115 results on '"C Betschart"'
Search Results
2. 275 TRANSURETHRAL INJECTION OF AUTOLOGOUS MUSCLE PRECURSOR CELLS FOR THE TREATMENT OF FEMALE STRESS URINARY INCONTINENCE – A PROSPECTIVE AND RANDOMIZED PHASE I CLINICAL TRIAL
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F Schmid, J Prange, M Kozomara, C Betschart, N Steinke, R Sousa, M Hunziker, F Lehner, M Veit, A Landsmann, A Boss, A Hötker, D Mohr-Haralampieva, and D Eberli
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2022
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3. Transurethral injection of autologous muscle precursor cells for the treatment of female stress urinary incontinence – a prospective and randomized phase I clinical trial
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F.A. Schmid, J.A. Prange, M. Kozomara, C. Betschart, R.A. Sousa, N. Steinke, M. Hunziker, F. Lehner, M. Veit, R. Grossmann, A. Landsmann, A.M. Hötker, A. Boss, D. Mohr-Haralampieva, and D. Eberli
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Urology - Published
- 2023
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4. [Gynecology: urinary incontinence - mini-review and case reports]
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D, Scheiner, D, Perucchini, D, Fink, and C, Betschart
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Aged, 80 and over ,Suburethral Slings ,Treatment Outcome ,Urinary Incontinence ,Urinary Bladder, Overactive ,Humans ,Female ,Prostheses and Implants ,Botulinum Toxins, Type A ,Middle Aged ,Algorithms ,Aged - Abstract
Although urinary incontinence affects one in three women, it is still a taboo topic. Today, effective conservative and surgical treatment options are available. When conservative therapies fail, minimally invasive surgical methods can be offered. The tension-free vaginal tape TVT is gold standard in the treatment of female stress urinary incontinence. In case of immobile urethra or in multi-morbid patients, the minimally invasive technique of periurethral injection of bulking agents may be useful. In patients with refractory overactive bladder, the intravesical injection of botulinum neurotoxin is available.
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- 2012
5. ChemInform Abstract: Synthesis of New Heterocyclic Systems by Photochemical Reactions of Chromium Carbene Complexes with Imidazolines
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C. Betschart and L. S. Hegedus
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chemistry.chemical_compound ,Chromium ,chemistry ,Organic chemistry ,chemistry.chemical_element ,General Medicine ,Carbene - Published
- 2010
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6. Perioperative Unterschiede zwischen retropubischer TVT-Schlinge und transobturatorischem out-in TOT Monarc und in-out TVT-O – Prospektiv randomisierte klinische Vergleichsstudie
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Daniele Perucchini, S. Kollbrunner, David Scheiner, C. Betschart, H. Werder, and Daniel Fink
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Gynecology ,medicine.medical_specialty ,business.industry ,Maternity and Midwifery ,medicine ,Obstetrics and Gynecology ,business - Published
- 2008
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7. [Primary malignant melanoma of the vagina--case report and review of the literature]
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C, Betschart, S, von Orelli, D, Mihic, and D, Fink
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Vaginal Neoplasms ,Palliative Care ,Middle Aged ,Combined Modality Therapy ,Positron-Emission Tomography ,Antineoplastic Combined Chemotherapy Protocols ,Vagina ,Disease Progression ,Humans ,Female ,Neoplasm Invasiveness ,Radiotherapy, Adjuvant ,Tomography, X-Ray Computed ,Melanoma - Abstract
The primary malignant melanoma of the vagina is a very rare tumor with less than 300 cases reported worldwide. Metastatic melanomas of the vagina are even rarer and only 5 cases have been reported so far. We describe the case of patient with a melanoma of the left side of the vagina with a tumor size of 6 cm and a tumor invasion of 2.5 cm. At the time of diagnosis there were no signs of nodal metastases in the positron emission tomography. In the literature, wide local excision with adjuvant radiotherapy is recommended, and radical surgery with adjuvant radiotherapy as second-line therapy. Both procedures show similar 5-year survival rates. To reduce the risk of metastases, we had planned an immunotherapy with interferon-alpha, which has been shown to improve relapse-free and overall survival in patients with high-risk cutaneous melanoma. Unfortunately, the cancer was found to have heavily metastasized 6 months later; the patient therefore received a palliative chemotherapy with dacarbazine and thalidomide.
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- 2005
8. Histomorphological analysis of the urogenital diaphragm in elderly women: a cadaver study.
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C. Betschart, D. Scheiner, C. Maake, M. Vich, L. Slomianka, D. Fink, and D. Perucchini
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RESPIRATORY organs , *CARDIOPULMONARY system , *AIR sacs (Bird anatomy) , *DIAPHRAGM (Anatomy) - Abstract
Abstract The objective of this study was to describe the histomorphological structure of the urogenital diaphragm in elderly women using a modern morphometric procedure. Biopsies were taken from the posterior margin of the urogenital diaphragm of 22 female cadavers (mean age, 87 years) using a 60-mm punch. Hematoxylin/eosin and Goldner sections were analyzed with the Cavalieri estimator. The mean thickness of the urogenital diaphragm was 5.5 mm. The main component was connective tissue. All biopsies contained smooth muscle. Eighteen biopsies contained more smooth muscle than striated muscle. In six of 22 biopsies, no striated muscle was found. The ratio of striated to smooth muscle to connective tissue was 1:2.3:13.3. Muscle fibers were dispersed in all parts of the urogenital diaphragm. The urogenital diaphragm of elderly women mainly consists of connective tissue. Smooth muscle was also found but to a lesser extent. The frequently used English term “perineal membrane” for the urogenital diaphragm is justified and well describes our findings in elderly women. [ABSTRACT FROM AUTHOR]
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- 2008
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9. ChemInform Abstract: Scope and Limitations of the Reductive Coupling of Aromatic Aldimine Derivatives with Formation of 1,2-Diarylethylenediamine Units, Using Low-Valent Titanium Reagents
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B. Schmidt, C. Betschart, and Dieter Seebach
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chemistry.chemical_classification ,Coupling ,Aldimine ,chemistry ,Scope (project management) ,Reagent ,chemistry.chemical_element ,Organic chemistry ,General Medicine ,Combinatorial chemistry ,Titanium - Published
- 1989
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10. ChemInform Abstract: DIASTEREOSELECTIVE SYNTHESIS OF NOVEL MANNICH BASES THROUGH TITANIUM DERIVATIVES
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Dieter Seebach, Martin Schiess, and C. Betschart
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chemistry ,chemistry.chemical_element ,General Medicine ,Combinatorial chemistry ,Titanium - Published
- 1984
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11. ChemInform Abstract: Preparation of 1,2-Diarylethylenediamines by Aminative Reductive Coupling of Aromatic Aldehydes with Low-Valent Titanium Reagents
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D. Seebach and C. Betschart
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Coupling (electronics) ,chemistry ,Reagent ,Polymer chemistry ,chemistry.chemical_element ,General Medicine ,Titanium - Published
- 1988
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12. ChemInform Abstract: Application of Low-Valent Titanium Reagents in Organic Synthesis
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D. Seebach and C. Betschart
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chemistry.chemical_compound ,Chemistry ,Reagent ,Inorganic chemistry ,Organic chemistry ,chemistry.chemical_element ,Organic synthesis ,General Medicine ,Titanium - Published
- 1989
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13. [Female urinary incontinence - diagnostics and therapies].
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Zachariah RR, Lange S, Keller N, Scheiner D, and Betschart C
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- Humans, Female, Urinary Incontinence, Stress therapy, Urinary Incontinence, Stress diagnosis, Diagnosis, Differential, Combined Modality Therapy, Urodynamics physiology, Electric Stimulation Therapy, Urinary Incontinence, Urge therapy, Urinary Incontinence, Urge diagnosis, Urinary Incontinence, Urge etiology, Cystoscopy, Urinary Incontinence therapy, Urinary Incontinence diagnosis, Urinary Incontinence etiology
- Abstract
Introduction: Urinary incontinence is a common complaint of both general practitioners and specialists. An accurate basic diagnosis with a structured medical history and bladder diary, urine analysis, gynaecological examination including pelvic floor assessment and a full bladder cough test can be supplemented by sonography, cystoscopy and urodynamic testing. This will help to differentiate between the different types of urinary incontinence, such as urge incontinence, stress incontinence and overflow incontinence. Treatment should be based on the type of urinary incontinence. Conservative treatments such as pelvic floor physiotherapy and pessaries can be supplemented by electrical stimulation for OAB and overflow incontinence, and various procedures such as TVT or bulking agents for stress incontinence, sacral neurostimulation for OAB and overflow incontinence., Competing Interests: Die Autorinnen und Autoren haben keine Interessenkonflikte im Zusammenhang mit diesem Artikel deklariert., (© 2024 Aerzteverlag medinfo AG.)
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- 2024
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14. Vulvodynia, Genital Eczema and Lichen Sclerosus: What are the Successful Treatments from a Patient's Perspective?
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Berger VC, Fierz R, Kolm I, Leeners B, and Betschart C
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Background: Genital pain treatment regimens range from local or systemic pharmacological to non-pharmacological, manual and psychosexual therapies with poor to moderate evidence for their efficiency. The aim of this study was to evaluate the subjective therapeutic response (genital pain relief) of different treatment modalities for vulvodynia and the most prevalent other vulvar pathologies, chronic vulvar eczema and lichen sclerosus by means of a cross-sectional survey., Material and Methods: A questionnaire-based cohort study that included 128 vulvodynia, 116 eczema and 79 lichen sclerosus patients was used. All patients attended the vulvar clinic at the University Hospital of Zurich. The patients who had been treated were surveyed from January to October 2022, using a customized online questionnaire consisting of 37 questions on symptoms and treatment outcomes for guideline-recommended treatment modalities. The study was approved by the Cantonal Ethics Review Board of Zurich., Results: Altogether, 41 patients with vulvodynia, 37 with vulvar eczema and 23 with lichen sclerosus returned the questionnaire. The three groups were similar regarding pain characteristics and comorbidities. All three patient groups reported having benefited from non-pharmacological treatment (improvement rate vulvodynia 54%; eczema 51%; lichen sclerosus 58%), from topical (55%; 55%; 75%) and from locally invasive (46%; 66%; 50%) treatments. Overall, there was no significant difference in subjective treatment outcome between non-pharmacological, locally invasive, and topical treatments for vulvodynia, eczema, and lichen sclerosus. However, the use of oral medication was reported to be significantly less effective (p-value 0.050)., Conclusion: In conclusion, we found that in the patients' perception, topical, invasive and non-pharmacological treatments, but not oral medications, are helpful for genital pain relief in women with vulvodynia, vulvar eczema, and lichen sclerosus. Therefore, we recommend an escalating therapy approach with first-line non-pharmacological treatments together with topical therapies., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Berger et al.)
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- 2024
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15. Assessment of pelvic organ prolapse with the Pelvic Inclination Correction System: defining the normal range and threshold to pathology.
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Ghafoor S, Beintner-Skawran S, Betschart C, Winklehner T, and Reiner CS
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- Humans, Female, Prospective Studies, Adult, Middle Aged, Reference Values, Aged, Pelvic Organ Prolapse diagnostic imaging, Magnetic Resonance Imaging methods
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Purpose: To define the normal range and threshold values for pathologic prolapse on MRI using the PICS line and assess its correlation with the pubococcygeal line (PCL)., Methods: This prospective, IRB-approved study included 20 nulliparous volunteers and 18 prolapse patients (POP-Q Stage ≥ 2). Organ positions (bladder, cervix, anorectal junction) relative to PICS and PCL were measured on dynamic MRI. Differences in organ position were compared. Receiver-operating characteristic (ROC) analysis was performed to identify cutoff values for prolapse using the PICS line. The correlation between PICS and PCL measurements was tested with Spearman's rank correlation., Results: In volunteers, median bladder and cervix positions measured to the PICS at rest were - 2.7 cm and - 5.3 cm compared to - 1.9 cm and - 2.7 cm in patients (p < 0.001). During straining, bladder and cervix were at - 0.9 cm and - 3.2 cm in volunteers versus + 2.5 cm and + 2.5 cm in patients (p < 0.001). Correlation was strong for PICS and PCL measurements for all three compartments (δ = 0.883-0.970, p ≤ 0.001). AUCs of PICS for the anterior and middle compartment were 0.98 (95% confidence interval [CI] 0.96-1.00, p < 0.001) and 0.96 (95% CI 0.89-1.00, p < 0.001) for differentiating patients from healthy volunteers. AUC for the posterior compartment was 0.76 (95% CI 0.57-0.96, p = 0.034)., Conclusion: PICS measurements reliably differentiate patients from volunteers in the anterior and middle compartment. Future studies need to identify a reliable threshold for the posterior compartment. PICS and PCL measurements are strongly correlated., (© 2024. The Author(s).)
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- 2024
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16. Quantitative 3D Analysis of Levator Ani Muscle Subdivisions in Nulliparous Women: MRI Feasibility Study.
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Moser N, Skawran S, Steigmiller K, Röhrnbauer B, Winklehner T, Reiner CS, and Betschart C
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Background: The levator ani muscle (LAM) is crucial for pelvic floor stability, yet its quantitative MRI assessment is only a recent focus. Our study aims to standardize the quantitative analysis of the LAM morphology within the 3D Pelvic Inclination Correction System (3D-PICS)., Methods: We analyzed 35 static MR datasets from nulliparous women examining the pubovisceral (PVM), iliococcygeal (ICM), coccygeal (COC), and puborectal muscle (PRM). The PVM consists of three origin-insertion pairs, namely the puboanal (PAM), puboperineal (PPM) and pubovaginal muscle (PVaM). The analysis included a quantitative examination of the morphology of LAM, focusing on the median location (x/y/z) (x: anterior-posterior, y: superior-inferior, z: left-right) of the origin and insertion points (a), angles (b) and lengths (c) of LAM. Inter-rater reliability was calculated., Results: Interindividual variations in 3D coordinates among muscle subdivisions were shown. In all, 93% of all origin and insertion points were found within an SD of <8 mm. Angles to the xz-plane range between -15.4° (right PRM) and 40.7° (left PAM). The PRM is the largest pelvic muscle in static MRI. The ICC indicated moderate-to-good agreement between raters., Conclusions: The accurate morphometry of the LAM and its subdivisions, along with reliable inter-rater agreement, was demonstrated, enhancing the understanding of normal pelvic anatomy in young nulliparous women.
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- 2024
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17. Impact of vaginal estriol on serum hormone levels: a systematic review.
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Kolokythas A, Betschart C, Wunder D, Janka H, and Stute P
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- Female, Humans, Estriol, Estrogens, Vagina, Menopause, Quality of Life
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The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief, there are several non-hormonal and hormonal vaginal products available. In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment. The aim of this systematic review was to assess the impact of vaginal E3 on serum sex hormone levels, an outcome that has been previously used to assess safety in similar products. In our review, we did not find any alterations in serum estrone, estradiol, testosterone, progesterone and sex hormone binding globulin levels after vaginal E3 application. In contrast, some studies showed a minimal and transient decrease in serum gonadotropin levels, which however remained within the postmenopausal range. Similarly, only a few studies reported a minimal and transient increase of serum E3 levels, with the rest reporting no changes. The lack of clinically relevant long-term changes in serum sex hormone levels supports the current literature providing evidence about the safety of vaginal E3 products.
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- 2024
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18. MRI characterization of pelvic floor ligaments in nulliparous women: Technique development and morphometry within the 3D pelvic inclination correction system (3D-PICS).
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Matter L, Hebeisen M, Beintner-Skawran S, Reiner CS, and Betschart C
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- Humans, Female, Reproducibility of Results, Ligaments, Articular, Magnetic Resonance Imaging methods, Research Design, Pelvic Floor diagnostic imaging, Ligaments diagnostic imaging
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Purpose: The aim of the MRI-study was to evaluate the visibility of the pelvic floor ligaments and to analyze the ligament morphometry in 3D space., Methods: Twenty-two nulliparous women underwent MRI with a ligament specific protocol. MR datasets were evaluated using the 3D Pelvic Inclination Correction System (3D-PICS). The round ligament (RL), sacrospinous ligament (SSL), sacrotuberous ligament (STL), urogenital diaphragm (UGD) and uterosacral ligament (USL) were analyzed. Qualitative and quantitative analysis was performed. 3D coordinates for origin and insertion points were determined relative to the symphysis; subsequently lengths and angles were calculated. Interrater reliability was calculated to validate the point determination method., Results: Moderate to good visibility was reported for the RL, the SSL, the STL and the UGD. Standard deviation of the points analyzed in the different dimensions vary from 1.5 mm to 21.3 mm. Origin and insertion points of the ligaments are found within a mean standard distance of 10.7 mm. The highest variability was seen in insertion points of RL, with a standard distance of 25.4 mm. The interrater reliability was good to very good (range of intraclass correlation coefficients (ICC) from 0.58 to 0.96), except for the UGD ventral points (ICC from 0.27 to 0.55)., Conclusions: This in-vivo MRI technique development study offers first exact data describing the pelvic floor ligaments in nulliparous women in 3D-PICS. Visibility, exact 3D coordinates of the origin and insertion points, lengths, angles and interrater reliability assessed for all parameters were evaluated morphometrically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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19. Repurposing of Bryophyllum pinnatum for dysmenorrhea treatment: a systematic scoping review and case series.
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Zurfluh L, Spinelli MG, Betschart C, and Simões-Wüst AP
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Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result from inflammatory processes and increased contractile activity in the myometrium. The reported use of Bryophyllum pinnatum preparations against inflammation and pain in ethnomedicine as well as current pharmacological data on their inhibition of myometrial contractility led us to hypothesize that this medicinal plant might be a new treatment option for dysmenorrhea. In the first part of the present work, clinical, in vivo, and in vitro studies on the anti-nociceptive and anti-inflammatory, as well as on myometrium relaxing properties of B. pinnatum are reviewed. In the second part, cases of five women with dysmenorrhea who were tentatively treated with a B. pinnatum product are described. The review revealed thirty-three experimental in vivo and in vitro studies, but no clinical study, reporting anti-nociceptive and anti-inflammatory effects of B. pinnatum extracts and compounds in a wide range of conditions. Moreover, sixteen publications on smooth muscle contractility revealed relaxing effects. The latter consisted of clinical evidence, as well as of in vivo and in vitro data. The evidence reviewed therefore provided a rational basis for the use of B. pinnatum in the treatment of dysmenorrhea. We subsequently set out to tentatively treat patients with a well-tolerated B. pinnatum product that is registered (without indication) and commonly used in obstetrics and gynecology in Switzerland. All five treated patients reported a reduction in pain symptoms and 4 out of 5 indicated a reduced intake of painkillers during menstruation. Taken together, the reviewed information on the pharmacological properties and clinical evidence of B. pinnatum extracts and compounds as well as the outcomes of all five patients in the case series support our hypothesis in favor of B. pinnatum as a new, well-tolerated therapeutic approach for dysmenorrhea. Prospective clinical studies are urgently needed., Competing Interests: MS is employed by Praxis Geburt and Familie, Dr. med. Werner Stadlmayr GmbH, Aarau, Switzerland. APS-W has received research funding from Weleda AG over the last 5 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zurfluh, Spinelli, Betschart and Simões-Wüst.)
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- 2023
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20. [Radiological imaging following pelvic prolapse surgery].
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Pausch AM, Betschart C, and Hötker AM
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- Humans, Female, Magnetic Resonance Imaging, Tomography, X-Ray Computed, Pelvic Organ Prolapse diagnostic imaging, Pelvic Organ Prolapse surgery
- Abstract
Clinical/methodical Issue: Pelvic organ prolapse is a common condition in women, for which both conservative and surgical interventions are available. Knowledge of the different surgical procedures and the materials used is essential for adequate radiological diagnosis after prolapse surgery in order to differentiate potential complications from normal postoperative changes., Standard Radiological Methods: In the immediate postoperative period, computed tomography (CT) is often the modality of choice for evaluating acute complications such as bleeding or organ injuries. Magnetic resonance imaging (MRI) provides excellent soft tissue contrast and is therefore generally preferred for assessing subacute and chronic complications., Methodical Innovations: Innovative techniques such as dynamic MRI protocols can improve the radiological assessment after prolapse surgery by enabling the evaluation of organ mobility., Performance: Radiological standard procedures such as computed tomography (CT) and MRI provide detailed and reliable information about the postoperative site and potential complications following prolapse surgery., Achievements: Radiological imaging plays an important role in the evaluation of patients after prolapse surgery, particularly when complications are suspected. Accurate radiological diagnosis can guide further appropriate therapeutic measures., (© 2023. The Author(s).)
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- 2023
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21. Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.
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Schmid FA, Prange JA, Kozomara M, Betschart C, Sousa RA, Steinke N, Hunziker M, Lehner F, Veit M, Grossmann R, Landsmann A, Hötker AM, Boss A, Mohr-Haralampieva D, and Eberli D
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- Humans, Female, Prospective Studies, Urethra diagnostic imaging, Muscles, Treatment Outcome, Urinary Incontinence, Stress therapy, Urinary Incontinence
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Introduction and Hypothesis: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients., Methods: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results., Results: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009)., Conclusion: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented., (© 2023. The Author(s).)
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- 2023
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22. Pelvic organ movements in asymptomatic nulliparous and symptomatic premenopausal women with pelvic organ prolapse in dynamic MRI: a feasibility study comparing midsagittal single-slice with multi-slice sequences.
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Ghafoor S, Beintner-Skawran SM, Stöckli G, Betschart C, and Reiner CS
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- Humans, Female, Prospective Studies, Feasibility Studies, Pelvis, Magnetic Resonance Imaging, Pelvic Organ Prolapse diagnostic imaging
- Abstract
Purpose: To compare multi-slice (MS) MRI sequences of the pelvis acquired at rest and straining to dynamic midsagittal single-slice (SS) sequences for the assessment of pelvic organ prolapse (POP)., Methods: This IRB-approved prospective single-center feasibility study included 23 premenopausal symptomatic patients with POP and 22 asymptomatic nulliparous volunteers. MRI of the pelvis at rest and straining was performed with midsagittal SS and MS sequences. Straining effort, visibility of organs and POP grade were scored on both. Organ points (bladder, cervix, anorectum) were measured. Differences between SS and MS sequences were compared with Wilcoxon test., Results: Straining effort was good in 84.4% on SS and in 64.4% on MS sequences (p = 0.003). Organ points were always visible on MS sequences, whereas the cervix was not fully visible in 31.1-33.3% on SS sequences. At rest, there were no statistically significant differences of organ point measurements between SS and MS sequences in symptomatic patients. At straining, positions of bladder, cervix, and anorectum were + 1.1 cm (± 1.8 cm), - 0.7 cm (± 2.9 cm), and + 0.7 cm (± 1.3 cm) on SS and + 0.4 mm (± 1.7 cm), - 1.4 cm (± 2.6 cm), and + 0.4 cm (± 1.3 cm) on MS sequences (p < 0.05). Only 2 cases of higher-grade POP were missed on MS sequences (both with poor straining effort)., Conclusion: MS sequences increase the visibility of organ points compared to SS sequences. Dynamic MS sequences can depict POP if images are acquired with sufficient straining effort. Further work is needed to optimize the depiction of the maximum straining effort with MS sequences., (© 2023. The Author(s).)
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- 2023
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23. Discovery of the TLR7/8 Antagonist MHV370 for Treatment of Systemic Autoimmune Diseases.
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Alper P, Betschart C, André C, Boulay T, Cheng D, Deane J, Faller M, Feifel R, Glatthar R, Han D, Hemmig R, Jiang T, Knoepfel T, Maginnis J, Mutnick D, Pei W, Ruzzante G, Syka P, Zhang G, Zhang Y, Zink F, Zipfel G, Hawtin S, Junt T, and Michellys PY
- Abstract
Toll-like receptor (TLR) 7 and TLR8 are endosomal sensors of the innate immune system that are activated by GU-rich single stranded RNA (ssRNA). Multiple genetic and functional lines of evidence link chronic activation of TLR7/8 to the pathogenesis of systemic autoimmune diseases (sAID) such as Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). This makes targeting TLR7/8-induced inflammation with small-molecule inhibitors an attractive approach for the treatment of patients suffering from systemic autoimmune diseases. Here, we describe how structure-based optimization of compound 2 resulted in the discovery of 34 (MHV370, ( S )-N-(4-((5-(1,6-dimethyl-1 H -pyrazolo[3,4- b ]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1 H -pyrazolo[4,3- c ]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide). Its in vivo activity allows for further profiling toward clinical trials in patients with autoimmune disorders, and a Phase 2 proof of concept study of MHV370 has been initiated, testing its safety and efficacy in patients with Sjögren's syndrome and mixed connective tissue disease., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)
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- 2023
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24. Robot-assisted pelvic floor reconstructive surgery: an international Delphi study of expert users.
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Simoncini T, Panattoni A, Aktas M, Ampe J, Betschart C, Bloemendaal ALA, Buse S, Campagna G, Caretto M, Cervigni M, Consten ECJ, Davila HH, Dubuisson J, Espin-Basany E, Fabiani B, Faucheron JL, Giannini A, Gurland B, Hahnloser D, Joukhadar R, Mannella P, Mereu L, Martellucci J, Meurette G, Montt Guevara MM, Ratto C, O'Reilly BA, Reisenauer C, Russo E, Schraffordt Koops S, Siddiqi S, Sturiale A, and Naldini G
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- Humans, Pelvic Floor surgery, Delphi Technique, Robotics, Surgery, Plastic, Robotic Surgical Procedures methods, Laparoscopy methods
- Abstract
Background: Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion., Methods: We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons' characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis., Results: The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy., Conclusion: Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit., (© 2023. The Author(s).)
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- 2023
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25. Preclinical characterization of the Toll-like receptor 7/8 antagonist MHV370 for lupus therapy.
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Hawtin S, André C, Collignon-Zipfel G, Appenzeller S, Bannert B, Baumgartner L, Beck D, Betschart C, Boulay T, Brunner HI, Ceci M, Deane J, Feifel R, Ferrero E, Kyburz D, Lafossas F, Loetscher P, Merz-Stoeckle C, Michellys P, Nuesslein-Hildesheim B, Raulf F, Rush JS, Ruzzante G, Stein T, Zaharevitz S, Wieczorek G, Siegel R, Gergely P, Shisha T, and Junt T
- Subjects
- Humans, Mice, Animals, Toll-Like Receptor 7 metabolism, Toll-Like Receptor 7 therapeutic use, Hydroxychloroquine pharmacology, Hydroxychloroquine therapeutic use, Interferons, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic metabolism, Autoimmune Diseases
- Abstract
Genetic and in vivo evidence suggests that aberrant recognition of RNA-containing autoantigens by Toll-like receptors (TLRs) 7 and 8 drives autoimmune diseases. Here we report on the preclinical characterization of MHV370, a selective oral TLR7/8 inhibitor. In vitro, MHV370 inhibits TLR7/8-dependent production of cytokines in human and mouse cells, notably interferon-α, a clinically validated driver of autoimmune diseases. Moreover, MHV370 abrogates B cell, plasmacytoid dendritic cell, monocyte, and neutrophil responses downstream of TLR7/8. In vivo, prophylactic or therapeutic administration of MHV370 blocks secretion of TLR7 responses, including cytokine secretion, B cell activation, and gene expression of, e.g., interferon-stimulated genes. In the NZB/W F1 mouse model of lupus, MHV370 halts disease. Unlike hydroxychloroquine, MHV370 potently blocks interferon responses triggered by specific immune complexes from systemic lupus erythematosus patient sera, suggesting differentiation from clinical standard of care. These data support advancement of MHV370 to an ongoing phase 2 clinical trial., Competing Interests: Declaration of interests All authors except S.A., B.B., H.I.B., J.D., D.K., P.M., F.R., and J.S.R. are current employees and shareholders of Novartis Pharma AG. MHV370 is described in patent WO2018047081., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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26. Bryophyllum pinnatum and Improvement of Nocturia and Sleep Quality in Women: A Multicentre, Nonrandomised Prospective Trial.
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Mirzayeva N, Forst S, Passweg D, Geissbühler V, Simões-Wüst AP, and Betschart C
- Abstract
Nocturia is a pathologic condition that significantly affects the quality of sleep. The aetiology of nocturia is multifactorial, and the evidence available on its management remains limited. Besides behavioural measures, validated pharmaceutical treatment options exist but are, however, associated with marked side effects. Prospective clinical studies with tablets prepared from the leaf press juice of the plant Bryophyllum pinnatum revealed a tendency towards reduction of micturition in patients with overactive bladder (OAB) and several improvements in sleep quality. These observations are in part supported by in vitro and in vivo data. In the present study, we investigated the effectiveness of Bryophyllum 50% chewable tablets in the treatment of nocturia and associated sleep disorders. Altogether, 49 women with idiopathic OAB and nocturia of ≥2 voids/night were treated with Bryophyllum 50% tablets for 3 weeks (350 mg chewable tablets, dosage 0-0-2-2 oral tablets; WELEDA AG, Arlesheim, Switzerland). Nocturia, voiding volumes at night (ml), quality of life, sleep quality, and daily sleepiness were assessed before and after treatment with a 3-day micturition diary, the International Consultation on Incontinence evaluating overactive bladder and related impact on quality of life (QoL) [ICIQ-OAB], the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS), respectively. The age of the study population was 68.5 ± 11.6 y. After treatment, nocturia diminished from 3.2 ± 1.4 to 2.3 ± 1.3 ( P < 0.001) and the PSQI score decreased from 7.7 ± 3.7 to 6.6 ± 3.4 ( P =0.004). Urgency, the ICIQ score, and the ESS lowered significantly, and the micturition volume showed a tendency to increase. No serious adverse drug reactions were reported, and compliance was good. The results show a beneficial effect on the nocturnal voids and sleep quality of women with OAB. Bryophyllum 50% tablets can be regarded as a well-tolerated alternative in the treatment of nocturia and broaden the repertoire of standard management., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Nurlana Mirzayeva et al.)
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- 2023
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27. Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/091, January 2022): Part 2 with Recommendations on Interventional/Surgical Therapy of Overactive Bladder, Surgical Treatment of Stress Urinary Incontinence and Diagnosis and Therapy of Iatrogenic Urogenital Fistula.
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Naumann G, Aigmüller T, Bader W, Bauer R, Beilecke K, Betschart Meier C, Bruer G, Bschleipfer T, Deniz M, Fink T, Gabriel B, Gräble R, Grothoff M, Haverkamp A, Hampel C, Henscher U, Hübner M, Huemer H, Kociszewski J, Kölbl H, Kölle D, Kropshofer S, Kuhn A, Nothacker M, Oelke M, Peschers U, Preyer O, Schultz-Lampel D, Tamussino K, Tunn R, Viereck V, and Reisenauer C
- Abstract
Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented., Competing Interests: Conflict of Interest The conflicts of interest of the authors are listed in the long version of the guideline ( https://register.awmf.org/de/leitlinien/detail/015-091 )./ Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie ( https://register.awmf.org/de/leitlinien/detail/015-091 ) aufgelistet., (Thieme. All rights reserved.)
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- 2023
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28. Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/091, January 2022): Part 1 with Recommendations on Diagnostics and Conservative and Medical Treatment.
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Naumann G, Aigmüller T, Bader W, Bauer R, Beilecke K, Betschart Meier C, Bruer G, Bschleipfer T, Deniz M, Fink T, Gabriel B, Gräble R, Grothoff M, Haverkamp A, Hampel C, Henscher U, Hübner M, Huemer H, Kociszewski J, Kölbl H, Kölle D, Kropshofer S, Kuhn A, Nothacker M, Oelke M, Peschers U, Preyer O, Schultz-Lampel D, Tamussino K, Tunn R, Viereck V, and Reisenauer C
- Abstract
Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed., Competing Interests: Conflict of Interest The conflicts of interest of all the authors are listed in the long version of the guideline ( https://register.awmf.org/de/leitlinien/detail/015-091 )./ Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie ( https://register.awmf.org/de/leitlinien/detail/015-091 ) aufgelistet., (Thieme. All rights reserved.)
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- 2023
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29. Comparison of in vivo visco-hyperelastic properties of uterine suspensory tissue in women with and without pelvic organ prolapse.
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Luo J, Swenson CW, Betschart C, Feng F, Wang H, Ashton-Miller JA, and DeLancey JOL
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- Female, Humans, Uterus physiology, Ligaments physiology, Magnetic Resonance Imaging, Pelvic Organ Prolapse
- Abstract
The uterine suspensory tissue (UST) complex includes the cardinal (CL) and uterosacral "ligaments" (USL), which are mesentery-like structures that play a role in resisting pelvic organ prolapse (POP). Since there is no information on the time-dependent material properties of the whole structure in situ and in vivo, we developed and tested an intraoperative technique to quantify in vivo whether there is a significant difference in visco-hyperelastic behavior of the CL and USL between women with and without POP. Thirteen women with POP (cases) and four controls scheduled for surgery were selected from an ongoing POP study. Immediately prior to surgery, a computer-controlled linear servo-actuator with a series force transducer applied a continuous, caudally directed traction force while simultaneously recording the resulting cervical displacement in the same direction. After applying an initial 1.1 N preload, a ramp rate of 4 mm/s was used to apply a maximum force of 17.8 N in three "ramp-and-hold" test trials. A simplified bilateral four-cable biomechanical model was used to identify the material behavior of each ligament. For this, the initial cross-section areas of the CL and USL were measured on 3-T magnetic resonance image-based 3D models from each subject. The time-dependent strain energy function of CL/USL was defined with a three-parameter hyperelastic Mooney-Rivlin material model and a two-term Prony series in relaxation form. When cases were compared with controls, the estimated time-dependent material constants of CL and USL did not differ significantly. These are the first measurements that compare the in vivo and in situ visco-hyperelastic response of the tissues comprising the CL and USL to loading in women with and without prolapse. Larger sample sizes would help improve the precision of intergroup differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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30. A meta-synthesis of qualitative studies on stress urinary incontinence in women for the development of a Core Outcome Set: A systematic review.
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Rada MP, Jones S, Betschart C, Falconi G, Haddad JM, and Doumouchtsis SK
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- Female, Humans, Outcome Assessment, Health Care, Prevalence, Qualitative Research, Quality of Life psychology, Urinary Incontinence, Stress therapy
- Abstract
Objective: Given the high variation of perceptions of women with stress urinary incontinence (SUI), qualitative meta-synthesis in this field appears warranted. We aimed to synthesize evidence on women's experiences of SUI by analyzing qualitative data., Methods: A literature search of Medline, Embase, Scopus, PsycInfo, and CINAHL databases was performed by a CHORUS Working Group, from inception to August 2020. Qualitative studies on women's perspectives on SUI were included. Thematic analysis was used as a conceptual approach to analyze the data and develop a set of overarching themes. The quality of studies was assessed based on the Critical Appraisal Skills Program tool., Results: Seven studies were included. Six themes encompassing women's perspectives on SUI emerged: experiencing SUI, awareness of SUI, treatments for SUI, sexuality, communication, and psychosocial effects. The quality appraisal of the studies showed good coherence., Conclusion: This study revealed six overarching themes, of which treatment had the highest prevalence. Assessment of women's perceptions of SUI in the context of a qualitative meta-synthesis may inform policy and practice around this condition, may guide and help set research priorities, and will ideally contribute to the development of a Core Outcome Set for SUI., (© 2021 International Federation of Gynecology and Obstetrics.)
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- 2022
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31. Outcome reporting in randomized controlled trials (RCTs) on the pharmacological management of idiopathic overactive bladder (OAB) in women; a systematic review for the development of core outcome sets (COS).
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Moussa R, Rada MP, Durnea C, Falconi G, Betschart C, Haddad JM, Sedgwick P, and Doumouchtsis SK
- Subjects
- Adult, Female, Humans, Muscarinic Antagonists therapeutic use, Outcome Assessment, Health Care, Randomized Controlled Trials as Topic, Treatment Outcome, Urinary Bladder, Overactive complications, Urinary Bladder, Overactive drug therapy, Urinary Incontinence complications
- Abstract
Introduction and Hypothesis: Evidence on OAB management remains suboptimal and methodological limitations in randomized control trials (RCTs) affect their comparability. High quality meta-analyses are lacking. This study aimed to compare selection and reporting of outcomes and outcome measures across RCTs as well as evaluate methodological quality and outcome reporting quality as a first stage in the process of developing core outcome sets (COS)., Methods: RCTs were searched using Pubmed, EMBASE, Medline, Cochrane, ICTRP and Clinicaltrials.gov from inception to January 2020, in English language, on adult women. Pharmacological management, interventions, sample size, journal type and commercial funding were documented. Methodological and outcome reporting quality were evaluated using JADAD and MOMENT scores., Results: Thirty-eight trials (18,316 women) were included. Sixty-nine outcomes were reported, using 62 outcome measures. The most commonly reported outcome domains were efficacy (86.8%), safety (73.7%) and QoL (60.5%). The most commonly reported outcomes in each domain were urgency urinary incontinence episodes (UUI) (52.6%), antimuscarinic side effects (76.3%) and change in validated questionnaire scores (36.8%). A statistically significant correlation was found between JADAD and MOMENT (Spearman's rho = 0.548, p < 0.05) scores. This indicates that higher methodological quality is associated with higher outcome reporting quality., Conclusions: Development of COS and core outcome measure sets will address variations and lead to higher quality evidence. We recommend the most commonly reported outcomes in each domain, as interim COS. For efficacy we recommend: UUI episodes, urgency and nocturia episodes; for safety: antimuscarinic adverse events, other adverse events and discontinuation rates; for QoL: OAB-q, PPBC and IIQ scores., (© 2022. The Author(s).)
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- 2022
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32. A new titanium-covered transobturator tape for surgical treatment of stress urinary incontinence.
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Fahrni AC, Betschart C, de la Jolinière JB, Dubuisson JB, Feki A, and Major AL
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- Female, Humans, Male, Polypropylenes, Prospective Studies, Titanium, Treatment Outcome, Urologic Surgical Procedures, Suburethral Slings, Urinary Incontinence surgery, Urinary Incontinence, Stress surgery
- Abstract
Introduction and Hypothesis: To assess the long-term satisfaction, cure rate and safety of a new titanium-covered transobturator tape compared to polypropylene tape for the treatment of stress urinary incontinence (SUI)., Methods: A prospective study was conducted with 151 patients. Seventy patients underwent transobturator sling surgery with titanium tape from 2011 to 2019, and a historical control group (CG) of 81 patients was treated with a noncoated tape and underwent incontinence surgery from 1999 to 2009. We compared patient-reported outcome measures (PROMs) with the incontinence outcome questionnaire (IOQ)., Results: The median follow-up was 2½ years in both groups. Based on responses to the IOQ, a statistically significantly shorter time of recovery (IOQ 15: 21.3 ± 26.4 [TG], 40.2 ± 38.5 [CG], p = 0.02), improvement of sex life (IOQ 13: 34.1 ± 29.4 [TG] vs. 65.3 ± 35.6 [CG], p = 0.01) and less voiding dysfunction (IOQ 19: 30.9 ± 28.1 [CG], 9.3 ± 18.6 [TG], p = 0.01) were observed in the TG. Objectively, no postoperative urinary retention was observed in the TG, but four cases were described in the CG. Ten patients needed a reoperation for SUI in the CG compared to three in the TG (p = 0.03)., Conclusion: The titanium-covered transobturator sling had superior recovery time, improved sexual function and reduced reoperation rate compared to a historical polypropylene group., (© 2021. The Author(s).)
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- 2022
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33. Structure-Based Optimization of a Fragment-like TLR8 Binding Screening Hit to an In Vivo Efficacious TLR7/8 Antagonist.
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Betschart C, Faller M, Zink F, Hemmig R, Blank J, Vangrevelinghe E, Bourrel M, Glatthar R, Behnke D, Barker K, Heizmann A, Angst D, Nimsgern P, Jacquier S, Junt T, Zipfel G, Ruzzante G, Loetscher P, Limonta S, Hawtin S, Andre CB, Boulay T, Feifel R, and Knoepfel T
- Abstract
Inappropriate activation of TLR7 and TLR8 is linked to several autoimmune diseases, such as lupus erythematosus. Here we report on the efficient structure-based optimization of the inhibition of TLR8, starting from a co-crystal structure of a small screening hit. Further optimization of the physicochemical properties for cellular potency and expansion of the structure-activity relationship for dual potency finally resulted in a highly potent TLR7/8 antagonist with demonstrated in vivo efficacy after oral dosing., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)
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- 2022
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34. Outcome reporting in trials on conservative interventions for pelvic organ prolapse: A systematic review for the development of a core outcome set.
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Khan K, Rada M, Elfituri A, Betschart C, Falconi G, Haddad JM, and Doumouchtsis SK
- Subjects
- Female, Humans, Outcome Assessment, Health Care, Patient Reported Outcome Measures, Pelvic Floor, Quality of Life, Surveys and Questionnaires, Pelvic Organ Prolapse therapy
- Abstract
Background: Significant risk of bias and limitations in outcome selections in trials evaluating conservative treatments for the management of Pelvic Organ Prolapse (POP) have been highlighted and preclude comparability of outcomes, synthesis of primary studies and high quality evidence., Objectives: As systematic review of the reported outcomes is the first step in the process of development of a Core Outcome Set (COS), we aimed to systematically review reporting of outcomes and outcome measures in Randomised Control Trials (RCTs) on conservative treatments for POP and develop an inventory of them for consideration as core outcome and outcome measures sets. We evaluated methodological quality, outcome reporting quality and publication characteristics and their associations among published RCTs., Study Design: Systematic review of RCTs identified from the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and MEDLINE (Pubmed). RCTs evaluating the effectiveness of conservative interventions for the management of POP were considered for inclusion. Outcomes and outcome measures were obtained from the RCTs and an inventory was created. Outcomes were grouped in domains and themes. Methodological quality, outcome reporting quality and publication characteristics were evaluated and statistically analysed., Results: Twenty-five trials (3179 women) were included and reported 31 outcomes and 50 outcome measures. Reporting rates of the outcomes investigated ranged between 4% and 56%. The most commonly reported outcome domains were patient reported symptoms, stage of POP expressed as POP-Q stage, and quality of life. Univariate analysis demonstrated no significant correlations of methodological and outcome reporting parameters., Conclusions: There is a need to increase comparability of RCTs. Reporting standardized outcomes included in a COS for conservative interventions for POP will facilitate the comparability across RCTs. While the process of developing COS is in progress, we propose the interim use of the three most commonly reported outcomes in each domain: patient-reported outcomes (symptom distress including bowel and urinary symptoms, sexual function), stage of prolapse and quality of life parameters using validated questionnaires (Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire/Health related quality of life (PFIQ-7/HRQOL) and Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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35. Developing Core Outcome Sets (COS) and Core Outcome Measures Sets (COMS) in Cosmetic Gynecological Interventions: Protocol for a Development and Usability Study.
- Author
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Doumouchtsis SK, Nama V, Falconi G, Rada MP, Manonai J, Iancu G, Haddad JM, and Betschart C
- Abstract
Background: Studies evaluating cosmetic gynecological interventions have followed variable methodology and reported a diversity of outcomes. Such variations limit the comparability of studies and the value of research-based evidence. The development of core outcome sets (COS) and core outcome measures sets (COMS) would help address these issues, ensuring a minimum of outcomes important to all stakeholders, primarily women requesting or having experienced cosmetic gynecological interventions., Objective: This protocol describes the methods used in developing a COS and COMS for cosmetic gynecological interventions., Methods: An international steering group within CHORUS, including health care professionals, researchers, and women with experience in cosmetic gynecological interventions from 4 continents, will guide the development of COS and COMS. Potential outcome measures and outcomes will be identified through comprehensive literature reviews. These potential COS and COMS will be entered into an international, multi-perspective web-based Delphi survey where Delphi participants judge which domains will be core. A priori thresholds for consensus will get established before each Delphi round. The Delphi survey results will be evaluated quantitatively and qualitatively in subsequent stakeholder group consensus meetings in the process of establishing "core" outcomes., Results: Dissemination and implementation of the resulting COS and COMS within an international context will be promoted and reviewed., Conclusions: This protocol presents the steps in developing a COS and COMS for cosmetic gynecological interventions. Embedding the COS and COMS for cosmetic gynecological interventions within future clinical trials, systematic reviews, and practice guidelines could contribute to enhancing the value of research and improving overall patient care., Trial Registration: Core Outcome Measures in Effectiveness Trials (COMET) 1592; https://tinyurl.com/n8faysuh., International Registered Report Identifier (irrid): PRR1-10.2196/28032., (©Stergios K Doumouchtsis, Vivek Nama, Gabriele Falconi, Maria Patricia Rada, Jittima Manonai, George Iancu, Jorge Milhem Haddad, Cornelia Betschart. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.11.2021.)
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- 2021
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36. Quality assessment of outcome reporting, publication characteristics and overall methodological quality in trials on synthetic mesh procedures for the treatment of pelvic organ prolapse for development of core outcome sets.
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de Mattos Lourenço TR, Pergialiotis V, Durnea CM, Elfituri A, Haddad JM, Betschart C, Falconi G, Nygaard CC, and Doumouchtsis SK
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- Humans, Outcome Assessment, Health Care, Prostheses and Implants, Treatment Outcome, Pelvic Organ Prolapse surgery, Surgical Mesh
- Abstract
Introduction and Hypothesis: Variations in outcome measures and reporting of outcomes in trials on surgery for pelvic organ prolapse (POP) using synthetic mesh have been evaluated and reported. However, the quality of outcome reporting, methodology of trials and their publication parameters are important considerations in the process of development of Core Outcome Sets. We aimed to evaluate these characteristics in randomized controlled trials on surgery for POP using mesh., Methods: Secondary analysis of randomized controlled trials on surgical treatments using synthetic mesh for POP previously included in a systematic review developing an inventory of reported outcomes and outcome measures. The methodological quality was investigated with the modified Jadad criteria. Outcome reporting quality was evaluated with the MOMENT criteria. Publication parameters included publishing journal, impact factor and year of publication., Results: Of the 71 previously reviewed studies published from 2000 to 2017, the mean JADAD score was 3.59 and the mean MOMENT score was 4.63. Quality of outcomes (MOMENT) was related to methodological quality (JADAD) (rho = 0.662; p = 0.000) and to year of publication (rho = 0.262; p = 0.028)., Conclusions: Methodological quality and outcome reporting quality appear correlated. However, publication characteristics do not have strong associations with the methodological quality of the studies. Evaluation of the quality of outcomes, methodology and publication characteristics are all an indispensable part of a staged process for the development of Core Outcome and Outcome Measure Sets., (© 2021. The Author(s).)
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- 2021
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37. Considering non-bladder aetiologies of overactive bladder: a functional neuroimaging study.
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Walter M, Leitner L, Betschart C, Engeler DS, Freund P, Kessler TM, Kollias S, Liechti MD, Scheiner DA, Michels L, and Mehnert U
- Subjects
- Adult, Case-Control Studies, Cognition, Cold Temperature, Female, Functional Neuroimaging, Humans, Magnetic Resonance Imaging, Mental Status and Dementia Tests, Saline Solution, Surveys and Questionnaires, Urinary Bladder diagnostic imaging, Urinary Bladder physiopathology, Urinary Bladder, Overactive physiopathology, Urodynamics, Brain diagnostic imaging, Brain physiopathology, Urinary Bladder, Overactive diagnostic imaging, Urinary Bladder, Overactive etiology
- Abstract
Objectives: To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation., Subjects/patients and Methods: We recruited 24 female participants, 12 with OAB (median [interquartile range, IQR] age 40 [32-42] years) and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms (median [IQR] age 34 [28-44] years), and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging using a 3-T scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100 mL body temperature (37 °C) saline using a MR-compatible and MR-synchronised infusion-drainage device until strong desire to void (HIGH-FILLING/DRAINING) and bladder filling with cold saline (4 °C, i.e. COLD). Whole-brain and region-of-interest analyses were conducted using Statistical Parametric Mapping, version 12., Results: Significant between-group differences were found for 3-day bladder diary variables (i.e. voiding frequency/24 h, P < 0.001; voided volume/void, P = 0.04; and urinary incontinence [UI] episodes/24 h, P = 0.007), questionnaire scores (International Consultation on Incontinence Questionnaire-Female LUT symptoms [overall, filling, and UI scores, all P < 0.001]; the Overactive Bladder Questionnaire short form [symptoms and quality-of-life scores, both P < 0.001]; the Hospital Anxiety and Depression Scale [anxiety P = 0.004 and depression P = 0.003 scores]), as well as urodynamic variables (strong desire to void, P = 0.02; maximum cystometric capacity, P = 0.007; and presence of detrusor overactivity, P = 0.002). Age, weight and cognitive function (i.e. Mini-Mental State Examination, P = 1.0) were similar between groups (P > 0.05). In patients with OAB, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex (VLPFC), and mid-cingulate cortex; and the COLD task elicited activity in the VLPFC, cerebellum, and basal ganglia. Compared to HCs, patients with OAB showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and VLPFC during HIGH-DRAINING., Conclusions: The present findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lacked activity in essential sensory processing areas, such as the insula. Instead, accessory areas, such as the cerebellum, showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent UI. The novel findings of the present study provide physiological evidence of the necessity to consider non-bladder aetiologies of bladder symptoms., (© 2021 The Authors BJU International © 2021 BJU International.)
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- 2021
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38. Evaluation of guidelines on the use of vaginal mesh implants for pelvic organ prolapse using the AGREE II instrument.
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Tsiapakidou S, Campani Nygaard C, Pape J, de Mattos Lourenço TR, Falconi G, Betschart C, and Doumouchtsis SK
- Subjects
- Female, Humans, Pessaries, Vagina surgery, Pelvic Organ Prolapse surgery, Surgical Mesh
- Abstract
Objective: To systematically evaluate the content and quality of national and international guidelines on vaginal mesh procedures for pelvic organ prolapse (POP)., Methods: We searched PubMed, Medline, Web of Science, and ScienceDirect from inception to March 2020 and organizations' websites. The quality of the guidelines was assessed independently by six appraisers using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument., Results: Five guidelines were included. Most guidelines recommended individualized treatments, clinical observation, and conservative treatment for asymptomatic women discouraging the use of mesh. Vaginal pessary and pelvic floor muscle training are unanimously considered effective treatments. Only two guidelines recommended weight loss. Each guideline recommended patient counseling supported by data on success rates and complications. Most guidelines highlighted the importance of a specialist experienced surgeon, multidisciplinary teams, and national/international registries. All guidelines highlighted potential benefits of the use of mesh and reported possible complications. The overall quality rating ranged between 4.2 and 6.3, suggestive of moderate to high quality. The highest mean score (92.5%) pertained to "Scope and Purpose" and "Clarity of Presentation", and the lowest to "Editorial Independence" (18%). Three out of five guidelines were "strongly recommended" by the appraisers., Conclusion: Although most guidelines were of moderate to high quality, methodological applicability, stakeholder involvement, and editorial independence were domains with low scores., (© 2021 International Federation of Gynecology and Obstetrics.)
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- 2021
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39. Systematic review and appraisal of clinical practice guidelines on pelvic organ prolapse using the AGREE II tool.
- Author
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Tsiapakidou S, Nygaard CC, Falconi G, Pape J, Betschart C, and Doumouchtsis SK
- Subjects
- Female, Humans, Databases, Factual, Pelvic Organ Prolapse diagnosis, Pelvic Organ Prolapse therapy, Practice Guidelines as Topic
- Abstract
Aims: To systematically evaluate the content and quality of national and international clinical guidelines on pelvic organ prolapse (POP)., Methods: We searched medical databases and organizations websites, to identify national and international guidelines on diagnosis and management of POP. Five authors independently assessed guidelines using the validated AGREE II tool. Its six domains include (1) scope and purpose, (2) stakeholder involvement, (3) rigor of development, (4) clarity of presentation, (5) applicability, and (6) editorial independence., Results: Eight guidelines met the inclusion criteria. Three hundred and thirteen different recommendations were identified. One hundred and ninety-nine recommendations were comparable across guidelines. Thirty-one recommendations were not supported by research evidence. Assessment by history and physical examination using the POP quantification system and consideration of imaging were recommendations featuring in all guidelines. Conservative treatment recommendations namely pelvic floor muscle training and vaginal pessaries were also found in all guidelines. Regarding surgical management, patient counseling, treating only symptomatic POP, consideration of apical fixation during surgical treatment, and use of biological or synthetic implants in recurrent cases were recommendations in all guidelines. Overall, the highest median scores were in the domains "scope and purpose" and "rigor of development". The lowest median score was for applicability (28.3%). Although the median score of "editorial independence" was high (85.4%), variability was also substantial (interquartile range: 12.5-100)., Conclusion: We identified variations in quality and deficiencies in certain areas, especially "applicability" and "editorial independence." Improvements in these key domains may enhance the quality and clinical impact of clinical practice guidelines., (© 2021 Wiley Periodicals LLC.)
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- 2021
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40. Patient-reported outcomes and outcome measures in childbirth perineal trauma research: a systematic review.
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Doumouchtsis SK, Loganathan J, Fahmy J, Falconi G, Rada M, Elfituri A, Haddad JM, Pergialiotis V, and Betschart C
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- Delivery, Obstetric, Female, Humans, Outcome Assessment, Health Care, Patient Reported Outcome Measures, Pregnancy, Parturition, Perineum
- Abstract
Introduction and Hypothesis: In evaluating the effectiveness of interventions in perineal trauma research, outcomes reported by patients should have a prominent focus. There is no international consensus regarding the use of either patient-reported outcomes (PROs) or tools used to determine these outcomes (patient-reported outcome measures, PROMs). The objective was to evaluate the selection, reporting and geographical variations of PROs and PROMs in randomised controlled trials (RCTs) on perineal trauma., Methods: We performed a systematic review of RCTs in perineal trauma research evaluating outcome and outcome measure reporting. We identified PROs and PROMs and grouped PROs into domains and themes, a classification system based on a medical outcome taxonomy., Results: Of 48 included RCTs, 47 reported PROs. In total, we identified 51 PROs. Outcome reporting consistency was low, with 27 PROs reported only once. Nine PROs were reported more than five times, the most frequent being perineal pain, with no geographical variation in reporting. Four themes encompassing 12 domains were identified. The most frequently reported theme was "Clinical", with 25 PROs grouped within four domains. "Resource use" and "Adverse events" themes were rarely reported, with only five PROs. PROMs also exhibited variation. Most common were visual analogue scale (VAS; 100 mm), Cleveland Clinic Continence Score, The Faecal Incontinence Quality of Life scale, VAS (0-10) and the McGill Pain Questionnaire., Conclusions: Significant heterogeneity in PROs and PROMs was observed among RCTs. Despite inconsistency, PROs are the most prevalent outcome in perineal trauma research. Patient-reported adverse events are underreported. Their use in determining the effectiveness and safety of interventions makes their integration important in perineal trauma core outcome sets. Identification and grouping of outcomes will assist future core outcome consensus studies., (© 2021. The International Urogynecological Association.)
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- 2021
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41. Interactive three-dimensional female pelvis model for teaching purposes.
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Singer AP, Winklehner T, and Betschart C
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- Computer Simulation, Education, Medical, Female, Humans, Muscle, Skeletal anatomy & histology, Pelvic Bones anatomy & histology, Pelvis blood supply, Pelvis innervation, Anatomy education, Models, Anatomic, Pelvis anatomy & histology
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- 2021
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42. Urotherapist activities in caring for patients with pelvic floor disorders: a prospective single-center observational study.
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Geissbuehler V, Forst S, Werner M, Schoenenberger CA, Berner R, and Betschart C
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- Adult, Advanced Practice Nursing, Aged, Cooperative Behavior, Female, Humans, Interprofessional Relations, Middle Aged, Outcome Assessment, Health Care, Patient Care, Pelvic Floor Disorders epidemiology, Pelvic Organ Prolapse epidemiology, Pelvic Pain epidemiology, Prospective Studies, Surveys and Questionnaires, Urinary Bladder, Overactive epidemiology, Urinary Tract Infections epidemiology, Muscle Strength physiology, Nurse Practitioners psychology, Patient Satisfaction statistics & numerical data, Pelvic Floor Disorders rehabilitation, Urinary Incontinence rehabilitation
- Abstract
Purpose: Patients with pelvic floor disorders are growing in number. The aim of this study is to outline the main activities of a urotherapist, an advanced nurse practitioner, in the care of patients with pelvic floor disorders and to evaluate patient satisfaction with the service urotherapists provide., Methods: The prospective single-center observational study was carried out from July 2016 to June 2018. Parameters used to assess the urotherapist activities included the number of consultations, type of counselling, time frame of consultations and therapy and patient satisfaction. In a subgroup of 38 patients, satisfaction with the urotherapy sessions was evaluated by a questionnaire., Results: Totally, 1709 patients were examined by urogynecologists. Five hundred and fourteen (30%) with chronic pelvic floor disorders were subsequently referred to a urotherapist. Of these patients, 60% were at least 65 years old. The most common pelvic floor disorders (221 patients; 43%) were an overactive bladder, recurrent urinary tract infections, chronic cystitis and pelvic pain syndrome; the second most common pelvic floor disorder was pelvic organ prolapsed (151 patients; 29%). Of the study subgroup comprising 38 patients, 32 (84%) returned the patient satisfaction questionnaire. All 32 patients specified their level of agreement with the urotherapist's professional competence, empathy, temporal availability and quality of advice as "agree to strongly agree.", Conclusions: Management by a urotherapist was highly appreciated. The role of the urotherapist as a care coordinator, their level of autonomy and barriers to the implementation in primary care requires further exploration.
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- 2021
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43. Glucocorticoid Receptor Beta and Its Prognostic Value on Treatment Response in Chronic Vulvar Dermatitis.
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Bernays V, Kowalewski MP, Dedes I, Kerl French K, Fink D, Kolm I, and Betschart C
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- Administration, Topical, Chronic Disease, Female, Humans, Keratinocytes drug effects, Prognosis, Receptors, Glucocorticoid antagonists & inhibitors, Retrospective Studies, Up-Regulation, Dermatitis pathology, Glucocorticoids pharmacology, Receptors, Glucocorticoid biosynthesis, Vulvar Diseases pathology
- Abstract
Background: Chronic vulvar dermatitis (CVD) is the most prevalent disease in gynecologic dermatology. The treatment mainly depends on topical glucocorticoids (TGC) but is challenged by insufficient treatment response. On a histological level, the upregulation of the glucocorticoid receptor β (GRβ), an inhibitor of the active glucocorticoid receptor α (GRα), is discussed as mechanism of glucocorticoid insensitivity., Objectives: To analyze whether the expression of GRβ protein at baseline in keratinocytes may predict responsiveness to TGC in patients with CVD., Methods: In this retrospective cohort study, clinical and biological data of 25 women with a histological diagnosis of chronic vulvar eczema were analyzed. Randomization was done according to the responsiveness to TGC treatment (responsive vs. nonresponsive). Clinical data and the expression of GRβ in the immunohistochemical stained biopsies were examined., Results: Fifty-two percent of women with CVD were nonresponsive to TGC. GRβ was abundantly expressed in the cytoplasma of keratinocytes of the vulvar epithelium, but no difference in the level of expression was found among GC responsive and nonresponsive patients in the semiquantitative (p = 0.376) and quantitative analysis (p = 0.894)., Conclusion: GRβ is highly expressed in keratinocytes of the vulvar epidermis affected by CVD, but GRβ expression was not increased in patients nonresponsive to TGC compared to responsive patients. Thus, the failure mechanism in nonresponders still remains to be elucidated., (© 2021 The Author(s) Published by S. Karger AG, Basel.)
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- 2021
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44. Discovery of potent, orally bioavailable in vivo efficacious antagonists of the TLR7/8 pathway.
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Alper PB, Deane J, Betschart C, Buffet D, Collignon Zipfel G, Gordon P, Hampton J, Hawtin S, Ibanez M, Jiang T, Junt T, Knoepfel T, Liu B, Maginnis J, McKeever U, Michellys PY, Mutnick D, Nayak B, Niwa S, Richmond W, Rush JS, Syka P, Zhang Y, and Zhu X
- Subjects
- Administration, Oral, Animals, Cell Line, Drug Evaluation, Preclinical, Half-Life, Humans, Interferon-gamma metabolism, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear metabolism, Male, Mice, Mice, Inbred BALB C, Piperazine administration & dosage, Piperazine pharmacokinetics, Piperazine pharmacology, Spleen cytology, Spleen drug effects, Spleen metabolism, Structure-Activity Relationship, Toll-Like Receptor 7 antagonists & inhibitors, Toll-Like Receptor 8 antagonists & inhibitors, Piperazine chemistry, Toll-Like Receptor 7 metabolism, Toll-Like Receptor 8 metabolism
- Abstract
Antagonism of the Toll-like receptors (TLRs) 7 and TLR8 has been hypothesized to be beneficial to patients suffering from autoimmune conditions. A phenotypic screen for small molecule antagonists of TLR7/8 was carried out in a murine P4H1 cell line. Compound 1 was identified as a hit that showed antagonistic activity on TLR7 and TLR8 but not TLR9, as shown on human peripheral blood mononuclear cells (hPBMCs). It was functionally cross reactive with mouse TLR7 but lacked oral exposure and had only modest potency. Chemical optimization resulted in 2, which showed in vivo efficacy following intraperitoneal administration. Further optimization resulted in 8 which had excellent in vitro activity, exposure and in vivo activity. Additional work to improve physical properties resulted in 15, an advanced lead that had favorable in vitro and exposure properties. It was further demonstrated that activity of the series tracked with binding to the extracellular domain of TLR7 implicating that the target of this series are endosomal TLRs rather than downstream signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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45. Target-Based Identification and Optimization of 5-Indazol-5-yl Pyridones as Toll-like Receptor 7 and 8 Antagonists Using a Biochemical TLR8 Antagonist Competition Assay.
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Knoepfel T, Nimsgern P, Jacquier S, Bourrel M, Vangrevelinghe E, Glatthar R, Behnke D, Alper PB, Michellys PY, Deane J, Junt T, Zipfel G, Limonta S, Hawtin S, Andre C, Boulay T, Loetscher P, Faller M, Blank J, Feifel R, and Betschart C
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- Animals, Cells, Cultured, Drug Discovery, Humans, Indazoles chemistry, Indazoles pharmacokinetics, Indazoles pharmacology, Lupus Erythematosus, Systemic metabolism, Male, Mice, Inbred C57BL, Models, Molecular, Pyridones pharmacokinetics, Rats, Sprague-Dawley, Toll-Like Receptor 7 chemistry, Toll-Like Receptor 7 metabolism, Toll-Like Receptor 8 chemistry, Toll-Like Receptor 8 metabolism, Lupus Erythematosus, Systemic drug therapy, Pyridones chemistry, Pyridones pharmacology, Toll-Like Receptor 7 antagonists & inhibitors, Toll-Like Receptor 8 antagonists & inhibitors
- Abstract
Inappropriate activation of endosomal TLR7 and TLR8 occurs in several autoimmune diseases, in particular systemic lupus erythematosus (SLE). Herein, the development of a TLR8 antagonist competition assay and its application for hit generation of dual TLR7/8 antagonists are reported. The structure-guided optimization of the pyridone hit 3 using this biochemical assay in combination with cellular and TLR8 cocrystal structural data resulted in the identification of a highly potent and selective TLR7/8 antagonist ( 27 ) with in vivo efficacy. The two key steps for optimization were (i) a core morph guided by a TLR7 sequence alignment to achieve a dual TLR7/8 antagonism profile and (ii) introduction of a fluorine in the piperidine ring to reduce its basicity, resulting in attractive oral pharmacokinetic (PK) properties and improved TLR8 binding affinity.
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- 2020
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46. A protocol for developing, disseminating, and implementing a core outcome set (COS) for childbirth pelvic floor trauma research.
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Doumouchtsis SK, Rada MP, Pergialiotis V, Falconi G, Haddad JM, and Betschart C
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- Consensus, Delphi Technique, Female, Humans, Pelvic Floor injuries, Pregnancy, Stakeholder Participation, Treatment Outcome, Delivery, Obstetric adverse effects, Outcome Assessment, Health Care methods, Pelvic Floor Disorders therapy, Research Design
- Abstract
Background: More than 85% of women sustain different degrees of trauma during vaginal birth. Randomized controlled trials on childbirth pelvic floor trauma have reported a wide range of outcomes and used different outcome measures. This variation restricts effective data synthesis, impairing the ability of research to inform clinical practice. The development and use of a core outcome set (COS) for childbirth pelvic floor trauma aims to ensure consistent use of outcome measures and reporting of outcomes., Methods: An international steering group, within CHORUS, an International Collaboration for Harmonising Outcomes, Research and Standards in Urogynaecology and Women's Health, including academic community members, researchers, healthcare professionals, policy makers and women with childbirth pelvic floor trauma will lead the development of this COS. Relevant outcome parameters will be identified through comprehensive literature reviews. The selected outcomes will be entered into an international, multi-perspective online Delphi survey. Subsequently and based on the results of the Delphi surveys consensus will be sought on 'core' outcomes., Discussion: Dissemination and implementation of the resulting COS within an international context will be supported and promoted. Embedding the COS for childbirth pelvic floor trauma within future clinical trials, systematic reviews, and clinical practice guidelines is expected to enrich opportunities for comparison of future clinical trials and allow better synthesis of outcomes, and will enhance mother and child care. The infrastructure created by developing a COS for childbirth pelvic floor trauma could be leveraged in other settings, for example, advancing research priorities and clinical practice guideline development.
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- 2020
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47. Guideline of the Swiss Society of Gynaecology and Obstetrics (SSGO) on acute and recurrent urinary tract infections in women, including pregnancy.
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Betschart C, Albrich WC, Brandner S, Faltin D, Kuhn A, Surbek D, and Geissbuehler V
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- Anti-Bacterial Agents therapeutic use, Female, Humans, Pregnancy, Retrospective Studies, Bacteriuria drug therapy, Gynecology, Obstetrics, Urinary Tract Infections diagnosis, Urinary Tract Infections drug therapy
- Abstract
Acute and recurrent urinary tract infections (UTIs) are common auto-infectious diseases transmitted from the intestinal tract. They affect the urinary tract either through recurrence or through persistence. The incidence of UTIs increases with age and comorbidities. In this guideline from the Swiss Society of Gynaecology and Obstetrics (SSGO), diagnosis and treatment of UTIs are grouped into uncomplicated and complicated cases. This is to our knowledge the first guideline that specifically considers UTIs in pregnancy and breastfeeding, and the prevention of UTIs in the context of urogynaecological diagnosis and surgery. Recommendations are based on observational, retrospective or randomised controlled studies. The level of evidence was rated according to recommendations made by the Oxford Centre of Evidence-based Medicine. In non-pregnant women and women <65 years with dysuria, pollakiuria and suprapubic pain, no urine diagnostic testing is needed. If the clinical presentation is unclear, urinary tests such as midstream urine stix or urine analysis should be used, and in cases of unclear or recurrent infections, a urine culture. Routine screening for asymptomatic bacteriuria (ASB) should not be carried out, and antibiotic treatment should be avoided in cases of incidentally detected ASB. As an exception, screening for bacteriuria should be carried out in patients prior to urogynaecological surgery where urinary drainage by catheter is necessary or probable. In pregnancy, systematic screening for ASB is not recommended, because most women with ASB do not develop complications during follow-up, and contamination of urine samples collected in pregnancy is common. Patients should be advised that most UTIs are self-limiting, that the symptoms can be relieved with non-steroidal anti-inflammatory drugs (NSAIDs) and that the same time is required to eradicate the bacteria using antibiotics or NSAIDs. For non-pregnant women with uncomplicated UTIs, a 48-hour-delayed antibiotic prescription is recommended, supplemented by NSAIDs for pain relief. If antibiotics are needed after 48 hours, or in case of direct antibiotic administration in pregnant women, the shortest possible course of treatment should be carried out. There is increasing interest in alternatives or complementary treatments to antibiotic therapy, especially for recurrent UTIs. Different recommendations and alternative medications are summarised. This short and comprehensive guideline provides quick answers for every day clinical questions concerning UTIs, especially for obstetricians and gynaecologists.
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- 2020
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48. Appraisal of clinical practice guidelines on the management of obstetric perineal lacerations and care using the AGREE II instrument.
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Nygaard CC, Tsiapakidou S, Pape J, Falconi G, Betschart C, Pergialiotis V, and Doumouchtsis SK
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- Delivery, Obstetric adverse effects, Episiotomy adverse effects, Episiotomy methods, Female, Humans, Lacerations prevention & control, Pregnancy, Anal Canal injuries, Lacerations therapy, Pelvic Floor injuries, Perineum injuries, Practice Guidelines as Topic standards
- Abstract
Pelvic floor trauma during childbirth is highly prevalent and is associated with long term risks of incontinence and pelvic organ prolapse. Societies and organizations have published clinical guidelines in order to standardise and improve the management of perineal care. The aim of this study was to systematically evaluate the quality of clinical guidelines on obstetric perineal trauma and care using the AGREE II instrument. We searched Medline, PubMed, Web of Science and ScienceDirect databases from inception until the 15th of December 2018 using the terms "guideline" OR "guidelines", OR "guidance", OR "recommendation" AND "obstetric anal sphincter injury", OR "perineal laceration" OR "perineal tear" OR "perineal trauma" OR "vaginal tear". Twelve guidelines were included, in English and Spanish.The assessment of the guidelines was performed using AGREE II by 5 appraisers.Ten guidelines scored more than 50 %, and 3 of them scored higher than 70 %. Two guidelines scored <50 % and were considered as low quality. Level of evidence and grade of recommendations were used by 7 guidelines of the 12 guidelines. Although some guidelines received high scores, there is space for improvement of the standards of guidelines., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)
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- 2020
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49. A systematic review of reported outcomes and outcome measures in randomized trials evaluating surgical interventions for posterior vaginal prolapse to aid development of a core outcome set.
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Lourenço TRM, Pergialiotis V, Durnea CM, Elfituri A, Haddad JM, Betschart C, Falconi G, Nygaard CC, Bergstrom L, Pattel M, and Doumouchtsis SK
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- Female, Humans, Postoperative Complications epidemiology, Randomized Controlled Trials as Topic, Surgical Mesh statistics & numerical data, Treatment Outcome, Outcome Assessment, Health Care statistics & numerical data, Uterine Prolapse surgery
- Abstract
Background: Recent systematic reviews have demonstrated wide variations on outcome measure selection and outcome reporting in trials on surgical treatments for anterior, apical and mesh prolapse surgery. A systematic review of reported outcomes and outcome measures in posterior compartment vaginal prolapse interventions is highly warranted in the process of developing core outcome sets., Objective: To evaluate outcome and outcome measures reporting in posterior prolapse surgical trials., Search Strategy: We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL)., Selection Criteria: Randomized trials evaluating the efficacy and safety of different surgical interventions for posterior compartment vaginal prolapse., Data Collection and Analysis: Two researchers independently assessed studies for inclusion, evaluated methodological quality, and extracted relevant data. Methodological quality, outcome reporting quality and publication characteristics were evaluated., Main Results: Twenty-seven interventional and four follow-up trials were included. Seventeen studies enrolled patients with posterior compartment surgery as the sole procedure and 14 with multicompartment procedures. Eighty-three reported outcomes and 45 outcome measures were identified. The most frequently reported outcomes were blood loss (20 studies, 74%), pain (18 studies, 66%) and infection (16 studies, 59%)., Conclusions: Wide variations in reported outcomes and outcome measures were found. Until a core outcome set is established, we propose an interim core outcome set that could include the three most commonly reported outcomes of the following domains: hospitalization; intraoperative, postoperative urinary, gastrointestinal, vaginal and sexual outcomes; clinical effectiveness., Prospero: CRD42017062456., (© 2019 International Federation of Gynecology and Obstetrics.)
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- 2020
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50. A systematic review and meta-synthesis of qualitative studies on pelvic organ prolapse for the development of core outcome sets.
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Rada MP, Jones S, Falconi G, Milhem Haddad J, Betschart C, Pergialiotis V, and Doumouchtsis SK
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- Female, Humans, Qualitative Research, Patient Reported Outcome Measures, Pelvic Floor Disorders physiopathology, Pelvic Floor Disorders psychology, Pelvic Organ Prolapse physiopathology, Pelvic Organ Prolapse psychology, Quality of Life
- Abstract
Aims: In the current climate of evidence-based health care, the aim of this meta-synthesis was to collect and systematically analyse data from primary qualitative studies on pelvic organ prolapse (POP), to identify patient-centered perspectives on the natural course of POP. Information acquired in this study may be useful for ongoing research towards the development of core outcome sets (COS) in pelvic floor disorders., Methods: A CHORUS Working Group performed a standardized search of three different databases (Medline, Embase, Scopus), from inception to October 2019. We selected qualitative studies on women's perspectives on POP that were published in the English language. Three reviewers independently evaluated the quality of eligible papers and highlighted recurrent themes based on patient perspectives., Results: Eighteen qualitative studies including a total of 497 patients were assessed in this analysis. Our study revealed five superordinate themes, recurrently encountered in qualitative studies on POP: awareness of POP (6 studies), communication (9 studies), treatments (10 studies), effects on quality of life (6 studies), and self-image (3 studies). Five out of 10 quality criteria were met by all the studies included, based on an assessment performed using the critical appraisal skills program., Conclusions: This is the first synthesis of qualitative studies that address POP-related experiences of women, highlighting five superordinate themes, of which treatment was the most commonly reported one. This synthesis' findings may guide quantitative research priorities and will hopefully contribute to the development of a COS for POP., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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