Zhanna Jumadilova

Patient-reported reasons for discontinuing overactive bladder medication

Study Type – Symptom prevalence (prospective cohort)
Level of Evidence 1b

ORIGINAL RESEARCH—OUTCOMES ASSESSMENT: Overactive Bladder and Women's Sexual Health: What is the Impact?

INTRODUCTION Overactive bladder (OAB) is quite prevalent and significantly affects health-related quality of life and daily functioning. AIM The impact of OAB on sexual health is currently not known. This qualitative study was conducted to gain a thorough understanding of OABs impact. METHODS Sexually active women with continent or incontinent OAB were recruited from urology and urogynecology clinics. Six focus groups of women (three continent and three incontinent) were conducted to assess the sexual health of women with OAB. Data were analyzed descriptively and qualitatively. MAIN OUTCOME MEASURES Qualitative data, Sexual Quality of Life Questionnaire-Female, Overactive Bladder Questionnaire. RESULTS Thirty-four women (11 continent; 23 incontinent) participated; mean age was 48.4 years; 76% were white, 67% postmenopausal, and 88% in a long-term relationship. Continent women reported more frequent sexual activity than incontinent women; 91% reported intercourse >or=1-3 times per month vs. 50% of incontinent women. Half of the incontinent women reported a reduction in sexual desire related to OAB, aging, and menopause. Over half of continent women experienced pain with intercourse, and the majority complained of having to interrupt intercourse to void. Although not all incontinent women reported incontinence during intercourse, the majority were embarrassed by their incontinence and OAB with resulting loss of self-image. Both continent and incontinent women reported difficulty achieving orgasm because of pain, fear of incontinence, or anxiety related to intercourse. Approximately a third of the women would not initiate discussion of sexual issues with their physicians, but all women expressed concern about the impact of OAB on their sexual life. CONCLUSION Overactive bladder with or without incontinence negatively affects womens sexual health, reducing sexual desire and ability to achieve orgasm. Given the impact of OAB on sexual health, sexual health should be routinely assessed by clinicians and addressed by researchers.

Bother Related to Bladder Control and Health Care Seeking Behavior in Adults in the United States

PURPOSE We measured patient reported bother due to overactive bladder syndrome, patterns of physician consultation and prescription medication use for overactive bladder symptoms in adults in the United States. MATERIALS AND METHODS A survey sample was derived from a consumer panel of 600,000 American households developed to match the United States Census of 260,000 adults. The survey included the Overactive Bladder-Validated 8 awareness tool, which includes 8 questions that measure the degree of bother due to specific bladder symptoms. A score of 8 or greater denotes probable overactive bladder. Additional questions probed treatment patterns, health care consultation, overactive bladder diagnosis, treatment type and prescription treatment used. A nonrespondent telephone survey in 1,004 participants was done to evaluate differences between mail survey respondents and nonrespondents. RESULTS The response rate was 63% (162,906 respondents). Women represented 55.1% of the sample and 21.8% of respondents were 65 years old or older. Symptom bother, as determined by an Overactive Bladder-Validated 8 score of 8 or greater, was reported by 26.6% of the total sample, including 23.7% of men and 28.9% of women. The percent of men and women reporting bother increased with age. Of respondents with probable overactive bladder only 45.7% had discussed the symptoms with a medical provider, 22.5% had previously used prescription medication for overactive bladder, 13.5% had used overactive bladder medication in the last 12 months and 8.1% were currently on treatment. CONCLUSIONS A substantial proportion of adults in the United States reported some degree of bother due to overactive bladder symptoms. The degree of bother was associated with age and gender. Overall less than half of patients with probable overactive bladder discussed the symptoms with a health care provider. A small proportion was prescribed medication and an even smaller proportion was currently on treatment.

Predictors of discontinuing overactive bladder medications

Study Type – Symptom prevalence (prospective cohort)
Level of Evidence 1b

Efficacy and Safety of Flexible Dose Fesoterodine in Men and Women with Overactive Bladder Symptoms Including Nocturnal Urinary Urgency

PURPOSE Awakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder. MATERIALS AND METHODS Subjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided. The primary end point was change from baseline to week 12 in the mean number of micturition related nocturnal urgency episodes per 24 hours. RESULTS Overall 963 subjects were randomized from 2,990 screened, and 82% of subjects treated with fesoterodine and 84% of those treated with placebo completed the study. Significant improvements in the primary end point (-1.28 vs -1.07), in nocturnal micturitions per 24 hours (-1.02 vs -0.85) and in nocturnal frequency urgency sum (-4.01 vs -3.42) were observed with fesoterodine vs placebo (all p ≤0.01). Health related quality of life measures (overactive bladder questionnaire Symptom Bother -20.1 vs -16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were improved with fesoterodine. CONCLUSIONS To our knowledge this is the first prospective study to assess antimuscarinic efficacy for reducing nocturnal urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency episodes vs placebo in subjects with overactive bladder.

Effects of the moderate CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fesoterodine in healthy subjects

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Available data suggest that fesoterodine dosage should not exceed 4 mg once daily when taken concomitantly with potent CYP3A4 inhibitors, such as ketoconazole. Currently, no information is available on whether dose adjustment is necessary when fesoterodine is administered with a moderate CYP3A4 inhibitor. WHAT THIS STUDY ADDS This study shows that adjustment of fesoterodine dose is not warranted when co-administered with a moderate CYP3A4 inhibitor. AIMS To assess the effects of fluconazole, a moderate CYP3A4 inhibitor, on the pharmacokinetics (PK) and safety/tolerability of fesoterodine. METHODS In this open-label, randomized, two-way crossover study, 28 healthy subjects (18-55 years) received single doses of fesoterodine 8 mg alone or with fluconazole 200 mg. PK endpoints, including the area under the plasma concentration-time curve from 0 to infinity (AUC(0,∞)), maximum plasma concentration (C(max) ), time to C(max) (t(max) ), and half-life (t(1/2) ), were assessed for 5-hydroxymethyl tolterodine (5-HMT), the active moiety of fesoterodine. RESULTS Concomitant administration of fesoterodine with fluconazole increased AUC(0,∞) and C(max) of 5-HMT by approximately 27% and 19%, respectively, with corresponding 90% confidence intervals of (18%, 36%) and (11%, 28%). There was no apparent effect of fluconazole on 5-HMT t(max) or t(½) . Fesoterodine was generally well tolerated regardless of fluconazole co-administration, with no reports of death, serious adverse events (AEs) or severe AEs. Following co-administration of fesoterodine with fluconazole, 13 subjects (48%) experienced a total of 40 AEs; following administration of fesoterodine alone, six subjects (22%) experienced a total of 19 AEs. The majority of AEs were of mild intensity. There were no clinically significant changes in laboratory or physical examination parameters. CONCLUSION Fesoterodine 8 mg single dose was well tolerated when administered alone or with fluconazole. Based on the observed increase in 5-HMT exposures being within the inherent variability of 5-HMT pharmacokinetics, adjustment of fesoterodine dose is not warranted when co-administered with a moderate CYP3A4 inhibitor provided they are not also inhibitors of transporters.

Effects of tolterodine ER on patient-reported outcomes in sexually active women with overactive bladder and urgency urinary incontinence

ABSTRACT Objective: To assess the effects of tolterodine extended release (ER) on patient-reported outcomes (PROs) in sexually active women with overactive bladder (OAB) and urgency urinary incontinence (UUI). Research design and methods: This multicenter, double-blind, placebo controlled trial included 411 women aged ≥18 years reporting OAB symptoms for ≥3 months; ≥8 micturitions per 24 hours (including ≥0.6 UUI episodes and ≥3 OAB micturitions) in 5-day bladder diaries at baseline, and being in a sexually active relationship for ≥6 months. Subjects randomized to placebo or tolterodine ER completed validated OAB- or incontinence-specific questionnaires, including the Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), Urgency Perception Scale (UPS), and the Incontinence Impact Questionnaire (IIQ) at baseline and week 12, as well as the Perception of Treatment Benefit and Treatment Satisfaction questions at week 12. This study is registered with ClinicalTrials.gov (identifier: NCT00143481) Results: The mean age of enrolled women was approximately 48 years. Compared with placebo, the tolterodine ER group reported significant baseline to week 12 improvements in PPBC responses (p = 0.0048); OAB-q Symptom Bother, total Health-Related Quality of Life (HRQL), and HRQL domain scores (all p < 0.05); IIQ Emotional Health domain scores (p < 0.05); proportions of subjects reporting treatment benefit (79 vs. 54%; p < 0.0001) and satisfaction (78 vs. 59%; p < 0.0001). Improvements on the UPS were not significantly different. Conclusions: Tolterodine ER treatment was associated with improvements in multiple OAB- and incontinence-specific PROs in a sexually active, relatively young, and racially diverse population of women. The findings provide clinicians with new insights into the impact of OAB and its treatment on HRQL in this population, which has been underrepresented in previous OAB studies. Study limitations include a potential underestimation of the impact of OAB symptoms resulting from the exclusion of women who may not be sexually active because of their urinary symptoms. Trial registration: ClinicalTrials.gov identifier: NCT00143481.

Defining urinary urgency: patient descriptions of "gotta go".

Urgency is a key symptom in the diagnosis of overactive bladder (OAB), yet its definition and measurement are subject to continuing debate whether urinary urgency is a pathologic sensation or an intensification of normal desire to pass urine. The objective of this research was to explore the concept of urgency among participants with OAB symptoms and to evaluate the content validity of the urinary sensation scale (USS).

Meeting the obligation to communicate clinical trial results to study volunteers.

Although the overwhelming majority of study volunteers want to receive information on the results of their participation in clinical trials, research suggests that most study volunteers never do. CISCRP – an independent nonprofit organization – in collaboration with Pfizer, conducted a study evaluating the feasibility and impact of a new process to inform study volunteers of the results of their clinical trials. Two process components were evaluated via surveys, focus groups, and interviews with volunteers and investigative site staff: a series of ongoing post-trial communications to set expectations for when trial results would be received; and routine development and delivery of the lay language trial results summary. The results of this assessment show that study volunteers and investigative site staff are extremely receptive to receiving clinical trial results and that the process of preparing and disseminating clinical trial results is feasible and generally easy to execute. The results also indicate that study volunteer comprehension of basic facts about their clinical trial pre- and post-test increased by as much as 65.6 percentage points, and suggest that this communication initiative may positively impact volunteer recruitment, retention and long-term trust in the clinical research enterprise.

PUK18 VALIDATION OF THE URINARY SENSATION SCALE (USS)

of Life Questionnaire (I-QOL)), and SF-6D preference scores were measured at enrollment and 24weeks after treatmentwith a single injection of botulinum toxin type A or placebo. We measured the correlation between SF-6D, I-QOL and UI episode change scores. We used multiple linear regressions to estimate the impact on SF-6D scores of 50%; 50%–99% and 100% reductions in UI episodes and a 10-point improvement in I-QOL. These thresholds are thought to be clinically significant and are often reported as trial outcomes. RESULTS: SF-6D change scores between enrollment and 24 weeks were moderately correlated with I-QOL change scores (rho = 0.41; p < 0.01) but non-significantly correlated with UI episode changes scores (rho = -0.19; p = 0.20). At 24weeks, mean (95%CI) daily UI episodes fell by 0.85 (0.04, 1.3) and mean I-QOL scores improved by 18 (12, 24). SF-6D scores increased by 0.03 (0.003, 0.058), due, primarily, to improvements in the role limitations domains. A 50% reduction in UI episodes was achieved by 49% of patients and corresponded to a 0.09 (0.02, 0.16) SF-6D increase. A 10-point increase in I-QOL was attained by 65% of patients and was associated with a 0.05 (-0.02, 0.12) SF-6D increase. CONCLUSIONS: These estimates provide preliminary data for decision analysts wishing to map UI outcomes to preference scores. The results demonstrate that clinically important changes in condition specific quality of life are reflected in SF-6D preference scores.