Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence?

Overactive bladder and urgency incontinence are common and distressing conditions in older people, for which the first-line pharmacological treatment is a bladder antimuscarinic agent. Of these, oxybutynin is often recommended in guidelines, but is associated with a higher incidence of adverse drug effects, and in particular has been suggested to have deleterious cognitive effects. Despite this, guidelines often suggest oxybutynin as first-line treatment, and insurance based healthcare systems often require oxybutynin to be used as a first-line therapy and fail before reimbursement for the cost of newer anticholinergics is authorised. We reviewed the literature of bladder antimuscarinics in older adults, using the headings overactive bladder, urinary frequency, urgency, urge, oxybutynin, antimuscarinic, older, older people, and frail. In general, oxybutynin had a similar efficacy to other anticholinergic drugs, but a higher incidence of adverse drug events, in particular significant yet unnoticed cognitive impairment. We conclude that oxybutynin should not be used in frail older people.

Neurogenic detrusor overactivity in adults: a review on efficacy, tolerability and safety of oral antimuscarinics.

OBJECTIVES: This review analyzed efficacy, tolerability and safety of oral antimuscarinic (AM) drugs in adults suffering from neurogenic detrusor overactivity (NDO). METHODS: A comprehensive search of major literature bases was conducted to identify all references. RESULTS: Thirty studies, thereof 16 randomized controlled trials (RCT), enrolling 1479 patients were identified and included in the review. Results were grouped in dose-finding, placebo- and active-controlled, flexible dose and combined high-dose AM drugs, and various studies. Key urodynamic outcome parameters, such as maximum detrusor pressure and maximum cystometric bladder capacity, demonstrated the efficacy of AM in NDO, following 2-3 weeks of treatment. Contrary to idiopathic detrusor overactivity (IDO), no placebo effects manifested. Other important parameters, such as impact on the upper urinary tract function and morphology, issues of continence, post-void residual urine, catheterisation, urinary tract infections and quality of life, were investigated to a limited extent only. Incidence rates of adverse events were comparable for NDO and IDO. Most of the studies, especially RCT, were undertaken with oxybutynin immediate release (IR), trospium chloride IR, propiverine IR and propiverine extended release. In NDO, these drugs are best investigated. CONCLUSIONS: AM drugs are effective in NDO, they normalize the intravesical pressure and increase cystometric bladder capacity. However, other important parameters are not adequately investigated so far and should be recognized in future studies.

Bladder compliance what does it represent: can we measure it, and is it clinically relevant?

AIMS: To report the conclusion of the Think Thank 8 on Compliance Discussions during the second ICI-RS meeting in 2010. METHODS: During a 3-day meeting a group of specialists discussed bladder compliance, what it represents, how it can be measured and if it is clinically relevant. RESULTS: Bladder compliance is the result of a mathematical calculation of the volume required for a unit rise of pressure measured during a cystometric filling. It gives an indication on how the different mechanisms in the bladder wall react on stretching. There is a need of standardization of measurement and suggestions for this are given in the text. Pitfalls are described and how to avoid them. There is a wide range of compliance values in healthy volunteers and groups of patients. Poor compliance needs to be defined better as it can have significant clinical consequences. Prevention and treatment are discussed. CONCLUSION: If compliance is correctly measured and interpreted, it has importance in urodynamic testing and gives information relevant for clinical management.

Desmopressin treatment regimens in monosymptomatic and nonmonosymptomatic enuresis: A review from a clinical perspective.

OBJECTIVE: To evaluate outcomes of desmopressin treatment in monosymptomatic enuresis (ME) and nonmonosymptomatic enuresis (NME). MATERIALS AND METHODS: PubMed was searched for all studies investigating enuresis, up to July 2009, in which desmopressin was administered alone or combined with other treatments. Each study was graded according to its respective level of evidence. RESULTS: Altogether, 99 studies enrolling 7422 patients were identified as fulfilling the inclusion criteria. In 76 studies, desmopressin was administered as monotherapy; in 29 it was combined with other treatments such as antimuscarinics and enuresis alarm. CONCLUSION: Studies incorporating a minor invasive versus a non-invasive diagnostic approach seem to achieve superior long-term success rates. Primary efficacy outcomes following desmopressin treatment are more favourable in ME than NME. Desmopressin administered with adjunct measures achieves superior outcomes compared to monotherapy, especially in NME. Compared to sudden withdrawal, the structured withdrawal programs show better long-term success and lower relapse rates. So far, no superiority has been shown for either time- or dose-dependent structured withdrawal programs. Most studies incorporated only small case series; only 25 studies with level of evidence 1 or 2 have been conducted. The broad range of mono- and adjunct treatments were evaluated according to the evidence based criteria recommended by the European Association of Urology.

Neurological patients need evidence-based urological care.

AIMS: To report the conclusion of the Think Thank on Neurourology discussions during the first ICI-RS meeting in 2009. METHODS: During a 3-day meeting a group of specialists discussed evidence-based medicine in neurourology and made suggestions for future research. RESULTS: In the vast majority of patients with neurological disease bladder dysfunction occurs. The actual rules of diagnosis and treatment lack a study related evidence base. From a long list of possible research subjects, prevalence, detrusor pressure, imaging, catheterization and surgery have been first discussed. CONCLUSION: In each of these subjects, research items are suggested which can help to improve the care in this patient group.

Neurologic urinary incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic urinary incontinence. METHODS: Through in debt literature review all aspects of neurological urinary incontinence were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment and surgical treatment of neurologic urinary incontinence, levels of evidence and grades of recommendation were made following ICUD criteria. CONCLUSIONS: Though data are available that advice and guide in the management of urinary incontinence in neurologic patients, not many data have a high level of evidence or permit a high grade of recommendation. More and well-structured research is needed.

Neurologic fecal incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic fecal incontinence (FI). METHODS: Through in debt literature review all aspects of neurologic urinary and FI were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment, and surgical treatment of neurologic FI levels of evidence and grades of recommendation were made. CONCLUSIONS: Though data are available that advice and guide in the management of FI in neurologic patients, not many data are with a high level of evidence or high grade of recommendation. More and well-structured research is needed.

Lower urinary tract symptoms in dementia with Lewy bodies, Parkinson disease, and Alzheimer disease.

OBJECTIVE: The present study sought to investigate lower urinary tract symptoms and urodynamic and cystometric findings in Parkinson disease (PD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). METHODS: Included were patients with frequency, urgency, incontinence, and nocturia, without major bladder outflow obstruction. The protocol comprised physical examination, urine analysis, prostate specific antigen, 24-hours frequency of micturition, mean voided volume (MVV), free flow before instrumentation (Qmax(before)), post-void residual volume (PVR), and cystometry. RESULTS: Fifteen patients with DLB and PD and 16 patients with AD were examined. MVV, PVR, Qmax(before) and with transurethral catheter, cystometric bladder capacity, and detrusor pressor at maximum flow were similar in the three groups and corresponded to values of the general elderly population. Urge episodes and urge incontinence were observed in 93 and 53% of the patients with DLB, 53 and 27% of the patients with PD, and 19 and 12% of the patients with AD, and detrusor overactivity in 92% of the patients with DLB, 46% of the patients with PD, and 40% of the patients with AD. CONCLUSIONS: Urgency and urge incontinence suggest detrusor overactivity, which was more prevalent in dementia with Lewy bodies than in Parkinson disease and Alzheimer disease, whereas mean voided volume, free flow, cystometric bladder capacity, and detrusor pressor were similar in the groups. Frequency of micturition could not be reliably assessed in patients with dementia.

[The value of intravesical electrostimulation in the treatment of acute prolonged bladder overdistension]. / Der Stellenwert der intravesikalen Elektrostimulation in der Therapie der akuten prolongierten Blasenüberdehnung.

BACKGROUND: The effectiveness of intravesical electrostimulation (IVES) in the treatment of acute prolonged bladder overdistension (PBO) was investigated. METHODS: Sixteen patients (female 11, male 5, ø 54 years) after PBO (bladder filling volume: 1317+/-320 ml) were evaluated: 11 after surgery and 5 after polytrauma, psychosomatic disorder or LV4 fracture. After exclusion of a neurogenic aetiology and a urodynamic examination, IVES was performed besides IC or suprapubic catheter. RESULTS: Group 1: six patients with a weak detrusor (p(detr. max.)<30 cmH(2)O); group 2: ten patients had detrusor acontractility. After 25 IVES sessions, group 1 showed a significant increase of p(detr. max.) (p=0.01) as well as a decrease in PVR (31% to 3% of bladder capacity, p=0.02). Group 2 had no significant increase of p(detr. max). CONCLUSIONS: Two-thirds of patients with a weak detrusor after PBO will regain balanced voiding after IVES due to detrusor reinforcement. With an acontractile detrusor only bladder sensation improves.

Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?

OBJECTIVE: To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. PATIENTS AND METHODS: Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. RESULTS: Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

Propiverine hydrochloride immediate and extended release: comparison of efficacy and tolerability in patients with overactive bladder.

INTRODUCTION: This study aims to compare the efficacy of propiverine hydrochloride immediate release (IR), propiverine hydrochloride extended release (ER) and placebo for the treatment of overactive bladder syndrome. The primary outcome measure is incontinence episode frequency, with secondary outcome measures including mean volume per void and quality of life as assessed on King's Health Questionnaire. MATERIAL AND METHODS: The double-blind, double-dummy, randomized study compared IR 15 mg twice daily, ER 30 mg once daily and placebo in 3 parallel groups. After a run-in period of 7 days, the patients were treated for 32 days. Nine hundred and eighty-eight patients were randomized, and 910 patients completed the protocol without major violations. RESULTS: The number of incontinence episodes/24 h decreased by 2.26 in the IR group (p < 0.001 vs. placebo), by 2.46 in the ER group (p < 0.0001 vs. placebo) and by 1.75 in the placebo group. The most frequent adverse event was dry mouth with 22.8% of the patients in the IR group, 21.7% in the ER group and 6.4% in the placebo group. The overall tolerability was rated 'very good' or 'good' by more than 80% of the investigators and patients in all 3 groups. CONCLUSIONS: Propiverine ER 30 mg once daily and propiverine IR 15 mg twice daily significantly reduce the number of incontinence episodes/24 h within a treatment period of 32 days. Both formulations are safe and well tolerated. The extended release formulation of propiverine is a suitable new option for the treatment of the overactive bladder.

[Oral anticholinergics in overactive bladder]. / Orale Anticholinergika bei überaktiver Blase.

Behavioural therapy and anticholinergics are the mainstays in the treatment of symptoms of overactive bladder in patients with idiopathic and neurogenic detrusor overactivity; they are the first-line treatment. Oxybutynin, propiverine, tolterodine and trospium chloride as well as the "newcomers" solifenacin and darifenacin are comparable in regards to their efficacy. However, based on different pharmacokinetics and pharmacodynamics with different resorption velocity, different metabolisation and different CNS penetration, the profile of adverse events is different, qualitatively and quantitatively. Substances that are resorbed slowly or available as slow-release formulations are tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier may compromise cognitive functions, especially in geriatric patients, who are already on cholinesterase inhibitors due to memory disorders. The following article gives an overview of the anticholinergics currently prescribed in patients with symptoms of overactive bladder with special attention to the influence of pharmacokinetics/pharmacodynamics on the adverse events profile including possible CNS side effects.

Neurourology and pelvic floor dysfunction.

The levator ani muscles, endopelvic fascia, and muscular structures of the sphincter and the pelvic floor musculature (PFM) comprise one system. The physiological organization of Onuf's nuclei and of levator ani motorneurons as well as the reflex control of the tonic activity, that is essential for the generation of maintained force in slow-twitch muscle fibers, is an important part of the normal function of this system. In the human the motor cortex is crucial in voluntary motor control also of PFM, but other areas in the brain are involved in activities of the PFM related to emotional behavior e.g. micturition. Coordination between the urinary bladder, the urethra and the PFM is mediated by multiple reflex pathways organized in the brain and spinal cord. Some reflexes promote urine storage, whereas others facilitate voiding. It is also possible that individual reflexes might be linked together in a serial manner to create complex feedback mechanisms. The control of striated muscle in neurological lesions of the lower urinary tract is an active area of research and is producing results that are relevant to the problems of the neurogenic and idiopathic overactive bladder, whether these are caused by central nervous system or peripheral nerve lesions.

Reused silicone catheter for clean intermittent catheterization (CIC): is it safe for spinal cord-injured (SCI) men?

STUDY DESIGN: Study of reusable catheter. OBJECTIVE: To investigate whether a silicone cathether reused over years for clean intermittent catheterization (CIC) was safe for spinal cord injured (SCI) men. SETTING: Maharaj Hospital, Chiang Mai, Thailand. METHOD: A cross-sectional study was obtained from SCI men who had used CIC with a reusable silicone catheter for more than a year. Demographic data, urological management and urinary tract complications focusing on the radiologic status of the urethra were reviewed and analyzed. In addition, two reused and one new catheters were studied under electron microscope for catheter morphology (surface and lumen) and stiffness. RESULTS: There were 28 SCI men included in this study. The average duration of CIC use was 4.8 years and the average time of usage for each catheter was 3 years (range 1-7 years). In all, 26 men previously used indwelling catheterization (ID) during the acute phase. In all, 23 men performed self-catheterization. Regarding urinary complications, three reported urethral bleeding, five had episodes of pus per urethra, five had epididymitis, four had passing stones, 18 had occasional foul smelly urine, 10 developed fever and cloudy urine during the past year. Of 17 patients who had ultrasonography done, four had pathologic findings in kidney and one had bladder calculi. Demographic data, urinary management and complications did not have significant relation to the abnormality of the urethrogram or urinary tract infection. However, where the frequency of CIC was higher, the abnormality of the urethra was lower (P<0.05). All had serum Cr level < or =1.3 mg/dl. Electron microscopic findings of reused catheters for 2 years revealed encrustation but no obstruction in the lumens and 20% increase in stiffness. CONCLUSION: The clinical outcome, especially with regard to urethral abnormalities with this reusable silicone catheter is as good as with a disposable one. However, to reuse urinary catheters, one should consider the increasing risk of infection. For SCI patients in developing countries, CIC with a reusable silicone catheter may be a suitable and safe choice if one cleans and applies it properly to reduce infection. In order to answer the question how long a person in a developing country should use the same silicone catheter, further research should be conducted.

[A suggested treatment algorithm in nocturnal enuresis with emphasis on partial responders]. / Therapiealgorithmus bei Enuresis nocturna.

Monotherapeutic strategies often have only partial success in primary nocturnal enuresis (PNE). This analysis evaluated whether adjuvant treatment strategies improve outcomes. PNE children were submitted to a distinct therapeutic strategy including urotherapy (behavioral modifications), a first-line and, if necessary, a second-line treatment period. Outcome was the relief of bedwetting, the follow-up was 3-79 months. Urotherapy was applied. Nonresponders were assigned to desmopressin as first-line treatment. For complete responders a structured withdrawal program was applied. Partial responders were assigned to adjuvant second-line treatment according to their individual symptomatology, masked at basic investigations, incorporating either anticholinergics (propiverine hydrochloride), biofeedback, alpha-blocker (alfuzosin), alarm or psychotherapy, in addition to desmopressin. Nonresponders were referred to specialized management. The study included 259 children suffering from PNE (92 girls, 167 boys, aged 5-18 years): 42 children were relieved from bedwetting after urotherapy and 136 children had a complete response to desmopressin. Three nonresponders were assigned to specialized management, 61 partial responders had adjuvant treatments, and 17 partial responders had no further treatment. The suggested treatment algorithm resulted in 227 complete responders, 29 partial responders, and 3 nonresponders. The need for preliminary urotherapy is evident. The proposed desmopressin monotherapeutic strategy, incorporating a structured withdrawal program, is more effective than the standard desmopressin treatment module. Applying adjuvant treatment modules improves the complete response rate up to 88%. In partial responders overall efficacy rates are improved further. Nonresponders (1.2%) will be referred to specialized management, but many partial responders will gain improvement sufficient to refrain from invasive procedures.

[Urodynamic phenomena in the aging bladder]. / Urodynamische Phänomene der alternden Blase.

Lower urinary tract symptoms increase with age in both sexes and are a major problem in the elderly due to the medical and bio-psycho-social consequences involved. Lower urinary tract dysfunctions in the elderly are generally multifactorial in origin and are classifiable to a large extent by age and pathology related changes. Urodynamic findings should never be interpreted without considering the medical history, bladder diary, clinical examination and other findings. Age related changes involve a decrease of voided volume and urinary flow and an increase in overactive bladder symptoms and post void residuals. Consequently, decreased maximum bladder capacity, terminal detrusor overactivity and detrusor overactivity with impaired contractile function are typically found in the elderly. Patients with terminal detrusor overactivity are well treated by bladder training and timed voiding, sometimes combined with anticholinergic drugs, whereas patients with phasic detrusor overactivity are often good candidates for non-invasive electrical neuromodulation.

Calculus anuria in a spina bifida patient, who had solitary functioning kidney and recurrent renal calculi.

STUDY DESIGN: Clinical case report with comments by colleagues from Austria, Belgium, Germany, Japan, and Poland. OBJECTIVES: To discuss challenges in the management of spinal bifida patients, who have marked kyphoscoliosis and no vascular access. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A female patient, who was born with spina bifida, paraplegia and solitary right kidney, had undergone ileal loop urinary diversion. Renal calculi were noted in 1986. Percutaneous nephrostolithotomy was performed in 1989 and there was no residual stone fragment. However, she developed recurrence of calculi in the lower pole of the right kidney in 1991. Intravenous urography, performed in 1995, revealed right staghorn calculus and hydronephrosis. Chest X-ray showed markedly restricted lung volume due to severe kyphoscoliosis. In 2000, she was declared unsuitable for anaesthesia due to a lack of venous access and a high likelihood of difficulty in weaning off the ventilator in the postoperative period. In June 2002, she developed anuria (urine output=18 ml/24 h) due to ball-valve-type obstruction by a renal stone at the ureteropelvic junction. Urea: 14.4 mmol/l; creatinine: 236 microl/l. Ultrasound showed right hydronephrosis. Percutaneous nephrostomy was performed. RESULTS: Following relief of urinary tract obstruction, there was postobstructive diuresis (3765 ml/24 h). However, the patient expired 19 days later due to progressive respiratory failure. CONCLUSION: In this spina bifida patient, who had reached the age of 35 years, severe kyphoscoliosis and lack of vascular access presented insurmountable challenges to implement the desired surgical procedure for removal of stones from a solitary kidney.