother and total health-related quality of life [HRQL] score), mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of urinary incontinence (UI) episodes/24 h, mean number of urgency UI episodes/24 h, mean volume voided/micturition, and mean number of nocturia episodes/night. Patients were instructed to complete the OABSS sheets at weeks −2, 0, 8 and 16 (or at discontinuation), OAB-q SF sheets at weeks 0, 8 and 16 (or at discontinuation) and patient voiding diaries at weeks 0, 4, 8, 12 and 16 (or at discontinuation).

RESULTS

Overall incidence of drug-related treatment-emergent AEs (TEAEs) was 23.3%. Almost all TEAEs were mild or moderate. The most common TEAE was constipation, with similar incidence in the groups receiving a dose increase to that observed in the groups maintained on the original dose. Changes in PVR volume, QTcF interval, pulse rate and blood pressure were not considered to be clinically significant and there were no reports of urinary retention. Significant improvement was seen for changes in efficacy endpoints from baseline to end of treatment (EOT) in all groups (patients receiving solifenacin 2.5 or 5 mg + mirabegron 25 or 50 mg).

CONCLUSIONS

Add-on therapy with mirabegron 25 mg once daily for 16 weeks, with an optional dose increase to 50 mg at week 8, was well tolerated in patients with OAB treated with solifenacin 2.5 mg or 5 mg once daily. There were significant improvements from baseline to EOT in OAB symptoms with combination therapy with mirabegron and solifenacin. Add-on therapy with mirabegron and an antimuscarinic agent, such as solifenacin, may provide an attractive therapeutic option.

Article of the week: The changing face of urinary continence surgery in England

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from John Withington and Arun Sahai discussing their paper.

If you only have time to read one article this week, it should be this one.

The changing face of urinary continence surgery in England: a perspective from the Hospital Episode Statistics database

John Withington, Sadaf Hirji and Arun Sahai

Guy’s and St Thomas’ NHS Hospitals’Trust, King’s College London, London, UK

OBJECTIVE

To quantify changes in surgical practice in the treatment of stress urinary incontinence (SUI), urge urinary incontinence (UUI) and post-prostatectomy stress incontinence (PPI) in England, using the Hospital Episode Statistics (HES) database.

PATIENTS AND METHODS

We used public domain information from the HES database, an administrative dataset recording all hospital admissions and procedures in England, to find evidence of change in the use of various surgical procedures for urinary incontinence from 2000 to 2012.

RESULTS

For the treatment of SUI, a general increase in the use of synthetic mid-urethral tapes, such as tension-free vaginal tape (TVTO) and transobturator tape (TOT), was observed, while there was a significant decrease in colposuspension procedures over the same period. The number of procedures to remove TVT and TOT has also increased in recent years. In the treatment of overactive bladder and UUI, there has been a significant increase in the use of botulinum toxin A and neuromodulation in recent years. This coincided with a steady decline in the recorded use of clam ileocystoplasty. A steady increase was observed in the insertion of artificial urinary sphincter (AUS) devices in men, related to PPI.

CONCLUSIONS

Mid-urethral synthetic tapes now represent the mainstream treatment of SUI in women, but tape-related complications have led to an increase in procedures to remove these devices. The uptake of botulinum toxin A and sacral neuromodulation has led to fewer clam ileocystoplasty procedures being performed. The steady increase in insertions of AUSs in men is unsurprising and reflects the widespread uptake of radical prostatectomy in recent years. There are limitations to results sourced from the HES database, with potential inaccuracy of coding; however, these data support the trends observed by experts in this field.

Editorial: Routine data expose a need for change

Withington et al. [1], in their analysis of changes in stress urinary incontinence (SUI) surgery in England, have tapped in to a rich seam of information which, as well as holding the promise of much more, also highlights a need for changed thinking about services and training. They have produced an excellent review of the use of Hospital Episode Statistics (HES) data to establish a pattern of changing surgical practice for the treatment of urinary incontinence in England. They rightly point out the great potential of using patient-specific linked data to explore other relationships between predictors and outcome. Widespread use of powerful data of this sort could, theoretically at least, help to answer research questions, as well as to plan service design and resource allocation.

The use of routine data by the NHS is a hot topic in the UK at present. An England wide database, Care.data, has been developed that plans to link anonymised routine data, automatically drawn from community care, hospital statistics, public health and social care databases. Whilst debate rages about the confidentiality issues, and conspiracy theories abound, some strident voices promote a vision of how such a databank will be used to address big health questions and to identify relationships between social conditions, healthcare and outcomes, which have not previously been possible. Similar projects exist in Wales and Scotland enjoying the acronyms of SAIL (Secure Anonymised Information Linkage) and SPIRE (The Scottish Primary Care Information Resource), and Northern Ireland also has plans in progress. These systems do differ subtly in detail but not in aspiration [2].

The authors’ findings confirm that lesser invasive procedures now dominate the treatment of SUI in women, and that the use of Botulinum toxin A for treating refractory urgency incontinence, despite the absence until recently of a license for its use, has become commonplace. Whilst demand for SUI surgery may have levelled off, following something of a surge in recent years, the demand for Botulinum toxin A treatment inevitably increases as patients become locked in to long-term retreatment programmes. With these numbers it should be possible for a hospital serving a population of, say, 250 000 to perform at least 40–50 of each procedure per annum. This is probably enough to sustain a routine service, consistent with recommendations from the National Institute for Health and Clinical Excellence (NICE), which described how surgeons should seek to maintain expertise through, amongst other things, having an adequate caseload [3].

Sacral neuromodulation (SNS), artificial sphincter, colposuspension, tape removal and augmentation cystoplasty are procedures that occupy the complex end of a range of surgical options for incontinence. These are patients who have often failed other treatments, defy easy categorisation, and are performed in relatively small numbers. SNS has not been adopted in the UK, as widely as might have been anticipated following NICE guidance in 2006, which strongly recommended its implementation – perhaps because of local difficulties in commissioning a procedure with such high capital costs. The low figures for all these procedures strengthen the argument to focus complex work into expert centres, where adequate numbers can be maintained and the next generation of specialists can be effectively trained.

Those who commission or plan service delivery, and those who design training programmes, need to take heed of this evidence. The nature of female and urodynamic urology has changed over recent years, now being characterised by 95% very routine procedures and 5% complex difficult cases. But if we centralise the 5% of complex work and leave those working in more peripheral hospitals able to offer only mid-urethral slings and Botulinum toxin A, then we have to reconsider the basis of specialist training. There is no point training a person to high levels of competence in complex procedures that they will never use in senior practice. The UK Continence Society is currently developing a set of minimum standards for service delivery and training, which will take this information into account.

The evidence presented by Withington et al. [1] is specific to England and it remains unclear how much these trends can be extrapolated to the UK nations with devolved healthcare, or indeed to other countries. However, Withington et al. [1] must be congratulated for highlighting both the power of routine data in clinical research, and specifically for identifying the dramatic changes in surgical practice of incontinence, which require an adaptive response from both the NHS and our specialist organisations.

Malcolm Lucas
Department of Urology, Morriston Hospital, Swansea, UK

References

  1. Withington J, Hirji S, Sahai A. The changing face of urinary continence surgery in England: a perspective from the hospital episode statistics database. BJU Int 2014; 114: 268–277
  2. National Institute for Health and Clinical Excellence. September 2013. Urinary incontinence: the management of urinary incontinence in women. Clinical guidelines CG171. Available at: https://guidance.nice.org.uk/CG171. Accessed April 2014

 

Video: Urinary continence surgery in England

The changing face of urinary continence surgery in England: a perspective from the Hospital Episode Statistics database

John Withington, Sadaf Hirji and Arun Sahai

Guy’s and St Thomas’ NHS Hospitals’Trust, King’s College London, London, UK

OBJECTIVE

To quantify changes in surgical practice in the treatment of stress urinary incontinence (SUI), urge urinary incontinence (UUI) and post-prostatectomy stress incontinence (PPI) in England, using the Hospital Episode Statistics (HES) database.

PATIENTS AND METHODS

We used public domain information from the HES database, an administrative dataset recording all hospital admissions and procedures in England, to find evidence of change in the use of various surgical procedures for urinary incontinence from 2000 to 2012.

RESULTS

For the treatment of SUI, a general increase in the use of synthetic mid-urethral tapes, such as tension-free vaginal tape (TVTO) and transobturator tape (TOT), was observed, while there was a significant decrease in colposuspension procedures over the same period. The number of procedures to remove TVT and TOT has also increased in recent years. In the treatment of overactive bladder and UUI, there has been a significant increase in the use of botulinum toxin A and neuromodulation in recent years. This coincided with a steady decline in the recorded use of clam ileocystoplasty. A steady increase was observed in the insertion of artificial urinary sphincter (AUS) devices in men, related to PPI.

CONCLUSIONS

Mid-urethral synthetic tapes now represent the mainstream treatment of SUI in women, but tape-related complications have led to an increase in procedures to remove these devices. The uptake of botulinum toxin A and sacral neuromodulation has led to fewer clam ileocystoplasty procedures being performed. The steady increase in insertions of AUSs in men is unsurprising and reflects the widespread uptake of radical prostatectomy in recent years. There are limitations to results sourced from the HES database, with potential inaccuracy of coding; however, these data support the trends observed by experts in this field.

Article of the week: Mirabegron is an effective treatment for OAB

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Phase III, randomised, double-blind, placebo-controlled study of the β3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder

Osamu Yamaguchi, Eiji Marui*, Hidehiro Kakizaki, Yukio Homma, Yasuhiko Igawa§, Masayuki Takeda, Osamu Nishizawa**, Momokazu Gotoh††, Masaki Yoshida‡‡, Osamu Yokoyama§§, Narihito Seki¶¶, Yasushi Ikeda*** and Sumito Ohkawa***

Division of Bioengineering and LUTD Research, School of Engineering, Nihon University, Koriyama, *Department of Human Arts Sciences, University and Graduate School of Human Arts Sciences, Saitama, Department of Urology, Asahikawa Medical University, Asahikawa, Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, §Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Department of Urology, University of Yamanashi, Yamanashi, **Department of Urology, Shinshu University, Matsumoto, ††Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, ‡‡Department of Urology, National Center for Geriatrics and Gerontology, Obu, §§Department of Urology, University of Fukui Faculty of Medical Sciences, Fukui, ¶¶Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, and ***Astellas Pharma Inc., Tokyo, Japan

Registered at clinicaltrials.gov (NCT00966004)

OBJECTIVE

• To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).

PATIENTS AND METHODS

• This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks.

• The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King’s Health Questionnaire.

• Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram.

RESULTS

• A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups.

• At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (–1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (–1.85 [2.555] vs –1.37 [3.191]; P = 0.025), incontinence episodes/24 h (–1.12 [1.475] vs –0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (–1.01 [1.338] vs –0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001).

• The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.

CONCLUSIONS

• Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

 

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