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.

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.

The role of inducible 70-kDa heat shock protein in cell cycle control, differentiation, and apoptotic cell death of the human myeloid leukemic HL-60 cells.

Several studies have suggested a role for heat shock proteins (hsps) during development and differentiation. However, relatively little is known about the role of hsp70 in controlling human hematopoietic cell differentiation and death. Here, we show that constitutive expression of human inducible 70-kDa heat shock protein (hsp70) promotes differentiation of HL-60 cells and prevents apoptosis that occurred after terminal differentiation or directly by apoptotic agents. After treatment with phorbol 12-myristate 13-acetate (PMA), hsp70-overexpressing cells (HL-60/hsp70) underwent rapid growth arrest and plastic adherence and expressed more CD14 than parental HL-60 or empty vector-transformed cells (HL-60/puro). HL-60/hsp70 cells also rapidly differentiated into granulocytes by addition of all-trans-retinoic acid, as assessed by phenotypic changes after staining with Wright-Giemsa. After differentiation into monocyte/macrophage-like cells or granulocytes, hsp70-overexpressing cells showed little evidence for apoptosis and had a prolonged survival, indicating that the survival-enhancing properties of hsp70 counteract programmed cell death that accompanies terminal differentiation. HL-60/hsp70 cells also showed more resistance than parental cells against apoptotic agents such as sodium nitroprusside, a NO-generating agent, or Taxol, a microtubule stabilizing agent. Further, heat shock of parental HL-60 cells at 42 degrees C for 3 h increased hsp70 levels, promoted plastic adherence (< 6 h) of the cells in respond to PMA, and protected cells from SNP or Taxol. Taken together, these studies demonstrate that hsp70 plays a crucial role in the differentiation of myeloid cells, participating in cell cycle controls and phenotypic changes, with protecting effects on apoptosis induced by different pathways.