41st Annual Meeting of the International Continence Society

August 29-September 2, 2011; Glasgow, UK
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Brain Activity as a Functional Assessment of Continence Control in Older Women

Glasgow, UK—Urinary incontinence carries a spectrum of functional impairments that are not easily detected by clinical measures. Analyzing brain activity, especially in the supplemental motor area (SMA), during bladder filling has the potential to be a marker of more advanced functional impairment in older women with urgency incontinence, according to Stasa D. Tadic, MD, MS, and colleagues, Division of Geriatrics, Department of Medicine, University of Pittsburgh, PA. The study was presented in a poster at the recent ICS meeting. Tadic discussed the data and their implications in an interview with Clinical Geriatrics.

“Brain activity involved in bladder control differs in women with different functional statuses of continence control and their ability to ‘hold their bladder,’” Tadic said. “Age and structural changes (damage) of white matter are important in particular since they associate with greater functional impairment of continence control as shown by this study.”

The study involved 30 functional, community-dwelling women aged 60 to 92 years (median age, 73 years) with urgency incontinence. While the women repeated cycles of bladder filling and emptying, brain activity was assessed using functional magnetic resonance imaging simultaneously with urodynamic monitoring. When the bladder was filled, approximately one-third (n = 9) of subjects exhibited detrusor overactivity (DO) and incontinence; the remaining women (n = 21) did not exhibit DO. The authors investigated whether this difference could be attributed to two different functional phenotypes that could be observed in brain activity during urgency (without DO) and/or in clinical characteristics related to continence, such as age, structural brain damage, and urodynamics.

The DO group demonstrated greater brain activations during urgency (preceding DO), especially in the SMA and adjacent regions, while the non-DO group demonstrated strong deactivations in the hippocampus and parahippocampal area (the grey matter cortical region of the brain). The DO group, which was an older group of women, exhibited stronger neural activity related to efforts to control the pelvic floor muscles and urethra, whereas the non-DO group showed stronger inhibitory deactivations in the prefrontal cortex. “In the scanner, older women with more white matter damage leaked urine and were losing control of the bladder easier than younger ones with less white matter damage,” said Tadic.

The authors concluded that a relationship does exist between brain activity during bladder filling and continence control, and the study confirms heterogenous phenotypes within a large group of individuals reporting urgency and urinary leakage. The study also suggests that functional brain imaging, combined with urodynamics, may be helpful for clinicians to distinguish severity of functional impairment and clinical phenotypes within urgency incontinence.

“[The study] should alert providers to check the structural brain scans and look for white matter changes in their patient with incontinence since the severity of these structural changes may account for the failure to respond to the standard treatments,” Tadic said. He noted that, since white matter changes are linked to urinary symptoms (ie, urgency) in both older men and older women, the results of the study may be extrapolated to men.

Tadic said that a larger study should be done to couple functional and structural brain imaging in a longitudinal cohort of older subjects with urinary urgency incontinence. “[Future] studies will help us to better define the relationship between neural activity involved in bladder control and structural changes in white (and grey) matter that progress with advanced age,” he said. “In addition, factors that contribute to incontinence in the elderly, such as cognition, mobility, and depression, should be studied along with imaging methods.”

This study was supported by the National Institutes of Health and the John A. Hartford Center of Excellence in Geriatric Medicine.
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Open-Label Phase of SOFIA Trial Shows Fesoterodine Is Efficacious and Well Tolerated in Elderly Individuals With Overactive Bladder

Glasgow, UK—The 12-week, randomized, double-blind (DB), placebo-controlled, parallel-group SOFIA (Study Of Fesoterodine In an Aging Population) trial assessed the efficacy, safety, and tolerability of flexible-dose fesoterodine (FESO), an oral antimuscarinic agent, in 794 individuals (≥65 years) with overactive bladder (OAB). A 12-week open-label (OL) phase followed the DB phase. During the DB phase, flexible-dose FESO was generally well tolerated and was associated with significant improvements in most patient-reported outcomes (PROs) and bladder diary variables. In a poster presented at the recent ICS meeting, researchers assessed the efficacy, safety, and tolerability of flexible-dose FESO during the 12-week OL phase of the trial.

Adrian Wagg, MB, FRCP, FHEA, Professor of Healthy Aging, University of Alberta, Edmonton, and colleagues found that “Improvements during 12 weeks of OL treatment with FESO allowed elderly men and women who received placebo during the DB phase to achieve similar improvements to those who initially received DB FESO.” Investigators also noted in the poster that individuals “who received FESO during the DB phase maintained their improvement over the 12-week OL phase with few additional adverse events.” FESO was generally well tolerated in the study participants.

Subjects included men and women with OAB symptoms for ≥3 months, a mean of ≥8 micturitions and ≥3 urgency episodes per 24 hours reported on 3-day baseline bladder diary, a Mini-Mental State Examination score of ≥20/30, and at least some moderate problems reported on the Patient Perception of Bladder Condition (PPBC) questionnaire. Randomization was stratified by age (>75 years and ≤75 years); there was a 1:1 ratio of FESO:placebo per age stratum. In addition, participants within each treatment group were randomized 1:1 to morning or evening dosing.

Individuals who had taken placebo during the DB phase of the trial started treatment with FESO 4 mg at the beginning of the OL phase. For these participants, the dose could be increased to 8 mg after 4 weeks of OL treatment and decreased again to 4 mg at any time thereafter. Those who had taken FESO during the DB phase of the trial, however, continued on the same dose that they had taken at the end of the DB phase. For these participants, the dose could be decreased at any time, but not increased.

Investigators assessed efficacy with bladder diaries that were completed on 3 consecutive days during the week before each visit, the PPBC, the Overactive Bladder Questionnaire (OAB-q), the Urgency Perception Scale (UPS), the Overactive Bladder Satisfaction Questionnaire (OAB-S), and the Treatment Benefit Scale (TBS).

Ninety percent (n = 282) and 88% (n = 299) of participants who had received DB FESO or placebo and completed the DB phase completed the OL phase, respectively. During OL FESO treatment, clinically significant improvements in diary variables (urgency episodes/24 hours and micturitions/24 hours) and PROs were reported in those who had received DB placebo, and the group who had received DB FESO maintained the week 12 improvements achieved during the DB phase. Those who had previously received DB placebo experienced greater improvements in diary variables, OAB-q, PPBC, and UPS from week 12 to 24. By week 24, the overall level of improvement in diary variables and PROs were comparable among all subjects, regardless of initial treatment group. Essentially, the group who received placebo “caught up” with those on active treatment.

Dry mouth and constipation were the most common adverse events during OL treatment. Three serious, treatment-related adverse events were reported: urinary retention, transient ischemic attack, and rash. Overall, the medication was effective and well tolerated, with few adverse cognitive effects reported throughout the entire trial.

This study was sponsored by Pfizer, Inc. Editorial support was provided by Complete Healthcare Communications, Inc., and was funded by Pfizer, Inc.
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Meta-analysis Suggests High Prevalence of Fecal Incontinence in Nursing Homes

Glasgow, UK—A meta-analysis of several studies and articles addressing fecal incontinence (FI) in elderly nursing home patients was presented by a team of Norwegian investigators at the recent ICS meeting. Titled Fecal Incontinence Among Elderly Patients in Nursing Homes: a Systematic Review of Prevalence and Risk Factors, the poster pointed to a widely varying but relatively high prevalence of FI among nursing home residents. Investigators also identified several comorbid conditions that seemed to correlate with an increased risk of FI.

After searching the literature for articles related to FI in nursing home residents, investigators selected 15 studies and 16 articles deemed relevant. Of these 31 studies, only 14 reported the prevalence of FI in nursing home residents, and this ranged from 10.3% to 63.6%. The greatest concordance in prevalence was observed among a group of six studies that placed it between 40% and 55%. Researchers noted several factors that might account for the tremendous disparity in prevalence rates among the studies. For example, the studies applied different definitions of FI, with variation in the frequency of bowel movements used to diagnose the condition. Studies also varied in how they defined a nursing home. The lack of demographic details for participating residents in many of the studies led the poster authors to hypothesize that major variation in patient characteristics between studies might account for some of the discrepancy in prevalence. The meta-analysis was also limited by the differing variables and definitions outlined in the included studies.

In all, nine studies identified an increased risk of FI associated with mobility-related factors. Specifically,  loss of activities of daily living, loss of mobility or poor mobility—including confinement to a wheelchair or bed—and truncal restraints correlated with an increased overall risk of FI. Together, the nine studies observed functional disability in 47% of patients with FI. Reduced cognitive functions (eg, dementia, cognitive impairment, mental function) were identified as contributing risks for FI in seven studies. Six studies reported increased risk associated with bowel/urinary tract dysfunction. Cumulatively, 70% of patients with FI in these six studies had issues with fecal loading, 44% had acute diarrhea, and 20% had loose stool; watery stool, tube feeding, urinary incontinence, and constipation were other related risk factors for FI. Another six studies determined that conditions such as stroke, neurological disease, comorbidity, diabetes, pressure ulcers, and impaired vision increased the likelihood of a resident developing FI; nearly half (47%) of patients in these six studies had a comorbid illness. These six studies also indicated a higher prevalence of FI among men and people who are not white.

Although the meta-analysis found great variance in the prevalence rates between studies, the authors said that their review “confirms the assumption that there is a high prevalence of FI among nursing home patients.” They recommended further research on FI in the nursing home population, conducting studies that apply a more consistent, coherent definition of FI and use measurement tools that have been
validated.