Persistence of solifenacin therapy in patients with overactive bladder in the clinical setting: a prospective, multicenter, observational study.

OBJECTIVES: The aim of this study was to evaluate the persistence with solifenacin therapy over a 12-month period in patients with overactive bladder (OAB). METHODS: This is a 52-week long, multicenter, prospective, observational study. The subjects were individuals ≥ 18 years old with OAB symptoms for ≥ 3 months, characterised by a total OAB Symptom Score (OABSS) of ≥ 3 and OABSS urgency item score of ≥ 2. Patients were prescribed 5 mg or 10 mg of solifenacin once daily for OAB symptoms. Drug persistence, reasons for discontinuation and factors related to the persistence were evaluated. RESULTS: A total of 1018 patients (329 men, 689 women) with a mean age of 59 years were included. The 52-week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36 weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in 13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94, 95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month period than were younger, male patients. The number of nocturia episodes was negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71-0.97). CONCLUSIONS: There was low persistence (22%) to solifenacin therapy for OAB symptoms over a 12-month period. Older patients, female patients and those with fewer episodes of nocturia were more persistent to therapy than were others.

The efficacy and tolerability of tarafenacin, a new muscarinic acetylcholine receptor M3 antagonist in patients with overactive bladder; randomised, double-blind, placebo-controlled phase 2 study.

OBJECTIVES: To evaluate the dose-response relationship of tarafenacin, an antimuscarinic agent in development phase, for efficacy and safety, at daily doses of 0.2 and 0.4 mg for the treatment of overactive bladder (OAB) PATIENTS AND METHODS: This multicentre, placebo-controlled, randomised, double-blind, phase 2b study was conducted. Patients were randomised to tarafenacin 0.2 mg, tarafenacin 0.4 mg or placebo daily for 12 weeks. Adult patients with OAB for at least 6 months, with an average of ≥ 8 micturitions per day and ≥ 3 incontinence episodes or a total of ≥ 6 urgency episodes per 3 days were enrolled. The primary objective was to compare the mean changes in the number of micturitions per 24 h of the two doses of tarafenacin compared with placebo from baseline to 12 weeks after treatment. RESULTS: A total of 334 patients were screened, of whom 235 patients were randomised. The mean decrease in the number of micturitions per 24 h from baseline to 12 weeks was statistically higher in the tarafenacin 0.4 mg group (-2.43 ± 2.21 times per day, p = 0.033) and non-statistically significant in the tarafenacin 0.2 mg group (-1.92 ± 2.45 times per day, p = 0.393) when compared with the placebo group (-1.77 ± 2.95 times per day). There were no statistically significant differences in the mean change of urgency episodes per 24 h among three groups. The most common adverse event was dry mouth. There were no significant differences in blurred vision and constipation compared with placebo. CONCLUSIONS: Tarafenacin 0.4 mg decreased the number of micturitions in patients with OAB after 12 weeks compared with placebo, and the dose-response relationship of tarafenacin 0.2 and 0.4 mg was confirmed. Both dose levels of tarafenacin were well tolerated.

A randomised, prospective double-blind, propiverine-controlled trial of imidafenacin in patients with overactive bladder.

AIM: To assess the efficacy and safety of imidafenacin compared with propiverine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: Patients with OAB symptoms were randomised to double-blind treatment with 0.1 mg of imidafenacin twice daily (group A) or propiverine 20 mg once daily (group B) for 12-week regimen, and assessed for efficacy and safety. The primary efficacy outcome was per cent change of weekly urgency urinary incontinence (UUI) episodes at week 12. The secondary efficacy outcomes were changes in the micturitions per day, urine volume voided per micturition, urgency episodes per day, complete disappearance of incontinence episodes and severity of urgency from baseline to week 12. Quality of life and safety profiles were also compared. RESULTS: Of 162 patients randomised, 140 completed the study protocol. The per cent change of weekly UUI episodes at week 12 was -69.1% in group A and -70.4% in group B (both p < 0.0001). The lower limit of 95% one-sided confidence interval of the difference between the groups was above the non-inferiority margin (-19.42%). Other voiding parameters and quality of life significantly improved at week 12 in both the groups. The discontinuation rates caused by adverse events were low in both the groups. While dry mouth was the most common adverse event (group A: 28.4% vs. B: 30.4%, p = 0.783), the severity of dry mouth was significantly less in the group A than B (p = 0.042) There were no significant differences in other safety profiles. CONCLUSIONS: After the 12-week treatment of imidafenacin 0.1 mg twice daily, all OAB symptoms and quality of life improved. Imidafenacin was not inferior to propiverine for the reduction of UUI episodes, and was better tolerated than propiverine in the safety profile. Our results indicate that imidafenacin is a safe and effective drug in Korean patients with OAB.

Patient-reported goal achievement after antimuscarinic treatment in patients with overactive bladder symptoms.

AIM: Standardised traditional outcome measures may fail to address factors that are important to patients and address irrelevant factors. Aim of this study was to assess patient-reported goals and goal achievement (GA) in the antimuscarinic treatment for overactive bladder (OAB) patients. METHODS: Men and women aged ≥ 18 years with OAB symptoms were eligible for the study. Treatment began with a dose of 10 mg oxybutynin, to be increased if necessary to 30 mg. Before treatment, each patient's primary treatment goal was identified. After 12-week treatment, patients reported GA using a Likert scale from 0 (no achievement) to 5 (complete achievement). Successful achievement was defined as a score of 4 or 5. Traditional outcome measures including voiding diaries, the OAB questionnaire short form, patient perception of bladder condition, and treatment benefit and satisfaction were assessed. Baseline characteristics affecting GA and the correlation between GA and traditional outcome measures were evaluated. RESULTS: A total of 303 goals were identified from 303 patients (51 men, 252 women). Of those, 72.3% addressed symptom relief and frequency as the most common target symptom. Other goals addressed were improving quality of life (13.5%) and eliminating coping behaviours (14.2%). After treatment, 42% had a successful GA with a median score of 3 (interquartile range; 2-4). Age had a negative effect on GA. Goal achievement was the outcome measure most correlated with treatment benefit and satisfaction. DISCUSSION AND CONCLUSIONS: Goal achievement can be a valuable outcome measure in OAB patients, addressing individual treatment goals and reflecting treatment benefit and patient satisfaction.

Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study.

PURPOSE: We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of >or= 8 voids per 24 h and episodes of urgency or urgency incontinence >or= 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King's Health Questionnaire. RESULTS: A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively). CONCLUSIONS: Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.

Strong independent association between obesity and essential hypertension.

Obesity and hypertension (HTN) are major risk factors for cardiovascular disease. Association between obesity and HTN has not been studied in a large populations following adjustment for comorbidities. The goal of this study was to evaluate any association between obesity and HTN after adjusting for baseline characteristics. We used ICD-9 codes for obesity and HTN from the Nationwide Inpatient Sample (NIS) databases. Two randomly selected years, 1992 and 2002, were chosen from the databases as two independent samples. We used uni- and multivariable analysis to study any correlation between obesity and HTN. The 1992 database contained a total of 6,195,744 patients. HTN was present in 37.2 % of patients with obesity versus 12% of the control group (OR: 4.36, CI 4.30-4.42, P < 0.001). The 2002 database contained a total of 7,153,982 patients. HTN was present in 50.7% of patients with obesity versus 25.6% of the control group (OR: 2.98, CI 2.96-3.00, P < 0.001). Using multivariable analysis adjusting for gender, hyperlipidaemia, age, smoking, type 2 diabetes and chronic renal failure, obesity remained correlated with HTN in both years (1992: OR 2.69, CI 2.67-2.72, P < 0.001; 2002: OR 2.98, CI 2.96-3.00, P < 0.001). The presence of obesity was found to be strongly and independently associated with HTN. The cause of this correlation is not known warranting further investigation.

A death in the family: household structure and mortality in rural Liaoning: life-event and time-series analysis, 1792-1867.

"Through a discrete-time life-event analysis of triennial household register data from a northeast Chinese village, Daoyi, between 1774 and 1873, we find that an individual's probability of dying, which we treat as an indicator of access to resources and the nature of household roles, was affected by the composition of their coresident kin.... Widows and widowers had higher mortality than the currently married. Orphans had higher mortality than children with at least one parent present. Reflecting the dependence of a wife's status on whether she had produced an heir for her husband, married women in young adulthood and middle age who had at least one son had substantially lower mortality than those without. Reflecting the strength of the claim that elderly males could make on household resources, children with coresident grandfathers had higher mortality than those without. Even though sons were supposed to be a form of old-age security, however, the death rate of the elderly was not reduced by the presence of sons and grandsons."

Comparative analysis of bladder wall compliance based on cystometry and biosensor measurements during the micturition cycle of the rat.

The stiffness characteristics of the empty and filling bladder and the modulating influence of oxybutynin were investigated using a new biosensor system. Studies were done comparing the stiffness measured using the pressure/volume relationship with direct biosensor monitoring on male and female rats during isovolumetric contractions elicited during the cystometrogram (CMG). Bladder stiffness at zero volume, measured in vitro using the biosensor, was evaluated and compared with the stiffness of the prostate, seminal vesicles, testicles, and uterus. In 5 small anesthetized male rats, in vivo isovolumetric studies were performed and bladder stiffness was measured during the storage and contraction phase of the CMG. In 6 mature female rats, change in bladder stiffness during isovolumetric contractions was investigated following intraarterial (i.a.) administration of 0.1 and 1.0 mg/kg of oxybutynin. After the in vivo CMG was completed, an in vitro CMG was done measuring bladder stiffness. The results show that bladder stiffness, measured during the storage phase of the CMG, increased in accordance with the stretched length of bladder wall. During the in vivo CMG, bladder stiffness increased consequent to a spontaneous contraction from 10.0 +/- 1.9 g/cm to 29.9 +/- 3.0 g/cm (P < 0.005). Oxybutynin produced a significant decrease in bladder stiffness during the storage phase of the CMG, as measured using the biosensor, which was concomitant with an increase in bladder compliance derived from pressure/volume data. The incremental change in stiffness, delta K, during isovolumetric contraction decreased due to i.a. oxybutynin in accordance with a decrease of maximum detrusor pressure. These results indicate that delta K is related to the active change of viscoelastic properties of bladder smooth muscle. These findings imply that direct measurement of the stiffness of the bladder wall possesses the potential to be an objective assessment of bladder biomechanical properties and of their functional response to obstruction and pharmacological intervention.

Chronology and urodynamic characterization of micturition in neurohormonally induced experimental prostate growth in the rat.

The purpose of this study was to evaluate the impact of chronic urinary tract obstruction which was produced in the rat using neurohormonally induced experimental prostate growth. In this model, we considered the chronology of changes in the micturition characteristics of awake rats relative to prostate weight and stiffness. The corresponding urodynamic characteristics of both the upper and lower tracts were evaluated in anesthetized animals relative to the development and extent of the obstruction produced. Prostate growth was produced by capitalizing on the synergistic properties afforded by the combined administration of dihydrotestosterone propionate (DHT) and the alpha1 adrenoreceptor antagonist prazosin (PRZ). DHT (1.25 mg/kg/day) was dissolved in 0.1 ml sesame oil (SO) and coadministered with PRZ 30 microg/kg/day subcutaneously for 14 days to 12 experimental rats. SO alone was given to 8 control rats. Micturition studies were first performed using all 20 awake rats, which were placed unrestrained in metabolic cages. Urodynamics of the upper and lower urinary tracts were repeated following anesthesia at the 5th, 10th, and 15th weeks after initiation of hormonal or SO treatment. Following the urodynamic studies, the rats were killed and prostates were removed and weighed, and stiffness was measured. Studies with awake rats show that hormonal treatment produces a significant and progressive increase in mean frequency of micturition, ranging from 0.63+/-0.16 in controls and reaching the maximum of 2.15+/-0.40/hr by the 10th wk. Results from urodynamic studies with anesthetized rats also show typical and progressive obstructive characteristics: maximum detrusor voiding pressure (Pdetmax) increased from 52.7+/-2.03 in controls to a maximum of 77.5+/-2.2 cm H2O by the 10th week; urethral opening pressure Puo likewise increased from 52.6+/-2.7 in controls to 73.3+/-2.1 cm H2O in experimental rats. The duration of time during which the detrusor sustains contraction during voiding also rose, from 16.8+/-1.8 sec in controls to 32.0+/-3.2 sec by the 10th week. There were no significant changes in bladder capacity, baseline filling pressures, or arterial pressures. Prostate weight increased significantly from 0.76+/-0.05 g in controls to 1.17+/-0.1 g by the 15th week. Similarly, stiffness increased from control values of 1.33+/-0.18 g/cm to a maximum of 3.59+/-0.14 g/cm by the 10th week. It is concluded that neurohormonally stimulated prostate growth in the rat is a suitable animal model for the study of the development of urinary tract obstruction. Obstructive characteristics were validated in both awake rats by the increase in the frequency of micturition and urodynamically under anesthesia in terms of elevations in maximum detrusor pressures, urethral opening pressure, detrusor contraction time, and prostatic stiffness. The effect of obstruction was further shown to be associated with vesicoureteral reflux during micturition and elevated upper tract pressures.

Effect of alpha1 adrenoceptor antagonist on the urodynamics of the upper and lower urinary tract of the male rat.

In this investigation, we examined the impact of the alpha1 adrenoceptor (alpha1-ADR) antagonist prazosin on the urodynamic characteristics of upper urinary tract function and associated micturition characteristics of the adult male rat. The focus of the study was to evaluate the extent to which prazosin affects urine production and ureteral transport relative to its effect on micturition. Control micturition studies were first performed using 28 awake Sprague-Dawley rats that were placed in metabolic cages for characterization of the frequency and mean and total volume voided over a 4-hr period. Following the control studies, the effect of intraperitoneal prazosin, 30 microg/kg, was evaluated under identical conditions. Urodynamic studies were done to identify the bladder filling and voiding characteristics of anesthetized rats that were infused with saline at a rate of 0.22 ml/min. From the urodynamic studies the parameters of bladder pressure (Pves) and volume (V) during filling, urethral opening (Puo) measured at the moment of micturition, and maximum detrusor pressure during voiding (Pdetmax) were evaluated. External sphincter electromyography was also monitored and recorded together with bladder pressure during voiding. Renal pelvic pressure was measured via a nephrostomy catheter and recordings were made simultaneously with bladder filling and voiding. The upper urinary tract was visualized using microscopic video imaging of the ureter, contrasted by perfusing the renal pelvis with indigo carmine. Characterization of upper tract transport was made in terms of renal pelvic pressure, ureteral peristaltic rate, and bolus length and velocity. The results show that in the awake rat, 30 microg/kg of prazosin decreased the urine production rate from 4.8 +/- 0.074 to 1.6 +/- 0.23 ml (P < 0.001) and micturition frequency by a similar proportion from 1.99 +/- 0.44 to 0.53 +/- 0.08/hr. In the lower urinary tract, prazosin did not change the baseline pressure of the bladder but produced significant dose-dependent decreases in Pdetmax, Puo, and frequency of micturition. In the upper urinary tract, ureteral and pelvic frequencies decreased, whereas the length of bolus increased significantly corresponding to increased doses of prazosin. These results suggest that, although prazosin facilitates micturition by reducing urethral opening pressure, it also reduces the rate of urine production and modulates the function of urine transport in the upper urinary tract.

An epidemiological study of enuresis in Korean children.

OBJECTIVE: To estimate the prevalence of enuresis in children of elementary school age, to evaluate the impact of enuresis on these children and their parents, and to identify the methods and effectiveness of managing enuresis. Subjects and methods A randomly selected cross-sectional study was conducted in one elementary school in each urban ward (nine schools) in Pusan, Korea. The parents of these 12 570 children aged 7-12 years were asked to complete questionnaires which included items about the presence and frequency of enuresis, its perceived impact and management. Enuresis was defined as an episode of wetting occurring at least once per month. RESULTS: The overall response rate to the questionnaire was 55.8% (girls 28.2%, boys 27.6%). The prevalence of nocturnal, diurnal and combined enuresis was 9.2%, 2.2% and 1.4%, respectively. The overall prevalence of enuresis declined with age from 20.4% at 7 years old to 5.6% at 12 years old; 342 (57.0%) parents and 318 (55. 6%) children were concerned about enuresis. The common self-help strategies were waking the child at night to void (38.1%) and restriction of water intake (25.7%). Of the enuretic children, only 13.7% had consulted a health worker. CONCLUSION: The prevalence rates for enuresis in Pusan are similar to those reported from European countries. Enuretic children and their parents were moderately concerned about enuresis and the parents primarily used self-management within the family.