A randomized trial comparing continence pessary to continence device (Poise Impressa®) for stress incontinence.

INTRODUCTION AND HYPOTHESIS: To conduct a multi-centered randomized trial evaluating stress urinary incontinence (SUI) treatment based on the Patient Global Impression of Improvement score after 4 weeks using a continence pessary (CP) or a disposable intravaginal continence device (DICD). The null hypothesis is no difference in treatment success between cohorts. METHODS: This parallel group, active treatment comparative effectiveness trial randomized women with SUI to either CP or DICD for 4 weeks in a 1:1 allocation ratio. Exclusion criteria included pregnancy, UTI, postmenopausal bleeding, neurogenic bladder, urinary retention, prolapse, contraindication to or prior treatment with CP/DICD, and prior SUI surgery. Assuming an 80% power, an alpha of 5% and 20% dropout, we needed 138 participants to detect 50% success with CP versus 25% with DICD. Due to slow enrollment, the study was stopped after 16 months with 50 participants enrolled. RESULTS: Of the 50 women enrolled, 25 (50%) were randomized to CP and 25 (50%) to DICD. Thirty-five of 50 (70%) completed a fitting, and 22/50 (44%) completed 4-week and 17/50 (34%) completed 6-month follow-up. Baseline characteristics were similar, and there was high treatment success in each cohort [80% (8/10) CP vs. 75% (9/12) DICD; p = 1.0]. DICD patients showed improvement on all questionnaires but had higher use of other therapies over 6 months. CP patients showed improvements except for lower sexual function scores at 4 weeks. No serious adverse events occurred. CONCLUSIONS: Most women fitted with a CP/DICD experienced treatment success after 4 weeks without serious adverse events.

Readmissions and perioperative outcomes for same-day versus next-day discharge after prolapse surgery.

INTRODUCTION AND HYPOTHESIS: We aimed to evaluate the safety of same-day discharge (SDD) compared with next-day discharge (NDD) after prolapse surgery on a national level hypothesizing that readmission and complication rates after SDD would not be higher than NDD. METHODS: We performed a retrospective cohort study using the National Surgical Quality Improvement Program database including 2014-2018. Current Procedural Terminology (CPT) codes were used to identify minimally invasive apical suspensions or obliterative procedures. Exclusion criteria were length of stay > 1 day, unrelated concomitant procedures, serious medical comorbidities, American Society of Anesthesiologists (ASA) Class >2, and complication during index admission. The primary outcome was 30-day readmission, and secondary outcomes included 30-day complications. RESULTS: 12,583 were included in analysis. SDD rate was 16.7%. The majority of women were white (91%) with a mean age of 59 years and mean body mass index of 28 kg/m². Medical comorbidities were similar between the SDD and NDD groups. Overall incidence of 30-day readmission was 1.7%. SDD had lower odds of 30-day readmission than NDD (aOR 0.63, 95% CI 0.41-0.98). SDD had lower odds of 30-day complications but this failed to reach statistical significance (aOR 0.67, 95% CI 0.44-1.03). CONCLUSIONS: In this cohort, 30-day readmission and complication rates were not higher after SDD compared to NDD in women undergoing minimally-invasive apical suspension or obliterative procedures. We interpret these findings carefully given study limitations but believe our findings support the safety of SDD after minimally invasive apical suspension or obliterative procedures in a low-risk population.

A pilot randomized controlled trial of vaginal estrogen on postpartum atrophy, perineal pain, and sexual function.

INTRODUCTION AND HYPOTHESIS: Vulvovaginal symptoms following perineal laceration may be worsened by atrophy related to decreased estrogen. Our objective was to evaluate the effect of local estrogen therapy in this setting. METHODS: We conducted a single-center, pilot, randomized, placebo-controlled trial of local estradiol in primiparous women with a second-degree or greater perineal laceration following a term vaginal delivery. Participants were randomized to twice weekly estradiol or placebo cream from delivery through 3 months postpartum. The primary outcome was a validated measure of vulvovaginal symptoms at 12 weeks postpartum. Secondary outcomes included measures of perineal pain, quality of life, sexual function, ease of use, likelihood of continued use, and adverse events. RESULTS: We planned to enroll 70 women; however, due to human subjects research restrictions related to the COVID-19 pandemic, enrollment was stopped early. A total of 59 women were randomized, 31 to the estradiol group and 28 to the placebo group. Nearly all participants (95%) were followed through 12 weeks with suggestion of marginal improvement in Vulvar Assessment Scale scores [-0.10; 90% CI = (-0.20, 0.01)] in those randomized to estradiol compared to placebo. Local estradiol was not associated with improvement in other measures, and only one non-serious adverse event was observed. CONCLUSIONS: In primiparous women with a perineal laceration, use of local estradiol showed minimal clinical benefit in vulvovaginal atrophy and related symptoms but appears to be acceptable and safe for postpartum use. Larger adequately powered trials enrolling a diverse group of postpartum women are needed to affirm these findings.

Fractional CO2 laser therapy for genitourinary syndrome of menopause for breast cancer survivors.

PURPOSE: Fractional CO2 laser therapy is an emerging treatment for genitourinary syndrome of menopause (GSM). The objective of this study was to determine the feasibility and preliminary efficacy of fractional CO2 laser therapy in breast cancer survivors. METHODS: This was a single arm feasibility study of breast cancer survivors with dyspareunia and/or vaginal dryness. Participants received three treatments of fractional CO2 laser therapy at 30-day intervals and returned for a 1-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in 80% of patients. We collected data on the Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Urinary Distress Index (UDI), and SAE. RESULTS: A total of 64 patients participated in the study. The majority of women had Estrogen receptor/Progesterone receptor (ER/PR) positive/Her2neu negative (n = 37; 63%), stage I (n = 32, 54%) or II (n = 19, 32%) breast cancer. Most were receiving endocrine therapy (n = 54, 92%), most commonly aromatase inhibitors (AI; n = 40, 68%). Fifty-nine (88.1%) of those enrolled completed all treatments according to protocol with no reported SAE. No patient withdrew due to SAE. The scores of the VAS (mean Δ - 0.99; 95% CI [- 1.19, - 0.79], p < 0.001)), FSFI (mean Δ 9.67; 95% CI [7.27, 12.1], p < 0.001), and UDI (mean Δ - 8.85; 95% CI [- 12.75, - 4.75], p < 0.001)) improved from baseline to follow-up. CONCLUSION: Fractional CO2 laser treatment for breast cancer survivors is feasible and appears to reduce GSM symptoms across treatment and follow-up.

Mode of anesthesia and major perioperative outcomes associated with vaginal surgery.

INTRODUCTION AND HYPOTHESIS: The primary aim was to compare the incidence of major perioperative complications in women undergoing vaginal reconstructive surgery with general, regional, and monitored anesthesia care using a national database. The secondary aim was to compare length of hospital stay, 30-day readmission rates, urinary tract infections, and reoperation rates between anesthesia types. MATERIALS AND METHODS: The National Surgical Quality Improvement Program database was used to study women undergoing vaginal surgery for pelvic floor disorders from 2006 to 2015 via Current Procedural Terminology codes. Demographic and clinical variables were abstracted. The incidence of major perioperative complications was defined as the occurrence of any of the following within 30 days of surgery: death, surgical-site infection, pneumonia, venous thromboembolism, intensive care unit admission, stroke, transfusion, sepsis, and myocardial infarction. Regression analysis was used to estimate the relative risks (RR) associated with anesthesia type for each outcome. RESULTS: From the database, we gathered data on 37,426 women who underwent vaginal reconstructive surgery between 2006 and 2015; 87.2% (n = 32,623) underwent general, 6.9% (n = 2565) regional, and 5.9% (n = 2238) monitored anesthesia care. Major perioperative complications occurred in 560 women (1.5%). Relative to general anesthesia, the adjusted risk of major perioperative complications was not significantly different in those receiving monitored or regional anesthesia [monitored vs. general, adjusted RR 0.74, 95% confidence interval (CI) 0.45-1.20; regional vs. general, adjusted RR 1.23, 95% CI 0.92-1.65]. DISCUSSION: Major perioperative complications in vaginal reconstructive surgery were uncommon, and no differences were observed between monitored, regional, and general anesthesia outcomes.

The incidence of transfusion and associated risk factors in pelvic reconstructive surgery.

BACKGROUND: Almost 400,000 female pelvic reconstructive operations were performed in 2010 for urinary incontinence and pelvic organ prolapse in the United States, and it is likely that this will continue to increase each year. There is a lack of population-based data evaluating the risk of blood transfusion after urogynecologic procedures. OBJECTIVE: We sought to assess the incidence of blood transfusion related to pelvic reconstructive surgery in a large national surgical quality database and to identify transfusion-associated risk factors. STUDY DESIGN: This retrospective cohort study was performed using the National Surgical Quality Improvement Program database from the years 2010 through 2014. All women undergoing surgery for pelvic floor disorders were identified by Current Procedural Terminology code. Demographic and clinical variables were abstracted. The incidence of blood transfusion was determined. A multivariate logistic regression analysis was performed to identify clinical factors independently associated with blood transfusion. RESULTS: A total of 54,387 women underwent pelvic reconstructive surgery from 2010 through 2014 in the National Surgical Quality Improvement Program database. Of these subjects, 686 (1.26%) received a blood transfusion. The median age was 57 (range 28-89) years. Of the population, 0.81% was underweight (body mass index <18.5), 27.0% was normal weight (body mass index 18.5-24.9), 35.6% was overweight (body mass index 25-29.9), and 36.7% was obese (body mass index ≥30). The majority of subjects in the study cohort were Caucasian (91.4%) followed by African Americans (4.6%); the remainder included Asian, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander. Hispanic ethnicity was reported in 9.3% of the population. American Society of Anesthesiologists class 1 and 2 represented a majority of the sample (76.5%). Concomitant hysterectomy was performed in 20,735 (38.1%) of the population. In the multivariate analysis, preoperative hematocrit <30% (odds ratio, 13.68; 95% confidence interval, 10.65-17.59), history of coagulopathy (odds ratio, 3.74; 95% confidence interval, 2.50-5.60), and concomitant hysterectomy (odds ratio, 1.77; 95% confidence interval, 1.49-2.12) were factors independently associated with receiving blood transfusion (all P < .05). When compared to American Society of Anesthesiologists class 1, patients who were class 3 (odds ratio, 2.82, P < .01; 95% confidence interval, 2.02-3.93) or class 4 (odds ratio, 6.56, P < .01; 95% confidence interval, 3.65-11.78) were more likely to require a transfusion. When compared to Caucasians, African Americans (odds ratio, 1.73, P < .01; 95% confidence interval, 1.27-2.36) and Hispanics (odds ratio, 1.92, P < .01; 95% confidence interval, 1.54-2.40) were more likely to require a transfusion. In this cohort, overweight (odds ratio, 0.75; 95% confidence interval, 0.62-0.93) and obese (odds ratio, 0.61; 95% confidence interval, 0.49-0.75) subjects were less likely to receive a transfusion. When compared to a vaginal approach, patients who had a minimally invasive approach (odds ratio, 0.63; 95% confidence interval, 0.49-0.83) were less likely to receive a transfusion, while those with an open approach were more likely to receive a transfusion (odds ratio, 5.43; 95% confidence interval, 4.49-6.56). Age was not a risk factor for transfusion. CONCLUSION: Transfusion after pelvic reconstructive surgery is uncommon. The variables associated with transfusion are preoperative hematocrit <30%, American Society of Anesthesiologists class, bleeding disorders, nonwhite race, Hispanic ethnicity, and concomitant hysterectomy. Recognition of these factors can help guide preoperative counseling regarding transfusion risk after pelvic reconstructive surgery and individualize preoperative preparation.

Urinary neurotrophic peptides in postmenopausal women with and without overactive bladder.

AIMS: The aim of this study was to compare the expression of urinary nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), and calcitonin-gene related peptide (CGRP) in women with and without overactive bladder (OAB). We sought to determine factors associated with higher expression of these neuropeptides. METHODS: Participants with OAB and age-matched controls were enrolled. Symptom severity was assessed with validated questionnaires. Urinary neurotrophin levels, symptom scores, and clinical data were compared between the groups. Multivariate analysis determined independent factors associated with urinary neurotrophin levels. RESULTS: Sixty-seven women (38 OAB, 29 controls) were included. Women with OAB and controls were similar in age, race, body mass index, parity, and smoking status. Women with OAB were more likely to report a history of pelvic pain and pelvic surgery. Neurotrophic factor levels normalized to urinary creatinine did not differ between the groups. Increasing age was associated with greater urinary levels of BDNF and NGF (ß = 0.23, 95%CI 0.11-0.34 and 0.75, 95%CI 0.17-1.33, respectively, P < 0.02). Higher urinary NGF was associated with increasing BMI (ß = 0.81, 95%CI 0.05-1.57, P = 0.04) while pain was associated with elevated urinary SP (ß = 0.21, 95%CI 0.09-0.33, P = 0.001). CONCLUSIONS: Our data does not support a relationship between urinary neurotrophin levels and OAB in age-matched postmenopausal women. Further research is necessary to elucidate the role of urinary neurotrophins in the diagnosis and management of OAB. Neurourol. Urodynam. 36:740-744, 2017. © 2016 Wiley Periodicals, Inc.

Concomitant apical suspensory procedures in women with anterior vaginal wall prolapse in the United States in 2011.

INTRODUCTION: Although the surgical restoration of apical support has been shown to decrease reoperation rates, it is unclear whether this has been incorporated into current practice. The aims of this study were to determine the rate of concomitant apical suspensory procedures in women with anterior vaginal wall prolapse undergoing surgical repair in 2011 and to identify associated factors. METHODS: This cross-sectional study queried the Nationwide Inpatient Sample for women with a primary diagnosis of cystocele who underwent prolapse repair in 2011. The study cohort was analyzed for demographics, concomitant procedures, and hospital characteristics. The rate of apical suspensory procedures was determined. Factors potentially associated with receiving concomitant apical suspensory procedure were evaluated using univariate analysis and multivariate logistic regression. RESULTS: A total of 2,900 women in the database had a primary diagnosis of cystocele and underwent surgical prolapse repair in 2011. 925 (31.9 %) subjects underwent a concomitant apical suspensory procedure. The mean age in the study cohort was 61.9 ± 12.8 years. Hysterectomies were performed in 11.1 % of subjects. 61.1 % were performed vaginally, 26.5 % laparoscopically, and 12.5 % abdominally. On multivariate analysis, age greater than 50 years, Caucasian race, concomitant hysterectomy, and an urban teaching hospital setting were independently associated with receiving concomitant apical suspensory procedure in 2011. CONCLUSIONS: Despite evidence that the restoration of apical support is important for optimal anterior support, the overall rate of concomitant apical suspensory procedures is low. Several factors may play a role in whether or not women receive an apical suspensory procedure. This study highlights opportunities to improve the quality of surgical care provided to women with anterior vaginal prolapse.

Kinetic and mechanistic characterisation of Choline Kinase-α.

Choline Kinase is a key component of the Kennedy pathway that converts choline into a number of structural and signalling lipids that are essential for cell growth and survival. One member of the family, Choline Kinase-α (ChoKα) is frequently up-regulated in human cancers, and expression of ChoKα is sufficient to transform cells. Consequently ChoKα has been studied as a potential target for therapeutic agents in cancer research. Despite great interest in the enzyme, mechanistic studies have not been reported. In this study, a combination of initial velocity and product inhibition studies, together with the kinetic and structural characterisation of a novel ChoKα inhibitor is used to support a mechanism of action for human ChoKα. Substrate and inhibition kinetics are consistent with an iso double displacement mechanism, in which the γ-phosphate from ATP is transferred to choline in two distinct steps via a phospho-enzyme intermediate. Co-crystal structures, and existing site-specific mutation studies, support an important role for Asp306, in stabilising the phospho-enzyme intermediate. The kinetics also indicate a distinct kinetic (isomerisation) step associated with product release, which may be attributed to a conformational change in the protein to disrupt an interaction between Asp306 and the phosphocholine product, facilitating product release. This study describes a mechanism for ChoKα that is unusual amongst kinases, and highlights the availability of different enzyme states that can be exploited for drug discovery.

Iatrogenic lower urinary tract injury at the time of pelvic reconstructive surgery: does previous pelvic surgery increase the risk?

INTRODUCTION AND HYPOTHESIS: The objective of this study was to evaluate whether a history of previous pelvic surgery is associated with lower urinary tract (LUT) injury at the time of pelvic reconstructive surgery (PRS). METHODS: A retrospective analysis of patients undergoing pelvic reconstructive surgery from 2006 to 2011 was performed. Patients were divided into two groups: those with previous pelvic surgery and those without previous pelvic surgery. A sample size analysis was performed to determine the number needed to detect at least a 3-fold difference in the rate of LUT injury. Demographic, historical, clinical, intraoperative, and postoperative data were analyzed. Associations between LUT injury and demographics, previous pelvic surgery, or other clinical risk factors were assessed using univariate and multivariate analyses. RESULTS: 685 women were included in the analysis: 514 (74.9%) with and 171 (25.1%) without prior pelvic surgery. The overall rate of LUT injury was 6%. Of the injuries, 3.2% were cystotomies, and 1.9% were ureteral obstructions. Previous pelvic surgery did not significantly affect the rate of LUT injury (OR 0.76, 95%CI 0.38-1.54). A diagnosis of prolapse, concurrent hysterectomy, anterior repair, and apical repair were significantly associated with LUT injury. After controlling for age and race, a diagnosis of prolapse remained significantly associated with LUT injury (OR 3.38, 95% CI 1.11-14.75). CONCLUSIONS: Prior pelvic surgery does not affect the rate of LUT injury in pelvic reconstructive surgery. The diagnosis of prolapse is a risk factor for LUT injury in women undergoing pelvic reconstructive surgery.

Perioperative Outcomes for Same- Versus Next-Day Discharge After Benign Vaginal Hysterectomy.

IMPORTANCE: While same-day discharge (SDD) after laparoscopic hysterectomy is well supported, studies for vaginal hysterectomy (VH) are lacking. OBJECTIVE: The aim of the study was to compare 30-day complications for SDD versus next-day discharge (NDD) after benign VH. STUDY DESIGN: This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2019. Vaginal hysterectomy with or without urogynecology procedures was identified by Current Procedural Terminology codes. The primary outcome was 30-day composite complications of SDD versus NDD after VH. Secondary outcomes compared reoperations rates, time to and reasons for reoperation, and complications between the groups. Composite complications included death, major infection or wound complication, thromboembolism, transfusion, cardiopulmonary complication, renal insufficiency/failure, stroke, or reoperation. Unadjusted and adjusted odds ratios were determined using univariate and multivariate analysis. RESULTS: Of 24,277 people included, 4,073 (16.8%) were SDD, which were more likely to be younger ( P < 0.001), less likely to have hypertension (23.4 vs 18.3%, P < 0.0001) or diabetes (4.5 vs 3.3%, P = 0.001), and had shorter surgical procedures (100.7 ± 47.5 vs 111.2 ±57.5 minutes, P < 0.0001). There was no difference in composite complications after SDD versus NDD and this remained true in multivariate analysis (2.0 vs 2.3%, P = 0.30, SDD; adjusted odds ratio, 0.9; 95% confidence interval, 0.7-1.1). There was no difference in reoperation rates (0.9 vs 0.9%, P = 0.94) or reasons for reoperation. Time to first complication was shorter for SDD versus NDD (11 vs 13 days, P = 0.47). CONCLUSION: In our cohort of low-risk patients, SDD after VH with or without urogynecology procedures did not have an increased odds of 30-day composite complications.

Comparison of Readmission Rates for Same-Day Versus Next-Day Discharge After Benign Vaginal Hysterectomy.

IMPORTANCE: Same-day discharge (SDD) for laparoscopic hysterectomy is shown to be safe and acceptable, but data for vaginal hysterectomy (VH) are lacking. OBJECTIVE: The aim of this study was to compare 30-day readmission rates, timing, and reasons for readmission for SDD versus next-day discharge (NDD) after VH. STUDY DESIGN: This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2019. Cases of VH with or without prolapse repair were identified by Current Procedural Terminology codes. The primary outcome was 30-day readmissions after SDD versus NDD. Secondary outcomes included reasons for and time to readmission and a subanalysis evaluating 30-day readmissions for those with prolapse repair. Unadjusted and adjusted odds ratios were determined using univariate and multivariate analyses. RESULTS: There were 24,277 women included; 4,073 (16.8%) were SDD. The 30-day readmission rate was low (2.0%; 95% confidence interval [CI], 1.8-2.2%), with no difference in odds of readmission for SDD versus NDD after VH in multivariate analysis (SDD adjusted odds ratio [aOR], 0.9; 95% CI, 0.7-1.2). Results were similar in our subanalysis of VH with prolapse surgery (SDD aOR, 0.94; 95% CI, 0.55-1.62). Median time to readmission was 11 days and did not differ (SDD interquartile range, 5, 16 [range, 0-29] vs NDD, 7, 16 [range, 1-30]; Z = -1.30; P = 0.193). The most common reasons for readmission were bleeding (15.9%), infection (11.6%), bowel obstruction (8.7%), pain (6.8%), and nausea/emesis (6.8%). CONCLUSIONS: Same-day discharge after VH did not have an increased odds of 30-day readmission compared with NDD. This study, with preexisting data, supports the practice of SDD after benign VH in low-risk patients.

Duodenal Metastasis From Primary Lung Adenocarcinoma: A Diagnostic and Therapeutic Challenge.

Distant metastasis from primary lung cancer is mostly seen in the liver, brain, adrenal glands and bones. Small bowel, specifically duodenum is a relatively unusual site for distant metastasis from lung carcinoma. This case reports a rare scenario of upper gastrointestinal bleeding caused by duodenal metastasis by a primary lung adenocarcinoma. A 43-year-old woman presented to the emergency department with complaints of progressive hemoptysis for the past three weeks. Esophagogastroduodenoscopy (EGD) revealed a 2.5 cm x 2.5 cm fungating villous mass-like structure in the first portion of the duodenum, with a normal-appearing esophagus and stomach. Biopsies were performed, which were histologically consistent with poorly differentiated malignant. The immunohistochemical (IHC) staining was consistent with metastatic disease from primary lung adenocarcinoma. Due to its rarity, there are no solidified guidelines for the management of duodenal metastasis from lung carcinoma. Our case was challenging due to the extensive metastasis and low functional status of the patient and was ultimately managed with home hospice.

A Qualitative Study to Understand the Impact of Caring for Traumatic Injury Survivors.

BACKGROUND: Following traumatic injury, an informal carer is often required to support recovery. Understanding the impact of caregiving is important to inform intervention design. AIM: to explore the impact of caring on family and caregiver finances, employment, social life, and psychological wellbeing. METHOD: Semi-structured interviews conducted with carers of traumatic injury survivors. Interviews were audio recorded, transcribed and thematically analysed, informed by the Roy Adaptation Model (RAM) and International Classification of Functioning, Disability and Health (ICF). RESULTS: Ten participants were interviewed. Key themes included (1) financial impact/employment issues, (2) relationships and support and (3) psychological impact. Most carers did not receive professional support with daily care post-discharge. Carers' employers responded positively, supporting them even after extensive leave. Carers received inconsistent communication whilst visiting trauma survivors in hospital; carers with healthcare experience were favoured. Navigating and receiving benefits was complex. Some carers found it difficult to accept the trauma survivor's injury, whilst others focused on achieving goals. CONCLUSIONS: Support from professional services is limited outside hospital settings for non-brain injuries. Future interventions and healthcare services should acknowledge the lack of psychological support for carers. Researchers should consider using the ICF/RAM when designing interventions to ensure the full impact on carers is addressed.

Mechanism of glycogen synthase inactivation and interaction with glycogenin.

Glycogen is the major glucose reserve in eukaryotes, and defects in glycogen metabolism and structure lead to disease. Glycogenesis involves interaction of glycogenin (GN) with glycogen synthase (GS), where GS is activated by glucose-6-phosphate (G6P) and inactivated by phosphorylation. We describe the 2.6 Å resolution cryo-EM structure of phosphorylated human GS revealing an autoinhibited GS tetramer flanked by two GN dimers. Phosphorylated N- and C-termini from two GS protomers converge near the G6P-binding pocket and buttress against GS regulatory helices. This keeps GS in an inactive conformation mediated by phospho-Ser641 interactions with a composite "arginine cradle". Structure-guided mutagenesis perturbing interactions with phosphorylated tails led to increased basal/unstimulated GS activity. We propose that multivalent phosphorylation supports GS autoinhibition through interactions from a dynamic "spike" region, allowing a tuneable rheostat for regulating GS activity. This work therefore provides insights into glycogen synthesis regulation and facilitates studies of glycogen-related diseases.

Engaging Women in Pelvic Floor Disorders Research Using the Internet.

OBJECTIVES: The objective of this study were (1) to assess the feasibility of using online platforms as recruitment tools for pelvic floor disorder studies and (2) to compare the prevalence of symptoms of incontinence and care-seeking behavior by online platform to previously published prevalence estimates. METHODS: We conducted a cross-sectional study among women to assess the prevalence of incontinence symptoms, level of bother, and care-seeking behavior. Participants were recruited through Facebook ads, ResearchMatch, or Reddit. The effectiveness of Facebook ads was assessed using the click through rate and an overall completion rate (number of completes over number of times an ad was shown). A nontargeted ad was posted to a Reddit thread in which research opportunities are advertised. For ResearchMatch, investigators sent a recruitment email. Effectiveness of this method was assessed by observing how many women completed the survey compared with the number of women who received it. RESULTS: Among the 7361 women who initiated the questionnaire, 6650 (90%) completed it. A majority of participants were recruited through ResearchMatch. Online platforms were successful in recruiting women across a wide age range (ages, 18-93 years). The overall prevalence of incontinence was 46.1% with women 45 years and older having the highest prevalence (64.6%). Common reasons for not seeking care included "not bothersome enough," "other health problems," and "being unsure about treatment." CONCLUSIONS: Internet-based recruitment was found to be feasible. The prevalence of incontinence was higher than has been reported in other population-based samples. Significant barriers to care exist, and further studies should focus on educational strategies.

Evaluating the Quality and Readability of Online Resources for Labiaplasty.

OBJECTIVES: The aim of this study was to evaluate the quality, readability, and accuracy of Web-based information regarding labiaplasty and to characterize the types of Web sites providing this information. METHODS: Investigators used 3 major search engines to query the internet using the search terms labiaplasty, labia reduction, and vaginal rejuvenation. Two validated tools were used to evaluate Web sites: the JAMA benchmark tool and the DISCERN instrument. Three physicians independently reviewed each Web site. Interrater agreement was assessed, and reviewer scores were averaged. Flesch-Kincaid reading ease and Flesch-Kincaid grade level of each site were assessed. Data were analyzed using Stata 14.0 (College Station, TX). RESULTS: Of the 112 Web sites reviewed, 100 Web sites were from North America, 9 from Europe, 2 from Australia, and 1 from Asia. The median score using the JAMA tool was 1.0 (0.33-4.0), indicating low accountability, whereas the median score using the DISCERN tool was 28 (18.7-77) of 80 with higher scores indicating higher quality. Cohen's weighted κ statistic (0.81) demonstrated near perfect agreement among reviewers for DISCERN scores. The median reading level was 11.9 (6.4-19.5). A majority of the Web sites (92) were for-profit businesses or blogs. CONCLUSIONS: The internet enables patients to research sensitive topics and seek answers without worry of social stigma. Online health-related information is a widely used yet poorly studied source of medical information. The majority of Web sites reviewed lack balanced, evidence-based information. Given the wide variation in the quality of information, physicians should guide patients to reputable online resources.

Promoting patient followup treatment with intra-detrusor onabotulinumtoxinA for overactive bladder.

INTRODUCTION: We aimed to characterize patient-related factors that promote followup of repeat onabotulinumtoxinA treatments for overactive bladder via a mixed-methods approach. METHODS: A retrospective chart review was conducted for patients who received intra-detrusor injection of onabotulinumtoxinA at our institution from 2011-2018, who were then surveyed to evaluate their experience, knowledge, and perceptions regarding onabotulinumtoxinA treatment and followup. Patients who received one onabotulinumtoxinA treatment and patients who underwent multiple treatments were compared to assess followup rates following initial treatment, group characteristics, patient comfort, and patient knowledge of needed retreatment. RESULTS: A total of 29.3% of patients received a single treatment and 70.7% of patients received multiple treatments. There was no difference in clinical, demographic, or intake variables between groups. Patients receiving multiple treatments reported having their first procedure in the operating room and reported greater improvement in symptoms and procedure comfort. This group was also more likely to understand that repeat treatments are necessary than those undergoing one treatment. CONCLUSIONS: No research to date has systematically explored patient-reported factors that promote retreatment of onabotulinumtoxinA for overactive bladder. This novel, mixed-methods approach indicates that patient comfort and patient knowledge were the strongest predictors of previous retreatment and anticipated retreatment, suggesting concrete avenues for improved periprocedural patient counselling and education.

Pilot study of fractional CO2 laser therapy for genitourinary syndrome of menopause in gynecologic cancer survivors.

PURPOSE: The objectives of this study were to evaluate the feasibility and efficacy of fractional CO2 laser therapy in gynecologic cancer survivors. METHODS: This was a pilot, multi-institutional randomized sham-controlled trial of women with gynecologic cancers with dyspareunia and/or vaginal dryness. Participants were randomized to fractional CO2 laser treatment or sham laser treatment. The primary aim was to estimate the proportion of patients who had improvement in symptoms based on the Vaginal Assessment Scale (VAS). Secondary aims included changes in sexual function assessed using the Female Sexual Functioning Index (FSFI) and urinary symptoms assessed using the the Urinary Distress Inventory (UDI-6). RESULTS: Eighteen women participated in the study, ten in the treatment arm and eight in the sham arm. The majority of participants had stage I (n = 11, 61.1 %) or II (n = 3, 16.7 %) endometrial cancer with adenocarcinoma histology (n = 9, 50 %). In total, 15 (83.3 %) of the participants completed all treatments and follow-up visit. There was no difference in the change in the median VAS score from baseline to follow-up. However, there was an improvement in change in the median total FSFI score with treatment compared with sham (Δ 6.5 vs -0.3, p = 0.02). The change in the median UDI-6 score was lower in the treatment arm (Δ -14.6 vs -2.1, p = 0.17), but this was not statistically significant. There were no reported serious adverse events. CONCLUSIONS: Fractional CO2 laser therapy is feasible in gynecologic cancer survivors, with preliminary evidence of safety. In addition, there was preliminary evidence of improvement in sexual function compared with sham treatment. Clinicaltrial.gov Identifier: NCT03372720 (OSU-17261; NCI-2017-02051).