Gopal H. Badlani, MD

It has been quite a while since a new drug was introduced to address quality-of-life issues in patients with overactive bladder (OAB). David Staskin, MD, has been the champion of many of the prior agents launched in the market and leads the presentation of the long-term safety profile of the β-3 adrenoceptor agonist vibegron detailed in a recent 

There have been a number of articles published on this drug, starting with Masaki Yoshida, MD, et al introducing the “novel” agent,

 to the long-term efficacy data in Japanese patients,

 to the post hoc analysis of the phase 2 data to evaluate its effect on nocturia.

 The EMPOWUR (NCT03492281) study mentioned in this month’s issue was published with 12 weeks of trial data.

There are several key questions. One, is this drug effective? The clear answer is yes. When compared with placebo in a large data set, it was marginally better than its comparator in efficacy, adverse effect of dry mouth, and discontinuation rate. The most remarkable data in this long-term report show its continued use in over 85% in this funded and monitored study, as it is much lower in real-world use.

The next question is, does this bring something new to the table compared with the other β-3 adrenoreceptor agonist mirabegron (Myrbetriq)? Vibegron has no interaction with CYP enzymes compared with mirabegron. When compared with tolterodine, the drug was slightly better in efficacy and dry mouth rate. The effect on heart rate, although a caution in the labeling for this class of agents, has not been a frequent clinical issue.

Will this change the paradigm of treatment? This is unlikely, as currently in the US, at least 2 antimuscarinics have to be tried before a β-3 agonist can be prescribed. The cost of the drug, when available, may make a difference, as right now there is only a single drug in this class of agents.

In this study, as well as with all other drugs for OAB previously studied, the placebo arm has a remarkable influence on voiding behavior, emphasizing the role of bladder diaries and behavioral influence of attention to the voiding parameters. Thus, apps to record voiding and/or prompt patients may be the biggest advance we make in this field.

 editorial consultant, is professor and vice chair of urology at Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.

1. Yoshida M, Takeda M, Gotoh M, et al. Vibegron, a novel potent and selective β 3-adrenoreceptor agonist, for the treatment of patients with overactive bladder: a randomized, double-blind, placebo-controlled phase 3 study. 

. 2018;73(5):783-790. doi:10.1016/j.eururo.2017.12.022

2. Yoshida M, Kakizaki H, Takahashi S, et al. Long-term safety and efficacy of the novel β 3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study. 

. 2018;25(7):668-675. doi:10.1111/iju.13596

3. Yoshida M, Takeda M, Gotoh M, et al. Efficacy of novel β 3 -adrenoreceptor agonist vibegron on nocturia in patients with overactive bladder: A post-hoc analysis of a randomized, double-blind, placebo-controlled phase 3 study. 

. 2019;26(3):369-375. doi:10.1111/iju.13877

4. Staskin D, Frankel J, Varano S, et al. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: 

. 2020;204(2):316-324. doi:10.1097/JU.0000000000000807

Articles

Gopal H. Badlani, MD, discusses the recently presented long-term safety profile of the β-3 adrenoceptor agonist vibegron.

Overactive bladder: Another agent attempts a step forward

 editorial consultant, is professor of urology, Wake Forest Baptist Medical Center, Winston-Salem, NC.

Many institutions and large practice units create manuals or standard operating procedure for response during a variety of crisis situations. We take online training for simulation of chemical spill, radiation, and infection, but there is no manual to follow in this burgeoning COVID-19 crisis. The rules of the “game” have changed day by day, sometimes within hours. The email traffic with a variety of instructions is so heavy that it is difficult to keep your thoughts steady.

There is one aspect of caring for yourself and another directing traffic for those under your leadership. The situation is different whether you’re in an academic center, federal site, or large private practice group setting, as opposed to a smaller practice where all decisions are made by you.

In an academic institution, a command structure is developing the policy, whereas in the federal (VA) system, it is being directed nationally. Since I work at both places and lead at the VA in the same region, the experience is somewhat similar but not exactly the same.

 We all prepare how to deal with a large number of cases coming through our trauma unit or a natural disaster, and the ER being overwhelmed. No one prepared for how “not to do” surgery. The decision had to be taken away from individual surgeons after the initial request to cut down elective cases. It took time to learn, the goal was to preserve or save personal protective equipment, and the OR could be a conduit for spreading the virus through asymptomatic carriers.

The traffic and personnel involved in doing a single case can be substantial. Weighing patient harm by waiting versus immediate surgery, as wait times are unknown, created a heated debate for some. At the VA it was more a leadership decision, as the unit chief has the ability to make that decision.

 That most visits can be managed with telemedicine is the new reward from this crisis. As we get more accustomed to the process, I can see the patients and physicians both adapting to this new norm. The revenue/reimbursement is not being questioned during the crisis, but time and effort will need to be addressed if this becomes the new norm. The role of ancillary staff has been critical in the process and not recognized easily. Shifting the appointment to a televisit, initiating the visit, updating all the requirements of a visit and setting up follow-up after an electronic visit are all key tasks that are the pillars to the success of this visit.

 In caring for patients, we often forget the safety of staff and self. Thus, reducing traffic coming into the clinic has become as important as traffic entering the hospital. Depending on the location (near or in a senior center) or the type of patient population could require complete shutdown of the location and moving the clinic to a temporary location where multiple surgical units could be served by a rotating the ancillary staff and providers, so as to manage staff illness if it were to happen.

Staff and physicians over 65 should be isolated as much as possible. Although residents and fellows are young, they need the same concern and protection, once again by creating rotating teams and keeping the rest available at home.

 Although email notifications are generic and multifold, creating a text group for leadership for quick notification became important as remote access in the VA system can be patchy. Scheduled calls each week at a set time for weekly updates and concerns is the second approach. Use of Zoom or another video-based platform for faculty meeting/education lectures at the university setting has been very successful.

Programs across the country are seeking teaching rounds that can be shared. A live presentation across the world was done successfully in a scheduled meeting in India at the cusp of travel restriction. It will be the wave of the future.

In the end, leadership is all about elevating and protecting those around you. Their success and well-being is a measure of achievement. Perspective is a view from afar and the wider angle is needed to reassess oneself; otherwise we remain zoomed in on the narrow focus of today, which passes before you know it.

"We take online training for simulation of chemical spill, radiation, and infection, but there is no manual to follow in this burgeoning COVID-19 crisis," writes Gopal H. Badlani, MD.

Leadership tips for your urology unit during the COVID crisis

 Editorial Consultant, is professor of urology, Wake Forest Baptist Medical Center, Winston-Salem, NC.

The new AUA guidelines on surgical management of BPH reflect changes primarily in new minimally invasive approaches to the management of the enlarged prostate. In considering what is new, one should think about indications for a given procedure, the individual patient’s goals, surgeon’s bias and learning curve, availability, and affordability of the technology.

Patient bother with male lower urinary tract symptoms such as slow flow, hesitancy, and sense of incomplete emptying and retention are most common. However, men with overactive bladder, nocturia, post-void dribble, and “older male with prostate” as indications are less responsive to surgical therapy.

Patient factors such as medical risk for anesthesia, use of antiplatelets/anticoagulants, gland size, and gland anatomy play a role in selecting the type of procedure, as do patient expectations, such as desire to maintain antegrade ejaculation at the expense of long-term success, catheter duration, and time from treatment to improvement (transient dysuria/frequency/incontinence/recurrent retention).

Surgeon variables are training and familiarity with a technique, number of patients treated in a month to enhance the learning curve, and desire to be on the forefront. Availability of a team to deal with transient issues post treatment and ability to manage secondary bleeding as well as re-treatment are other variables.   

Availability of new technology is also dependent on clinical setting, such as a trial at a center of excellence or hospital partner/large group willing to support it. The surgeon bias is difficult to assess.

The individual technologies are discussed in the “Hands On” article in this issue (page 1), which mentions enucleation as a technique that needs to be considered when the gland is larger. It appears that many of the ablative technologies such as lasers and the bipolar device can achieve enucleation, albeit some require use of a morcellation device. Added indications for minimally invasive surgical therapies such as large glands and median lobe require an experienced practitioner.

Cost is a hidden factor in the United States and other countries where health insurance covers approved technology but is a real factor where cost is out of pocket. Hospitalization is expensive in the U.S. but a less important factor in other countries. Capital and disposable cost is a factor in low- and middle-income countries where traditional monopolar TURP still rules despite the safety of saline-based ablation devices.

After participating in a number of trials from balloon dilation to water ablation and publishing on them, my conclusion is to do what you know best, learn a new technology from an expert (preferably hands on), and consider participating in a clinical trial (based on patient volume and institutional support). Shorten your learning curve by accumulating cases and doing them in a short time, stay with technology to overcome initial hurdles, and be honest about your outcomes (not what is published in the literature by the expert).

“The expectations of life depend upon diligence; the mechanic that would perfect his work must first sharpen his tools.”-Confucius

"My conclusion is to do what you know best, learn a new technology from an expert, and consider participating in a clinical trial,” writes Gopal H. Badlani, MD.

Alternatives to TURP: Consider these variables

 is a fellow in female pelvic medicine and reconstructive surgery, and 

is vice chair and professor of urology, Wake Forest Baptist Health, Winston-Salem, NC.

From the time Lapides popularized the use of self-intermittent or clean intermittent catheterization 

 it has improved the quality of life of patients with neurogenic bladder due to a variety of conditions. Reuse of catheters for intermittent catheterization was the norm and still is common practice; it is in fact, the standard of care in some health care systems. In many developing countries, patients have limited access to medical supplies necessitating reusable catheters. It was not too long ago in the United States that insurances covered only four catheters per month, but in 2008 Medicare/Medicaid allowed for patients to receive up to 200 catheters per month.

The authors of a study by Madero-Morales et al provide answers to what many urologic providers and patients need (see article 

What was lacking in the literature was a head-to-head comparison of intermittent catheterization with single-use versus reusable catheters (cleansed with 0.5% benzalkonium chloride) with a primary endpoint of urinary tract infections (defined as having a positive urine culture and symptoms). In this study of 75 patients with an average age of 12.7 years, they found that the rate of urinary tract infection did not differ between the groups: 35.2% with single-use catheters vs. 36.8% with reusable catheters (OR: 0.877, 95% CI: 0.42, 2.76). Rates of asymptomatic bacteriuria also did not differ between the two groups.

Interestingly, being unable to walk and having vesicoureteral reflux grade 2 or higher were identified as risk factors for having a symptomatic UTI in both groups. In the reusable catheter group, male gender and presence of a bladder diverticulum were risk factors for developing a UTI.

One of the arguments against reusable catheters is the variability among cleansing methods and patient adherence to a sanitation regimen. In this study, the catheters were washed with plain soap and water, stored in a container with benzalkonium chloride, and used for 1 week. Although this regimen is simple enough, having protocols designed for patients who spend part of their day outside the home is needed.

A topic of interest and debate is the environmental impact of the waste that humans generate. It is estimated that the generated waste of single-use intermittent catheterization is between 26,500 and 235,400 pounds per day, with the vast majority of urinary catheters made from non-biodegradable materials 

 We should all be considering alternatives to help reduce waste going to our landfills. Perhaps with policies and protocols for reusable urinary catheters, we can help lower waste while maintaining patient safety. Reduce, reuse, and recycle!

Single-use catheters were introduced as a means to decrease the risk of developing UTIs, and many patients in the Western world cannot fathom the idea of a reusable catheter, especially when multiple health care providers are telling them this. However, the author of this study essentially calls this “fake news.” Patient perception is an important aspect of developing an effective treatment plan, and we should be able to arm patients with accurate data to help them make an informed decision.

If reusable catheters are going to be presented as an option, future research should be focused on determining the number of times a catheter may be reused, developing a protocol for sanitation, identifying additional risk factors that may contribute to UTIs, and calculating potential cost savings and affordability. With further insight into these factors, reusable catheters can again become a standard of care.

Also, while we are on the subject, use of antibiotics should be limited to symptomatic UTIs and not bacteriuria in patients performing self-intermittent or clean intermittent catheterization.

Send your comments to Drs. Smith and Dr. Badlani c/o 

"Patient perception is an important aspect of developing an effective treatment plan, and we should be able to arm patients with accurate data to help them make an informed decision," write Whitney Renee Smith, MD, and Gopal H. Badlani, MD.

Gopal H. Badlani, MD

Articles

Overactive bladder: Another agent attempts a step forward

Leadership tips for your urology unit during the COVID crisis

Alternatives to TURP: Consider these variables

Are reusable catheters safe? Study provides an answer