Assessment of pelvic organ prolapse with the Pelvic Inclination Correction System: defining the normal range and threshold to pathology.

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.

MRI characterization of pelvic floor ligaments in nulliparous women: Technique development and morphometry within the 3D pelvic inclination correction system (3D-PICS).

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.

Repurposing of Bryophyllum pinnatum for dysmenorrhea treatment: a systematic scoping review and case series.

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.

[Radiological imaging following pelvic prolapse surgery]. / Bildgebung des postoperativen Beckenbodens.

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.

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.

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.

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

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.

Robot-assisted pelvic floor reconstructive surgery: an international Delphi study of expert users.

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.

Bryophyllum pinnatum and Improvement of Nocturia and Sleep Quality in Women: A Multicentre, Nonrandomised Prospective Trial.

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.

Comparison of in vivo visco-hyperelastic properties of uterine suspensory tissue in women with and without pelvic organ prolapse.

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.

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).

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.

Outcome reporting in trials on conservative interventions for pelvic organ prolapse: A systematic review for the development of a core outcome set.

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).

A new titanium-covered transobturator tape for surgical treatment of stress urinary incontinence.

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.

A meta-synthesis of qualitative studies on stress urinary incontinence in women for the development of a Core Outcome Set: A systematic review.

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.

Developing Core Outcome Sets (COS) and Core Outcome Measures Sets (COMS) in Cosmetic Gynecological Interventions: Protocol for a Development and Usability Study.

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.

Systematic review and appraisal of clinical practice guidelines on pelvic organ prolapse using the AGREE II tool.

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.

Patient-reported outcomes and outcome measures in childbirth perineal trauma research: a systematic review.

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.

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.

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.

Glucocorticoid Receptor Beta and Its Prognostic Value on Treatment Response in Chronic Vulvar Dermatitis.

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 ß (GRß), an inhibitor of the active glucocorticoid receptor α (GRα), is discussed as mechanism of glucocorticoid insensitivity. OBJECTIVES: To analyze whether the expression of GRß 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 GRß in the immunohistochemical stained biopsies were examined. RESULTS: Fifty-two percent of women with CVD were nonresponsive to TGC. GRß 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: GRß is highly expressed in keratinocytes of the vulvar epidermis affected by CVD, but GRß expression was not increased in patients nonresponsive to TGC compared to responsive patients. Thus, the failure mechanism in nonresponders still remains to be elucidated.

Considering non-bladder aetiologies of overactive bladder: a functional neuroimaging study.

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.

Evaluation of guidelines on the use of vaginal mesh implants for pelvic organ prolapse using the AGREE II instrument.

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.