Effect of Behavioral and Pelvic Floor Muscle Therapy Combined With Surgery vs Surgery Alone on Incontinence Symptoms Among Women With Mixed Urinary Incontinence

Sung, Vivian W.; Borello‐France, Diane; Newman, Diane K.; Richter, Holly E.; Lukacz, Emily S.; Moalli, Pamela; Weidner, Alison C.; Smith, Ariana L.; Dunivan, Gena C.; Ridgeway, Beri; Nguyen, John N.; Mazloomdoost, Donna; Carper, Benjamin; Gantz, Marie G.

doi:10.1001/jama.2019.12467

Cited by 63 publications

(53 citation statements)

References 45 publications

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“…Current therapy against myotoxicity include surgical intervention and antioxidants [ 2 , 48 , 49 , 50 , 51 ]. However, these therapies are limited due to cost, immune rejection and side effects in other organs [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis

2020

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Doxorubicin (Dox)-induced muscle toxicity (DIMT) is a common occurrence in cancer patients; however, the cause of its development and progression is not established. We tested whether inflammation-triggered cell death, “pyroptosis” plays a role in DIMT. We also examined the potential role of exosomes derived from embryonic stem cells (ES-Exos) in attenuating DIMT. C57BL/6J mice (10 ± 2 wks age) underwent the following treatments: Control (saline), Dox, Dox+ES-Exos, and Dox+MEF-Exos (mouse-embryonic fibroblast-derived exosomes, negative control). Our results demonstrated that Dox significantly reduced muscle function in mice, which was associated with a significant increase in NLRP3 inflammasome and initiation marker TLR4 as compared with controls. Pyroptosis activator, ASC, was significantly increased compared to controls with an upregulation of specific markers (caspase-1, IL-1β, and IL-18). Treatment with ES-Exos but not MEF-Exos showed a significant reduction in inflammasome and pyroptosis along with improved muscle function. Additionally, we detected a significant increase in pro-inflammatory cytokines (TNF-α and IL-6) and inflammatory M1 macrophages in Dox-treated animals. Treatment with ES-Exos decreased M1 macrophages and upregulated anti-inflammatory M2 macrophages. Furthermore, ES-Exos showed a significant reduction in muscular atrophy and fibrosis. In conclusion, these results suggest that DIMT is mediated through inflammation and pyroptosis, which is attenuated following treatment with ES-Exos.

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Section: Discussionmentioning

confidence: 99%

Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis

2020

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“…A total of 128 participants are required to detect a moderate effect size of 0.5 between the groups based on a two-sided significance level of 0.05 and 80% power [ 30 ]. Assuming a 15% drop out rate based on a previous RCT to evaluate behavioral therapy in women with mixed urinary incontinence [ 31 ], we set the target sample size at 150 participants.…”

Section: Methodsmentioning

confidence: 99%

Cognitive behavioral therapy for overactive bladder in women: study protocol for a randomized controlled trial

et al. 2020

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Background Overactive bladder (OAB) symptoms affect daily life by decreasing health-related quality of life (HRQol). However, there remain no very effective treatment for OAB. Pharmacotherapy is one of the best treatments, but it is not always efficient and may incur adverse events. Although behavioral therapy is another effective treatment, there are very few structured treatment manuals on how to prescribe behavioral therapy to treat OAB for whom. Cognitive behavioral therapy (CBT) is a psychotherapy consisting of structured sessions to solve problems with the collaborative empiricism between therapists and patients. OAB symptoms are supposed to worsen with cognitive distortion, and CBT is expected to be effective in treating OAB by modifying such cognitive processes. In this trial, we will evaluate the efficacy of CBT for OAB. Methods A randomized, controlled, open-label, multicenter parallel-group superiority trial will be conducted. Participants with moderate to severe OAB symptoms with or without pharmacotherapy will be recruited and will be randomly allocated 1:1 to two different groups by minimization (age, baseline OAB severity, treatment status, types of intervention, and treating institutions). The intervention group will be prescribed an individual CBT program covering six techniques in 4 sessions (30 min each), with or without pharmacotherapy. The primary outcome is the change scores in an OAB-questionnaire (OAB-q) from baseline to the end of the trial (week 13). Secondary outcomes will include other patient reported outcome measures and the frequency volume chart. All analyses will be conducted on an intention-to-treat principle. Discussion This trial will determine the efficacy of CBT to treat OAB using a rigorous methodology. The effectiveness of CBT with a structured manual may not only lead to a new treatment option for patients suffering from OAB symptoms, but may also reduce the social burden by OAB. Trial registration UMIN-CTR Clinical Trial, CTR-UMIN000038513 . Registered on November 7, 2019.

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“…After Duke University Institutional Review Board approval (Pro #00102155), we conducted a reanalysis of sequencing data generated from the Human Microbiome Study in the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence HMS-ESTEEM Study. (5) The HMS-ESTEEM study was a supplemental translational study embedded within the ESTEEM randomized trial (11) conducted by 8 clinical sites within the Pelvic Floor Disorders Network (PFDN). 3 Briefly, this was a cross-sectional analysis of microbiome data obtained from women with mixed urinary incontinence (MUI) and age-matched controls.…”

Section: Methodsmentioning

confidence: 99%

Updating urinary microbiome analyses to enhance biologic interpretation

Siddiqui

Brubaker

et al. 2021

Preprint

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Objective: An approach for assessing the urinary microbiome is 16S rRNA gene sequencing, where a segment of the bacterial genome is amplified and sequenced. Methods used to analyze these data are rapidly evolving, although the research implications are not known. This re-analysis of an existing dataset aimed to determine the impact of updated bioinformatic and statistical techniques. Methods: A prior Pelvic Floor Disorders Network (PFDN) study compared the urinary microbiome in 123 women with mixed urinary incontinence (MUI) and 84 controls. We used the PFDN unprocessed sequencing data of V1-V3 and V4-V6 16S variable regions, processed operational taxonomic unit (OTU) tables, and de-identified clinical data. We processed sequencing data with an updated bioinformatic pipeline, which used DADA2 to generate amplicon sequence variant (ASV) tables. Taxa from ASV tables were compared to OTU tables generated from the original processing; taxa from different variable regions (e.g., V1-V3 versus V4-V6) after updated processing were also compared. After updated processing, data were analyzed with multiple filtering thresholds. Several techniques were tested to cluster samples into microbial communities. Multivariable regression was used to test for associations between microbial communities and MUI, while controlling for potentially confounding variables. Results: Of taxa identified through updated bioinformatic processing, only 40% were identified originally, though taxa identified through both methods represented >99% of sequencing data in terms of relative abundance. When different 16S rRNA gene regions were sequenced from the same samples, there were differences noted in recovered taxa. When the original clustering methods were applied to reprocessed sequencing data, we confirmed differences in microbial communities associated with MUI. However, when samples were clustered with a different methodology, microbial communities were no longer associated with MUI. Conclusions: Updated bioinformatic processing techniques recover many different taxa compared to prior techniques, though most of these differences exist in low abundance taxa that occupy a small proportion of the overall microbiome. Detection of high abundance taxa are not significantly impacted by bioinformatic strategy. However, there are different biases for less abundant taxa; these differences as well as downstream clustering methodology and filtering thresholds may affect interpretation of overall results.

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Effect of Behavioral and Pelvic Floor Muscle Therapy Combined With Surgery vs Surgery Alone on Incontinence Symptoms Among Women With Mixed Urinary Incontinence

Cited by 63 publications

References 45 publications

Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis

Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis

Cognitive behavioral therapy for overactive bladder in women: study protocol for a randomized controlled trial

Updating urinary microbiome analyses to enhance biologic interpretation

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