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ABSTRACT: To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof-of-concept study.
Double-blind, double-dummy, three-armed comparison of flupirtine extended release (400 mg/day, titrated to 600 mg/day), tolterodine extended release (4 mg/day) and placebo for 12 weeks.
When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine-exposed patients, the study was prematurely discontinued. Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks.
Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.
British Journal of Clinical Pharmacology 11/2011; 73(5):821-5. · 2.96 Impact Factor
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ABSTRACT: Urinary incontinence (bedwetting, enuresis) is the commonest urinary symptom in children and adolescents and can lead to major distress for the affected children and their parents. Physiological and non-physiological types of urinary incontinence are sometimes hard to tell apart in this age group.
This article is based on selected literature retrieved by a PubMed search and on an interdisciplinary expert consensus.
Nocturnal enuresis has a variety of causes. The main causative factors in monosymptomatic enuresis nocturna (MEN) are an impaired ability to wake up when the bladder is full, due to impaired or absent perception of fullness during sleep, and an imbalance between bladder capacity and nocturnal urine production. On the other hand, non-monosymptomatic enuresis nocturna (non-MEN) is usually traceable to bladder dysfunction, which is also the main cause of diurnal incontinence. A basic battery of non-invasive diagnostic tests usually suffices to determine which type of incontinence is present. Further and more specific testing is indicated if an organic cause is suspected or if the treatment fails. The mainstay of treatment is urotherapy (all non-surgical and non-pharmacological therapeutic modalities). Some patients, however, will need supportive medication in addition. Urinary incontinence has different causes in children and adults and must therefore be diagnosed and treated differently as well. All physicians who treat the affected children (not just pediatricians and family doctors, but also pediatric nephrologists, urologists, pediatric surgeons, and child psychiatrists) must be aware of the specific features of urinary incontinence in childhood.
09/2011; 108(37):613-20. · 2.92 Impact Factor
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MMW Fortschritte der Medizin 12/2010; 152(51-52):37.
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Schahnaz Alloussi,
Gerd Mürtz,
Reinhard Braun,
Ulrich Gerhardt,
Martina Heinrich,
Eva Hellmis,
Werner Horn, Daniela Marschall-Kehrel,
Kurt Niklas,
Michael Raabe,
Thomas Rössler,
Beatrix Seibt,
Stefan Siemer,
Daniela Schultz-Lampel,
Heiko Walter,
Burkhard Wiedeking,
Saladin Alloussi,
Paul Bock,
Gerhard Strugala,
Helmut Madersbacher
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ABSTRACT: To compare, in a retrospective observational cohort study, the efficacy, tolerability and safety of propiverine and oxybutynin in children with urge incontinence (UI) due to overactive bladder.
Medical records were scrutinized for children with UI. As a primary efficacy outcome variable the achievement of continence after treatment with variable doses of propiverine or oxybutynin was assessed. Weekly UI episodes and daily voiding frequency were evaluated as secondary efficacy outcomes. Tolerability was evaluated by the rate of adverse events, adverse drug reactions caused by antimuscarinics and premature treatment termination.
At 16 study centres, 621 children aged 5-14 years with UI due to overactive bladder were enrolled. After anticholinergic treatment (437 propiverine, 184 oxybutynin) continence was achieved in 61.6% and 58.7% of the patients after 186 and 259 days, respectively. There were clinically relevant improvements in voiding frequency across treatment groups. Daily doses of propiverine were markedly below the recommendations (0.54 vs 0.8 mg/kg body weight), daily doses of oxybutynin were according to the recommendations (0.31 vs 0.2-0.4 mg/kg body weight) at treatment initiation. There was a significantly more favourable tolerability to propiverine than oxybutynin for the overall rate of adverse events (3.9% vs 16.3%, odds ratio 4.813), adverse drug reactions caused by propiverine or oxybutynin (2.8% vs 9.2%) and premature treatment termination due to adverse drug reactions (1.6% vs 4.4%).
Propiverine and oxybutynin are effective in children with UI due to overactive bladder. Sufficient treatment periods of at least 2, preferably 3-4, months are the crucial factors for a successful treatment. The tolerability profile of propiverine is better than for oxybutynin.
BJU International 12/2009; 106(4):550-6. · 2.84 Impact Factor
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ABSTRACT: In this national, multicenter, retrospective survey we tested whether structured withdrawal of desmopressin, in which dose frequency rather than dose quantity was gradually decreased, would improve outcome.
Enrolled in the study were 487 monosymptomatic enuretic patients from a total of 181 centers (The Enuresis Algorithm of Marschall Survey Group). At study outset 41% of patients had 7 wet nights per week, 45% had 3 to 6 and 14% had fewer than 3. All patients were treated with desmopressin, which was abruptly terminated or tapered with analogue by a structured scheme. Response rates were compared in the groups according to International Children's Continence Society guidelines.
The 173 children with abrupt termination had a 51% response rate, including a full and partial response in 44.1% and 27%, respectively, and no response in 22%. The 314 children with tapering had a 72% response rate, including a full and partial response in 66.8% and 24%, and no response in 4% (p <0.0001). Enuresis frequency with abrupt termination decreased from 21 wet nights per month before treatment to 6. The tapering group had 21 wet nights per months before and 2 after treatment (p <0.0001). Followup at 1 month showed fewer than 2 wet nights per month in 57% of cases with abrupt termination and in 80% with tapering (p <0.0001). Pretreatment had no influence. No severe side effects occurred.
This national, multicenter, retrospective analysis proves that antidiuretic treatment followed by a structured withdrawal program is superior to regular treatment with abrupt termination in enuretic children. Hence, desmopressin followed by structured withdrawal should be the standard. It is also superior to published outcomes of alarm treatment.
The Journal of urology 08/2009; 182(4 Suppl):2022-6. · 4.02 Impact Factor
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Daniela Marschall-Kehrel
European Urology 12/2008; · 8.49 Impact Factor
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ABSTRACT: Until now no confirmatory clinical trial in children suffering from nonneurogenic overactive bladder (OAB) and urinary incontinence could demonstrate superiority for antimuscarinics over placebo.
The following study was conducted to prove efficacy and tolerability of propiverine compared to placebo.
A randomized, double-blind, placebo-controlled phase 3 trial with parallel-group design in children aged 5-10 yr was performed. Prior to the 8-wk medical therapy urologic baseline diagnostics, a 3-wk lifestyle advice (urotherapy) was established.
After re-evaluation of in- and exclusion criteria and uroflowmetry, only children fulfilling the requested criteria were allocated to a body-weight-adjusted therapy (10 or 15 mg propiverine twice daily or corresponding placebo).
Efficacy parameters derived from bladder diary and a micturition volume protocol. Decrease in voiding frequency per day was chosen as primary efficacy parameter; secondary endpoints included voided volume and incontinence episodes. A safety assessment was conducted.
Of 171 randomized children, 87 were treated with propiverine and 84 with placebo. The primary efficacy parameter showed a decrease in voiding frequency (-2.0 episodes for propiverine versus -1.2 for placebo; p=0.0007). Superiority could also be demonstrated for voided volume (31.4 vs. 5.1 ml; p<0.0001) and incontinence episodes (-0.5 vs. -0.2 episodes per d; p=0.0005). The trial design did not allow for separate evaluation of the effect of urotherapy prior to medical treatment. Propiverine was well-tolerated in children. Altogether 23% of side-effects were reported for propiverine and 20% for placebo.
This clinical trial showed superior efficacy of propiverine over placebo and good tolerability for the treatment of children suffering from OAB and urinary incontinence. An important additional factor for the success of the trial was a modified trial design with previous urotherapy.
ClinicalTrials.gov Identifier: NCT00603343.
European urology 05/2008; 55(3):729-36. · 7.67 Impact Factor
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ABSTRACT: To evaluate the efficacy and tolerability of tolterodine extended release (ER) in men and women with overactive bladder (OAB).
We analyzed data from two 12-wk, placebo-controlled trials of tolterodine ER (4mg QD). Patients completed 7-d bladder diaries and rated the urgency sensation associated with each micturition on a 5-point urgency rating scale. Micturitions were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-5), or severe OAB (4-5). Changes in micturitions during 24-h, daytime, and nocturnal intervals were assessed.
At baseline, 73% (547 of 745) of men and 57% (539 of 953) of women were continent. By week 12, tolterodine ER (n=848) reduced OAB and severe OAB micturitions during 24-h, daytime, and nocturnal intervals in both sexes compared with placebo (n=850). Adverse event rates were low and similar across treatment and gender.
In men and women with OAB, tolterodine ER reduced OAB and severe OAB micturitions, and was well tolerated.
European Urology 05/2007; 51(4):1054-64; discussion 1064. · 8.49 Impact Factor
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ABSTRACT: Patient perceptions of overactive bladder (OAB) symptoms, expectations for treatment benefit, and overall treatment satisfaction share complex relations. Multiple studies have demonstrated associations between factors, such as age, sex, and ethnicity, and patient perceptions of OAB symptoms, especially urgency urinary incontinence. Perceptions of OAB are also shaped by symptom severity and impact on health-related quality of life, as well as by perceptions of family members, caregivers, and clinicians. The literature further suggests discrepancies in the reporting among patients, physicians, and family members/caregivers of the impact that urinary symptoms have on patients' emotional well-being, productivity, and daily life. Understanding the factors that affect patients' perceptions is important because these perceptions affect treatment expectations, which may predict treatment outcomes. Studies designed to evaluate the relations between expectations for OAB treatment and patient satisfaction have not been performed to date, but studies in other patient populations suggest that expectations of positive outcomes are associated with greater treatment satisfaction. We emphasize that patient satisfaction with treatment is directly related to fulfillment of positive expectations, and that patient expectations should be realistic and agreed on by patient and physician. We also discuss strategies that may be used by physicians managing patients with OAB to develop stronger patient-physician partnerships, including the effective communication required to make treatment decisions and set realistic expectations.
Urology 09/2006; 68(2 Suppl):29-37. · 2.43 Impact Factor
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Daniela Marschall-Kehrel
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ABSTRACT: Adequate sleep is a basic requirement for good health. Adults generally require 7 to 8 hours of sleep per night. Sleep deprivation is associated with a decreased ability to perform tasks controlled by the frontal lobe, such as planning, concentration, motor performance, and high-level intellectual skills. Constant poor-quality sleep can also cause excessive daytime sleepiness, depression, and immune function compromise. In addition, continued sleep disruption has been associated with an increased risk for mortality.
Urology 01/2005; 64(6 Suppl 1):21-4. · 2.43 Impact Factor
