VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY
combinations of mirabegron with 10 mg solifenacin are actually lower than the dry mouth rate reported with solifenacin alone. Hypertension rates varied, with 11.7% and 14.1% of patients taking 25 mg and 50 mg mirabegron alone, respectively, being recorded as having hypertension as opposed to 8.6% of those taking placebo. Interestingly the rates with 5 or 10 mg solifenacin were less than those recorded in the 50 mg mirabegron alone group. Studies of larger numbers of patients and fewer groups will obviously be necessary to confirm some of the suggestions made in this article. However, it certainly appears that the 2 agents can be combined with a minimum, if any, increase in adverse event profile and with an improvement in at least some efficacy parameters. It would seem that the goal would be to achieve the efficacy of high dose antimuscarinic therapy alone by combining a b-agonist with low dose antimuscarinic therapy, resulting in a lower incidence of adverse events than would be seen with higher dose antimuscarinic therapydan obvious advantage for patients, which might improve compliance with oral therapy for OAB. Alan J. Wein, MD, PhD (hon)
Re: Urodynamic Studies for Management of Urinary Incontinence in Children and Adults C. M. Glazener and M. C. Lapitan Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, Scotland Cochrane Database Syst Rev 2012; 1: CD003195.
Abstract available at http://jurology.com/ Editorial Comment: Here we go again. This is a noble effort by the Cochrane Collaboration to discover if treatment according to a urodynamic based diagnosis, compared to treatment based on history and examination, leads to more effective clinical care and better clinical outcomes. The authors concluded, “When women with incontinence are assessed using urodynamics in addition to clinical methods, they may be more likely to receive treatment, or to have their management plan changed. However, there was not enough evidence to show whether these differences in management resulted in differences in health outcomes, such as incontinence, quality of life or economic outcomes, compared to women who did not have urodynamic tests.” It was noted that insufficient data were available to evaluate the use of urodynamics in men, children or those with neurological diseases. Further randomized trials were recommended, and the comment was made that such trials would need about 400 people in each arm to have 80% power to detect a 10% difference in incontinence rates at a significance level of 5%. Such studies should include subjective and objective assessment of cure and improvement, adverse events, effect on clinical decision making, patient opinion and satisfaction, quality of life and economic outcome measures. Alan J. Wein, MD, PhD (hon)
Re: Biomarkers in Lower Urinary Tract Symptoms/Overactive Bladder: A Critical Overview T. Antunes-Lopes, C. D. Cruz, F. Cruz and K. D. Sievert Translational NeuroUrology, Institute for Molecular and Cell Biology, and Department of Experimental Biology, Faculty of Medicine of Porto, University of Porto and Department of Urology, Hospital de S. Joa˜o, Porto, Portugal, and Department of Urology, Eberhard-Karls University, Tubingen, Germany Curr Opin Urol 2014; 24: 352e357.
Abstract available at http://jurology.com/ Editorial Comment: To quote the authors, “Biomarkers are objectively measurable characteristics that may be used to define the presence of a condition (diagnostic biomarker), its severity and progression (prognostic biomarker) or the response to a particular treatment (predictive biomarker)”!
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VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY
It would seem that it is also true that to be labeled a biomarker, a quantifiable product must perform in one of the 3 scenarios and do it reproducibly. These authors, anchored by 2 stalwarts in the field, review several molecules in the urine and/or blood and other physiological parameters, touted by some as biomarkers for overactive bladder. My interpretation of their conclusion is that none of the biomarkers satisfies the criteria. With respect to overactive bladder, a biomarker should be able to guide a particular form of treatment and improve outcome. The value of the current group of proposed “biomarkers” is that they may suggest and help us to better understand some of the pathophysiological mechanisms underlying the signs and symptoms associated with this symptom syndrome. Alan J. Wein, MD, PhD (hon)
Re: Pre-Operative Urodynamics in Women with Stress Urinary Incontinence Increases Physician Confidence, but Does Not Improve Outcomes P. Zimmern, H. Litman, C. Nager, L. Sirls, S. R. Kraus, K. Kenton, T. Wilson, G. Sutkin, N. Siddiqui, S. Vasavada and P. Norton; Urinary Incontinence Treatment Network UT Southwestern Medical Center, Dallas, Texas Neurourol Urodyn 2014; 33: 302e306.
Abstract available at http://jurology.com/ Editorial Comment: This is an interesting secondary analysis of certain data in the ValUE (Value of Urodynamic Evaluation) trial,1 the conclusion of which is that in a group of women with demonstrable stress urinary incontinence (SUI) on office evaluation, predominant symptoms of SUI, no history of surgery for incontinence and a normal post-void residual the office evaluation alone was not inferior to evaluation with urodynamic studies and did not compromise surgery success. However, urodynamics did shift physician diagnosis from not confident to confident for the entities of intrinsic sphincter deficiency and overactive bladder wet. Lesser but statistically significant scores for indicating increased confidence were also associated with the diagnosis of stress urinary incontinence, overactive bladder dry and voiding phase dysfunction, although less strongly. Confidence scores of the clinical diagnosis were rated on a scale of 1 (not very confident) to 5 (extremely confident). What the small numerical changes in “confident” mean in terms of clinical significance is unknown. The implication of this seems to be that the concept of “degree of certainty,” which I first heard from Dr. Jerry Blaivas, is an important factor in determining whether an individual performs urodynamics preoperatively in patients with clear SUI and in more complicated patients with incontinence. Some individuals require more certainty than others, and there does not seem to be a valid ethical reason or, at this point, a financial reason not to proceed with urodynamics under these circumstances. Those surgeons who are supremely confident and who have never had a bad result, or think they have not, will need less confirmation, but the decision will be an individual one and will vary with the past and present history of the patient and her individual characteristics, the confusability of the signs and symptoms, and the local medicolegal climate regarding failure and postprocedural complications. In the future if and when 1 fee is paid yearly to care for a specific problem, it will be easy to tell those individuals who really feel that urodynamics are worthwhile and in which scenarios. Alan J. Wein, MD, PhD (hon) 1. Nager CW, Brubaker L, Litman HJ et al: A randomized trial of urodynamic testing before stress-incontinence surgery. N Engl J Med 2012; 366: 1987.
combinations of mirabegron with 10 mg solifenacin are actually lower than the dry mouth rate reported with solifenacin alone. Hypertension rates varied, with 11.7% and 14.1% of patients taking 25 mg and 50 mg mirabegron alone, respectively, being recorded as having hypertension as opposed to 8.6% of those taking placebo. Interestingly the rates with 5 or 10 mg solifenacin were less than those recorded in the 50 mg mirabegron alone group. Studies of larger numbers of patients and fewer groups will obviously be necessary to confirm some of the suggestions made in this article. However, it certainly appears that the 2 agents can be combined with a minimum, if any, increase in adverse event profile and with an improvement in at least some efficacy parameters. It would seem that the goal would be to achieve the efficacy of high dose antimuscarinic therapy alone by combining a b-agonist with low dose antimuscarinic therapy, resulting in a lower incidence of adverse events than would be seen with higher dose antimuscarinic therapydan obvious advantage for patients, which might improve compliance with oral therapy for OAB. Alan J. Wein, MD, PhD (hon)
Re: Urodynamic Studies for Management of Urinary Incontinence in Children and Adults C. M. Glazener and M. C. Lapitan Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, Scotland Cochrane Database Syst Rev 2012; 1: CD003195.
Abstract available at http://jurology.com/ Editorial Comment: Here we go again. This is a noble effort by the Cochrane Collaboration to discover if treatment according to a urodynamic based diagnosis, compared to treatment based on history and examination, leads to more effective clinical care and better clinical outcomes. The authors concluded, “When women with incontinence are assessed using urodynamics in addition to clinical methods, they may be more likely to receive treatment, or to have their management plan changed. However, there was not enough evidence to show whether these differences in management resulted in differences in health outcomes, such as incontinence, quality of life or economic outcomes, compared to women who did not have urodynamic tests.” It was noted that insufficient data were available to evaluate the use of urodynamics in men, children or those with neurological diseases. Further randomized trials were recommended, and the comment was made that such trials would need about 400 people in each arm to have 80% power to detect a 10% difference in incontinence rates at a significance level of 5%. Such studies should include subjective and objective assessment of cure and improvement, adverse events, effect on clinical decision making, patient opinion and satisfaction, quality of life and economic outcome measures. Alan J. Wein, MD, PhD (hon)
Re: Biomarkers in Lower Urinary Tract Symptoms/Overactive Bladder: A Critical Overview T. Antunes-Lopes, C. D. Cruz, F. Cruz and K. D. Sievert Translational NeuroUrology, Institute for Molecular and Cell Biology, and Department of Experimental Biology, Faculty of Medicine of Porto, University of Porto and Department of Urology, Hospital de S. Joa˜o, Porto, Portugal, and Department of Urology, Eberhard-Karls University, Tubingen, Germany Curr Opin Urol 2014; 24: 352e357.
Abstract available at http://jurology.com/ Editorial Comment: To quote the authors, “Biomarkers are objectively measurable characteristics that may be used to define the presence of a condition (diagnostic biomarker), its severity and progression (prognostic biomarker) or the response to a particular treatment (predictive biomarker)”!
219
220
VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY
It would seem that it is also true that to be labeled a biomarker, a quantifiable product must perform in one of the 3 scenarios and do it reproducibly. These authors, anchored by 2 stalwarts in the field, review several molecules in the urine and/or blood and other physiological parameters, touted by some as biomarkers for overactive bladder. My interpretation of their conclusion is that none of the biomarkers satisfies the criteria. With respect to overactive bladder, a biomarker should be able to guide a particular form of treatment and improve outcome. The value of the current group of proposed “biomarkers” is that they may suggest and help us to better understand some of the pathophysiological mechanisms underlying the signs and symptoms associated with this symptom syndrome. Alan J. Wein, MD, PhD (hon)
Re: Pre-Operative Urodynamics in Women with Stress Urinary Incontinence Increases Physician Confidence, but Does Not Improve Outcomes P. Zimmern, H. Litman, C. Nager, L. Sirls, S. R. Kraus, K. Kenton, T. Wilson, G. Sutkin, N. Siddiqui, S. Vasavada and P. Norton; Urinary Incontinence Treatment Network UT Southwestern Medical Center, Dallas, Texas Neurourol Urodyn 2014; 33: 302e306.
Abstract available at http://jurology.com/ Editorial Comment: This is an interesting secondary analysis of certain data in the ValUE (Value of Urodynamic Evaluation) trial,1 the conclusion of which is that in a group of women with demonstrable stress urinary incontinence (SUI) on office evaluation, predominant symptoms of SUI, no history of surgery for incontinence and a normal post-void residual the office evaluation alone was not inferior to evaluation with urodynamic studies and did not compromise surgery success. However, urodynamics did shift physician diagnosis from not confident to confident for the entities of intrinsic sphincter deficiency and overactive bladder wet. Lesser but statistically significant scores for indicating increased confidence were also associated with the diagnosis of stress urinary incontinence, overactive bladder dry and voiding phase dysfunction, although less strongly. Confidence scores of the clinical diagnosis were rated on a scale of 1 (not very confident) to 5 (extremely confident). What the small numerical changes in “confident” mean in terms of clinical significance is unknown. The implication of this seems to be that the concept of “degree of certainty,” which I first heard from Dr. Jerry Blaivas, is an important factor in determining whether an individual performs urodynamics preoperatively in patients with clear SUI and in more complicated patients with incontinence. Some individuals require more certainty than others, and there does not seem to be a valid ethical reason or, at this point, a financial reason not to proceed with urodynamics under these circumstances. Those surgeons who are supremely confident and who have never had a bad result, or think they have not, will need less confirmation, but the decision will be an individual one and will vary with the past and present history of the patient and her individual characteristics, the confusability of the signs and symptoms, and the local medicolegal climate regarding failure and postprocedural complications. In the future if and when 1 fee is paid yearly to care for a specific problem, it will be easy to tell those individuals who really feel that urodynamics are worthwhile and in which scenarios. Alan J. Wein, MD, PhD (hon) 1. Nager CW, Brubaker L, Litman HJ et al: A randomized trial of urodynamic testing before stress-incontinence surgery. N Engl J Med 2012; 366: 1987.
