Functional connectivity of the brain in older women with urgency urinary incontinence.
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ABSTRACT:
SUBMITTER: Clarkson BD
PROVIDER: S-EPMC6469490 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Functional connectivity of the brain in older women with urgency urinary incontinence.
Clarkson Becky D BD Karim Helmet T HT Griffiths Derek J DJ Resnick Neil M NM
Neurourology and urodynamics 20180727 8
<h4>Background</h4>The brain's role in continence is critical but poorly understood. Although regions activated during bladder stimulation have been identified, little is known about the interaction between regions. In this secondary analysis we evaluate resting state and effective connectivity in older women treated for urgency urinary incontinence (UUI).<h4>Method</h4>54 women ≥60 years old with UUI and 10 continent women underwent fMRI scanning during provocation of urinary urgency, both befo ...[more]
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Project description:This study's aims were to detect and quantify bacterial DNA in the urine of randomized trial participants about to undergo treatment for urinary urgency incontinence (UUI) without clinical evidence of urinary tract infection (UTI) and to determine if the presence of bacterial DNA in baseline urine relates to either baseline urinary symptoms or UTI risk after urinary tract instrumentation.Women without clinical evidence of baseline UTI were randomized to cystoscopic onabotulinum toxin A injection and oral placebo medication versus cystoscopic placebo injection and active oral medication. Bacterial DNA in participants' catheterized urine was measured by quantitative polymerase chain reaction (qPCR).Bacterial DNA was detected in the urine of 38.7 % of participants (60 out of 155). In these 60 qPCR-positive participants, baseline daily UUI episodes were greater than in the 95 qPCR-negative participants (5.71 [±2.60] vs 4.72 [±2.86], p?=?0.004). Neither symptom severity by questionnaire nor treatment outcome was associated with qPCR status or with qPCR level in qPCR-positive subjects. In contrast, the presence of urinary bacterial DNA was associated with UTI risk: only 10 % of the qPCR-positive women developed a UTI post-treatment, while 24 % of the qPCR-negative women did so. The median qPCR level for qPCR-positive samples did not differ significantly by UTI status (UTI 2.58?×?10(5) vs no UTI 1.35?×?10(5) copies/mL, p?=?0.6).These results may indicate a urinary bacterial contribution to both baseline UUI and the risk of post-treatment UTI.
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Project description:Introduction and hypothesisWe describe the rationale and methodology for a study comparing mind-body treatment and pharmacotherapy in women with urgency urinary incontinence (UUI). To explore brain associations in UUI, a subset of patients will also undergo functional magnetic resonance imaging (fMRI). We hypothesize that hypnotherapy, a mind-body intervention, will be at least as effective as pharmacotherapy in treating UUI. We also hypothesize that fMRI findings will change following treatment, with changes potentially differing between groups.MethodsWe describe the development and design challenges of a study comparing the efficacy of hypnotherapy and conventional pharmacotherapy in the treatment of UUI. The study randomizes women to either of these treatments, and outcome measures include bladder diaries and validated questionnaires. Sample size estimates, based on a noninferiority test (alpha = 0.025, beta = 0.20), after considering dropout subjects and subjects lost to follow-up, indicated that approximately 150 woman would be required to test the hypothesis that hypnotherapy is not inferior to pharmacotherapy within a 5 % noninferiority margin. The study will also evaluate fMRI changes in a subset of participants before and after therapy. Challenges included designing a study with a mind-body therapy and a comparison treatment equally acceptable to participants, standardizing the interventions, and confronting the reality that trials are time-consuming for participants who have to make appropriate accommodations in their schedule.ResultsStudy enrollment began in March 2013 and is ongoing.ConclusionsWe describe the design of a randomized controlled trial comparing mind-body therapy and pharmacotherapy in the treatment of UUI and the challenges encountered in its implementation.
| S-EPMC5393944 | biostudies-literature
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| S-EPMC4161260 | biostudies-literature
Project description:The purpose of this study was to characterize the urinary microbiota in women who are planning treatment for urgency urinary incontinence and to describe clinical associations with urinary symptoms, urinary tract infection, and treatment outcomes.Catheterized urine samples were collected from multisite randomized trial participants who had no clinical evidence of urinary tract infection; 16S ribosomal RNA gene sequencing was used to dichotomize participants as either DNA sequence-positive or sequence-negative. Associations with demographics, urinary symptoms, urinary tract infection risk, and treatment outcomes were determined. In sequence-positive samples, microbiotas were characterized on the basis of their dominant microorganisms.More than one-half (51.1%; 93/182) of the participants' urine samples were sequence-positive. Sequence-positive participants were younger (55.8 vs 61.3 years old; P = .0007), had a higher body mass index (33.7 vs 30.1 kg/m(2); P = .0009), had a higher mean baseline daily urgency urinary incontinence episodes (5.7 vs 4.2 episodes; P < .0001), responded better to treatment (decrease in urgency urinary incontinence episodes, -4.4 vs -3.3; P = .0013), and were less likely to experience urinary tract infection (9% vs 27%; P = .0011). In sequence-positive samples, 8 major bacterial clusters were identified; 7 clusters were dominated not only by a single genus, most commonly Lactobacillus (45%) or Gardnerella (17%), but also by other taxa (25%). The remaining cluster had no dominant genus (13%).DNA sequencing confirmed urinary bacterial DNA in many women with urgency urinary incontinence who had no signs of infection. Sequence status was associated with baseline urgency urinary incontinence episodes, treatment response, and posttreatment urinary tract infection risk.
| S-EPMC4556587 | biostudies-literature
Project description:AIMS:Urgency urinary incontinence (UUI) is a major problem for seniors. The underlying mechanisms of disease and therapy are unknown. We sought structural brain abnormalities that might underlie the functional differences previously observed by functional Magnetic Resonance Imaging in UUI patients versus controls, or among UUI responders versus non-responders to therapy-and thereby reveal potential disease mechanisms and therapeutic targets. METHODS:Secondary study of a trial of biofeedback-assisted pelvic floor muscle training (BFB) in 60 women (>60 yrs) with UUI, plus 11 age-matched continent controls. Brain structural abnormalities were investigated using: (1) white-matter hyperintensities (WMH); (2) diffusion tensor imaging (DTI) to reveal white-matter pathways with impaired integrity; and (3) voxel-based morphometry (VBM) to show regions of atrophy or hypertrophy. RESULTS:WMH burden was greater in UUI patients than controls (globally and in superior longitudinal fasciculus and cingulum), suggesting a possible causal connection. WMH burden was unexpectedly greater in responders than non-responders to BFB, and appeared to increase in non-responders but not in responders. DTI revealed even worse integrity of the cingulum than was apparent by WMH. VBM showed parahippocampal atrophy in UUI. CONCLUSIONS:Many women with UUI have white-matter damage that interferes with pathways critical to bladder control; they can be taught by techniques like BFB to exert stronger control over the bladder. For others, in whom abnormalities of key brain areas are less marked, UUI's cause may reside elsewhere, and therapy targeting these brain centers may be less effective than therapy targeting the bladder or other brain centers.
| S-EPMC6473817 | biostudies-literature
Project description:Treatment of urgency urinary incontinence has focused on pharmacologically treating detrusor overactivity. Recent recognition that altered perception of internal stimuli (interoception) plays a role in urgency urinary incontinence suggests that exploration of abnormalities of brain function in this disorder could lead to better understanding of urgency incontinence and its treatment.We sought to: (1) evaluate the relationship between bladder filling, perceived urgency, and activation at brain sites within the interoceptive network in urgency urinary incontinence; (2) identify coactivation of other brain networks that could affect interoception during bladder filling in urgency incontinence; and (3) demonstrate interaction between these sites prior to bladder filling by evaluating their resting-state connectivity.We performed an observational cohort study using functional magnetic resonance imaging to compare brain function in 53 women with urgency urinary incontinence and 20 controls. Whole-brain voxelwise analyses of covariance were performed to examine differences in functional brain activation between groups during a task consisting of bladder filling, hold (static volume), and withdrawal phases. The task was performed at 3 previously established levels of baseline bladder volume, the highest exceeding strong desire to void volume. All women continuously rated their urge on a 0- to 10-point Likert scale throughout the task and a mixed measures analysis of variance was used to test for differences in urge ratings. Empirically derived regions of interest from analysis of activation during the task were used as seeds for examining group differences in resting-state functional connectivity.In both urgency urinary incontinent participants and controls, changes in urge ratings were greatest during bladder filling initiated from a high baseline bladder volume and urgency incontinent participants' rating changes were greater than controls. During this bladder-filling phase urgency incontinent participant's activation of the interoceptive network was greater than controls, including in the left insula and the anterior and middle cingulate cortex. Urgency incontinent participant's activation was also greater than controls at sites in the ventral attention network and posterior default mode network. Urgency incontinent participant's connectivity was greater than controls between a middle cingulate seed point and the dorsal attention network, a "top-down" attentional network. Control connectivity was greater between the midcingulate seed point and the ventral attention network, a "bottom-up" attentional network.Increasing urge was associated with greater urgency incontinent participant than control activation of the interoceptive network and activation in networks that are determinants of self-awareness (default mode network) and of response to unexpected external stimuli (ventral attention network). Differences in connectivity between interoceptive networks and opposing attentional networks (ventral attention network vs dorsal attention network) were present even before bladder filling (in the resting state). These findings are strong evidence for a central nervous system component of urgency urinary incontinence that could be mediated by brain-directed therapies.
| S-EPMC5045785 | biostudies-literature
Project description:BackgroundAnticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed.MethodsWe performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events.ResultsOf 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P=0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P=0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P=0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P=0.01) and urinary tract infections (13% vs. 33%, P<0.001).ConclusionsOral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.).
| S-EPMC3543828 | biostudies-literature
Project description:BACKGROUND:Women with refractory urgency urinary incontinence (ie, unresponsive to behavioral and pharmacological interventions) are treated with onabotulinumtoxinA or sacral neuromodulation. OBJECTIVE:The objective of the study was to compare treatment efficacy and adverse events in women <65 and ?65 years old treated with onabotulinumtoxinA or sacral neuromodulation. STUDY DESIGN:This study was a planned secondary analysis of a multicenter, randomized trial that enrolled community-dwelling women with refractory urgency urinary incontinence to onabotulinumtoxinA or sacral neuromodulation treatments. The primary outcome was a change in mean daily urgency urinary incontinence episodes on a bladder diary over 6 months. Secondary outcomes included ?75% urgency urinary incontinence episode reduction, change in symptom severity/quality of life, treatment satisfaction, and treatment-related adverse events. RESULTS:Both age groups experienced improvement in mean urgency urinary incontinence episodes per day following each treatment. There was no evidence that mean daily urgency urinary incontinence episode reduction differed between age groups for onabotulinumtoxinA (adjusted coefficient, -0.127, 95% confidence interval, -1.233 to 0.979; P = .821) or sacral neuromodulation (adjusted coefficient, -0.698, 95% confidence interval, -1.832 to 0.437; P = .227). Among those treated with onabotulinumtoxinA, women <65 years had 3.3-fold greater odds of ?75% resolution than women ?65 years (95% confidence interval, 1.56 -7.02). Women <65 years had a greater reduction in Overactive Bladder Questionnaire Short Form symptom bother scores compared with women ?65 years by 7.49 points (95% confidence interval, -3.23 to -11.74), regardless of treatment group. There was no difference between quality of life improvement by age. Women ?65 years had more urinary tract infections following onabotulinumtoxinA and sacral neuromodulation (odds ratio, 1.9, 95% confidence interval, 1.2-3.3). There was no evidence of age differences in sacral neuromodulation revision/removal or catheterization following onabotulinumtoxinA treatment. CONCLUSION:Younger women experienced greater absolute continence, symptom improvement, and fewer urinary tract infections; both older and younger women had beneficial urgency urinary incontinence episode reduction, similar rates of other treatment adverse events, and improved quality of life.
| S-EPMC5803754 | biostudies-literature
Project description:PURPOSE:We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes. MATERIALS AND METHODS:First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ?0.01 and p ?0.004 represented moderate evidence of an association with outcomes. RESULTS:Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother. CONCLUSIONS:Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.
| S-EPMC5433900 | biostudies-literature