Effectiveness and safety of a novel, collapsible pessary for management of pelvic organ prolapse.

BACKGROUND: Pessaries are an effective treatment for pelvic organ prolapse, yet currently available pessaries can cause discomfort during removal and insertion. An early feasibility trial of an investigational, collapsible pessary previously demonstrated mechanical feasibility during a brief 15-minute office trial. Longer-term, patient-centered safety and efficacy data are needed. OBJECTIVE: This study aimed to assess the effectiveness and safety of the investigational vaginal pessary for pelvic organ prolapse at 3 months. STUDY DESIGN: This was a prospective, 7-center, open-label equivalence study with participants serving as their own controls. Subjects were current users of a Gellhorn or ring pessary with ≥stage 2 prolapse. Subjective and objective data were collected at baseline for 1 month while subjects used their current pessary. Data were then collected throughout a 3-month treatment phase with the study pessary. The primary outcome was change in Pelvic Floor Distress Inventory-20 score. Secondary outcome measures included objective assessment of prolapse support, changes in the Pelvic Floor Impact Questionnaire-7, and pain with insertion and removal, measured using a visual analog scale. Data from subjects fitted with the study pessary were analyzed using an intention-to-treat approach, and those who dropped out were assigned scores at the upper limit of the predefined equivalence limits. Secondary per protocol analyses included subjects who completed treatment. The study was powered to 80% with a minimal important change equivalence limit of 18.3 points on the Pelvic Floor Distress Inventory-20 scale. Square root transformations were used for nonparametric data, and P values were adjusted for multiple comparisons. RESULTS: A total of 78 subjects were enrolled, however, 16 withdrew before study pessary placement. The study pessary was fitted in 62 subjects (50 ring and 12 Gellhorn pessary users), and 48 (62%) completed the 3-month intervention. The change in Pelvic Floor Distress Inventory-20 scores at 3 months demonstrated equivalence when compared with the subjects' baseline scores (mean difference, -3.96 [improvement]; 90% confidence interval, -11.99 to 4.08; P=.002). Among those completing study, the Pelvic Floor Distress Inventory-20 scores, equivalence was not demonstrated and scores favored the study pessary (mean difference, -10.45; 90% confidence interval, -20.35 to 0.54; P=.095). Secondary outcomes included objective measures of support, which were similar (mean difference: Ba, 0.54 cm; Bp, 0.04 cm, favoring study pessary; improvement in mean Pelvic Floor Impact Questionnaire-7 scores for those who completed the trial: before, 32.23; after, 16.86; P=.019), and pain with insertion and removal, which was lower with the study pessary than with the subject's own pessary (mean difference visual analog scale score insertion, 9.91 mm; P=.019; removal, 11.23 mm; P=.019). No serious adverse events related to the pessary were reported. CONCLUSION: Equivalence was demonstrated in the primary outcome of the study pessary when compared with current, noncollapsible pessaries in terms of change in severity and bother of pelvic floor symptoms. Among participants who completed the trial, the Pelvic Floor Impact Questionnaire-7 improved with study pessary use and change in Pelvic Floor Distress Inventory-20 scores were nonequivalent, favoring the study pessary. Subjects reported significantly lower pain scores with both pessary insertion and removal with the novel collapsible pessary when compared with their standard pessary.

An evaluation of pelvic floor disorders in a public and private healthcare setting.

INTRODUCTION AND HYPOTHESIS: The objectives were to determine whether a difference exists in the duration of pelvic floor disorder (PFD) symptoms among patients presenting to urogynecologists in two healthcare systems: private and county; and to elucidate differences in baseline characteristics, type of PFDs, symptom severity and management, stratified by healthcare plans. METHODS: A multi-center retrospective study was conducted including new patients presenting to three urogynecology clinics between March 2016 and May 2018: one private clinic (site A) and two public clinics in the same county healthcare system (sites B and C). Baseline data included age, race, BMI, parity, and comorbidities. Primary outcome was "time to presentation" defined as PFD duration in months. Secondary outcomes were symptom severity and PFD management, analyzed by healthcare setting and insurance type. RESULTS: A total of 1,055 private and 439 public patients were included. Patients in the public setting were younger (54 vs 61 years, p<0.001), largely Hispanic (76% vs 14%, p<0.001), of higher parity (4 vs 3, p=0.001), and had more comorbidities, with a predominance of county-funded healthcare plans. There was no difference in duration of symptoms between the public and private groups respectively (54 vs 56 months, p=0.94). Patients in the public setting had more severe urinary incontinence (3 vs 2 pads/day, p<0.001) and prolapse (stages 3-4, 71% vs 61%, p=0.004); however, they had lower rates of surgical management for stress incontinence and prolapse. Differences in fecal incontinence could not be evaluated owing to small sample size. CONCLUSIONS: Public patients presented younger with more severe symptoms but had lower rates of surgery for PFDs traditionally managed surgically.

Diuretic use and risk of falls in older women with urinary incontinence.

OBJECTIVE: To determine the association between diuretic use and falls in community-dwelling older women with urinary incontinence (UI). METHODS: We conducted an analytic cross-sectional study using patients' electronic medical records. Patients were women with UI, 65 years or older seen at a urogynecology clinic between January 1, 2018 and September 30, 2019. We used logistic regression analysis to explore the associations between falls and diuretic use. RESULTS: The study included 108 women, mean age of 75.2 ±7.5 years. Twenty-two (20%) reported one or more falls within the past year and 32 (30%) were diuretic users. Fall prevalence in diuretic users and non-users were 25% (8/32) and 18.4% (14/76), respectively. Diuretic use was not associated with falls (OR = 0.74, 95%CI = 0.22-2.52). Post-hoc analysis revealed inadequate sample size. CONCLUSIONS: Diuretics use may not be a risk factor for falls in ambulatory older women with UI. A larger sample will be needed to confirm.

C-Clamp Technique: A Retrospective Review of a Novel Technique to Prevent Bladder Injury in Retropubic Midurethral Slings.

IMPORTANCE: Synthetic mesh midurethral slings have become the criterion-standard treatment for stress urinary incontinence with urethral hypermobility in women. Iatrogenic bladder injury is a known risk of the procedure. OBJECTIVE: Our objective was to show that a novel "C-clamp technique" can significantly reduce the risk of bladder and urethral injury at the time of bottom-up retropubic synthetic mesh midurethral sling placement. STUDY DESIGN: We conducted a retrospective review of the electronic medical records using Current Procedural Terminology coding of a single surgeon who performed synthetic mesh midurethral slings. Medical records were reviewed for demographic and clinical data for all bottom-up retropubic synthetic mesh midurethral slings placed using a novel C-clamp technique. All operative reports were reviewed for bladder and urethral injury at the time of implantation of the synthetic mesh midurethral sling using the C-clamp technique. RESULTS: Two hundred one consecutive bottom-up retropubic synthetic mesh midurethral slings were placed using the C-clamp technique from April 2012 through June 2022. The average age was 51 years (29-86 years); the average weight was 82 kg (46 -139 kg); and the average body mass index was 31 kg/m2 (15-57 kg/m2). No patients sustained a bladder or urethral injury at the time of implantation of a retropubic synthetic mesh midurethral sling using the C-clamp technique. CONCLUSION: The novel C-clamp technique shows promise in eliminating the risk of iatrogenic bladder and urethral injury at the time of implanting a bottom-up retropubic synthetic mesh midurethral sling.

Biophysical and Biochemical Characterization of the Receptor Binding Domain of SARS-CoV-2 Variants.

The newly emerging SARS-CoV-2 variants are potential threat and posing new challenges for medical intervention due to high transmissibility and escaping neutralizing antibody (NAb) responses. Many of these variants have mutations in the receptor binding domain (RBD) of SARS-CoV-2 spike protein that interacts with the host cell receptor. Rapid mutation in the RBD through natural selection to improve affinity for host receptor and antibody pressure from vaccinated or infected individual will greatly impact the presently adopted strategies for developing interventions. Understanding the nature of mutations and how they impact the biophysical, biochemical and immunological properties of the RBD will help immensely to improve the intervention strategies. To understand the impact of mutation on the protease sensitivity, thermal stability, affinity for the receptor and immune response, we prepared several mutants of soluble RBD that belong to the variants of concern (VoCs) and interest (VoIs) and characterize them. Our results show that the mutations do not impact the overall structure of the RBD. However, the mutants showed increase in the thermal melting point, few mutants were more sensitive to protease degradation, most of them have enhanced affinity for ACE2 and some of them induced better immune response compared to the parental RBD.

RBD decorated PLA nanoparticle admixture with aluminum hydroxide elicit robust and long lasting immune response against SARS-CoV-2.

Nanoparticles-based multivalent antigen display has the capability of mimicking natural virus infection characteristics, making it useful for eliciting potent long-lasting immune response. Several vaccines are developed against global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However these subunit vaccines use mammalian expression system, hence mass production with rapid pace is a bigger challenge. In contrast E. coli based subunit vaccine production circumvents these limitations. The objective of the present investigation was to develop nanoparticle vaccine with multivalent display of receptor binding domain (RBD) of SARS-CoV-2 expressed in E. coli. Results showed that RBD entrapped PLA (Poly lactic acid) nanoparticle in combination with aluminum hydroxide elicited 9-fold higher immune responses as compared to RBD adsorbed aluminum hydroxide, a common adjuvant used for human immunization. It was interesting to note that RBD entrapped PLA nanoparticle with aluminum hydroxide not only generated robust and long-lasting antibody response but also provided Th1 and Th2 balanced immune response. Moreover, challenge with 1 µg of RBD alone was able to generate secondary antibody response, suggesting that immunization with RBD-PLA nanoparticles has the ability to elicit memory antibody against RBD. Plaque assay revealed that the antibody generated using the polymeric formulation was able to neutralize SARS-CoV-2. The RBD entrapped PLA nanoparticles blended with aluminum hydroxide thus has potential to develop asa subunit vaccine against COVID-19.

Racial and ethnic disparities in chronic health conditions among women with a history of gestational diabetes mellitus.

Background: This study aims to examine and determine the role of race/ethnicity in chronic conditions in women diagnosed with gestational diabetes mellitus (GDM) during any of their previous pregnancies. Methods: We used the National Health and Nutrition Examination Survey (NHANES) from2007-2016 to identify women who self-reported prior GDM and chronic disease diagnoses such as cardiovascular disease, hypertension, depression, and type 2 diabetes mellitus (T2DM).We used bivariate analysis using the chi-square test (χ²) and multiple logistic regressions to perform statistical test for associations, taking into consideration design and sample weight. Results: Among participants with prior GDM diagnoses, black women had a 74.4% prevalence of chronic disease, followed by Whites, 58.5% Hispanics, 58.0%, and Asians, 51.9% (P=0.009).Black women with prior GDM diagnoses had 2.4 odds of having chronic conditions compared to Whites (adjusted odds ratio [AOR]=2.40, 95% confidence interval [CI] = 1.28-4.50). In addition, they had higher odds of being former smokers (AOR=1.73, 95% CI=1.01-2.96),current smokers (AOR=1.96, 95% CI=1.06-3.61), having a body mass index (BMI) of 25-29.9(AOR=2.55, 95% CI=1.10-5.87), or a BMI ≥30 (AOR=4.09, 95% CI = 2.05-8.17) compared to their White counterparts. Hispanic women had lower odds of being diagnosed with GDM and associated chronic diseases. Conclusion: Black women with GDM were disproportionally affected and at higher risk to be diagnosed with chronic conditions. Smoking and obesity were strongly associated with chronic disease diagnoses. Our findings also suggest a 'Hispanic Paradox', requiring further study. These findings inform primary care clinicians and Obstetricians, and Gynecologists of at-risk patients who could benefit from lifestyle modification recommendations and counseling.

Barriers to Care Affecting Presentation to Urogynecologists in a Community Setting.

OBJECTIVE: To evaluate barriers to care for patients presenting to urogynecologists and determine how these barriers differ in private and public/county health care settings. METHODS: Standardized anonymous questionnaires were distributed from May 2018 to July 2018 to new patients presenting to a urogynecologist at three institutions: two private health care clinics (sites A and B) and one public/county hospital clinic (site C). Patients identified symptom duration, symptom severity, and factors inhibiting presentation to care from a list of barriers. Patients then identified the primary barrier to care. RESULTS: One hundred nine questionnaires were distributed, and 88 were submitted, resulting in an 81% response rate (31 from site A, 30 from site B, 27 from site C). In analysis of the private versus public setting, there was no statistical difference between age (58 years vs 57 years, P = 0.69), body mass index (28 vs 30, P = 0.301), symptom duration (24 months vs 16 months, P = 0.28), or severity respectively. When asked to identify the primary barrier to presentation, patients in the private setting stated they did not know to see a specialist (26.2%, P = 0.002), while patients in the public setting could not obtain a closer appointment time (22.2% vs 13.1%, P = 0.35. Additionally, patients in the public setting were more likely to cite lack of health care coverage as a barrier to care (18.5% vs 1.6%, P = 0.01). CONCLUSION: This study highlights barriers that can contribute to the disparity of care seen in our patient population. Efforts should be made to acknowledge and mitigate hindrances impacting access to care.

Nipple and areolar hyperpigmentation secondary to the use of estradiol spray on the ipsilateral forearm skin: a report of two cases.

BACKGROUND: Metered transdermal estradiol spray may cause ipsilateral hyperpigmentation of the nipple and areola. CASES: Two women who were using transdermal estradiol spray for the treatment of postmenopausal symptoms developed hyperpigmentation of the ipsilateral areola and nipple. The appearance was variable in onset and did not appear to be related to the duration of use. CONCLUSION: Estradiol transdermal spray can have the rare side effect of ipsilateral nipple and areolar hyperpigmentation. The time of onset can vary.

Intrinsic urethral sphincteric deficiency: critical analysis of various diagnostic modalities.

PURPOSE OF REVIEW: The proper diagnosis of intrinsic urethral sphincteric deficiency among women with urinary incontinence carries important implications for determining the most effective medical or surgical therapy. Numerous diagnostic tests have been described attempting to make an accurate and comprehensive assessment of urethral function, but all suffer from a lack of standardization or inconsistently quoted reference values. This paper will review the literature on the positive aspects and limitations of commonly employed procedures to diagnose intrinsic urethral sphincteric deficiency. RECENT FINDINGS: Specific urodynamic studies, including the 'active' valsalva leak-point pressure and the 'static' urethral pressure profile are commonly used to determine urethral competence. However, these tests measure specific aspects of the continence mechanism under different clinical conditions, which limits the direct comparison between them. More complex techniques such as Doppler ultrasound, video-urodynamics and both static and dynamic magnetic resonance imaging are attempting to validate the urodynamic findings for urethral function. This approach may encourage the standardization of these procedures and parameters for diagnosing intrinsic urethral sphincteric deficiency. SUMMARY: A single definitive test for the diagnosis of intrinsic urethral sphincteric deficiency does not exist. Instead, multiple tests should be employed to reach a consensus for the diagnosis. This should include a complete voiding history, simple office examinations, and advanced studies such as urethrocystoscopy, urodynamics and possibly radiological evaluations. Understanding the limitations and variabilities of their equipment and the specific studies utilized should enable practitioners to standardize the approach for determining the extent of urethral dysfunction.