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PubMed2002

Does gender or age affect the efficacy and safety of tolterodine?

PURPOSE: We compared the importance of patient age and gender relative to the intensity of baseline symptoms of overactive bladder in the therapeutic response to the muscarinic receptor antagonist tolterodine. MATERIALS AND METHODS: Data from an open label, observational study of 2,250 patients with overactive bladder treated for 12 weeks with tolterodine were analyzed for alterations in frequency, urgency and urge incontinence, and for global efficacy and tolerability using logistic regression analysis, stratifying for gender, age, baseline symptom intensity and tolterodine dose. RESULTS: Gender or tolterodine dose were not consistently associated with altered treatment efficacy. Greater age was associated with a slight but statistically significant decrease in treatment efficacy. Patients with great baseline symptom intensity had greater treatment associated improvement but a lesser chance to become symptom-free. Even with a large number of patients no statistically significant gender or age associated alterations in the tolerability of tolterodine treatment were detected. CONCLUSIONS: The extent of the therapeutic response to tolterodine is largely determined by the extent of baseline symptoms. While gender does not affect the efficacy or tolerability of tolterodine in a clinically relevant manner, advanced age is associated with a slight decrease in efficacy but not in tolerability.

Age Factors↗

PubMed2002

Effect of apomorphine on intracavernous pressure and blood pressure in conscious, spinalized rats.

Apomorphine, given subcutaneously (s.c.), induces erection and bladder overactivity in rats through stimulation of dopamine (D1- and D2-like) receptors in the central nervous system. In paraplegic patients, apomorphine was reported to cause bladder overactivity. This suggests that apomorphine may have a spinal site of action also for stimulation of erection. The present study was initiated to evaluate the effect of apomorphine on erectile function in spinalized rats. Apomorphine (100 microg/kg, s.c.) was given to awake, unrestrained male Sprague-Dawley rats (300 g) with or without spinal cord injury, made at the Th 8 level 2 weeks before the experiment. Intracavernous pressure changes from baseline were evaluated as time to first response to apomorphine (TFR; sec), number of phasic pressure changes in the first 30 min (PP30), duration (D; sec) of the phasic pressure changes, the amount of increase in tonic peak pressure (TPP; cmH2O), and burst peak pressure (BPP; cmH2O). Blood pressure (cmH2O) was recorded via an intra-arterial catheter. Apomorphine, 100 microg/kg, caused no significant differences in TFR (217.8 vs 271.2), PP30 (6.4 vs 6.5), D (38.9 vs 37.6.), TPP (51.0 vs 54.0) and BPP (128.9 vs 160.4) between normal (n=8) and spinalized rats (n=6). However, blood pressure decreased significantly more in spinalized than in normal animals (17.7 vs 43.3; P<0.05). The results suggest that both in normal rats, and in rats with spinal cord injury, apomorphine given s.c., can produce erection. This finding supports the use of apomorphine for treatment of erectile dysfunction in paraplegia patients. However, due consideration should be given to possible decreases in blood pressure.

Animals↗

PubMed2005

Effects of botulinum toxin B on refractory detrusor overactivity: a randomized, double-blind, placebo controlled, crossover trial.

PURPOSE: Open, observational studies of intradetrusor injections of botulinum toxin for detrusor overactivity have reported beneficial effects. We tested the efficacy and safety of botulinum toxin B for the treatment of the overactive bladder in a randomized, double-blind, placebo controlled crossover trial. MATERIALS AND METHODS: A total of 20 patients 18 to 80 years old with detrusor overactivity unresponsive to oral antimuscarinic agents participated in the study. They were injected with either placebo (20 ml normal saline) or botulinum toxin B (5,000 IU diluted up to 20 ml) intravesically in a day case setting. After 6 weeks the treatments were crossed over without washout in line with previous findings. The primary outcome was the paired difference in change in average voided volumes. Frequency, incontinence episodes and paired differences in quality of life measured by the King's Health Questionnaire were the secondary outcome measures. RESULTS: The Wilcoxon signed ranks test was used to test the paired difference in change between treatment phases. Little carryover was noted in the second arm placebo and the placebo data from both arms were included in analysis. There were clinically statistically significant paired differences in the change in average voided volume, urinary frequency and episodes of incontinence between active treatment and placebo (average voided volume: 95% CI difference 16, 122; Z2.5; p = 0.012/weekly frequency: 95% CI -21, -1; Z2.1, p=0.033/weekly incontinence: 95% CI -26, -7; Z3.3; p = 0.001). There were similarly significant paired differences in the change in quality of life affecting 5 domains of the King's Health Questionnaire. CONCLUSIONS: This double-blind, placebo controlled, crossover study provides evidence of the efficacy of botulinum toxin B in the treatment of overactive bladder. Autonomic side effects were observed in 4 patients. The short duration of action will presumably limit the use to patients who have experienced tachyphylaxis with botulinum toxin A.

Administration, Intravesical↗

PubMed1998

Tolterodine.

Tolterodine is a competitive muscarinic receptor antagonist which has recently been launched for the treatment of overactive bladder. Tolterodine shows functional selectivity for the bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity. It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use. In patients with overactive bladder, toleterodine significantly reduces the frequency of micturition and number of incontinence episodes, while increasing the average volume voided. The onset of pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is maintained during long term treatment. In comparative trials, tolterodine and oxybutynin are equivalent in terms of efficacy. However, tolterodine is significantly better tolerated than oxybutynin, particularly with respect to the incidence and severity of dry mouth. No clinically relevant ECG changes have been noted with tolterodine.

Animals↗

PubMed1997

Stimulation of bladder activity by volume, L-dopa and capsaicin in normal conscious rats--effects of spinal alpha 1-adrenoceptor blockade.

To study possible differences in alpha 1-adrenoceptor involvement in the spinal mechanisms mediating bladder activity induced by volume (bladder filling), central (L-dopa), and peripheral (capsaicin) stimulation, we investigated if these types of bladder activity were modified by intrathecal (i.t.) or intra-arterial (i.a.) administration of the alpha 1-adrenoceptor antagonist, indoramin. Indoramin is selective for the alpha 1A-adrenoceptor subtype, whereas most clinically used alpha 1-adrenoceptor antagonists, including doxazosin, have no subtype selectivity. The drug effects were studied by continuous cystometry in normal, conscious rats and rats with bladder activity evoked by intraperitoneal L-dopa (50 mg/kg after carbidopa pretreatment), or by intravesical capsaicin (30 microM). I.t. indoramin (50 nmol) significantly decreased micturition pressure, and increased bladder capacity and micturition volume. Dribbling incontinence due to urinary retention was observed in one of ten rats. L-dopa-stimulated bladder overactivity was significantly attenuated by i.t. or i.a. indoramin (50 nmol). Similar effects of i.t. and i.a. doxazosin (50 nmol) have been reported previously. Intravesical capsaicin (30 microM) caused bladder activity, which was attenuated by i.t. indoramin (50 nmol), but not by i.t. doxazosin (50 nmol). I.a. indoramin did not reduce capsaicin-induced bladder activity; doxazosin was moderately effective. The results suggest that the bulbospinal micturition reflex evoked by bladder filling and L-dopa involves a descending pathway where transmission is partly mediated by spinal alpha 1-adrenoceptors. Bladder overactivity evoked by intravesical capsaicin, which elicits a vesicospinal-vesical reflex, was not affected by i.t. doxazosin in a dose that attenuates activity mediated through the bulbo-spinal pathway. This suggests less involvement of spinal alpha 1-adrenoceptors in the vesico-spinal-vesical than in the bulbo-spinal voiding reflex.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2004

Cerebral control of bladder function.

Symptoms such as overactive bladder represent disorders of bladder control. Functional brain scanning by positron emission tomography and functional magnetic resonance imaging suggest that normal control is exerted by a network of regions in the emotional nervous system, including periaqueductal gray, thalamus, insula, anterior cingulate, and prefrontal cortex. The network receives afferent signals, converts them to bladder sensations, and brings them to conscious attention, together with an unpleasant affect (desire to void) that motivates bladder emptying and thus maintains homeostasis. In patients with poor control, brain response to bladder filling differs; cerebral control is abnormal, even in the absence of involuntary detrusor contraction. Behavioral therapy and electrical stimulation appear to be possible treatments.

Brain↗

PubMed1989

Voiding dysfunction in patients with human T-lymphotropic virus type-1-associated myelopathy (HAM).

Voiding dysfunction was evaluated in 16 of 17 patients with human T-lymphotropic virus type-1 associated myelopathy (HAM). Among 16 patients 11 had both frequency and difficulty in voiding and 12 had urge incontinence of urine. Sensation of vesical filling and voiding remained either intact or only slightly suppressed in all patients. Residual urine ranging from 50 to 320 ml was observed in 14 patients. Urodynamic studies showed in every patient an overactive bladder with involuntary detrusor contraction. Only 2 patients had detrusor sphincter synergia, 6 patients had complete detrusor sphincter dyssynergia and 8 patients had incomplete detrusor sphincter dyssynergia. An overactive bladder associated with detrusor sphincter dyssynergia and less affected vesical sensation seems to be a characteristic urodynamic finding in HAM. These results combined with other neurological findings suggest that in patients with HAM lateral columns of the spinal cord between sacral and ponsmesencephalic micturition centre are mainly affected and that the posterior columns of the spinal cord are relatively less affected.

Adult↗

PubMed2004

Comparison of in vitro selectivity profiles of solifenacin succinate (YM905) and current antimuscarinic drugs in bladder and salivary glands: a Ca2+ mobilization study in monkey cells.

We investigated the effects of the new muscarinic receptor antagonist solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] and the current antimuscarinic drugs for the treatment of overactive bladder (oxybutynin, tolterodine and darifenacin) on intracellular Ca(2+) mobilization in response to M(3) muscarinic receptor activation in bladder smooth muscle and submandibular gland cells isolated from Cynomolgus monkeys. Solifenacin concentration-dependently inhibited carbachol-induced Ca(2+) mobilization, with affinity constant values (pKi) of 8.5 +/- 0.053 in bladder smooth muscle cells and 8.2 +/- 0.051 in submandibular gland cells (n = 5). The pKi value of solifenacin was almost equivalent to the values of oxybutynin, tolterodine and darifenacin in bladder smooth muscle cells (8.7, 8.5 and 8.4, respectively), while being lower than those in submandibular gland cells (9.0, 8.7 and 8.8, respectively). The bladder-selectivity index (Ki ratio: submandibular gland/bladder) for solifenacin (2.1) was statistically higher, moreover, than those for oxybutynin, tolterodine and darifenacin (0.51, 0.65 and 0.46, respectively). These findings consequently indicate solifenacin's unique profile in terms of its selectivity for bladder smooth muscle cells over salivary gland cells in non-human primates, relative to oxybutynin, tolterodine and darifenacin. Solifenacin may, therefore, confer a promising therapeutic advantage for reducing adverse effects, such as dry mouth, exhibited by current antimuscarinic therapy for overactive bladder.

Animals↗

PubMed2002

Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats.

PURPOSE: Adenosine triphosphate (ATP) (Sigma Chemical Co., St. Louis, Missouri) is known to contract animal as well as human detrusor muscle and recent investigations have shown an involvement of ligand gated purinergic-1 receptors in detrusor contraction. In addition, ligand gated purinergic-3 receptors have been demonstrated on suburothelial sensory nerves (C-fibers) and may be involved in distention induced initiation of the micturition reflex. We tested the hypothesis that ATP given intravesically can stimulate afferent nerves and initiate the micturition reflex. MATERIALS AND METHODS: Continuous cystometry was performed in conscious, freely moving, normal female Sprague-Dawley rats. Cystometric parameters were evaluated before and after drug administration. RESULTS: Instilled intravesically ATP (10 mM.) induced bladder overactivity in 6 animals with a mean increase in voiding pressure plus or minus standard error of 73 +/- 9 to 107 +/- 9 cm. water (p <0.01), mean baseline pressure increase of 5.32 +/- 0.58 to 12.71 +/- 1.01 cm. water (p <0.01) and mean bladder capacity decrease of 1.13 +/- 0.25 to 0.75 +/- 021 ml. (p <0.01). Lower concentrations had no significant effect. The effects of ATP were abolished by pretreatment with the ganglion blocker hexamethonium (40 mg./kg. ), nitric oxide synthase substrate L-arginine (Sigma Chemical Co.) (200 mg./kg. ) and neurokinin-2 receptor antagonist 123 (S)-N-methyl-N 123 4-(acetylamino-4-phenyl piperidone)-2-(3,4-dichlorophenyl) butyl 125 benzamide (Molecular Probes, Leiden, The Netherlands) (4 nmol.) given intravenously, the ligand gated purinergic-3 antagonist 2'-(or 3')-O-(trinitrophyl)adenosine 5'-triphosphate (50 microM./kg.) given intravenously and the k channel opener ZD6169 given intravesically.(ATP). CONCLUSIONS: ATP given intravesically can induce bladder overactivity, probably by stimulating suburothelial C-fibers. The data suggest that several mediators and mechanisms are involved in mechano-afferent transduction in the bladder.

Adenosine Triphosphate↗

PubMed2003

The impact on health-related quality of life of stress, urge and mixed urinary incontinence.

OBJECTIVE: To examine the impact of each type of urinary incontinence (stress, urge, and mixed) on health-related quality of life (HRQL). SUBJECTS AND METHODS: The USA National Overactive Bladder Evaluation (NOBLE) programme of prevalence was used to identify respondents with incontinence based upon telephone survey responses. A nested case-control study was then conducted on respondents with symptoms of an overactive bladder (OAB), and on age and gender-matched controls; this consisted of the respondents completing a series of questionnaires, including the OAB-q (an HRQL scale for OAB), the Medical Outcomes Study (MOS) Short-Form-36 (SF-36), the MOS Sleep Scale, and the Center for Epidemiological Studies - Depression (CES-D) scale. Respondents were categorized into subgroups according to the primary cause of urine loss, i.e. sudden/uncomfortable urge to urinate (urge, UI), physical pressure (stress, SI), or both (mixed, MI). Descriptive analyses, t-tests and analysis of variance with post hoc comparisons were used. RESULTS: Of the 919 participants in the nested case-control study, 171 reported incontinence, i.e. UI (69), SI (62) and MI (40). Among this cohort, 82.5% were female, 85.4% were Caucasian and the population had a mean age of 55.9 years. All OAB-q subscale scores were significantly (P < 0.01) worse among those with MI than with SI. Respondents with UI reported significantly higher levels of symptom bother and lower sleep scores (both P < 0.001) than those with SI. There were no differences in HRQL between the MI and UI groups. Voiding frequency and nocturia episodes did not differ among the groups but compared with the SI group, both UI and MI groups reported significantly higher ratings of urinary urge intensity (P < 0.001) and rated their need for medical care significantly higher (P < 0.01). The MI group reported more incontinence episodes (P = 0.02) than the SI group. CONCLUSION: Compared with SI, respondents with UI and MI reported not only significantly greater ratings of urinary urge intensity and more incontinence episodes, but also significantly worse HRQL. These results are consistent with previous findings which indicated a greater impact on HRQL for the urge component of MI than for the stress component.

Case-Control Studies↗

PubMed2005

Clinical pharmacokinetics of trospium chloride.

Trospium chloride, a quaternary amine with anticholinergic properties, is used for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency. The pharmacokinetics of trospium chloride have been investigated in healthy volunteers, in patients with renal and hepatic impairment, and in those with symptoms of overactive bladder, after oral, intravenous and intravesical administration. After oral administration, absorption of the hydrophilic trospium chloride is slow and incomplete. Peak plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4-5 hours after administration of a 20 mg immediate-release preparation. The mean bioavailability is approximately 10% and decreases by concomitant food intake (to a mean of 26% of the fasting area under the plasma concentration-time curve [AUC]). Trospium chloride displays dose proportional increases in AUC and Cmax after a single dose within the clinically relevant dose range (20-60 mg). The mean volume of distribution is approximately 350-800 L. The drug is minimally (mean approximately 10%) metabolised to spiroalcohol by hydrolysis, is 50% plasma protein bound and does not cross the blood-brain barrier. Urinary excretion of the parent compound plays a major role in the disposition of the drug, with a mean renal clearance of 29 L/h (accounting for approximately 70% of total clearance) and a mean elimination half-life ranging from 10 to 20 hours. Elimination of the drug is slowed in patients with renal insufficiency, and population pharmacokinetic modelling has demonstrated that drug clearance is correlated with serum creatinine concentration. Thus, dose reduction is needed in patients with severe renal impairment (i.e. creatinine clearance < 30 mL/min). To date, no clinically relevant pharmacokinetic drug-drug interactions have been identified; the drug does not bind to any of the drug metabolising cytochrome P450 enzymes. The pharmacokinetics of the drug are compatible with twice-daily administration. A once-daily schedule may also be appropriate, but this regimen needs formal clinical evaluation.

Administration, Oral↗

PubMed2003

Intravesical oxybutynin: a local anesthetic effect on bladder C afferents.

PURPOSE: Intravesical oxybutynin is used to control bladder overactivity in patients who are refractory to or cannot tolerate oxybutynin given orally. Although it is clinically effective, the mode of action of intravesical oxybutynin remains unclear. We tested the influence of intravesical oxybutynin on single fiber pelvic nerve afferents from the rat bladder. MATERIALS AND METHODS: A total of 15 single afferent bladder units were identified. Based on conduction velocity they were grouped as Adelta or C fibers. The effect of repeat bladder filling was studied on the mechanosensitive properties of these units. Oxybutynin was than instilled and left in the bladder for 15 minutes. Unitary afferent activity was again analyzed 15, 60 and 90 minutes after the drug was removed. RESULTS: Repeat bladder filling did not change nerve activity in Adelta or C fibers. At 15 minutes after oxybutynin was washed out of the bladder C fiber afferents responded significantly less to intravesical pressure and volume compared with control filling. At 60 minutes C fibers partly regained mechanosensivity. After 90 minutes sensitivity still increased without achieving the response level before oxybutynin. No significant changes were noted in Adelta fibers during repeat bladder filling or after oxybutynin instillation. CONCLUSIONS: In this study we showed that intravesical oxybutynin has a direct anesthetic effect within the bladder wall. It temporarily desensitizes C fiber afferents, which could explain its clinical benefits in decreasing symptoms of bladder overactivity. No measurable effect was found on Adelta fibers.

Administration, Intravesical↗

PubMed2003

Antenatal urodynamic studies in the fetal lamb: experimental protocol and preliminary results.

OBJECTIVES: To set up a fetal lamb model for intrauterine fetal urodynamic studies. METHODS: Fourteen fetal lambs underwent placement of a bladder catheter at a mean gestational age of 87 days. Three fetuses also had a partial urethral obstruction by the simultaneous placement of a peri-urethral constricting ring. Urodynamic and ultrasound studies were performed weekly by the filling cystometry method. RESULTS: Hundred and six voiding cycles were recorded during 25 urodynamic studies between 84- and 133-days gestation. All voiding profiles were biphasic with a mean duration of 4.2 min (range 1-10), a mean voiding pressure of 23 cm of water (range 7-33) and a mean periodicity of 19.2 min (range 11-50). The obstructed animals had bladder overactivity. This correlated with ultrasound and post-mortem findings of megacystis and bilateral hydroureteronephrosis. The fetal mortality rate was 85.7% and the mean duration of survival post surgery was 45 +/- 5.7 days. CONCLUSION: Serial urodynamic studies could be performed in a fetal lamb model. Following partial urethral obstruction, bladder overactivity was observed.

Animals↗

PubMed2005

Extracorporeal pelvic floor magnetic stimulation in children with voiding dysfunction.

OBJECTIVE: To determine the effect of extracorporeal pelvic floor magnetic stimulation in children with an overactive bladder, as although such stimulation is an effective treatment for voiding dysfunction such as urge incontinence (UI) and urgency-frequency syndrome, experience in children is scarce. PATIENTS AND METHODS: This prospective study included 42 children diagnosed with an overactive bladder, based on urodynamic or video-urodynamic study; a complete follow-up was available in 34. The children were grouped into those with UI only, not monosymptomatic nocturnal enuresis (nMNE), or MNE, according to their symptoms. Clinical variables were assessed by recording a voiding and nocturnal enuresis diary before and after magnetic stimulation, the latter being administered twice a week for 4 weeks using a size-adjusted magnetic chair (each session took 20 min). RESULTS: The UI only and nMNE group had a significant decrease in voiding frequency and frequency of UI (P < 0.05); the MNE group also had a significant decrease in voiding frequency (P < 0.05). There was a significant increase in functional bladder capacity in all groups (P < 0.05) but no significant decrease in the mean volume and frequency of NE in the nMNE and MNE groups (P > 0.05). CONCLUSIONS: Extracorporeal pelvic floor magnetic stimulation has an acute effect on voiding dysfunction such as urge syndrome in children. However, controlled studies with a sham-stimulation group and various durations of stimulation are necessary for its application as a primary treatment for voiding dysfunction in children.

Child↗

PubMed2003

Muscarinic receptors: what we know.

An understanding of muscarinic receptors is tantamount to an understanding of overactive bladder. The M(3) muscarinic receptor subtype is responsible for detrusor smooth muscle contraction and it exerts an exocrine function in the salivary glands. Alterations in the receptor's response to acetylcholine as a result of injury may lead to hypersensitivity and overactivity. The M(2) receptor subtype, which is mainly responsible for cardiac function, is the muscarinic receptor of highest proportion in the detrusor. M(2) also may play a role in detrusor contraction in injury and pathologic states. Muscarinic antagonists are the mainstay of pharmacotherapy for overactive bladder, but those that are available are not tissue specific. Growing knowledge of the nuances of receptor-ligand behavior and interaction between muscarinic receptors subtypes may provide novel targets for future drug development, improve efficacy, and reduce bothersome side effects.

Animals↗

PubMed2004

Risk factors for febrile urinary tract infection in children with myelodysplasia treated by clean intermittent catheterization.

OBJECTIVE: To identify the factors involved in the incidence of febrile urinary tract infection (UTI) in a retrospective study of children with myelodysplasia who were treated by clean intermittent catheterization. METHODS: A total of 76 myelodysplastic children were included in the present study. Any factors, including urodynamic parameters and urinary tract abnormalities, that may have been associated with the incidence of febrile UTI were evaluated using both a univariate analysis and a multiple logistic regression analysis. RESULTS: Of the 76 patients, 19 (25%) had one or more episodes of febrile UTI. A univariate analysis showed low bladder compliance (<10 mL/cmH2O), detrusor overactivity, bladder trabeculation and the presence of vesico-ureteral reflux (VUR) to be significant factors in the incidence of febrile UTI. The presence of detrusor overactivity and a low bladder compliance, in addition to the presence of VUR, were found to be significant factors for the incidence of febrile UTI using a multivariate analysis. CONCLUSION: These results demonstrate that, in addition to VUR, urodynamics linked to bladder storage function disorder appear to be directly correlated with the cause of febrile UTI in children with myelodysplasia.

Age Factors↗

PubMed2001

Bladder injection of "naked" hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo.

The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 microg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.

Administration, Intravesical↗

PubMed2026

Symptom assessment and health-related quality of life in children with lower urinary tract dysfunction: A retrospective cross-sectional study.

INTRODUCTION: Lower urinary tract dysfunction (LUTD) significantly impacts children's health-related quality of life (HRQoL), but key determinants of this impairment remain incompletely understood within a patient-centered framework. METHODS: This retrospective cross-sectional study enrolled 272 children with LUTD. Clinical symptoms were assessed using the Dysfunctional Voiding Scoring System (DVSS) and the Overactive Bladder Symptom Score (OABSS), and HRQoL via the Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scales. RESULTS: The mean total PedsQL score was 83.66 ± 16.07, with the School Functioning domain being the most impaired (73.75 ± 20.94). Univariate analysis identified older age (≥11 years), daytime urinary leakage, overactive bladder (OAB) symptoms, and abnormal DVSS scores as factors associated with reduced HRQoL (all P < 0.05); multivariate regression further confirmed only older age and abnormal DVSS were independent influencing factors (both P < 0.001). A significant negative correlation existed between the total DVSS score and the total PedsQL score (r = -0.390, P < 0.01), indicating that greater symptom severity predicts poorer overall HRQoL. CONCLUSION: This study indicates that in children with LUTD, the severity of voiding dysfunction (quantified by DVSS) is inversely correlated with HRQoL. Voiding dysfunction impairs multiple domains of daily functioning, including physical well-being, emotional adjustment, social interaction, and school performance. Shifting from a symptom-focused to a patient-centered care model and integrating routine HRQoL assessment into standard clinical management can optimize clinical practice for pediatric LUTD.

Humans↗