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Biomedical subjects

Vik Khullar

Publications and source records attributed to Vik Khullar.

At least 19 recordsLinked to original sources
PubMed2006

Achieving continence with antimuscarinic therapy for overactive bladder: effects of baseline incontinence severity and bladder diary duration.

OBJECTIVE: To examine the continence ('dryness') rate as an outcome measure of the efficacy of antimuscarinic treatment, and to explore how changes in bladder diary duration, baseline severity of urinary incontinence (UI), and study population characteristics affected this outcome. PATIENTS AND METHODS: Urgency UI is a symptom of overactive bladder (OAB) and antimuscarinic agents are a first-line treatment for OAB symptoms; several studies have used dryness rate as an efficacy endpoint, calculated as the percentage of patients who record no UI episodes in a diary period. We performed a post hoc analysis of data from a 12-week, multicentre, randomized, double-blind, placebo-controlled trial of tolterodine extended-release (ER) in patients with symptoms of urinary frequency (> or =8 voids/24 h) and urgency UI (> or =5 episodes/week). Patients with stress UI were excluded. Diary entries from the 3-, 5-, and 7-day periods immediately preceding the baseline and the week 12 visit were used to assess the relationships between the percentage of patients reporting total dryness at week 12, diary duration (3, 5, or 7 days), baseline number of weekly UI episodes (1-6, 7-13, 14-20, > or = 21), and population analysed (intent-to-treat, ITT, or per protocol, PP). The mean changes in weekly UI episodes from baseline to week 12 are also reported by diary duration and baseline frequency of UI for patients treated with tolterodine-ER. RESULTS: The total dryness rates decreased with increasing diary duration and greater frequency of UI at baseline. Analysis of the ITT population also showed lower dryness rates than the PP population. However, the mean reductions in weekly UI episodes for the ITT and PP populations were consistent across diary duration for each level of baseline UI frequency. CONCLUSION: 'Dryness' varies with diary duration, baseline frequency of UI, and the population analysed. Comparisons of dryness rates between studies might lead to erroneous conclusions when these factors are not considered.

Adult↗
PubMed2006

The effects of duloxetine on urethral function and sphincter morphology.

The aim of our study was to investigate the effect of duloxetine on urethral function and sphincter ultrasound morphology in 54 women, who were referred to a urogynecology unit, with urodynamic stress incontinence. All completed a King's Health Questionnaire and a patient global assessment of improvement (PGI-I) question and underwent urethral pressure profilometry, measurement of urethral retro-resistance pressure (URP), and ultrasound of the striated urethral sphincter. The investigations were repeated after 8 weeks of duloxetine 40 mg twice daily in 36 women who continued the medication. After 8 weeks of duloxetine, the mean URP increased significantly compared to baseline (53.8 to 60.8 cm H2O; p=0.001), and sphincter thickness was significantly higher (1.8 to 2.0 mm; p<0.001). There was a significant increase in the maximum urethral closure pressure (MUCP) (52.7 to 59.2 cm H2O; p=0.006) but not of functional urethral length. Subanalysis of responders (improved on duloxetine) showed a significant increase in URP (50.3 to 59.1 cm H2O; p=0.001), sphincter thickness (1.7 to 2.1 mm; p<0.001), and MUCP (50.2 to 58.1 cm H2O; p=0.03). These changes were not seen in nonresponders. This study has demonstrated objective changes in urethral ultrasound morphology and function after duloxetine therapy, which relate to improved continence. A larger longer term study is required to assess if these changes persist over time. In summary, duloxetine therapy for urodynamic stress incontinence results in an increase in urethral closure pressure, URP measurement, and urethral striated sphincter thickness.

Adult↗
PubMed2006

The relationship of urethral resistance pressure and pressure flow parameters in women with lower urinary tract symptoms.

This prospective study aims to evaluate the relationship between urethral resistance pressure (URP) and pressure flow parameters in women with lower urinary tract symptoms (LUTS). Consecutive women with LUTS attending three tertiary referral urodynamic clinics were asked to undergo urodynamic evaluation, pressure flow studies and URP measurement. The pressure flow parameters such as detrusor pressures at the start of flow (ODP), detrusor pressure at peak flow rate (PdetQmax), peak flow rate (Qmax) and detrusor pressure at the end of flow (CDP) were measured. The relationship between URP and pressure flow parameters was evaluated as well as differences between each urodynamic group. Two hundred seventy-nine women attended for urodynamic investigations. Two hundred twenty-three (79.9%) women had good quality pressure flow measurements and were included in the study. The mean age was 58 years (range 21-83). Women with urodynamic stress incontinence had significantly lower URP and ODP than those with detrusor over-activity [54.8 (+/-17.9) and 12.4 (+/-4.1) cmH(2)O, respectively, vs 85.6 (+/-21.4) and 33.7 (+/-13.3) cmH(2)O, respectively) (p<0.05, Bonferroni test). Furthermore, women with urodynamic stress incontinence have significantly lower PdetQmax values as well as higher Qmax than women with competent urethral sphincters (p<0.05, Bonferroni test). There was a significant correlation between ODP, PdetQmax, Qmax and URP measurements. In urodynamic stress incontinence, both URP and pressure flow parameters are reduced. Although the trend for values of both tests were similar and there was a significant correlation between these tests, we should consider that urethral function at rest differ from that during voiding due to activation of additional mechanisms. Therefore, further study is needed to confirm our results.

Adult↗
PubMed2006

SIS graft for anterior vaginal wall prolapse repair--a case-controlled study.

The purpose of this study was to assess the effect on quality of life and prolapse severity of traditional anterior repair compared to anterior repair with a small intestine submucosa (SIS) graft. This report was designed as a case-control study. The sample of this study consisted of 14 women who underwent traditional anterior repair and 14 women who underwent anterior repair with SIS graft (SG) at a London teaching hospital. All women were assessed preoperatively and at 6 and 24 months postoperatively using a validated prolapse quality of life questionnaire and pelvic organ quantification system (POP-Q). Quality-of-life outcomes included the following: (1) General health perception, (2) Prolapse impact, (3) Role limitations, (4) Physical limitations, (5) Social limitations, (6) Personal relationships, (7) Emotions, (8) Sleep/Energy, and (9) Severity measures. The pelvic organ quantification measurement measured nine specific points relating to the anterior and posterior wall of the vagina, vaginal apex, genital hiatus (GH) and perineal body (PB). At 6-month follow-up, the SG repair group showed significant improvement in all quality-of-life parameters measured. In comparison to traditional repair, it was significantly better in improving role limitations, physical limitations and emotions. Both operations significantly improved prolapse quality-of-life severity measures. SG repair improved all POP-Q measurements significantly, except total vaginal length (TVL), whereas traditional repair improved some measurements (AA, midline point of anterior vaginal wall 3 cm proximal to the external urethral meatus; BA, most distal dependant position of the anterior vaginal wall from the vaginal vault or anterior fornix to AA; C, most distal/dependant edge of cervix or vault; AP, point on midline posterior vaginal wall 3 cm proximal to hymenal ring; BP, most distal/dependant point on the posterior vaginal wall from vault or posterior fornix to AP) but not others (location of posterior fornix (D), TVL, GH and PB). At 2-year follow-up, there was no significant difference between the two groups in terms of quality-of-life outcomes or prolapse severity measurements. Surgery for vaginal prolapse results in marked improvement in quality of life and prolapse severity. The greater improvement seen initially in the SG anterior group was not seen at 2-year follow-up.

Adult↗
PubMed2006

The effects of antimuscarinics on health-related quality of life in overactive bladder: a systematic review and meta-analysis.

The objective of this study was to review the effects of antimuscarinic treatments on health-related quality of life (HRQL) in patients with overactive bladder (OAB). MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the Cumulative Index to Nursing and Allied Health Literature databases were searched from 1966 through August 2004 for randomized controlled trials of antimuscarinic agents. HRQL data from included trials were extracted, and meta-analysis was performed where possible. Of 56 trials included, 25 (45%) reported HRQL and/or patient-reported outcomes. The most commonly used instruments were the Incontinence Impact Questionnaire (3 trials), the King's Health Questionnaire (KHQ; 5 trials), the Medical Outcomes Study Short Form-36 (2 trials), the Gaudenz Appraisal Questionnaire (3 trials), and the Urogenital Distress Inventory (2 trials). Results from the meta-analyses of placebo-controlled trials showed statistically significant differences in favor of antimuscarinic therapy. Differences in HRQL as assessed using the KHQ were also clinically meaningful. The meta-analysis results of active-controlled trials did not show significant differences among antimuscarinic agents. This review provides evidence that antimuscarinics provide an HRQL benefit to patients with OAB. HRQL outcomes using validated instruments are recommended for inclusion in active-controlled trials, and agreement on the most appropriate HRQL instrument is now required.

Controlled Clinical Trials as Topic↗
PubMed2006

Urethral retro-resistance pressure and urodynamic diagnoses in women with lower urinary tract symptoms.

OBJECTIVE: This study determines whether the retrograde urethral retro-resistance pressure (URP) measurement discriminates between urodynamic diagnoses in a group of women. DESIGN: A prospective observational study. SETTING: Urogynaecology units of three tertiary referral teaching hospitals. POPULATION: Women with lower urinary tract symptoms. METHODS: Consecutive women attending the urodynamic clinics of three tertiary referral teaching hospitals were studied using a validated urinary symptom questionnaire, URP measurement and urodynamic evaluation between February and July 2004. The URP mean values were compared with urinary symptoms and urodynamic diagnoses, using the independent t test correction for multiple measurements. MAIN OUTCOME MEASURES: Retrograde URP, urodynamic diagnoses and urinary symptoms. RESULTS: One hundred and eighty-five women were recruited. Women with urodynamic stress incontinence (USI) have significantly lower URP than women with competent urethral sphincters (P < 0.05, independent t test). Women with mixed urodynamic incontinence had values of URP intermediate between women with detrusor overactivity (DOA) and those with USI. In the mixed group, URP mean values were not significantly different from those with DOA and competent sphincters or USI (P > 0.05, independent t test). There was no significant difference between mean URP values and different urinary symptoms (P > 0.05, independent t test). CONCLUSIONS: There are significantly different URP measurements between women with DOA and those with USI. However, the URP is not a diagnostic tool.

Adult↗
PubMed2005

Changes in urethral resistance in the presence of detrusor activity.

This was a prospective study performed at two tertiary referral teaching hospitals. The aim of our study was to investigate changes in urethral resistance with the bladder full compared to empty in women with different urodynamic diagnoses. Consecutive women attending the urodynamic clinics were asked to undergo urethral retro-resistance pressure (URP) measurement with the bladder empty and then full. 106 women were recruited - 25 had normal urodynamic studies, 17 had detrusor overactivity, 57 had urodynamic stress incontinence and 7 had mixed incontinence. Women with urodynamic stress incontinence have lower URP values than women with normal urodynamic studies or those with detrusor overactivity with the bladder empty (p = 0.01). Women with normal urodynamic studies and urodynamic stress incontinence showed a statistically significant rise in URP with the bladder full (p = 0.013 and p = 0.003, respectively). In women with detrusor overactivity, the converse was seen - URP was significantly lower with the bladder full compared to empty (p = 0.004). Our study has shown that bladder filling alters URP measurement and bladder volume should be standardised for reporting URP.

Adult↗
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

The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the tolerability, safety and efficacy of antimuscarinic drugs used to treat overactive bladder and to identify any differences between individual antimuscarinics. METHODS: Medline, Embase, CCTR and Cinahl databases were searched for published RCTs including an antimuscarinic agent from 1966 to August 2004. Data from included trials were extracted and meta-analysed where possible. RESULTS: Fifty-six trials were included. The antimuscarinics were found to be safe and efficacious. All antimuscarinics apart from oxybutynin IR were found to be well tolerated. Dry mouth was the most commonly reported adverse event and no drug was associated with an increase in any serious adverse event. There were significant differences between the antimuscarinics in rates of withdrawal and rates and range of adverse events and efficacy outcomes. CONCLUSIONS: The antimuscarinics have different tolerability and safety profiles, which are clinically significant.

Clinical Trials as Topic↗
PubMed2005

"Unblinding" in randomized controlled drug trials for urinary incontinence: Implications for assessing outcomes when adverse effects are evident.

AIMS: To determine whether women with urinary incontinence (UI) can identify their allocation in a randomized controlled trial (RCT) of tolterodine (TOL), and whether correct identification is associated with outcomes and adverse effects (AEs). METHODS: Exploratory analysis of a randomized, double-blind, placebo (PLC)-controlled trial of TOL 4 mg daily for 8 weeks in 743 women with urge-predominant mixed UI. Patient perception of their randomization was assessed at trial end. Main outcome measures were 7-day bladder diaries, patient perception of improvement, and UI-specific quality of life (QoL). RESULTS: TOL produced a significant decrease in urge UI episodes compared to PLC (78% vs. 51%, P = 0.0001). Fifty-one percent of women correctly identified their randomization (58% on TOL vs. 37% on PLC, P < 0.001). Women who assumed they took TOL had better bladder diary outcomes than those who assumed they took PLC. Within each assumption group, patient perception outcomes were similar, regardless of actual randomization. QoL improved in all domains except general health for women on TOL. In women who assumed they took TOL, significant drug benefit was evident in three domains. Moderate-severe dry mouth was higher in those who assumed they took TOL (7.3% vs. 0%, P < 0.0001). CONCLUSIONS: Greater than fifty percent of women in this RCT of antimuscarinic treatment were "unblinded" to their randomization. Patient assumption of randomization was associated with bladder diary and perception outcomes, specific QoL domains, and dry mouth. Efficacy of urge incontinence drugs should be considered in the context of patient assumptions, expectations, and "unblinding" by easily evident side effects.

Aged↗
PubMed2005

A randomized crossover trial to examine administration techniques related to the Bristol female lower urinary tract symptom (BFLUTS) questionnaire.

AIMS: To investigate whether two methods of assessing lower urinary tract symptoms, interview-assisted standardized questionnaires, and self-completed standardized questionnaires, were comparable. METHODS: Women referred to a tertiary urogynecology urodynamic clinic with lower urinary tract symptoms were recruited. The psychometrically robust Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire was used to assess urinary symptoms. A randomized crossover design for questionnaire completion was used: Group A-an initial interview-assisted questionnaire at the urodynamic clinic with a follow-up postal questionnaire; or Group B-an initial pre-out-patient postal questionnaire followed up by a second interview-assisted questionnaire whilst attending a scheduled urodynamic clinic. RESULTS: A total of 114 women were randomized for initial questionnaire administration method to achieve 72 completed sets (63%). Total scores were higher on self-completion compared to interview, this difference was not significant [t = -1.951, P > 0.05]. No item had perfect agreement between postal and interview methods and generally, interview-assisted questions had lower scores, indicating better health status. The items with the worst agreement (slight or moderate) were those concerned with sexual health, with women giving lower scores, exaggerating health on interview. For example bother of vaginal discomfort (kappa(w) = 0.09), compared to question assessing frequency (kappa(w) = 0.65). CONCLUSIONS: This data suggests women respond differently to the BFLUTS questionnaire when data is collected by self-completion in the woman's home compared to interviews. No individual question item had perfect agreement between the two methods of administration. Overall, individual question items were scored higher on self-completion than interview.

Adult↗
PubMed2005

Changes in urethral function with bladder filling in the presence of urodynamic stress incontinence and detrusor overactivity.

OBJECTIVE: The purpose of this study was to assess the effect of detrusor overactivity and bladder filling on urethral function with the use of urethral profilometry. STUDY DESIGN: Women with symptoms of urinary incontinence were recruited from our urodynamic clinic. All of the women underwent videocystourethrography and urethral pressure profilometry with the bladder empty and then full. The maximum urethral closure pressure, mean urethral pressure, functional urethral length, and pressure transmission ratios for each quartile were analyzed. RESULTS: Thirty-five women were recruited: 17 women had urodynamic stress incontinence, and 18 women had detrusor overactivity. In women with urodynamic stress incontinence, there was a significant increase in maximum urethral closure pressure and pressure transmission ratios over all quartiles when the bladder was full compared with empty. In women with detrusor overactivity, there was a significant decrease in functional urethral length and pressure transmission ratios in the second and third quartile of the urethral pressure profiles when the bladder was full compared with empty. CONCLUSION: Decreases in functional urethral length and pressure transmission ratios with bladder filling in those women with detrusor overactivity are at variance with the normal physiologic response to bladder filling, which suggests that urethral function is affected by the presence of abnormal detrusor activity and that the valid assessment of urethral function may not be possible if the detrusor overactivity is not treated.

Adult↗
PubMed2005

The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects.

OBJECTIVE: To review the concept of urinary urgency and its practical measurement in clinical trials, and advance the hypothesis that while urge is experienced by normal people, urgency is always pathological. METHODS: According to the International Continence Society (ICS) definition, urgency is the primary symptom of the overactive bladder (OAB) syndrome, but in clinical trials there are inconsistencies in both the definition and assessment of urgency. We searched the PubMed and BIOSIS databases for publications and abstracts related to the clinical assessment of urgency in patients with OAB. RESULTS: The differentiation of urgency from the normal physiological desire to void is discussed. In clinical studies of OAB, urgency has been measured both qualitatively and quantitatively. Existing qualitative assessment scales for urgency are deficient in accuracy, validation or both, and are largely inconsistent with the currently accepted ICS definition of urgency. The quantitative assessment of urgency by diary entry has been validated and may be the most accurate, reproducible and clinically meaningful method available for measuring this variable. CONCLUSION: Based on the existing ICS definition of urgency as 'a compelling desire to pass urine that is difficult to defer', the concept of qualitative assessment of urgency may be flawed.

Clinical Trials as Topic↗
PubMed2005

The relationship of vaginal prolapse severity to symptoms and quality of life.

OBJECTIVE: To assess the relationship and location of vaginal prolapse severity to symptoms and quality of life. DESIGN: A prospective observational study. SETTING: Urogynaecology Unit, Imperial College, St Mary's Hospital, London. POPULATION: Women with and without symptoms of vaginal prolapse. METHODS: All women completed a validated Prolapse Quality of Life (P-QOL) questionnaire. This included a urinary, bowel and sexual symptom questionnaire. All women were examined using the Pelvic Organ Prolapse Quantification system (POP-Q). POP-Q scores in those with and without prolapse symptoms were compared. Urinary and bowel symptoms and sexual function were compared and related to prolapse severity and location. MAIN OUTCOME MEASURES: POP-Q scores, P-QOL scores, urinary and bowel symptoms and sexual function. RESULTS: Three hundred and fifty-five women were recruited-233 symptomatic and 122 asymptomatic of prolapse. The median P-QOL domain scores ranged between 42-100 in symptomatic women and 0-25 in those who were asymptomatic. The stage of prolapse was significantly higher in those symptomatic of prolapse (P < 0.001) except for perineal body (PB) measurement. Urinary symptoms were not correlated with uterovaginal prolapse severity whereas bowel symptoms were strongly associated with posterior vaginal wall prolapse. Cervical descent was found to have a relationship with sexual dysfunction symptoms. CONCLUSIONS: Women who present with symptoms specific to pelvic organ prolapse demonstrate greater degrees of pelvic relaxation than women who present without symptoms. Prolapse severity and quality of life scores are significantly different in those women symptomatic of prolapse. There was a stronger relationship between posterior prolapse and bowel symptoms than anterior prolapse and urinary symptoms. Sexual dysfunction was related to cervical descent.

Adolescent↗
PubMed2004

P-QOL: a validated questionnaire to assess the symptoms and quality of life of women with urogenital prolapse.

To develop a simple, valid, reliable questionnaire to assess the severity of symptoms and their impact on the quality of life in women with urogenital prolapse. Women recruited from gynaecology outpatient clinics were asked to complete a prolapse quality of life questionnaire (P-QOL) before their hospital visit. At the time of the visit, they were examined supine using the International Continence Society (ICS) prolapse score (POP-Q). A second P-QOL was posted and completed by patients 2 weeks later. The validity was assessed by measuring levels of missing data, comparing symptom scores between affected and asymptomatic women and comparing symptom scores with objective prolapse stages. The internal reliability was assessed by measuring the Cronbach alpha coefficient; 155 symptomatic and 80 asymptomatic women were studied. Severity according to P-QOL strongly correlated with the vaginal examination findings (p < 0.01, rho > 0.5). The total scores for each P-QOL domain were significantly different between symptomatic and asymptomatic women (p < 0.001). All items achieved a Cronbach alpha greater than 0.80 showing good inter-rater reliability. The test-retest reliability confirmed a highly significant correlation between the total scores for each domain. A P-QOL questionnaire for English-speaking patients has been developed which is reliable and valid.

Adult↗
PubMed2004

The open bladder neck: a significant finding?

Women with lower urinary tract symptoms were retrospectively studied. They were all investigated using a urinary symptoms questionnaire, a frequency-volume chart and videocystourethrography. An open bladder neck was recorded at maximum cystometric capacity with the patient standing in the left lateral position, if contrast medium entered the proximal urethra at rest in the absence of a detrusor contraction or an increase in intra-abdominal pressure. Women with neurological disorders were excluded. Of 4500 women, 2,593 (57.6%) had a single urodynamics diagnosis and were included in the study: 1207 (46.5%) had urodynamics diagnosis of urodynamic stress incontinence, 558 (21.5%) had detrusor overactivity, 118 (4.6%) had sensory urgency, and 710 (27.4%) had a normal urodynamic study. Out of the 2,593 women included, 776 women (29.9%) had an open bladder neck at rest while 1817 (70.1%) had a closed bladder neck at rest. Only 45% (542/1207) of women with urodynamic stress incontinence had an open bladder neck at rest. Seventy percent (542/776) of women with an open bladder neck had a diagnosis of urodynamic stress incontinence whilst 73% of women with detrusor overactivity and 93% of those with sensory urgency had a closed bladder neck. An open bladder neck at rest is not diagnostic of urethral sphincter incompetence but is associated with urodynamic stress incontinence. It is not associated with urgency as few women with sensory urgency and detrusor overactivity were found to have an open bladder neck. Imaging the bladder neck at rest has questionable value.

Adult↗
PubMed2004

Pressure flow study: a useful diagnostic test of female lower urinary tract symptoms.

AIMS: To compare pressure flow parameters in the different urodynamic diagnoses in women with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Urodynamic traces of women with LUTS were prospectively studied. Detrusor pressures at the start of flow (ODP), detrusor pressure at peak flow rate (PdetQmax), peak flow rate (Qmax) and detrusor pressure at the end of flow (CDP) were measured and compared with different urodynamic diagnoses. RESULTS: Six hundred and twenty one women were prospectively investigated between September 2000 and February 2002. Only 85% (529/621) of women had good quality pressure flow studies and was included in the study. Women with detrusor overactivity have higher ODP, CDP and PdetQmax than women with urethral sphincter incompetence. All these pressure flow parameters are significantly lower in women with urethral sphincter incompetence than continent women (P < 0.05, Bonferroni test). Qmax was significantly greater in women with urodynamic stress incontinence compared to women who had detrusor overactivity (P < 0.05, Bonferroni test). Women with mixed incontinence had pressure flow parameters intermediate between women with detrusor overactivity and those with urodynamic stress incontinence. CONCLUSIONS: Pressure flow parameters appear to be useful urodynamic tools in the evaluation of women with LUTS as they help the clinician in assessing the urethral and detrusor function.

Adult↗