PURPOSE:To assess the frequency with which environmental cues, which might constitute Pavlovian-conditioned stimuli, occur with urgency and leakage symptoms associated with overactive bladder syndrome (OAB).

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The lack of an alternative to antimuscarinics has led to the search for new drug targets for overactive bladder (OAB) symptoms.

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INTRODUCTION AND HYPOTHESIS: Posterior tibial nerve stimulation (PTNS) is a percutaneous method of peripheral, sacral neuromodulation.

Its current use is limited; however, published data suggest PTNS may be an effective treatment for overactive bladder (OAB).

METHODS: We systematically reviewed the literature on PTNS for treatment of idiopathic OAB in women from January 2000 to August 2010 published in English in MEDLINE/PubMed, Embase, and Cochrane databases. We included randomized controlled trials or observational studies reporting objective outcome measures with the use of either the Urgent PC or Stoller Afferent Nerve Stimulator (SANS) for PTNS. Studies were considered "good quality" if results from objective measures were provided for ≥20 women, results distinguished between type of OAB symptom, and data were reported separately for female subjects.

RESULTS: Of the 136 identified articles, 17 met inclusion criteria for data abstraction; 4 of the 17 studies met our criteria for good quality and reported success rates of 54-93 %. Recurrent limitations in the literature were pooling of results for male and female subjects and lack of differentiation in the data on specific symptoms of OAB treated. Short-term follow-up and infrequent use of a control arm were also noted shortcomings of reviewed studies.

CONCLUSIONS: Limited high quality data exist on PTNS for OAB in women. Although initial studies have demonstrated promise, more comprehensive evaluation of PTNS is needed to support its universal use for the treatment of OAB in women.

Written by: 
Levin PJ, Wu JM, Kawasaki A, Weidner AC, Amundsen CL. Are you the author? 
Duke University, 5324 McFarland Drive, Suite 310, Durham, NC, 27707, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

Reference: Int Urogynecol J. 2012 Mar 13. Epub ahead of print. 
doi: 10.1007/s00192-012-1712-4

PubMed Abstract 
PMID: 22411208

Do you constantly feel like you've  “gotta go”?  When you leave the house, do you always look where the nearest bathroom is, just in case?  

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INTRODUCTION AND HYPOTHESIS: This is a systematic review of clinical data assessing the safety, efficacy and tolerability of fesoterodine in randomised control trials (RCTs) in the treatment of overactive bladder (OAB).

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Persistence with long-term medication in chronic diseases is typically low and that for overactive bladder medication is lower than average.

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The condition of OAB is symptom based and defined by the International Continence Society (ICS) standardization committee as urgency, with or without urgency incontinence, usually with frequency and nocturia, if there is no proven infection or other obvious pathology.

• Urgency with at least one other symptom is essential to diagnose OAB.
• Urgency is the central symptom, defined by the ICS as the complaint of a sudden compelling desire to void that is difficult to defer.
• The normal urge to void is terms the desire to void, by the ICS and is used to describe normal filling sensation.
• Urgency incontinence is defined as involuntary leakage of urine, accompanied or immediately preceded by urgency.
• The symptom of “increased daytime frequency” is the complaint by the patient who considers that they void too often throughout the day.
• Although the ICS has not defined normal daytime voiding frequency, many references and clinical trials have reported baselines of 8 - 10 daytime voids as normal. Variables include the intake of liquids and medications that may increase voiding frequency.
• The symptom of nocturia is the complaint that the individual is awakened from sleep at night one or more times to void.
• Urgency urinary incontinence (UUI) is disproportionately more common among women.
• The impact of OAB on health related quality of life is substantial.

Treatment of OAB:

The goals for treatment are directed towards improving the patients quality of life by decreasing symptom severity balanced with managing treatment sside effects.

Conservative treatment:

• Behavioral and lifestyle modifications, timed voiding, pelvic floor muscle therapy and biofeedback. These therapies require effort from the patient.
• Conservative therapies are effective, well tolerated, safe, and preferred by many patients. 
• It is generally appropriate that the least invasive treatment that takes into account patient preferences and offers a reasonable chance for success be used first.
• Although it is important to rule out serious underlying or associated conditions, invasive testing is rarely required before initiating treatment with conservative measures.

Treatments - Behavioral Therapy

• Behavioral therapy describes a group of treatments founded on the prinicpal that the incontinent patient can be educated about his or her condition and develop strategies to minimize or eliminate UI.
• Education is the core of all the behavioral therapies.
• The behavioral techniques are implemented through patient education aiming at healthy bladder habits, while suppressing urgency to improve continence and decrease symptom severity.
• Pelvic Floor Muscle training - goal is improving muscle strength and control
• Bladder diary - The largest voided volume on a diary correlates with the cystometric capacity defined by urodynamic testing
• Urge Inhibition - goal is to break the cycle of rushing to the toilet in response to urgency
• Scheduled voiding - goal is to normalize frequency
• Fluid management
• The different treatment approaches are unified by education about normal urinary tract function.
• Pelvic floor muscle training is both a behavioral therapy (education about anatomy and function of the muscles, learning to use the muscles properly to control lower urinary tract function) and a physical therapy (strengthening the muscles to improve function).
• PFMT consists of repetitive contractions of the pelvic floor muscles; various techniques including quick flicks or rapid, intense muscle contractions and sustained pelvic contractions can be effective. The quick flicks are more effective at suppressing urgency and detrusor overativity while sustained contractions are more effective at improving occlusion of the sphincteric unit during increases in intra-abdominal pressure. 
• The goal of therapy is to increase the strength and control of the pelvic floor muscles such that maximal force can be generated when needed to overcome urgency and leakage.
• Bladder training starts a patient voiding on a fixed time interval schedule with the intention that the patient will urinate before experiencing urgency and UI.
• It can be used with or without medical therapy.
• Most OAB patients can benefit from multimodality therapy including bladder training, PFMT, and medical therapy.
• After appropriate evaluation, sacral neuromodulation, botulinum toxin injections, and surgical reconstruction/diversion are options for refractory OAB.

Pharmacologic Management of OAB:

• Antimuscarinic agents are the first line pharmacologic treatment for OAB.
• Antimuscarinics produce symptomatic improvement by reducing urgency and therefore reducing UUI and frequency, decreasing detrusor overactivity or involuntary contractions of the bladder muscle, and increasing bladder capacity. 
• Antimuscarinic agents have demonstrated in clinical trials that they improve continent days, mean voided volume, urgency episodes, and micturition frequency.
• They have for the most part demonstrated improvement in health related quality of life. 
• Across large patient samples, all of the currently available antimuscarinics appear to have comparable efficacy but do show some measurable differences in tolerability.

Neuromodulation in the Treatment of OAB: 

Percutaneous Tibial Nerve Stimulation (PTNS), a non-invasive way of modulating pelvic reflexes via projections from the posterior tibial nerve.

• Urgent® PC (Uroplasty, Inc., Minnetonka, MN, USA) is an office-based procedure approved by the US Food and Drug Administration that is used to deliver stimulation to the posterior tibial nerve using a 34-gauge needle electrode placed slightly cephalad to the medial malleolus. 
• The recommended course of treatment is 12 weekly sessions of 30 minutes each.
• The Overactive Bladder Innovative Therapy (OrBIT) trial was a randomized, multicenter, control trial that compared PTNS with tolterodine ER; 79.5% of patients in the PTNS arm reported cure or improvement in symptoms compared with 54.8% of the tolterodine group as measured by the global response assessment (p = 0.01).
• Objective measures, including urinary frequency, urge UI episodes, urge severity, nighttime voids, and volume voided, showed similar improvement in the two groups. 
• The authors concluded that PTNS was a clinically significant treatment alternative for OAB. 
• 33 month data is recently avaiable that demonstrates no difference from the 12 week data.  

 References:

• Abrams P, Andersson KE: Muscarinic receptor antagonists for overactive bladder. BJU Int 2007; 100(5):987-1006.
• Abrams P, Cardozo L, Fall M, et al: The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21(2):167-178.
• Andersson KE: Treatment of overactive bladder: other drug mechanisms. Urology 2000; 55(5A):51-57.
• Andersson KE: Potential benefits of muscarinic M3 receptor selectivity. Eur Urol Suppl 2002; 1(4):23-28.
• Andersson KE: Antimuscarinics for treatment of overactive bladder. Lancet Neurol 2004; 3(1):46-53.
• Andersson KE, Gratzke C: Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat Clin Pract Urol 2007; 4(7):368-378.
• Asplund R, Aberg H: Desmopressin in elderly subjects with increased nocturnal diuresis: a two month treatment study. Scand J Urol Nephrol 1993; 27:77-81.
• Burgio KL, Locher JL, Goode PS, et al: Behavioral vs. drug treatment for urge urinary incontinence in older women. JAMA 1998; 280:1995-2000.
• Chancellor MB, Fowler CJ, Apostolidis A, et al: Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol 2008; 5(6):319.
• Cruz F, Silva C: Botulinum toxin in the management of lower urinary tract dysfunction: contemporary update. Curr Opin Urol 2004; 14(6):329-334.
• Diokno AC, Burgio K, Fultz NH, et al: Medical and self-care practices reported by women with urinary incontinence. Am J Manag Care 2004; 10:69-78.
• Giannantoni A, Mearini E, Del Zingaro M, Porena M: Six-year follow-up of botulinum toxin A intradetrusorial injections in patients with refractory neurogenic detrusor overactivity: clinical and urodynamic results. Eur Urol 2009; 55(3):705-711.
• Goode PS: Predictors of treatment response to behavioral therapy and pharmacotherapy for urinary incontinence. Gastroenterology 2004; 126(Suppl. 1):S141-S145.
• Hashim H, Abrams P: Pharmacologic management of women with mixed urinary incontinence. Drugs 2006; 66(5):591.
• Karsenty G, Denys P, Amarenco G, et al: Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol 2008; 53(2):275.
• Mattiasson A, Abrams P, Van Kerrebroeck P, et al: Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo-controlled study in men. BJU Int 2002; 89(9):855-862.
• Nitti VW: Botulinum toxin for the treatment of idiopathic and neurogenic overactive bladder: state of the art. Rev Urol 2006; 8(4):198.
• Novara G, Galfano A, Secco S, et al: A systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. Eur Urol 2008; 54(4):740-763.
• Payne CK: Behavioral therapy for the overactive bladder. Urology 2000; 55:3-6.
• Rembratt A, Riis A, Norgaard JP: Desmopressin treatment in nocturia; an analysis of risk factors for hyponatremia. Neurourol Urodyn 2006; 25(2):105.
• Sahai A, Khan MS, Dasgupta P: Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial. J Urol 2007; 177(6):2231-2236.
• Schurch B, Schmid DM, Stöhrer M: Treatment of neurogenic incontinence with botulinum toxin A. N Engl J Med 2000; 342:665.
• Subak LL, Wing R, West DS, et al: PRIDE Investigators. Weight loss to treat urinary incontinence in overweight and obese women. N Engl J Med 2009; 360(5):481-490.
• Thüroff JW, Chartier-Kastler E, Corcus J, et al: Medical treatment and medical side effects in urinary incontinence in the elderly. World J Urol 1998; 16(Suppl. 1):S48-S61.
• Wheeler Jr JS, Walter JS, Chintam RS, et al: Botulinum toxin injections for voiding dysfunction following SCI. J Spinal Cord Med 1998; 21:227-229.
• BOTOX® Prescribing Information on Detrusor Overactivity associated with a Neurologic Condition (1.1) Allergan Inc. 8/2011.
• DETROL® and DETROL® LA (tolterodine tartrate extended release capsules) Prescribing Information, Pfizer Inc.
• DITROPAN XL® (oxybutynin chloride) Extended Release Tablets Prescribing Information, Ortho-McNeil, 7/2011.
• ENABLEX® Prescribing Information, Warner Chilcott. resourced: 4/2012.
• GELNIQUE- oxybutynin chloride gel, Watson Pharma Inc. 3/2012.
• SANCTURA XR® (trospium chloride extended release capsules)Prescribing Information, Allegan Inc. 2011
• TOVIAZ® (fesoterodine fumarate) Prescibing Information, Pfizer Inc. 6/2011.
• OXYTROL®, oxybutynin transdermal system Prescribing Information, Watson Pharma Inc. 4/2011.
• VESICARE®, solifenacin Prescribing Information , Astellas Pharma US Inc. 1/2012. 

The overactive bladder (OAB) is a prevalent problem, with considerable effects on the quality of life of affected individuals and substantial health economic costs.

The condition is symptom based and defined by the International Continence Society (ICS) standardization committee as urgency, with or without urgency incontinence, usually with frequency and nocturia, if there is no proven infection or other obvious pathology.

• Urgency with at least one other symptom is essential to diagnose OAB.
• Urgency is the central symptom, defined by the ICS as the complaint of a sudden compelling desire to void that is difficult to defer.
• The normal urge to void is terms the desire to void, by the ICS and is used to describe normal filling sensation.
• Urgency incontinence is defined as involuntary leakage of urine, accompanied or immediately preceded by urgency.
• The symptom of “increased daytime frequency” is the complaint by the patient who considers that they void too often throughout the day.
• Although the ICS has not defined normal daytime voiding frequency, many references and clinical trials have reported baselines of 8 - 10 daytime voids as normal. Variables include the intake of liquids and medications that may increase voiding frequency.
• The symptom of nocturia is the complaint that the individual is awakened from sleep at night one or more times to void.

Etiology - OAB:

• Neurologic disease is associated with a high prevalence of lower urinary tract dysfunction (LUTD).
• OAB increases with increasing age.

Prevalence of OAB:

• The NOBLE study established the prevalence of OAB in more than 5000 community-dwelling individuals in the United States using a validated computer-assisted telephone interview.
• Men and women had the same prevalence of OAB overall (16.0% and 16.9%, respectively) as defined by the ICS.
• Men were shown to have a higher prevalence of “OAB dry” (13.4% as opposed to 7.6% in women)
• Women had a higher prevalence of “OAB wet” (9.3% as opposed to 2.6% in men).
• In women the prevalence of “OAB wet” rose from 2.0% in the youngest group (ages 18 to 24) to 19.1% in those 65 to 74 years of age.
• Men, on the other hand, did not experience an increase in “OAB wet” until older: 8.22% for those 65 to 74 and 10.2% for those 75 years and older.
• Using the standardized ICS definition of OAB, the EPIC study reported the prevalence of OAB in four European countries and in Canada, reporting an overall OAB prevalence of 11.8%.
• Both types of OAB have a significant impact on the patients’ quality of life.
• OAB is a chronic condition, and ongoing quality of life impairment can be anticipated in many patients.

Clinical Evaluation:

• Patients with OAB may present to health care professional in primary care, OBGYN, or urology.
• It is critical for the healthcare professional to hear the patient defining either signs or symptoms of OAB.
• OAB is a condition that requires management, and “cure” is not a realistic possibility. Appropriate expectations and explanation are important to the success of patient treatments.
• An initial assessment gives a diagnosis and the basis for empirical treatment.
• Establish the patient's desire for treatment and which therapies are open to consideration..

History to include:

• Presence or absence, incidence, severity, and bother for each of the OAB symptoms including urgency incontinence.
• Other lower urinary tract symptoms (LUTS) should also be assessed.
• Presence or absence of dysuria and hematuria.
• Nature and volume of fluid intake.
• Whether occult neurologic disease could be present.
• Obstetric and gynecologic history, previous surgery/radiotherapy, bowel symptoms, and drug history.
• Other medical issues
• Dipstick urinalysis is necessary to exclude hematuria or urinary tract infection.
• A significant postvoid residual volume must be considered when evaluating OAB.

Symptom assessment questionnaires provide valuable information for baseline assessment and follow-up of treatment response.

• The bladder diary is essential for assessing OAB and excluding additional problems such as polydipsia or nocturnal polyuria.

Mixed Urinary Incontinence

• Mixed OAB is where OAB and stress urinary incontinence (SUI) are both present.
• Mixed urinary incontinence (MUI) is the complaint of involuntary leakage associated with urgency and with exertion, effort, sneezing, or coughing.
• The history can be helpful; the primary problem in mixed UI is often that component (the stress or the urge) that occurred first chronologically.
• The voiding diary can provide important information on chronological order.
• When OAB is the predominant problem the void volumes should be small both day and night.
• If there are small daytime voids with little or no nocturia and a large first morning void the urgency symptoms tend to be a manifestation of SUI, perhaps stimulated as a few drops of urine leak into the proximal urethra with activity and trigger a sense of urgency.
• Pelvic organ prolapse can have a similar effect. When SUI is suspected to be the primary component, a short-term trial of one of the vaginal support devices may clarify the picture.
• If the symptoms are relieved by the device the patient may decide to continue using it or feel more confident that surgical intervention will be successful.
• A pessary trial is doubly important before correcting pelvic organ prolapse (with or without UI).
• Elevation of a cystocele will unmask occult sphincteric incompetence in approximately 50% of patients who are continent with the prolapse.
• If an ambulatory trial of a pessary is not performed, then a pessary or vaginal packing may be used during preoperative urodynamic testing.
• The urethral stent/plug devices are relatively contraindicated in this patient population because clinical experience suggests that they typically aggravate the underlying urge and become totally ineffective.

Mixed Incontinence

Mixed incontinence is the combination of urinary symptoms and fecal incontinence.

References:

• Abrams P, Artibani W, Cardozo L, et al: Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn 2009; 28(4):287.
• References:
• Abrams P, Cardozo L, Fall M, et al: The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21(2):167-178.
• Abrams P, Klevmark B: Frequency volume charts: an indispensable part of lower urinary tract assessment. Scand J Urol Nephrol Suppl 1996; 179:47-53.
• Al-Hayek S, Belal M, Abrams P: Does the patient's position influence the detection of detrusor overactivity?. Neurourol Urodyn 2008; 27(4):279-286.
• Brading AF: A myogenic basis for the overactive bladder. Urology 1997; 50(6A Suppl.):57-67.
• Coyne KS, Elinoff V, Gordon DA, et al: Relationships between improvements in symptoms and patient assessments of bladder condition, symptom bother and health-related quality of life in patients with overactive bladder treated with tolterodine. Int J Clin Pract 2008; 62:925-931.
• Coyne KS, Sexton CC, Irwin DE, et al: The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study. BJU Int 2008; 101(11):1388-1395.
• de Groat WC: A neurologic basis for the overactive bladder. Urology 1997; 50(6A Suppl.):36-52.
• Fitzgerald MP, Kenton KS, Brubaker L: Localization of the urge to void in patients with painful bladder syndrome. Neurourol Urodyn 2005; 24:633-637.
• Irwin DE, Milsom I, Hunskaar S, et al: Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 2006; 50(6):1306-1314.
• rwin DE, Milsom I, Kopp Z, et al: Prevalence, severity, and symptom bother of lower urinary tract symptoms among men in the EPIC study: impact of overactive bladder. Eur Urol 2009; 56:14-20.
• Milsom I, Abrams P, Cardozo L, et al: How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001; 87(9):760-766.
• Stewart WF, Van Rooyen JB, Cundiff GW, et al: Prevalence and burden of overactive bladder in the United States. World J Urol 2003; 20(6):327-336.

CONTEXT: There is a lack of evidence about the efficacy and safety of anticholinergic drugs and about the optimal anticholinergic drug, if any, for the treatment of adult neurogenic detrusor overactivity (NDO).

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Overactive bladder (OAB) is a common condition, particularly in the elderly.

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