Vik Khullar

Publications (91)269.8 Total impact

• Article: OnabotulinumtoxinA 100 U Significantly Improves All Idiopathic Overactive Bladder Symptoms and Quality of Life in Patients with Overactive Bladder and Urinary Incontinence: A Randomised, Double-Blind, Placebo-Controlled Trial.

  Christopher Chapple, Karl-Dietrich Sievert, Scott Macdiarmid, Vik Khullar, Piotr Radziszewski, Christopher Nardo, Catherine Thompson, Jihao Zhou, Cornelia Haag-Molkenteller
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  ABSTRACT: BACKGROUND: Overactive bladder (OAB) syndrome with urinary incontinence (UI) is prevalent in the population and impairs health-related quality of life (HRQOL). OBJECTIVE: To assess the impact on efficacy, safety, and HRQOL of onabotulinumtoxinA (BOTOX(®), Allergan, Inc.) treatment in patients with OAB with UI. DESIGN, SETTING, AND PARTICIPANTS: This pivotal, multicentre, double-blind, randomised, placebo-controlled, phase 3 study enrolled patients with idiopathic OAB with ≥3 urgency UI episodes over 3 d and ≥8 micturitions per day who were inadequately managed by anticholinergics. INTERVENTION: OnabotulinumtoxinA at a 100U dose (n=277) or placebo (n=271), administered as 20 intradetrusor injections of 0.5ml. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Co-primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale (TBS) at week 12. Additional end points included other OAB symptoms (episodes of urinary urgency incontinence, micturition, urgency, and nocturia) and HRQOL (Incontinence Quality of Life [I-QOL], King's Health Questionnaire [KHQ]). Safety assessments included adverse events (AEs), postvoid residual (PVR) urine volume, and initiation of clean intermittent catheterisation (CIC). RESULTS AND LIMITATIONS: OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 (-2.95 for onabotulinumtoxinA versus -1.03 for placebo; p<0.001). Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo (p ≤ 0.01). Patients perceived a significant improvement in their condition, as measured by patients with a positive treatment response on the TBS (62.8% for onabotulinumtoxinA versus 26.8% for placebo; p<0.001). Clinically meaningful improvements from baseline in all I-QOL and KHQ multi-item domains (p<0.001 versus placebo) indicated positive impact on HRQOL. AEs were mainly localised to the urinary tract. Mean PVR was higher in the onabotulinumtoxinA group (46.9ml versus 10.1ml at week 2; p<0.001); 6.9% of onabotulinumtoxinA patients versus 0.7% of placebo patients initiated CIC. CONCLUSIONS: OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinically relevant improvements in all OAB symptoms, patient-reported benefit, and HRQOL in patients inadequately managed by anticholinergics. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00910520.
  European urology 04/2013; · 7.67 Impact Factor
• Article: Effects of drug cessation after flexible-dose fesoterodine in patients with overactive bladder.

  Vik Khullar, Linda Cardozo, Con J Kelleher, Timothy Hall, John Ryan, Caty Ebel Bitoun, Amanda Darekar, Daniel Arumi, Adrian Wagg
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  ABSTRACT: OBJECTIVE: To determine the course of overactive bladder (OAB) symptoms after 4 weeks of no treatment following a 12-week study of the efficacy and safety of flexible-dose fesoterodine in patients with OAB who were enrolled in the UK healthcare system. There are limited data available on the natural time course of OAB symptoms after the cessation of treatment. PATIENTS AND METHODS: In the open-label UK Study Assessing Flexible-dose Fesoterodine in Adults trial, patients aged ≥18 years with self-reported OAB symptoms for ≥3 months, a mean of at least eight micturitions per 24 h and three or more urgency episodes per 24 h on a 3-day bladder diary at baseline, and at least moderate bladder-related problems reported on the Patient Perception of Bladder Condition (PPBC) at baseline, were treated with fesoterodine for 12 weeks. All patients received fesoterodine 4 mg once daily for the first 4 weeks, at which time they could choose to increase the dose to 8 mg once daily, based on a discussion of treatment efficacy and tolerability with the investigator, or they could remain on fesoterodine 4 mg for the remaining 8 weeks. The 12-week treatment period was followed by a 4-week follow-up period of no fesoterodine treatment. Patients completed 3-day bladder diaries and the PPBC at baseline, week 4, end of treatment (week 12) and end of the follow-up period (week 16); the King's Health Questionnaire at baseline, end of treatment (week 12) and end of the follow-up period (week 16); and the Benefit, Satisfaction and Willingness to Continue questionnaire at week 12. RESULTS: After 12 weeks of fesoterodine treatment, patients had clinically meaningful improvements in bladder diary variables and King's Health Questionnaire domains; 79% (254/322) of patients reported an improvement on the PPBC. After 4 weeks of no treatment, most patients deteriorated back to week 4 levels or worse on all bladder diary and patient-reported outcomes. Patients who expressed a benefit from fesoterodine treatment, satisfaction with their treatment or a willingness to continue treatment showed greater improvement from baseline to week 12 and greater deterioration from week 12 to week 16 than patients who did not respond positively on the Benefit, Satisfaction and Willingness to Continue questionnaire. Both men and women showed a meaningful deterioration in bladder diary variables and patient-reported outcomes at week 16; baseline symptom severity, age and week 4 dose escalation status did not appear to affect outcome deterioration at week 16. CONCLUSIONS: At 4 weeks after fesoterodine was discontinued, patients showed an increase in the frequency of OAB symptoms, an increase in the severity of bladder-related problems and a reduction in health-related quality of life. Many patients with OAB who respond to antimuscarinics may require treatment for more than 12 weeks because symptoms recur as early as 4 weeks after the cessation of therapy.
  BJU International 03/2013; · 2.84 Impact Factor
• Article: Long-term safety, tolerability and efficacy of flexible-dose fesoterodine in elderly patients with overactive bladder: Open-label extension of the SOFIA trial.

  Adrian Wagg, Vik Khullar, Martin C Michel, Matthias Oelke, Amanda Darekar, Caty Ebel Bitoun
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  ABSTRACT: AIMS: To assess the long-term safety, tolerability, and efficacy of flexible-dose fesoterodine in elderly patients with OAB. METHODS: Patients aged ≥65 years who completed a 12-week, randomized, double-blind, placebo-controlled trial were eligible for the 12-week, open-label (OL) extension phase. Patients who received double-blind placebo started on fesoterodine 4 mg and could increase to 8 mg after 4 or 8 weeks of OL treatment, while fesoterodine-treated patients continued on their double-blind dose; only one dose escalation or de-escalation was permitted. Discontinuations and adverse events (AEs) were monitored, and patients completed 3-day bladder diaries and patient-reported outcomes at the beginning and end of the 12-week OL phase. RESULTS: Six hundred fifty-four patients entered the 12-week OL extension (mean age 72 years; 52% women). AEs were reported by 30.7% and 48.1% of patients who had received double-blind fesoterodine and placebo, respectively; 1.9% and 9.4%, discontinued due to AEs, respectively. Patients who received double-blind fesoterodine maintained their efficacy response. After 12 weeks of OL treatment, efficacy outcomes in patients who received double-blind placebo were similar to those who had received double-blind fesoterodine. On average, the efficacy response was maintained for the duration of the study. CONCLUSIONS: Fesoterodine was well tolerated and improvements in OAB symptoms and quality of life measures were not diminished with longer-term treatment of patients aged ≥65 years. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.
  Neurourology and Urodynamics 03/2013; · 2.96 Impact Factor
• Article: Flexible-Dose Fesoterodine in Elderly Adults with Overactive Bladder: Results of the Randomized, Double-Blind, Placebo-Controlled Study of Fesoterodine in an Aging Population Trial.

  Adrian Wagg, Vik Khullar, Daniela Marschall-Kehrel, Martin C Michel, Matthias Oelke, Amanda Darekar, Caty E Bitoun, David Weinstein, Ian Osterloh
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  ABSTRACT: OBJECTIVES: To assess the efficacy and safety of flexible-dose fesoterodine in elderly adults with overactive bladder (OAB). DESIGN: Twelve-week, randomized, double-blind, placebo-controlled trial. SETTING: Sixty-one outpatient clinics in Europe, Israel, and Turkey. PARTICIPANTS: Seven hundred ninety-four individuals aged 65 and older (47% male) with OAB symptoms for 3 months or longer, mean of eight or more micturitions and three or more urgency episodes per 24 hours, at least some moderate problems on Patient Perception of Bladder Condition (PPBC), and Mini-Mental State Examination (MMSE) score of 20 or greater. INTERVENTIONS: Participants were randomized to fesoterodine or placebo for 12 weeks, with stratification according to age (>75 vs ≤75) and dosing time (morning vs evening). Participants receiving fesoterodine started on 4 mg and could increase to 8 mg at week 4 or 8 and de-escalate to 4 mg at week 8 (sham escalation for placebo). MEASUREMENTS: Changes from baseline in bladder-diary variables (primary endpoint, urgency episodes) and patient-reported outcomes including OAB Questionnaire, Treatment Benefit Scale (TBS), PPBC, Urgency Perception Scale (UPS), and OAB Satisfaction Questionnaire (OAB-S); all observed or reported adverse events. RESULTS: By week 8, 64% of fesoterodine-treated and 71% of placebo-treated participants opted for dose escalation. At week 12, the fesoterodine group had statistically significantly greater improvement than the placebo group in urgency episodes, micturitions, nocturnal micturitions, incontinence pad use, and OAB Questionnaire scores but not urgency urinary incontinence episodes. Responder rates on TBS, PPBC, UPS, and OAB-S were statistically significantly higher with fesoterodine. Improvements in most diary variables and participant-reported outcomes were greater with fesoterodine than placebo in participants in both age groups and when administered in the morning and evening. Rates of dry mouth and constipation were 34% and 9% with fesoterodine and 5% and 3% with placebo, respectively. Rates of adverse events and discontinuations were generally similar in participants in both age groups. There was no change in MMSE score. CONCLUSION: Fesoterodine was associated with significantly greater improvements in most diary variables and participant-reported outcomes than placebo and was generally well tolerated in older people.
  Journal of the American Geriatrics Society 01/2013; · 3.74 Impact Factor
• Article: Biomarkers in overactive bladder.

  Alka A Bhide, Rufus Cartwright, Vik Khullar, G Alessandro Digesu
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  ABSTRACT: A biomarker is an indicator of a particular disease. It is generally used to define the presence (diagnostic biomarker), severity, progression (prognostic biomarker) of a condition and/or its response to a specific treatment (predictive biomarker). Biomarkers can be specific cells, enzymes, hormones, genes or gene products, which can be detected and measured in parts of the body such as blood, urine or tissue. Therefore, biomarkers have been suggested to play an important role in both the clinical assessment and the management of patients, as well as in the research setting. Recently, interest has gathered in urinary biomarkers as a tool to assess overactive bladder (OAB), potentially playing a role in the diagnosis, disease progression and monitoring response to treatment. Urinary biomarkers identified so far include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), prostaglandins, cytokines and C-reactive protein. The aim of this review was to review the published literature on biomarkers in OAB. A literature review using Pub Med, clinicaltrials.gov and the controlled trials online registries was performed from 1970 up to June 2012. The search keywords were: the International Continence Society (ICS) definition of "OAB", "nerve growth fac- tor" (NGF), "brain derived growth factor" (BDNF), "prostaglandins," "cytokines," "genetic biomarkers" and "C reactive protein".The results were limited for fully published English-language articles. The search was then subsequently expanded to include urinary biomarkers in interstitial cystitis and bladder pain where relevant. Each of the studies/articles was reviewed, interpreted and discussed to consider the role of urinary biomarkers in OAB. Using the search criteria, a total of 20 studies (animal and human) that investigated the role of urinary biomarkers in OAB were identified. Full text versions of these articles were obtained and reviewed. Studies on NGF suggested that urinary levels were higher in OAB patients and decreased with antimuscarinic and botulinum toxin treatment. BDNF studies have demonstrated raised levels in OAB and also increased levels in situations of acute bladder inflammation. The role of urinary prostaglandins, cytokines and CRP does not appear to be specific to the OAB disease process according to the current available evidence. Based on the evidence so far NGF and BDNF appear to be the most promising biomarkers in OAB. Although still in their infancy these neurotrophic factors could potentially diagnose OAB, replacing urodynamics and aiding in monitoring disease progression and response to treatment in addition to clinical symptoms.
  International Urogynecology Journal 01/2013; · 1.83 Impact Factor
• Article: Botulinum neurotoxin type A injection of the pelvic floor muscle in pain due to spasticity: a review of the current literature.

  Alka A Bhide, Federica Puccini, Vik Khullar, Suzy Elneil, G Alessandro Digesu
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  ABSTRACT: The role of muscle spasm is not a new concept in the genesis of pain. Botulinum neurotoxin type A (BoNTA) has been successfully employed in a variety of muscular and inflammatory conditions. The aim of our study was to review the published literature on the role of BoNTA injection of the pelvic floor muscle in the management of women with chronic pelvic pain (CPP). A systematic search of the literature published up to June 2012 on the use of BoNTA in the treatment of female pelvic floor muscle spasm was carried out using relevant search terms in MEDLINE and EMBASE databases. The results were limited to full-text English language articles. Relevant trials as well as relevant reviews were selected and analyzed by two independent reviewers. Five studies (2 case reports, 1 prospective pilot study, 1 retrospective study and 1 randomised double-blind placebo controlled study) were included in this systematic review. Overall, BoNTA has shown to be beneficial in relieving CPP related to pelvic floor spasm. The role of BoNTA as a treatment of CPP has been recognized for more than 10 years. Although data are still scarce preliminary results are encouraging. BoNTA is an attractive option for refractory CPP related to pelvic floor muscle spasm, but further studies using validated and reproducible outcome measures are needed, to establish its effectiveness, safeness, technique, optimal dosage, and duration of symptom relief.
  International Urogynecology Journal 01/2013; · 1.83 Impact Factor
• Article: Prevalence of pubovisceral muscle avulsion in a general gynecology cohort: A computed tomography (CT) study.

  Alexandros Derpapas, Alessandro G Digesu, Mohamad Hamady, Pasquale Gallo, Chiara Dell'utri, Gopalan Vijaya, Vik Khullar
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  ABSTRACT: AIMS: To calculate the prevalence of pubovisceral muscle (PM) avulsion in a cohort of women presenting at a university hospital for non-urogynecological conditions. METHODS: Women with or without symptoms of PFD were studied in a tertiary referral urogynecology center between February and October 2010. Women were recruited from the Department of Radiology, where they were referred for a CT pelvis scan due to various pathologies. Assessment of participants included a detailed clinical interview, completion of King's Health and Prolapse-Quality of Life (P-QOL) questionnaires and spiral CT scan of the pelvis. Bilateral attachments of the PM to the pubic rami were identified in the plane of minimal hiatal dimensions, when present, and measurement of the levator symphysis gap (LSG) was taken in cases with PM complete detachment. Bivariate analysis between the PM maximum thickness and different obstetric variables was performed by using Spearman's correlation test (P < 0.05). RESULTS: One hundred ten women were included in the analysis. The overall prevalence of PM avulsion was 6.4% (7/110). In cases with confirmed avulsion, the levator sympysis gap (LSG) ranged from 17.30 to 25.40 mm. The left PM was found to be significantly thinner in parous women and in those with a history of prolonged second stage of labor. CONCLUSIONS: The prevalence of pubovisceral muscle avulsion using CT scanning in a general gynecology cohort is 6.4%. Thinning of the pubovisceral muscle occurs with parity and protracted labor and is more prominent on the left portion of the muscle. Neurourol. Urodynam. © 2012 Wiley Periodicals, Inc.
  Neurourology and Urodynamics 10/2012; · 2.96 Impact Factor
• Article: Real-time in vivo assessment of levator ani muscle deformation in women.

  Alexandros Derpapas, Alessandro G Digesu, Gopalan Vijaya, Ruwan Fernando, Vik Khullar
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  ABSTRACT: OBJECTIVE: To study the deformation of the levator ani muscle in vivo with the use of real-time ultrasound imaging of the pelvic floor. STUDY DESIGN: Thirty-two women with symptoms of pelvic floor dysfunction underwent real-time in vivo assessment of the strain of the pelvic floor during Valsalva effort. All participants underwent clinical examination, urodynamics and 3D/4D translabial ultrasound scan of the pelvic floor. The deformation curves of the levator ani muscle were plotted and the difference in compliance according to the grade of urogenital prolapse was measured. One-way ANOVA and Spearman's correlation were used to test for significance of the relationship between variables (significance level P<0.05). Test-retest analysis of the ultrasound measurements of the levator hiatal dimensions was also conducted using intra-class correlation coefficient (ICC). RESULTS: The deformation curve of the levator hiatus showed a non-linear relationship with gradually increased Valsalva force, which was quite pronounced in the pubourethralis subdivision of the levator ani muscle complex. Women with significant pelvic organ prolapse demonstrated a less compliant levator ani muscle close to its origin from the pubic bone than women with non-significant prolapse (median maximum strain 26% vs 32%, respectively, P=0.03). CONCLUSIONS: Real-time in vivo assessment of levator ani muscle deformation in women is feasible and yields significant information.
  European journal of obstetrics, gynecology, and reproductive biology 08/2012; · 1.97 Impact Factor
• Article: Differential profile analysis of urinary cytokines in patients with overactive bladder: comment.

  Rufus Cartwright, Vik Khullar, Massimo Mangino
  International Urogynecology Journal 05/2012; 23(8):1141; author reply 1143. · 1.83 Impact Factor
• Article: Phase IIb, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to determine effects of elocalcitol in women with overactive bladder and idiopathic detrusor overactivity.

  G Alessandro Digesu, Elena Verdi, Linda Cardozo, Lorenza Olivieri, Vik Khullar, Enrico Colli
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  ABSTRACT: To evaluate the efficacy and safety of elocalcitol in the treatment of women with overactive bladder and idiopathic detrusor overactivity. The study was a multicenter, double-blind, randomized, placebo-controlled, parallel-group trial of women with overactive bladder symptoms recruited from 48 European tertiary referral centers. The participants were randomized to receive either placebo or elocalcitol, 75 μg/d or 150 μg/d for 4 weeks. A 3-day bladder diary, the Urgency Perception Scale, the Patient's Perception of Bladder Condition, and urodynamics were used before and after treatment. Vital signs, laboratory blood tests, 24-hour urine collection, and electrocardiography were also performed to assess the safety. The analysis of covariance test was used to compare the treatment groups. The primary objective was to evaluate the change in bladder volume at the first involuntary detrusor contraction from baseline. A total of 308 women were studied. No significant change was seen in the urodynamic parameters between the placebo and elocalcitol groups, except for the bladder volume at the first desire to void. The frequency of incontinence episodes was significantly reduced in the elocalcitol group compared with the placebo group (P = .02). The Patient's Perception of Bladder Condition score improved significantly after treatment for the women receiving elocalcitol compared with those receiving placebo (P = .02). Treatment with both doses of elocalcitol was well tolerated, and no differences versus placebo were observed. Although the primary endpoint was not achieved, elocalcitol appears to be an effective and well-tolerated drug for the treatment of women with overactive bladder and idiopathic detrusor overactivity. However, the multicenter setting for the use of urodynamics might have biased the results of our study.
  Urology 05/2012; 80(1):48-54. · 2.43 Impact Factor
• Article: Changes in detrusor muscle oxygenation during detrusor overactivity contractions.

  Gopalan Vijaya, Giuseppe A Digesu, Alexandros Derpapas, Demetri C Panayi, Ruwan Fernando, Vik Khullar
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  ABSTRACT: To investigate changes in the oxygenated and deoxygenated haemoglobin (Hb) of the bladder wall during voluntary and involuntary detrusor contractions. Women with lower urinary tract symptoms were recruited from a urodynamics clinic. Near infra-red spectroscopy, a non-invasive optical technique which monitors changes in tissue oxygenation, was used to measure oxygenated and deoxygenated haemoglobin simultaneously while the women underwent urodynamics. All data were compared using paired sample t-test. Fifty-five women with a mean age of 52 years were enrolled into the study. In the 23 women with detrusor overactivity (15 with isolated detrusor overactivity and 8 with mixed urinary incontinence) there was a statistically significant rise in deoxygenated Hb during involuntary detrusor contractions at maximum detrusor pressure compared to the start of filling (p=0.02). There was no statistically significant change between Hb parameters measured at the start of the filling phase and those measured during voluntary detrusor contraction at pdetQmax (detrusor pressure at maximum flow rate). The mean detrusor pressure measured during voiding, however, was significantly higher than the maximum pressure during involuntary detrusor contractions (p=0.03). There is a significant rise in the deoxygenated Hb in the detrusor muscle during detrusor overactivity, which is not seen during voiding even when the pdetQmax was higher than the peak detrusor pressure during involuntary contractions. These interesting changes in detrusor muscle oxygenation during involuntary detrusor contraction need to be explored further to assess if deoxygenation plays a role in the pathogenesis of detrusor overactivity.
  European journal of obstetrics, gynecology, and reproductive biology 04/2012; 163(1):104-7. · 1.97 Impact Factor
• Article: Fesoterodine in randomised clinical trials: an updated systematic clinical review of efficacy and safety.

  Chiara Dell'utri, G Alessandro Digesu, Alka Bhide, Vik Khullar
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  ABSTRACT: This is a systematic review of clinical data assessing the safety, efficacy and tolerability of fesoterodine in randomised control trials (RCTs) in the treatment of overactive bladder (OAB). We performed a MEDLINE literature search of articles published between 2005 and 2010 regarding the efficacy and safety of fesoterodine. The US Food and Drug Administration Web site was also searched for RCTs. Two studies demonstrated significant improvement of OAB symptoms with fesoterodine compared with placebo. Two phase III studies showed both doses of fesoterodine to be more effective than placebo for most symptoms. Another phase III trial confirmed the superiority of 8 mg fesoterodine compared with tolterodine ER 4 mg. Dry mouth was the commonest side effect. Fesoterodine is effective for treating OAB symptoms. Its once-daily dosing regime and the flexibility to increase the dose are appealing factors.
  International Urogynecology Journal 03/2012; 23(10):1337-44. · 1.83 Impact Factor
• Article: Use of mirabegron in treating overactive bladder.

  Alka A Bhide, G Alessandro Digesu, Ruwan Fernando, Vik Khullar
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  ABSTRACT: The lack of an alternative to antimuscarinics has led to the search for new drug targets for overactive bladder (OAB) symptoms. The presence of β-3 adrenoreceptors in the bladder has been confirmed, and they are known to have a role in bladder relaxation. Targeting these receptors improves bladder compliance on filling and increases bladder capacity. MEDLINE literature search on efficacy and safety of mirabegron was performed. The US Food and Drug Administration Web site, clinicaltrials.gov, and controlled-trials.com online trial registries were searched for English-language articles containing the term "mirabegron". Finally, abstracts from recent International scientific meetings were searched for randomised controlled trials (RCTs). Studies show that mirabegron reduces the number of micturitions and incontinence episodes in a 24-h period compared with placebo. Dry mouth and gastrointestinal disturbances are the most common side effects, but these have been rated as mild to moderate. A small rise in mean heart rate and blood pressure has been shown. Further investigations are ongoing and results are awaited. Although mirabegron is metabolised by CYP2D6, it is also thought to inhibit the activity of this enzyme. Therefore, potential drug interactions with other CYP2D6 substrates need to be further studied. Mirabegron is a promising alternative to antimuscarinics. Further information on its long-term use in terms of efficacy, safety, and tolerability is awaited.
  International Urogynecology Journal 03/2012; 23(10):1345-8. · 1.83 Impact Factor
• Article: Patient-reported outcomes and different approaches to urinary parameters in overactive bladder: what should we measure?

  Vik Khullar
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  ABSTRACT: Overactive bladder (OAB) is highly prevalent and associated with considerable impact on patient health-related quality of life (HRQoL). Assessment of HRQoL can reveal the burden of disease and post-intervention improvement. This review aims to highlight the importance of HRQoL assessment and outline the tools available for use in clinical trials and real-world clinical practice. A number of validated measures of HRQoL specific to OAB have been developed, offering greater sensitivity and responsiveness over generic instruments. These condition-specific, multi-dimensional and single-item global questionnaires are particularly useful for the multiple and varied symptoms of OAB, as they reflect the patient's needs, concerns and values. Measurements for lower urinary tract symptoms, e.g. bladder diaries, are being compared with HRQoL instruments to provide greater understanding of the disease and treatment from the patient's perspective. Therapeutic interventions to improve OAB symptoms should also be evaluated for their effect on the patient's HRQoL.
  International Urogynecology Journal 02/2012; 23(2):179-92. · 1.83 Impact Factor
• Article: Intraobserver and interobserver reliability of the three-dimensional ultrasound imaging of female urethral sphincter using a translabial technique.

  G Alessandro Digesu, Nishee Calandrini, Alexandros Derpapas, Pasquale Gallo, Shahla Ahmed, Vik Khullar
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  ABSTRACT: The aim of the study was to assess the interobserver and intraobserver reliability of translabial 3D ultrasound imaging of the urethral sphincter in non-pregnant nulliparous asymptomatic women. A study using a 3D translabial ultrasound on thirty-seven women was performed. Urethral sphincter parameters were measured by the same experienced clinician 2 weeks apart. Multiple axial cross-sectional areas at 1-mm distances were used to calculate urethral sphincter volumes. The same measurements were carried out by a second experienced clinician to assess the interobserver reliability. We found an excellent intraobserver reliability (interclass correlation coefficient, ICC >0.8) and good interobserver reliability (ICC >0.6). The described technique using multiple axial cross-sectional areas at set distances and a translabial approach is a reliable and accurate tool in the evaluation of the urethral sphincter. This should be used instead of mathematical formulas as the urethral sphincter is not a uniform geometrical sphere. The technique and values reported may help clinicians in the assessment of women with lower urinary tract disorders.
  International Urogynecology Journal 01/2012; 23(8):1063-8. · 1.83 Impact Factor
• Article: Antimuscarinic effects on current perception threshold: a prospective placebo control study.

  Gopalan Vijaya, G Alessandro Digesu, Alexandros Derpapas, Caroline Hendricken, Ruwan Fernando, Vik Khullar
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  ABSTRACT: To evaluate the effect of Tolterodine on urethral and bladder afferent nerves in women with detrusor overactivity (DO) in comparison to placebo, by studying the changes in the current perception threshold (CPT). Women with overactive bladder symptoms and idiopathic DO were recruited and randomized in a double-blind manner between placebo and tolterodine extended release. All women underwent CPT testing of the bladder and urethra using a Neurometer constant current stimulator. CPT values were determined at three frequencies, including 2,000 Hz (corresponding to Aβ-fibers), 250 Hz (corresponding to Aδ-fibers), and 5 Hz (corresponding to C fibers) before and 7 days on treatment. CPT values before and on treatment were compared using a Wilcoxon Signed Rank test. Twenty women (mean age 46 years) were studied. There was no statistical difference between the two groups in terms of age, ethnicity, severity of symptoms and pre-treatment CPT values. Only in the tolterodine group there was a significantly increased CPT value at 5 and 250 Hz upon both urethral and bladder stimulation after 1 week of treatment. When compared with placebo, women taking tolterodine had significantly increased Bladder CPT values at 5 Hz (P-value <0.05). The electrical stimulation with 5 Hz was described as urgency. This is a randomized placebo control study evaluating the effect of antimuscarinics on sensory nerve function in women with DO. Our results support the animal studies that antimuscarinics have an effect on sensory function.
  Neurourology and Urodynamics 01/2012; 31(1):75-9. · 2.96 Impact Factor
• Article: Racial differences in female urethral morphology and levator hiatal dimensions: an ultrasound study.

  Alexandros Derpapas, Shahla Ahmed, Gopalan Vijaya, Giuseppe Alessandro Digesu, Lesley Regan, Ruwan Fernando, Vik Khullar
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  ABSTRACT: To compare the urethral sphincter morphology and levator hiatal dimensions between white and black premenopausal nulliparous asymptomatic women using 3D/4D translabial ultrasonography. Nulliparous black and white women were recruited in a tertiary gynecological center. All women were completely asymptomatic for pelvic floor dysfunction. Women were assessed with 3D/4D translabial ultrasound scan of the pelvic floor, at rest. Measurements of the total urethral sphincter volume (TSV), rhabdosphincter volume, (RSV) and levator hiatal dimensions (LH) were taken at rest, after voiding. Twenty-three white and 14 black women (37 in total) were investigated. Subjects did not differ by age or body mass index (BMI). Black women were found to have significantly larger rhabdosphincters (RS) than their white counterparts (8.88 cm(3)  ± 1.65 vs. 5.97 cm(3)  ± 1.82, respectively, P = 0.000). With respect to levator hiatal dimensions at rest, black women had a significantly wider transverse diameter (LHt) than white women (mean difference of LHt = 0.43 cm, 95% CI 0.08-0.78, P < 0.05). Asymptomatic black nulliparous women have significantly larger rhabdosphincters than their white counterparts. Racial differences in the female urethral morphology could provide an insight on the pathophysiology of stress urinary incontinence.
  Neurourology and Urodynamics 12/2011; 31(4):502-7. · 2.96 Impact Factor
• Article: Comment on Kirby et al.: Preoperative voiding detrusor pressures do not predict stress incontinence surgery outcomes.

  G Alessandro Digesu, Alexandros Derpapas, Vik Khullar
  International Urogynecology Journal 12/2011; 23(3):379-80; author reply 381-2. · 1.83 Impact Factor
• Article: Time-to-effect with darifenacin in overactive bladder: a pooled analysis.

  Vik Khullar, Jenelle Foote, Yodit Seifu, Mathias Egermark
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  ABSTRACT: This study was conducted to assess time-to-effect with darifenacin in patients with overactive bladder (OAB). Efficacy and safety data were pooled from 1,059 patients (19-88 years, 85% women) randomized to darifenacin 7.5 or 15 mg once daily or matched placebo in three double-blind 12-week studies. Patients completed electronic bladder symptom diaries (number of micturitions/day; incontinence episodes/day; urgency episodes/day). A post hoc efficacy analysis was performed on the earliest recorded timepoints. The full analysis population comprised 1,053 patients. Statistically significant improvements were observed in all OAB symptoms (except nocturnal awakenings) for both darifenacin doses versus placebo at week 2, with further improvements over 6 and 12 weeks. Both darifenacin doses significantly improved all OAB symptoms from as early as days 6-8 versus placebo. Darifenacin 7.5 and 15 mg significantly reduced OAB symptoms throughout the study. The rapid onset-of-effect is desirable to patients with OAB and useful for their clinical management.
  International Urogynecology Journal 12/2011; 22(12):1573-80. · 1.83 Impact Factor
• Article: Validation of Persian version of the Prolapse Quality-of-Life questionnaire (P-QOL).

  Marzieh Nojomi, G Alessandro Digesu, Vik Khullar, Negar Morovatdar, Ladan Haghighi, Mansoureh Alirezaei, Steven Swift
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  ABSTRACT: The aim of this study was to evaluate the validity and reliability of a Persian translation of the Prolapse Quality-of-Life (P-QOL) questionnaire in women with pelvic organ prolapse (POP). One hundred and twenty-four women with POP symptoms and 125 asymptomatic women were studied. The asymptomatic group was used for discriminant validity. Seventy-two percent (89/124) of the symptomatic women had stage ≥ 2 POP while 86% (108/125) of the asymptomatic women had a stage <2 POP. All domains of the Persian P-QOL have a Cronbach's alpha coefficient greater than 0.7 (0.78-0.97) and were significantly different between symptomatic and asymptomatic women indicating a good discriminant validity (<0.01). The test-retest reliability confirmed a highly significant correlation. All items of P-QOL questionnaire correlated significantly with the objective vaginal examination findings (construct validity) except for personal relationship and emotions. The Persian version of the P-QOL is a valid and reliable tool to assess QOL of women with POP.
  International Urogynecology Journal 08/2011; 23(2):229-33. · 1.83 Impact Factor