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Biomedical subjects

P Dwyer

Publications and source records attributed to P Dwyer.

At least 19 recordsLinked to original sources
PubMed2004

Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder.

OBJECTIVES: To evaluate the efficacy, tolerability and safety of darifenacin, a once-daily M3) selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB). METHODS: This multicentre, double-blind, placebo-controlled, parallel-group study enrolled 561 patients (19-88 years; 85% female) with OAB symptoms for >6 months, and included some patients with prior exposure to antimuscarinic agents. After washout and a 2-week placebo run-in, patients were randomised (1:4:2:3) to once-daily oral darifenacin controlled-release tablets (3.75 mg [n=53], 7.5 mg [229] or 15 mg [n=115]) or matching placebo (n=164) for 12 weeks. Patients recorded daily incontinence episodes, micturition frequency, bladder capacity (mean volume voided), frequency of urgency, severity of urgency, incontinence episodes resulting in change of clothing or pads and nocturnal awakenings due to OAB using an electronic diary during weeks 2, 6 and 12 (directly preceding clinic visits). Tolerability data were evaluated from adverse event reports. RESULTS: Darifenacin 7.5 mg and 15 mg had a rapid onset of effect, with significant improvement compared with placebo being seen for most parameters at the first clinic visit (week 2). This effect was sustained through week 12. At this time the number of incontinence episodes per week was reduced from baseline by 67.7% with darifenacin 7.5 mg and 72.8% with darifenacin 15 mg compared with 55.9% with placebo (p=0.010 and p=0.017, respectively, versus placebo). The 3.75 mg group (null dose arm) was included for proof of concept of dose flexibility, therefore formal sample sizing and statistical analysis were not performed for this group. Darifenacin 7.5 mg and 15 mg, respectively, were significantly superior to placebo for improvements in micturition frequency (p<0.001, p<0.001), bladder capacity (p<0.040, p<0.001), frequency of urgency (p<0.001, p=0.005), severity of urgency (p<0.001, p=0.002) and number of incontinence episodes leading to a change in clothing or pads (p<0.001, p=0.002). There was no significant reduction in nocturnal awakenings due to OAB. The most common adverse events were mild-to-moderate dry mouth and constipation. However, no patients withdrew from the study as a result of dry mouth and discontinuation related to constipation was rare (0.6% placebo versus 0.9% darifenacin). In addition, there was a low need for laxative use, with no difference between the darifenacin groups and those taking placebo. There were no reports of blurred vision and the CNS and cardiac safety profile was comparable to placebo. CONCLUSIONS: Darifenacin significantly improves the major symptoms of OAB. No significant CNS (primarily M1-receptor mediated) adverse events or cardiac (primarily M2-receptor mediated) adverse events were identified in this study, as may be predicted from the M3 selective receptor profile of darifenacin.

Adult↗
PubMed2003

Direct repair vs. overlapping sphincter repair: a randomized, controlled trial.

PURPOSE: The aim of this study was to compare the results of two surgical techniques (direct end-to-end vs. overlapping) of delayed repair of a localized anterior defect of external anal sphincter after an obstetric trauma. METHODS: During a five-year period, 23 patients were randomly assigned to direct end-to-end repair (n = 12) or overlapping sphincter repair (n = 11), using 2-0 PDS sutures. Two patients from each group had an internal anal sphincter defect that also was repaired. All patients had a normal pudendal nerve terminal motor latency preoperatively. Evaluations included endoanal ultrasound, anorectal manometry, and neurophysiologic evaluation. Continence was assessed by the Cleveland Clinic Continence Score (0-20; 0, perfect continence; 20, complete incontinence). RESULTS: The two groups were comparable with regard to age (median, 45 years), past history of sphincter repair (n = 2), and posterior vaginal repair. There was no major morbidity. The wound-healing rate was identical between the two groups. However, of the patients undergoing overlapping repair, two had fecal impaction, and one had a urinary retention. Median preoperative continence score was 17 in both the direct-repair group (score, 8-20) and the overlap group (score, 7-20). At a median follow-up of 18 months, the improvement in continence was similar between the two surgical groups, with a median continence score of 3, respectively. In both surgical groups there was a significant and similar improvement in maximum squeeze pressure and in the functional anal canal length postoperatively (P < 0.05), but the mean resting pressure was relatively unchanged. In the overlap group, one patient developed a unilaterally prolonged pudendal nerve terminal motor latency that was persistent 22 months after surgery, and two patients had impaired fecal evacuation postoperatively. CONCLUSIONS: This randomized, controlled study suggests that the outcome is similar whether direct end-to-end or overlapping repair of a sphincter defect is performed. Overlapping repair might be associated with more difficulties with fecal evacuation and a prolonged pudendal nerve terminal motor latency postoperatively.

Adult↗
PubMed2001

Pubovaginal or vicryl mesh rectus fascia sling in intrinsic sphincter deficiency.

The aim of this study was to compare the pubovaginal sling with a new Vicryl mesh rectus fascia (VMRF) sling in the surgical treatment of low urethral pressure genuine stress incontinence. Fifty-one consecutive women who had a VMRF (n = 27) or a pubovaginal sling (n = 24) procedure between March 1995 and December 1997 were evaluated. The patient-determined subjective success rate of the VMRF sling (85%) was significantly higher than that of the pubovaginal sling (58%) in women with low urethral pressure stress incontinence (P=0.03). The objective success rates following the VMRF and the pubovaginal sling were 52% and 50%, respectively. The prevalence of postoperative symptomatic voiding dysfunction and de novo detrusor instability was 7% after the VMRF sling and 25% following the pubovaginal sling (P = 0.08). The VMRF sling had a higher patient-determined success rate and a lower complication rate than the pubovaginal sling, and should be considered in the surgical management of women with low urethral pressure stress incontinence.

Adult↗
PubMed2001

A new intravaginal device for stress incontinence in women.

OBJECTIVE: To compare two versions of the same type of disposable intravaginal device (the Conveen Continence Guard, CCG, and the Contrelle Continence Tampon, CCT, Coloplast a/s, Humlebaek, Denmark) for treating stress incontinence in women. PATIENTS AND METHODS: Women with the predominant symptom of stress incontinence were recruited from four centres in Denmark, Australia and the UK. The women were assessed using a 24-h pad-test, uroflowmetry, postvoid residual urine volume and a voiding diary before treatment, and after 5 weeks using each of the two devices. Vaginal swabs and specimens of urine were sent for culture, and a questionnaire about the subjective effect and adverse events completed at each visit. In all, 94 women were recruited, of whom 62 (66%) completed the study. RESULTS: Both devices reduced the amount of leakage significantly, but the CCT reduced urine loss significantly more than the CCG. Uroflowmetry values and residual urine volume were unchanged when using the two devices. Vaginal culture showed no abnormality during the study period, and only one woman was treated for a urinary tract infection. Side-effects were few and not serious. The women found both devices easy to prepare, insert and use; two-thirds preferred the CCT to the CCG. CONCLUSION: The new intravaginal device (CCT) is more effective for treating stress incontinence than the currently available version (CCG), and patient acceptability of the new device seems to be superior.

Adult↗
PubMed2000

Confirmation of onychomycosis by in vivo confocal microscopy.

Onychomycosis is common in adults and constitutes 20% of all nail disease. Widely used methods to confirm a clinical diagnosis of onychomycosis often yield negative results (ie, potassium hydroxide [KOH] preparation) or are slow (ie, dermatophyte cultures). We report a case of onychomycosis in which we used in vivo confocal microscopy to diagnose the disease; we also correlated our findings with results from routine KOH preparations. On the basis of our findings, we hypothesize that in vivo confocal microscopy may be faster and more accurate than the conventional microscope used in KOH preparations in the diagnosis of onychomycosis.

Adult↗
PubMed2000

Telephone-administered cognitive-behavioral therapy for the treatment of depressive symptoms in multiple sclerosis.

This study examined the efficacy of an 8-week telephone-administered cognitive-behavioral therapy (CBT) for the treatment of depressive symptomatology in multiple sclerosis (MS) patients. The treatment, Coping with MS (CMS), included a patient workbook designed to structure the treatment, provide visual aids, and help with homework assignments. Thirty-two patients with MS, who scored at least 15 on the Profile of Mood States Depression-Dejection scale, were randomly assigned to either the telephone CMS or to a usual-care control (UCC) condition. Depressive symptomatology decreased significantly in the CMS condition compared with the UCC condition. Furthermore, adherence to interferon beta-1a, a disease-modifying medication for the treatment of MS, was significantly better at the 4-month follow-up among patients who received CMS as compared with those in the UCC condition.

Adaptation, Psychological↗
PubMed1999

Course of depression during the initiation of interferon beta-1a treatment for multiple sclerosis.

OBJECTIVE: To examine the hypothesis that increases in depression after initiation of treatment with interferon beta-1a for multiple sclerosis can be explained as representing a return to pretreatment levels of depression. DESIGN: Level of depression in patients with multiple sclerosis was assessed at 3 time points: 2 weeks before initiation of interferon beta-la treatment, at initiation of treatment, and at 2-month follow-up. SETTING: A health maintenance organization. PATIENTS: Fifty-six patients with confirmed relapsing forms of multiple sclerosis. MAIN OUTCOME MEASURE: The depression-dejection scale of the Profile of Mood States. RESULTS: Patients who scored high on the depression measure 2 weeks before the initiation of interferon beta-1a treatment showed significant reduction in depression at the initiation of treatment. However, depression returned nearly to initial levels within 2 months. CONCLUSIONS: These findings suggest that increases in depression after initiation of interferon beta-1a treatment are related to level of depression 2 weeks before initiation of treatment. Physicians should assess history of depression for all patients in whom interferon beta-1a treatment is initiated. Patients with a recent history of depression are at risk for increased depression within 2 months after starting interferon beta-1a treatment, even though they may not be depressed at the time of treatment initiation.

Adjuvants, Immunologic↗
PubMed1999

Transanal repair of rectocele corrects obstructed defecation if it is not associated with anismus.

PURPOSE: Rectocele is often associated with anorectal symptoms. Various surgical techniques have been described to repair the rectocele. The surgical results are variable. This study evaluated the results of transanal repair of rectocele, with particular emphasis on the impact of concomitant anismus on postoperative functional outcome. METHODS: Fifty-nine consecutive females who underwent transanal repair of rectocele for obstructed defecation were prospectively reviewed. All 59 patients were parous with a median parity of 2 (range, 1-6) and a median age of 58 (range, 46-68) years. The median length of follow-up was 19 (range, 6-40) months. Anismus was detected by anorectal physiology and defecography. The functional outcome was assessed by a standard questionnaire, physical examination, anorectal manometry, neurophysiology, and defecography. The quality-of-life index was obtained using a visual analog scale (from 1-10, with 10 being the best). RESULTS: The functional outcome of transanal repair of rectocele was superior in patients without anismus. Forty (93 percent) of the 43 patients without anismus showed improved evacuation after repair compared with 6 (38 percent) of the 16 patients with anismus (P<0.05). The quality-of-life index improved (9 vs. 4) if anismus was not present (P<0.05). There were minimal complications. Hemorrhage requiring blood transfusion (2 units) occurred in one patient and urinary retention in another. CONCLUSION: Transanal repair of rectocele is safe and, in the absence of anismus, effectively corrects obstructed defecation.

Aged↗
PubMed1999

The Burch colposuspension for recurrent urinary stress incontinence following retropubic continence surgery.

OBJECTIVE: To evaluate the Burch colposuspension with Cherney incision in women with recurrent urinary stress incontinence after retropubic continence surgery. DESIGN: A retrospective review. PARTICIPANTS: All 53 women had recurrent urinary stress incontinence after retropubic continence surgery with an average of 2.1 (range 1-5) previous failed continence procedures per woman. MAIN OUTCOME MEASURES: Subjective and objective success rates and complications including detrusor instability, voiding difficulties and genital prolapse. RESULTS: Forty-seven women (89%) had no or occasional (< one episode per week) stress or urge incontinence. One woman had persistent stress incontinence and five urge incontinence. Forty-two women (80%) rated their surgery as being highly successful and 38 women (72%) had no urinary leakage due to genuine stress incontinence or detrusor instability on repeat urodynamic evaluation. Three women (6%) developed de novo detrusor instability post-operatively. Two women (4%) had voiding difficulties post-operatively that necessitated the use of intermittent self-catheterisation for at least four months. The median length of follow up was nine months (4-72). In 39 women (73%), marked retropubic fibrosis was found at the time of surgery. CONCLUSIONS: Marked retropubic fibrosis should be expected in women with recurrent stress incontinence after retropubic continence surgery. The Burch colposuspension with the assistance of the Cherney incision and sharp dissection of retropubic fibrosis is an effective and safe procedure for women with this condition.

Adult↗
PubMed1999

Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.

PURPOSE: We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity. MATERIALS AND METHODS: In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects. RESULTS: After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events. CONCLUSIONS: Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.

Adult↗
PubMed1999

Bladder microvasculature in women with interstitial cystitis.

PURPOSE: A cardinal cystoscopic finding in women with interstitial cystitis is mucosal small vessel hemorrhage or glomerulations after hydrodistention. We quantified and compared microvascular density and endothelial proliferation in the bladder biopsies of women with interstitial cystitis and a control group of women who were undergoing incontinence or prolapse surgery. MATERIALS AND METHODS: We performed computer assisted image analysis and immunohistochemical studies to compare differences in the blood vessel count, and proportional area in the bladder suburothelium and deeper submucosa of bladder biopsies of 52 women, including 26 with interstitial cystitis. Routine light microscopy features were examined and correlated with microvascular density. RESULTS: In the bladder biopsies of women with interstitial cystitis there was a lower blood vessel count (p = 0.01), and a lower proportion of the total image consisted of blood vessel wall (p = 0.03) in the suburothelium than in control biopsies. We noted no difference in the blood vessel count of the deeper submucosa or in the degree of endothelial cell proliferation. Suburothelial blood vessel differences correlated with the degree of histological change, such as edema, inflammatory infiltrate and vascular congestion. CONCLUSIONS: We found decreased microvascular density in the suburothelium but not in the deeper submucosa in bladder biopsies of women with interstitial cystitis.

Cystitis, Interstitial↗
PubMed1998

Side effect profile and adherence to in the treatment of multiple sclerosis with interferon beta-1a.

This study examines the course of patient-reported side effects during the first 4 months of treatment for multiple sclerosis (MS) with interferon beta-1a (IFN beta-1a), and the relationship of those side effects to discontinuation of medication. Flu-like symptoms, muscle aches and chills decreased over the first 2 months of treatment but did not change over the second 2 months. Loss of feeling or numbness, tingling and depression increased over 4 months, however these side effects were generally mild. Loss of feeling or numbness and tingling at 2 month follow-up were significantly related to discontinuation of IFN beta-1a by 4 month follow-up.

Adolescent↗
PubMed1997

Allergic contact dermatitis to adhesive tape and contrived disease.

A case of allergic contact dermatitis, caused by colophony in an orthopaedic tape, is presented. This failed to heal, despite removal of the allergen. Only after a period of observation in hospital and, finally, gentle confrontation with the patient, did it become clear that the perpetuation of the dermatitis was an example of contrived disease.

Adult↗