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      Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility

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          Abstract

          We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure-related adverse events (AE) at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 ± 4.8 months in DHIC patients and 7.2 ± 3.3 months in OAB patients ( p = 0.03). We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC.

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          Most cited references20

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          Diabetic bladder dysfunction: current translational knowledge.

          Diabetes mellitus, a metabolic disorder caused by an absolute or relative deficiency of insulin, is a debilitating and costly disease with multiple serious complications. Lower urinary tract complications are among the most common complications of diabetes mellitus. The most common, bothersome lower urinary tract complication of diabetes mellitus is diabetic cystopathy or diabetic bladder dysfunction. We reviewed the current translational knowledge of diabetic bladder dysfunction. We performed a search of the English literature through PubMed. The key words used were diabetes and bladder dysfunction or cystopathy. Our data and perspective are provided for consideration of the future direction of research. Despite traditional recognition of diabetic bladder dysfunction as a voiding problem characterized by poor emptying and overflow incontinence, recent clinical and experimental evidence indicate storage problems such as urgency and urge incontinence in diabetes mellitus cases. Recent experimental evidence from studies of diabetic bladder dysfunction in small animal models of diabetes mellitus show a temporal effect on diabetic bladder dysfunction. Early phase diabetes mellitus causes compensated bladder function and the late phase causes decompensated bladder function. The temporal theory could plausibly provide the scientific road map to correlate clinical and experimental findings, and identify the role of mechanisms such as polyuria, hyperglycemia, oxidative stress, autonomic neuropathy and decompensation of the bladder contractile apparatus in the creation of clinical and experimental manifestations of diabetic bladder dysfunction. Diabetic bladder dysfunction includes time dependent manifestations of storage and emptying problems. Identifying mechanistic pathways would lead to the identification of therapeutic intervention.
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            The pathophysiology of urinary incontinence among institutionalized elderly persons.

            Although 1 million institutionalized elderly persons have urinary incontinence, little is known about the causes of this problem. We conducted clinical and physiologic studies to determine the causes of established incontinence in a representative sample of 605 institutionalized elderly persons (mean age, 89 years), of whom 40 percent were chronically incontinent of urine. Detailed urodynamic studies in 94 of the 245 incontinent patients (77 women and 17 men; 38 percent) showed that detrusor overactivity was the predominant cause in 61 percent, with concomitant impaired detrusor contractility present in half these patients. Other causes among women were stress incontinence (21 percent), underactive detrusor (8 percent), and outlet obstruction (4 percent). Among the relatively few men in this sample, outlet obstruction accounted for 29 percent of the cases. In 35 percent of the patients, at least two coexisting probable causes of incontinence were identified. Diagnoses among patients with impaired mobility or mentation differed little from those in unimpaired patients. We conclude that the pathophysiology of incontinence in this population is complex; that detrusor hyperreflexia with normal contractility ("uninhibited bladder") accounts for the minority of cases (29 percent), even among patients with dementia; and that the causes of incontinence are as diverse in severely impaired elderly persons as in those who are unimpaired.
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              The other bladder syndrome: underactive bladder.

              Detrusor underactivity, or underactive bladder (UAB), is defined as a contraction of reduced strength and/or duration resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span. UAB can be observed in many neurologic conditions and myogenic failure. Diabetic cystopathy is the most important and inevitable disease developing from UAB, and can occur silently and early in the disease course. Careful neurologic and urodynamic examinations are necessary for the diagnosis of UAB. Proper management is focused on prevention of upper tract damage, avoidance of overdistension, and reduction of residual urine. Scheduled voiding, double voiding, al-blockers, and intermittent self-catheterization are the typical conservative treatment options. Sacral nerve stimulation may be an effective treatment option for UAB. New concepts such as stem cell therapy and neurotrophic gene therapy are being explored. Other new agents for UAB that act on prostaglandin E2 and EP2 receptors are currently under development. The pharmaceutical and biotechnology industries that have a pipeline in urology and women's health may want to consider UAB as a potential target condition. Scientific counsel and review of the current pharmaceutical portfolio may uncover agents, including those in other therapeutic fields, that may benefit the management of UAB.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                18 March 2016
                March 2016
                : 8
                : 3
                : 82
                Affiliations
                [1 ]Department of Urology, En Chu Kong Hospital, College of Medicine, National Taiwan University, Taipei 23702, Taiwan; ericwcc@ 123456ms27.hinet.net
                [2 ]Department of Biomedical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan
                [3 ]Department of Urology, Buddhist Tzu Chi General Hospital, and Tzu Chi University, Hualien 97002, Taiwan; chenglinglee@ 123456gmail.com
                Author notes
                [* ]Correspondence: hck@ 123456tzuchi.com.tw ; Tel.: +886-3-856-0794
                Article
                toxins-08-00082
                10.3390/toxins8030082
                4810227
                26999209
                748e40f8-483d-487a-b053-9ebee6e3ad1a
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 February 2016
                : 11 March 2016
                Categories
                Article

                Molecular medicine
                underactive detrusor,overactive bladder,onabotulinumtoxina
                Molecular medicine
                underactive detrusor, overactive bladder, onabotulinumtoxina

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