Associated factors of vaginal laxity and female sexual function: a cross-sectional study.

BACKGROUND: Female sexual dysfunction (FSD), including vaginal laxity (VL), can lead to a decrease in quality of life and affect partner relationships. AIM: We aimed to investigate the associated factors of VL and FSD and their relationship with other pelvic floor disorders in a female population. METHODS: This cross-sectional study was conducted at Chelsea and Westminster Hospital from July to December 2022. All women referred to clinical care at the urogynecology clinic were included. Participants were assessed according to sociodemographic and clinical aspects, the Pelvic Organ Prolapse Quantification system, sexual function, VL, sexual attitudes, sexual distress, sexual quality of life, vaginal symptoms, and pelvic floor disorders. Unadjusted and adjusted associated factors of VL and FSD were analyzed. OUTCOMES: The primary outcome was the identification of the associated factors of VL and FSD in a female population, and secondary outcomes included the association between VL and pelvic organ prolapse (POP) with the questionnaire scores. RESULTS: Among participants (N = 300), vaginal delivery, multiparity, perineal laceration, menopause, and gel hormone were significantly more frequent in those reporting VL (all P < .05). When compared with nulliparity, primiparity and multiparity increased the odds of VL by approximately 4 and 12 times, respectively (unadjusted odds ratio [OR], 4.26 [95% CI, 2.05-8.85]; OR, 12.77 [95% CI, 6.53-24.96]). Menopause and perineal laceration increased the odds of VL by 4 and 6 times (unadjusted OR, 4.65 [95% CI, 2.73-7.93]; OR, 6.13 [95% CI, 3.58-10.49]). In multivariate analysis, menopause, primiparity, multiparity, and POP remained associated with VL. CLINICAL IMPLICATIONS: Parity, as an obstetric factor, and menopause and staging of POP, as clinical factors, were associated with VL. STRENGTHS AND LIMITATIONS: The investigation of associated factors for VL will contribute to the understanding of its pathophysiology. The study design makes it impossible to carry out causal inference. CONCLUSION: Menopause, primiparity, multiparity, and POP were highly associated with VL complaints in multivariate analysis.

Treatment of women with vaginal laxity: systematic review with meta-analysis.

BACKGROUND: Despite several treatments that have been used for women reporting vaginal laxity (VL), to our knowledge no systematic review is available on the topic so far. AIM: In this study, we sought to summarize the best available evidence about the efficacy and safety of interventions for treating VL, whether conservative or surgical. METHODS: A comprehensive search strategy was performed in Medline, Embase, Scopus, Web of Science, and Cochrane Library for reports of clinical trials published from database inception to September 2022. Studies selected for inclusion were in the English language and were performed to investigate any type of treatment for VL, with or without a comparator, whether nonrandomized studies or randomized controlled trials (RCTs). Case reports and studies without a clear definition of VL were excluded. OUTCOMES: The outcomes were interventions (laser, radiofrequency, surgery, and topical treatment), adverse effects, sexual function, pelvic floor muscle (PFM) strength, and improvement of VL by the VL questionnaire (VLQ). RESULTS: From 816 records, 38 studies remained in the final analysis. Laser and radiofrequency (RF) were the energy-based treatment devices most frequently studied. Pooled data from eight observational studies have shown improved sexual function assessed by a Female Sexual Function Index score mean difference (MD) of 6.51 (95% CI, 5.61-7.42; i2 = 85%, P < .01) before and after intervention, whether by RF (MD, 6.00; 95% CI, 4.26-7.73; i2 = 80%; P < .001) or laser (MD, 6.83; 95% CI, 5.01-8.65; i2 = 92%; P < .01). However, this finding was not shown when only 3 RCTs were included, even when separated by type of intervention (RF or laser). When RF treatment was compared to sham controls, VLQ scores did not improve (MD, 1.01; 95% CI, -0.38 to 2.40; i2 = 94%; P < .001). Patient PFM strength improved after interventions were performed (MD, 4.22; 95% CI, 1.02-7.42; i2 = 77%; P < .001). The ROBINS-I (Risk Of Bias In Nonrandomized Studies of Interventions) tool classified all non-RCTs at serious risk of bias, except for 1 study, and the risk of bias-1 analysis found a low and unclear risk of bias for all RCTs. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) certainty of the evidence was moderate for sexual function and the VLQ questionnaire and low for PFM strength. CLINICAL IMPLICATIONS: Sexual function in women with VL who underwent RF and laser treatment improved in observational studies but not in RCTs. Improvement in PFM strength was observed in women with VL after the intervention. STRENGTHS AND LIMITATIONS: Crucial issues were raised for the understanding of VL, such as lack of standardization of the definition and for the development of future prospective studies. A limitation of the study was that the heterogeneity of the interventions and different follow-up periods did not make it possible to pool all available data. CONCLUSIONS: Vaginal tightening did not improve sensation in women with VL after intervention, whereas RF and laser improved sexual function in women with VL according to data from observational studies, but not from RCTs. PFM strength was improved after intervention in women with VL.

VDR, CXCR1, CXCR2, PSCA Polymorphisms and Recurrent Urinary Tract Infections in Women: Genetic Association Study.

INTRODUCTION AND HYPOTHESIS: Urinary tract infection (UTI) is one of the most common human infections. Evidence suggests that there might be a genetic predisposition to UTI. Previous small candidate gene studies have suggested that common variants in genes involved in the immune response to UTI could increase susceptibility to the development of recurrent UTI (rUTI). The objective was to conduct a gene association study to replicate previous gene association studies identifying single nucleotide polymorphisms (SNPs) putatively associated with rUTI in adult women. METHODS: Women with a history of rUTI and healthy controls were recruited (n = 1,008) from gynaecology outpatient clinics. Participants completed a signed consent form and questionnaire for phenotyping. DNA was extracted from blood or saliva samples for each participant. Putative associated SNPs were identified from a comprehensive systematic review of prior gene association studies. Primers for each selected SNP were designed, and genotyping was conducted using a competitive polymerase chain reaction (PCR) method. The Chi-squared test was used to assess the association between each variant and rUTI. Genotyping quality was assessed by checking for deviation from Hardy-Weinberg equilibrium. RESULTS: We found no association between SNPs tested in the VDR (p = 0.16, p = 0.09, p = 0.36), CXCR1 (p = 0.09), CXCR2 (p = 0.39), PSCA (p = 0.74) genes, and rUTI in adult women. CONCLUSIONS: To our knowledge, this is the largest study to date, finding no significant associations. Previously reported positive associations may have been due to type 1 error, or genotyping errors. Future studies should adjust for confounders and employ adequate sample sizes. A greater understanding of the genetic components associated with rUTI may influence future treatment guidelines and screening for susceptible patients.

Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis. STUDY ELIGIBILITY CRITERIA: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L. METHODS: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty. RESULTS: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures. CONCLUSION: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. CONCLUSION: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.

Genetic polymorphisms associated with urinary tract infection in children and adults: a systematic review and meta-analysis.

INTRODUCTION: The lifetime risk of urinary tract infection is known from first-degree relative studies to be highly heritable. Associations have also been observed across the life course from pediatric urinary tract infection to recurrent urinary tract infection in adulthood, suggesting lifelong susceptibility factors. Candidate gene studies and genome-wide association studies have tested for genetic associations of urinary tract infection; however, no contemporary systematic synthesis of studies is available. OBJECTIVE: We conducted a systematic review to identify all genetic polymorphisms tested for an association with urinary tract infection in children and adults; and to assess their strength, consistency, and risk of bias among reported associations. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: PubMed, HuGE Navigator and Embase were searched from January 1, 2005 to November 16, 2023, using a combination of genetic and phenotype key words. STUDY APPRAISAL AND SYNTHESIS METHODS: Fixed and random effects meta-analyses were conducted using codominant models of inheritance in metan. The interim Venice criteria were used to assess their credibility of pooled associations. RESULTS: After removing 451 duplicates, 1821 studies reports were screened, with 106 selected for full-text review, 22 were included in the meta-analysis (7 adult studies and 15 pediatric studies). Our meta-analyses demonstrated significant pooled associations for pediatric urinary tract infection with variation in CXCR1, IL8, TGF, TLR4 and VDR; all of which have plausible roles in the pathogenesis of urinary tract infection. Our meta-analyses also demonstrated a significant pooled association for adult urinary tract infection with variation in CXCR1. All significant pooled associations were graded according to their epidemiological credibility, sample sizes, heterogeneity between studies, and risk of bias. CONCLUSION: This systematic review provides a current synthesis of the known genetic architecture of urinary tract infection in childhood and adulthood; and should provide important information for researchers analysing future genetic association studies. Although, overall, the credibility of pooled associations was weak, the consistency of findings for rs2234671 single nucleotide polymorphisms of CXCR1 in both populations suggest a key role in the urinary tract infection pathogenesis.

Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review.

BACKGROUND: De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. METHODS: We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. RESULTS: We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). CONCLUSION: De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. TRIAL REGISTRATION: OSF (Open Science Framework): https://osf.io/ueq32 .

Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology.

Pelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform an exome chip study in 526 women with POP and 960 control women to identify single nucleotide variants (SNVs) associated with the disease. We then integrated the functional interactions between the POP candidate proteins derived from the exome chip study and other POP candidate molecules into a molecular landscape. We found significant associations between POP and SNVs in 54 genes. The proteins encoded by 26 of these genes fit into the molecular landscape, together with 43 other POP candidate molecules. The POP landscape is located in and around epithelial cells and fibroblasts of the urogenital tract and harbors four interacting biological processes-epithelial-mesenchymal transition, immune response, modulation of the extracellular matrix, and fibroblast function-that are regulated by sex hormones and TGFB1. Our findings were corroborated by enrichment analyses of differential gene expression data from an independent POP cohort. Lastly, based on the landscape and using vaginal fibroblasts from women with POP, we predicted and showed that metformin alters gene expression in these fibroblasts in a beneficial direction. In conclusion, our integrated molecular landscape of POP provides insights into the biological processes underlying the disease and clues towards novel treatments.

Timing of symptomatic venous thromboembolism after surgery: meta-analysis.

BACKGROUND: The timing at which venous thromboembolism (VTE) occurs after major surgery has major implications for the optimal duration of thromboprophylaxis. The aim of this study was to perform a systematic review and meta-analysis of the timing of postoperative VTE up to 4 weeks after surgery. METHODS: A systematic search of MEDLINE, Scopus, and CINAHL databases was performed between 1 January 2009 and 1 April 2022. Prospective studies that recruited patients who underwent a surgical procedure and reported at least 20 symptomatic, postoperative VTE events by time were included. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a Poisson regression model, and the GRADE approach was used to rate the certainty of evidence. RESULTS: Some 6258 studies were evaluated, of which 22 (11 general, 5 urological, 4 mixed, and 2 orthopaedic postoperative surgical populations; total 1 864 875 patients and 24 927 VTE events) were eligible. Pooled evidence of moderate certainty showed that 47.1 per cent of the VTE events occurred during the first, 26.9 per cent during the second, 15.8 per cent during the third, and 10.1 per cent during the fourth week after surgery. The timing of VTE was consistent between individual studies. CONCLUSION: Although nearly half of symptomatic VTE events in first 4 weeks occur during the first postoperative week, a substantial number of events occur several weeks after surgery. These data will inform clinicians and guideline developers about the duration of postoperative thromboprophylaxis.

Hundreds of millions of surgical procedures are performed annually worldwide. Blood clots in legs and lungs represent serious, and sometimes fatal, complications of surgery. To prevent these complications, clinicians often give blood thinners to patients. To optimize the starting time and duration of use of blood thinners, it is crucial to know when blood clots occur after surgery. This study summarized the timing of blood clots after surgery based on a systematic review and meta-analysis of 22 prospective studies including thousands of patients with blood clots from various surgical fields. Of blood clots occurring within 4 weeks after surgery, 47 per cent occurred by the first, 74 per cent by the second, and 90 per cent by the third week after surgery. These research results are useful for patients, clinicians, and guideline developers to guide the starting time and duration of use of blood thinners after surgery.

Randomized controlled trials in de-implementation research: a systematic scoping review.

BACKGROUND: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. METHODS: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. RESULTS: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). CONCLUSIONS: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. REGISTRATION: OSF Open Science Framework hk4b2.

International Urogynecological Consultation (IUC): pathophysiology of pelvic organ prolapse (POP).

INTRODUCTION AND HYPOTHESIS: This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models. MATERIALS AND METHODS: An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added. RESULTS: The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81-3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24-3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02-1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP. CONCLUSIONS: Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.

Laparoscopic sacrohysteropexy versus vaginal hysterectomy and apical suspension: 7-year follow-up of a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Laparoscopic mesh sacrohysteropexy offers a uterine-sparing alternative to vaginal hysterectomy with apical suspension, although randomised comparative data are lacking. This study was aimed at comparing the long-term efficacy of laparoscopic mesh sacrohysteropexy and vaginal hysterectomy with apical suspension for the treatment of uterine prolapse. METHODS: A randomised controlled trial comparing laparoscopic mesh sacrohysteropexy and vaginal hysterectomy with apical suspension for the treatment of uterine prolapse was performed, with a minimum follow-up of 7 years. The primary outcome was reoperation for apical prolapse. Secondary outcomes included patient-reported mesh complications, Pelvic Organ Prolapse Quantification, Patient Global Impression of Improvement in prolapse symptoms and the International Consultation on Incontinence Questionnaire Vaginal Symptoms, Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and PISQ-12 questionnaires. RESULTS: A total of 101 women were randomised and 62 women attended for follow-up at a mean of 100 months postoperatively (range 84-119 months). None reported a mesh-associated complication. The risk of reoperation for apical prolapse was 17.2% following vaginal hysterectomy (VH) and 6.1% following laparoscopic mesh sacrohysteropexy (LSH; relative risk 0.34, 95% CI 0.07-1.68, p = 0.17). Laparoscopic sacrohysteropexy was associated with a statistically significantly higher apical suspension (POP-Q point C -5 vs -4.25, p = 0.02) and longer total vaginal length (9 cm vs 6 cm, p < 0.001). There was no difference in the change in ICIQ-VS scores between the two groups (ICIQ-VS change -22 vs -25, p = 0.59). CONCLUSION: Laparoscopic sacrohysteropexy and vaginal hysterectomy with apical suspension have comparable reoperation rates and subjective outcomes. Potential advantages of laparoscopic sacrohysteropexy include a lower risk of apical reoperation, greater apical support and increased total vaginal length.

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations. METHODS: Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria. RESULTS: We screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at the ESR1 gene (OR 0.67 95% CI 0.46-0.98, I2 = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11-1.82, I2 = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39-0.96, I2 = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66-0.96, I2 = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies. CONCLUSION: The genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.

Shared decision-making in urology and female pelvic floor medicine and reconstructive surgery.

Shared decision-making (SDM) is a hallmark of patient-centred care that uses informed consent to help guide patients with making complex health-care decisions. In SDM, patients and providers work together to determine the best course of action based on both the current available evidence and the patient's values and preferences. SDM not only provides a framework for the legal and ethical obligations providers need to fulfil for informed consent, but also leads to improved knowledge of treatment options and satisfaction of decision-making for patients. Tools such as decision aids have been developed to support SDM for complex decisions. Several decision aids are available for use in the field of urology and female pelvic medicine and reconstructive surgery, but these decision aids are also associated with barriers to SDM implementation including patient, provider and systematic challenges. However, solutions to such barriers to SDM include continued development of SDM tools to improve patient engagement, expand training of providers in SDM communication models and a process to encourage implementation of SDM.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Evidence-based Urology: When Is a Study or Meta-analysis Big Enough?

Both designing a clinical study and drawing conclusions from studies about the effect of treatments require justification of the sample size via judicious choice of the endpoint and power. Such an a priori power calculation limits the chances of mistakenly claiming a lack of clinical significance if no statistically significant difference between two treatments can be detected. Calculating the sample size for a new trial furthermore requires assessment of existing evidence to determine if its results will contribute to an updated meta-analysis. To rate the power of a meta-analysis, determination of the optimal information size is suggested, following the same principles as for calculating the power of a single trial. Even though these sample size considerations might seem like an additional hurdle, they are necessary to conduct clinical studies and meta-analysis that provide the optimal benefit for both clinicians and patients. PATIENT SUMMARY: Before conducting a clinical trial, researchers should determine how many patients need to be included to detect a difference between treatments. Even though a study might find a statistical difference between treatments, this does not necessarily mean that the difference is relevant for clinical use. These analyses before starting a study are important for producing worthwhile usable evidence for clinicians and patients.

Host-biomaterial interactions in mesh complications after pelvic floor reconstructive surgery.

Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those treated using transvaginal PPL mesh placement for prolapse, experience intractable pain and mesh exposure or extrusion. Explanted tissue from patients with complications following transvaginal implantation of mesh is typified by a dense fibrous capsule with an immune cell-rich infiltrate, suggesting that the host immune response has a role in transvaginal PPL mesh complications through the separate contributions of the host (patient), the biological niche within which the material is implanted and biomaterial properties of the mesh. This immune response might be strongly influenced by both the baseline inflammatory status of the patient, surgical technique and experience, and the unique hormonal, immune and microbial tissue niche of the vagina. Mesh porosity, surface area and stiffness also might have an effect on the immune and tissue response to transvaginal mesh placement. Thus, a regulatory pathway is needed for mesh development that recognizes the roles of host and biological factors in driving the immune response to mesh, as well as mandatory mesh registries and the longitudinal surveillance of patients.

ARTS: A Large, International Trial of Thromboprophylaxis in Intra-abdominal, Gynecologic, and Urologic Surgery.

ARTS will be the first trial to compare anticoagulation with a direct oral anticoagulant (apixaban) versus no anticoagulation among patients undergoing intra-abdominal, gynecologic, or urologic surgery at sufficiently similar risk of deep vein thrombosis or pulmonary embolism and major bleeding.