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Simon Hill

Publications and source records attributed to Simon Hill.

8 recordsLinked to original sources
PubMed2006

Current and future trends in the management of overactive bladder.

Urinary incontinence is a common problem which increases in prevalence in association with advancing age and has a significant adverse effect upon well-being and quality of life. It is not the "benign" condition that many take it for. Overactive bladder (frequency-urgency syndrome) is the commonest bladder problem in late life, affecting up to 41% of over-75-year-old individuals, and the elderly experience more severe disease. This small series should provide the reader with a comprehensive overview of the current thinking in the assessment and management of patients with overactive bladder syndrome, explores the history of the condition and current approaches to its medical and surgical management and explores where management may change in more complex populations. The current state and future developments in pharmacological therapy are also outlined.

Aged↗
PubMed2005

Dose response with darifenacin, a novel once-daily M3 selective receptor antagonist for the treatment of overactive bladder: results of a fixed dose study.

This study evaluated the efficacy, tolerability, and safety of darifenacin, an M3 selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB). In a multicenter, double-blind, placebo-controlled dose-ranging study, 439 adult OAB patients (85.4% female) were randomized to darifenacin controlled-release tablets 7.5 mg (n = 108), 15 mg (n = 107) or 30 mg (n = 115) qd, or placebo (n = 109) for 12 weeks. Darifenacin significantly reduced the median number of incontinence episodes/week (-68.7, -76.5, and -77.3% from baseline at 7.5, 15, and 30 mg, respectively, vs -46% with placebo, all p < 0.01) and dose relatedly improved micturition frequency, frequency and severity of urgency, nocturia, and bladder capacity. Darifenacin was well tolerated. Adverse events were commonly mild to moderate dry mouth and constipation. There were no safety concerns. Darifenacin is effective and well tolerated in the treatment of OAB, with 7.5 and 15 mg doses offering flexibility of dosing for optimal treatment outcome.

Adult↗
PubMed2005

Stress incontinence injection therapy: what is best for our patients?

OBJECTIVE: Urethral injection (periurethral/intraurethral bulking) is an established, minimally invasive therapy for stress urinary incontinence (SUI). This review aims to determine which women should potentially benefit from, and be considered as candidates for, injection therapy and to elucidate what we are trying to achieve. METHODS: Based on MEDLINE database searches, all aspects of urethral injection were examined, including patient selection, safety, injection technique, efficacy, quality of life, goals and cost. RESULTS: Such therapy has a low complication rate, improves or cures about 3 out of 4 women, as shown in mainly short-term studies, and improves patients' quality of life. It can be used in the majority of patients with uncomplicated SUI. Therefore, injection therapy may be considered as a first-line treatment option for patients who have failed conservative therapy such as pelvic floor exercises and who decline or have a contraindication for pharmacological treatment. However, the decision of whether to use this type of treatment must be based on an informed discussion between the physician and patient--this dialogue should incorporate questions about patients' own treatment goals. Injection therapy appears to have the profile required to meet patients' goals, based on the findings that a procedure with an improvement in incontinence, minimal short-term risk, no long-term risk, and performed in a clinic, would be acceptable. CONCLUSION: Investigating and trying to achieve patients' own treatment goals will ultimately enable us to do what is best for our patients, but current evidence suggests that injection therapy is a valid option worth discussing with many patients.

Biocompatible Materials↗
PubMed2004

Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancer.

PURPOSE: Virus-directed enzyme prodrug therapy depends on selective delivery of virus encoding a prodrug-activating enzyme to tumor, followed by systemic treatment with prodrug to achieve high levels of the activated cytotoxic at the intended site of action. The use of the bacterial enzyme nitroreductase to activate CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) to a short lived, highly toxic DNA cross-linking agent has been demonstrated in tumor xenografts. In this study, we report the first clinical trial investigating the feasibility, safety, and transgene expression of a replication-defective adenovirus encoding nitroreductase (CTL102) in patients with liver tumors. PATIENTS AND METHODS: Patients with resectable primary or secondary (colorectal) liver cancer received a single dose of CTL102 delivered by direct intratumoral inoculation 3 to 8 days before surgical resection. RESULTS: Eighteen patients were treated with escalating doses of CTL102 (range, 10(8)-5 x 10(11) virus particles). The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Dose-related increases in tumoral nitroreductase expression measured by immunohistochemical analysis have been observed. CONCLUSION: Direct intratumoral inoculation of CTL102 to patients with primary and secondary liver cancer is feasible and well tolerated. The high level of nitroreductase expression observed at 1 to 5 x 10(11) virus particles mandates further studies in patients with inoperable tumors who will receive CTL102 and CB1954.

Adenoviridae↗
PubMed2004

Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial.

OBJECTIVES: To examine the efficacy and tolerability of antimuscarinic therapy in women with urge-predominant mixed incontinence. METHODS: This was a double-blind, randomized, placebo-controlled trial comprising 854 women with urge-predominant mixed incontinence, including urge incontinence (five or more episodes per week), urinary frequency (eight or more micturitions on average in 24 hours), and urgency in combination with stress incontinence. Women received 8 weeks of treatment with tolterodine tartrate extended-release (ER) 4 mg or placebo once daily. The outcome measures included urge incontinence episodes per week, stress incontinence episodes per week, micturition frequency per 24 hours, urgency episodes per 24 hours, volume voided per micturition, patient perception of bladder condition, and assessment of treatment benefit. RESULTS: After 8 weeks, tolterodine ER produced a statistically significant decrease in the weekly urge incontinence episodes compared with placebo (-12.3 versus -8.0; P <0.0001). Other micturition variables improved significantly more with tolterodine ER. No difference was found between treatment groups regarding the change in the number of stress incontinence episodes. A significantly greater proportion of patients receiving tolterodine ER than those receiving placebo reported improvement in bladder condition (61% versus 46%; P <0.001) and treatment benefit (76% versus 55%; P <0.001). After 8 weeks, the tolterodine ER group had experienced statistically significant improvements compared with the placebo group in 9 of 10 quality-of-life domains. The frequency of adverse events was similar between treatment groups. CONCLUSIONS: Tolterodine ER is an effective treatment of urge urinary incontinence, frequency, and urgency in women with concomitant stress urinary incontinence. The efficacy of tolterodine ER in reducing urge incontinence episodes was unaffected by the presence of stress incontinence. The results of this study support the first-line use of antimuscarinic therapy to treat the urge incontinence component of urge-predominant mixed incontinence.

Adult↗
PubMed2003

Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine.

OBJECTIVE: To evaluate the effect of once-daily, extended-release tolterodine on urinary urgency in patients with overactive bladder. METHODS: Patients with urinary frequency (eight or more micturitions per 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral treatment with tolterodine extended release 4 mg once daily (n=398) or placebo (n=374) for 12 weeks. Efficacy was assessed by use of patient perception evaluations. RESULTS: The results presented are a secondary analysis of this double-blind, placebo-controlled study. Of patients treated with tolterodine extended release, 44% reported improved urgency symptoms (compared with 32% for placebo), and 62% reported improved bladder symptoms (placebo, 48%) (both P<.001 compared with placebo). The odds of reducing urgency and improving bladder symptoms were 1.68 and 1.78 times greater, respectively, for patients in the tolterodine extended release group than for patients receiving placebo. In response to urgency, there was a more than six-fold increase in the proportion of patients able to finish a task before voiding in the tolterodine extended release group. The proportion of patients unable to hold urine upon experiencing urgency was also decreased by 58% with tolterodine, compared with 32% with placebo (P<.001). The proportion of patients reporting "much benefit" from treatment was greater for tolterodine extended release than for placebo (43% versus 24%; P<.001). The only adverse events with an incidence of greater than 5% were dry mouth, headache, and constipation, with only dry mouth markedly more frequent with tolterodine than with placebo. CONCLUSION: Tolterodine extended release has demonstrable efficacy in reducing the severity of urinary urgency and is associated with improvements in overactive bladder symptoms that are meaningful to patients.

Administration, Oral↗