Supplements

A β3 Agonist, Mirabegron for the Treatment of Overactive Bladder - Supplement

As part of an added supplement, we at UroToday International Journal present the following added information regarding the article "Androgen Insensitivity Syndrome: Case Report With Review of the Literature." Reponses are provided by corresponding author Dr. Fotios Dimitriadis.

Q. What does your contribution add to the present knowledge? What's essential to understand about in terms of clinical practice?

A. Overactive bladder syndrome (OAB) has a negative impact on quality of life and social functioning. OAB affects 16.6% of the European population aged over 40 years, and it has a prevalence of 17% in the United States and 12% in Japan. Both men and women are equally affected by OAB, and the incidence rate increases with age. OAB syndrome has been caused by detrusor overactivity (DO), which is a urodynamic diagnosis based on the occurrence of involuntary detrusor contraction during cystometry. Currently, antimuscarinic drugs represent the first-line treatment for OAB. However, adverse effects such as dry mouth, pruritus, blurred vision, and constipation, among many others. The limitations of efficacy hinder their use.

Two muscarinic subtypes, M2 and M3, are present in the bladder. Although M2 is most abundant in detrusor cells (70 to 80 %), the M3 subtype is the major receptor mediating stimulation of detrusor contractions. In fact, beta-adrenoceptors in the bladder body of experimental animals and humans mediate relaxation to noradrenalin via β3-adrenoceptors, whereas in the same time noradrenaline stimulates contraction of the urethral and bladder neck smooth muscle via α1-adrenoceptors. Mirabegron, a novel selective b3-adorenoceptor agonist, is in development for the treatment of OAB. The current contribution underlines the potential pharmaceutical benefit of mirabegron in the treatment of OAB.

Q. Will this replace existing techniques or therapies now or in the near future? Will it impact the standard of care?

A. Phase II placebo-controlled clinical trials showed that mirabegron significantly improved the majority of variables when administered to patients with OAB. Mirabegron has been well tolerated with significant efficacy in reducing the number of incontinence episodes and mean micturition frequency. Commonly reported adverse effects were gastrointestinal adverse events and headache. This could impact the standard of care since the lower propensity of mirabegron to cause dry mouth and constipation may make it an attractive drug candidate for the treatment of OAB symptoms. Thus, the pharmaceutical armament of the treatment of OAB could be enhanced with a novel category of drugs, namely the b3-adorenoceptor agonists that could corroborate to the present standard pharmaceutical treatment of OAB or replace it when its efficacy is not the expected one.

Q. What are the three things that this technology does or enables that I should know to impact clinical practice? What's your take-home message for me as your colleague?

A. Mirabegron decreases the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats, and it decreases the frequency of non-micturition bladder contraction without the increase in residual urine in a rat bladder outlet obstruction model. This data indicate that mirabegron has good selectivity and agonist potency for β3-adrenoceptors and has different effects on bladder activity during filling from antimuscarinics.

Mirabegron enhances urine storage function at low-pressure bladder filling, without affecting the voiding contraction in the anesthetized rat bladder, suggesting that mirabegron significantly increases bladder capacity and does not directly inhibit voiding bladder contractions.

In phase II clinical trials (BLOSSOM and DRAGON studies), treatment with mirabegron was statistically and significantly superior to placebos with respect to the secondary efficacy variables mean volume per micturition, mean number of micturitions, mean number of incontinence episodes, nocturia episodes, urge incontinence episodes, and mean urgency episodes per 24 hours. Thus, these studies demonstrated that mirabegron significantly improved the majority of variables compared with placebos when administered to patients with OAB. Regarding the safety of mirabegron treatment, it causes less adverse events (mainly headache, urinary tract infection, blurred vision, and vascular disorders) compared to antimuscarinic drugs.

Mirabegron will be the first β3-adrenoceptor agonist to be released in patients with OAB. It has been demonstrated to be well tolerated and to have dose-dependent reduction of micturition frequency, episodes of urgency, and nocturia in OAB patients. The lower tendency of mirabegron to cause dry mouth and constipation may make it an appealing drug candidate for the treatment of OAB symptoms in elderly patients. The long-term safety data, including the risk of drug-related cardiac and vascular events caused by mirabegron in wider studies, is still awaited.

Comparison of the Impact of Degarelix and Leuprolide on the Health-Related Quality of Life of Patients with Prostate Cancer: Results of a 12-Month Phase III Clinical Trial - Supplement

As part of an added supplement, we at UroToday International Journal present the following added information regarding the article "Androgen Insensitivity Syndrome: Case Report With Review of the Literature." Reponses are provided by corresponding author Dr. Bo-Eric Persson.

Q. What does your contribution add to the present knowledge? What's essential to understand about in terms of clinical practice?

A. This paper reports the first study comparing the effect of a GnRH agonist (leuprolide) and a GnRH antagonist (degarelix) on health-related quality of life (HRQoL) in patients with prostate cancer. In clinical practice, this is an important outcome for patients, as the symptoms of prostate cancer and the side effects of long-term ADT can have an impact on HRQoL. The results of this 1-year study show that GnRH agonists and antagonists differ in terms of their impact on HRQoL. The deterioration of mental HRQoL was significantly lower in degarelix-treated patients, and treatment with leuprolide had a seemingly more favorable impact on bodily pain and insomnia (although baseline insomnia levels were significantly lower in the degarelix group). In patients with metastatic disease, several HRQoL domains were significantly improved with degarelix versus leuprolide, including global health status.

Q. Will this replace existing techniques or therapies now or in the near future? Will it impact the standard of care?

A. As well as the significant improvements in some aspect of HRQoL versus leuprolide, degarelix was also associated with other clinical benefits in the same study. Unlike leuprolide, degarelix was not associated with testosterone surges or microsurges. It reduced testosterone and PSA levels significantly faster than leuprolide, and it significantly improved PSA progression-free survival compared with the agonist. Taken together, these data suggest that GnRH antagonists may replace GnRH agonists as first-line agents for patients with prostate cancer.

Q. What are the three things that this technology does or enables that I should know to impact clinical practice? What's your take-home message for me as your colleague?

A. Degarelix is associated with a significantly lower decline of mental HRQoL compared with leuprolide in patients with prostate cancer; in addition, in those patients with metastatic disease, it offers a significant improvement in overall HRQoL versus leuprolide. Combined with its additional effects on PSA progression-free survival, the take-home message is that degarelix is an effective, first-line agent for prostate cancer, with a number of clinical benefits over GnRH agonists.

Clean Intermittent Catheterization Following Urethral Stricture Surgery Using a Low Friction Catheter Versus Conventional Plastic Catheter: A Prospective, Randomized Trial - Supplement

As part of an added supplement, we at UroToday International Journal present the following added information regarding the article "Androgen Insensitivity Syndrome: Case Report With Review of the Literature." Reponses are provided by corresponding author Dr. Sallami Satáa.

Q. What does your contribution add to the present knowledge?

A. Clean intermittent catheterization is an efficient way of preventing recurrence after endoscopic urethrotomy. The question is: what type of catheter should be used? Through this prospective and randomized study, we concluded that the hydrophilic catheter type “Lofric” significantly increased the degree of comfort and satisfaction and decreased the feeling of pain when the catheter was removed or inserted compared with a conventional and classic Nelaton polyvinyl chloride catheter. Moreover, complications and recurrent rates were comparable between the 2 types.

Q. What's essential to understand about in terms of clinical practice? 

A. We recommend low-friction hydrophilic catheters to prevent urethral stricture recurrences with better quality of life.

Q. Will this replace existing techniques or therapies now or in the near future?

A. We advise urologists and nurses to avoid the use of conventional Nelaton polyvinyl chloride catheters in clean, intermittent catheterization.

Q. Will it impact the standard of care?

A. The use of low-friction hydrophilic catheters should be considered the standard in clean, intermittent catheterization.

Q. What are the three things that this technology does or enables that I should know to impact clinical practice?

A. The use of low-friction hydrophilic catheters is significantly more comfortable, more satisfactory, less painful (when the catheter was removed or inserted), compared with a conventional and classic Nelaton polyvinyl chloride catheter.

Q. What's your take-home message for me as your colleague? 

A. When clean, intermittent catheterization is considered, low-friction hydrophilic catheters must be used.

 

Androgen Insensitivity Syndrome: Case Report With Review of the Literature - Supplement

As part of an added supplement, we at UroToday International Journal present the following added information regarding the article "Androgen Insensitivity Syndrome: Case Report With Review of the Literature." Reponses are provided by corresponding author Dr. Gajanan Bhat. 

Q. What does your contribution add to the present knowledge? What's essential to understand about in terms of clinical practice? 

A. The most important thing in a clinical practice is the proper clinical examination. In our case, the patient was being treated for primary amenorrhea by various clinicians purely based on some lab reports bypassing the clinical examination. Hence the diagnosis was delayed. Here I would like to emphasize the importance of clinical examination.

Q. Will this replace existing techniques or therapies now or in the near future? Will it impact the standard of care?

A. The case report is not aimed at changing the present standard of care at all. Hence the question doesn't arise.

Q. What are the three things that this technology does or enables that I should know to impact clinical practice? What's your take-home message for me as your colleague? 

A. My take-home message is very clear: No investigation can substitute proper clinical examination. Never attempt a shortcut in clinical practice.

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