Cost Effectiveness of Additional Preoperative Telephone Call to Increase Surgical Preparedness: Analysis of a Randomized Clinical Trial.

INTRODUCTION AND HYPOTHESIS: There is a need for cost effective interventions that increase surgical preparedness in urogynecology. METHODS: We performed an ancillary prospective economic evaluation of the Telehealth Intervention to Increase Patient Preparedness for Surgery (TIPPS) Trial, a randomized multicenter trial that evaluated the impact of a preoperative telehealth call on surgical preparedness in women undergoing urogynecologic surgery. A within-trial analysis from the health care sector and societal perspective was performed. Cost-effectiveness was computed from health care sector and societal perspectives, with an 8-week time horizon. RESULTS: A total of 126 women were included in our analysis. QALYs gained were similar between groups (telehealth 0.1414 + 0.0249; usual care 0.1409 + 0.0179). The cumulative mean per-person costs at 8 weeks from the healthcare sector perspective were telehealth call: $8696 +/- 3341; usual care: $8473 +/- 3118 (p = 0.693) and from the societal perspective were telehealth call: $11,195 + 5191; usual care: $11,213 +/- 4869 (p = 0.944). The preoperative telehealth call intervention was not cost effective from the health care sector perspective with an ICER of $460,091/QALY (95%CI -$7,382,608/QALY, $7,673,961) using the generally accepted maximum willingness to pay threshold of $150,000/QALY (Neumann et al. N Engl J Med. 371(9):796-7, 2014). From the societal perspective, because incremental costs per QALY gained were negative $-35,925/QALY (95%CI, -$382,978/QALY, $317,226), results suggest that preoperative telehealth call dominated usual care. CONCLUSIONS: A preoperative telehealth call is cost effective from the society perspective. CLINICAL TRIAL REGISTRATION: Registered with http://ClinicalTrials.gov . Date of registration: March 26, 2019 Date of initial participant enrollment: June 5, 2019 URL: https://clinicaltrials.gov/ct2/show/record/NCT03890471 Clinical trial identification number: NCT03890471.

Validation of the Surgical Preparedness Assessment in women with pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: We sought to further develop and validate the Surgical Preparedness Assessment (SPA) scale to evaluate patient preparedness for urogynecological surgery. METHODS: This was a planned ancillary analysis of a randomized controlled trial (RCT) evaluating the impact of a preoperative telehealth call on patient preparedness for urogynecological surgery. Patients completed the Preoperative Preparedness Questionnaire (PPQ), the modified Preparedness for Colorectal Cancer Surgery Questionnaire (PCSQ), the Pelvic Floor Distress Inventory (PFDI-20), the Satisfaction Decision Scale (SDS), and the Decision Regret Scale (DRS). Content validity was established through expert opinion and patient cognitive interviews. Factor analysis identified item grouping into domains. Cronbach's alpha reported internal consistency. Known group validity was assessed by comparing intervention arms. External validity was evaluated by comparing intervention arms and correlations with SDS and DRS. RESULTS: Eleven items and 3 domains met the criteria (information needs, satisfaction and pain, and catheterization). Cronbach's alpha values were acceptable for domains and ranged from 0.74 to 0.93. SPA scores did not correlate with other patient-reported outcomes. Mean SPA scores were lower among women who received a telehealth call vs those who did not (1.30 ± 0.31 vs 1.51 ± 0.44; p = 0.002). CONCLUSIONS: The content-valid SPA demonstrates high internal consistency and known group validity.

An evidence-based microscopic hematuria care pathway optimizes decision-making among providers.

INTRODUCTION AND HYPOTHESIS: Microscopic hematuria (MH) has many etiologies in women and requires specific gynecologic evaluation. We created a standardized MH pathway to serve as an evidence-based decision aid for providers in our practice. METHODS: Using a modified Delphi process, a multidisciplinary team reviewed existing guidelines for MH diagnosis and treatment to reach consensus on care pathway components. RESULTS: Entry into the care pathway by an advanced practice provider is determined by the finding of ≥3 red blood cells per high-power field (RBC/HPF) on microscopic urinalysis. Initial evaluation includes history and physical exam. If there are signs of a gynecologic cause of MH, the conditions are treated and repeat urinalysis is performed in 6 months. If repeat urinalysis shows persistent MH or there are no other apparent causes for MH, we proceed with risk stratification. Through shared decision-making, low-risk patients may undergo repeat urinalysis in 6 months or cystoscopy with urinary tract ultrasound. For intermediate-risk patients, cystoscopy and urinary tract ultrasound are recommended. For high-risk patients, cystoscopy and axial upper urinary tract imaging are recommended. If evaluation is positive, urology referral is provided. If evaluation is negative, low-risk patients are released from care, but intermediate-risk or high-risk patients undergo repeat urinalysis in 12 months. If repeat urinalysis is positive, shared decision-making is used to determine a plan. CONCLUSIONS: We developed an MH care pathway to standardize care of women with MH across a multidisciplinary group. This pathway serves as a component of value-based care and supports evidence-based care by providers.

Functional characterization of a PROTAC directed against BRAF mutant V600E.

The RAF family kinases function in the RAS-ERK pathway to transmit signals from activated RAS to the downstream kinases MEK and ERK. This pathway regulates cell proliferation, differentiation and survival, enabling mutations in RAS and RAF to act as potent drivers of human cancers. Drugs targeting the prevalent oncogenic mutant BRAF(V600E) have shown great efficacy in the clinic, but long-term effectiveness is limited by resistance mechanisms that often exploit the dimerization-dependent process by which RAF kinases are activated. Here, we investigated a proteolysis-targeting chimera (PROTAC) approach to BRAF inhibition. The most effective PROTAC, termed P4B, displayed superior specificity and inhibitory properties relative to non-PROTAC controls in BRAF(V600E) cell lines. In addition, P4B displayed utility in cell lines harboring alternative BRAF mutations that impart resistance to conventional BRAF inhibitors. This work provides a proof of concept for a substitute to conventional chemical inhibition to therapeutically constrain oncogenic BRAF.

Evidence-based pelvic floor disorder care pathways optimize shared decision making between patients and surgeons.

INTRODUCTION AND HYPOTHESIS: Evidence-based care pathways improve care standardization and patient outcomes. We created pelvic organ prolapse (POP) and stress urinary incontinence (SUI) care pathways as decision aids for our multidisciplinary team to use when counseling patients. METHODS: Using a modified Delphi process, an expert team reviewed existing guidelines and literature to reach consensus on pathway definitions and components. RESULTS: Entry to the care pathways occurs via an advanced practice provider visit. Symptom and quality-of-life questionnaires as well as open-ended patient goals are used to guide patient-provider shared decision making. All treatment choices, including surgical and nonsurgical management, are presented to patients by advanced practice providers. Patients electing nonsurgical management follow-up by telehealth (preferred) or in-person visits as determined by the care pathway. Surgeon consultations are scheduled for patients desiring surgery. Surgical patients undergo urodynamics, simple cystometrics or deferred bladder testing according to the urodynamics clinical pathway. Postoperative follow-up includes telehealth visits and minimizes in-person visits for women with uncomplicated postoperative courses. Patients with resolution of symptoms are graduated from clinic and return to their referring physician. The pathways are revised following publication of new compelling evidence. CONCLUSIONS: We developed POP and SUI care pathways to standardize care across a diverse provider group. Advanced practice providers use care pathways with patients as shared decision-making tools for initial evaluation of patients with prolapse and incontinence. These pathways serve as components of value-based care and encourage team members to function independently while utilizing the full scope of their training.

A telehealth intervention to increase patient preparedness for surgery: a randomized trial.

INTRODUCTION AND HYPOTHESIS: Methods to increase surgical preparedness in urogynecology are lacking. Our objective was to evaluate the impact of a preoperative provider-initiated telehealth call on surgical preparedness. METHODS: This was a multicenter randomized controlled trial. Women undergoing surgery for pelvic organ prolapse and/or stress urinary incontinence were randomized to either a telehealth call 3 (± 2) days before surgery plus usual preoperative counseling versus usual preoperative counseling alone. Our primary outcome was surgical preparedness, as measured by the Preoperative Prepardeness Questionnaire. The Modified Surgical Pain Scale, Pelvic Floor Distress Inventory-20, Patient Global Impressions of Improvement, Patient Global Impressions of Severity, Satisfaction with Decision Scale, Decision Regret Scale, and Clavien-Dindo scores were obtained at 4-8 weeks postoperatively and comparisons were made between groups. RESULTS: Mean telehealth call time was 11.1 ± 4.11 min. Women who received a preoperative telehealth call (n = 63) were significantly more prepared for surgery than those who received usual preoperative counseling alone (n = 69); 82.5 vs 59.4%, p < 0.01). A preoperative telehealth call was associated with greater understanding of surgical alternatives (77.8 vs 59.4%, p = 0.03), complications (69.8 vs 47.8%, p = 0.01), hospital-based catheter care (54 vs 34.8%, p = 0.04) and patient perception that nurses and doctors had spent enough time preparing them for their upcoming surgery (84.1 vs 60.9%, p < 0.01). At 4-8 weeks, no differences in postoperative and patient reported outcomes were observed between groups (all p > 0.05). CONCLUSIONS: A short preoperative telehealth call improves patient preparedness for urogynecological surgery.

Patient-defined goals for the treatment of fecal incontinence: a qualitative analysis among women attending a urogynecology clinic.

INTRODUCTION AND HYPOTHESIS: Fecal incontinence treatment goals are understudied and are not described for women presenting to care. Our objective was to explore patient-reported goals for fecal incontinence management among women presenting for care at a pelvic floor disorders clinic and develop a conceptual framework that captures the range of desired treatment outcomes. METHODS: A qualitative analysis of patient-reported goals for women with fecal incontinence attending a pelvic floor disorders clinic from October 2017-November 2019 was conducted. A team-based approach was used to identify themes and emerging concepts and develop a conceptual framework. RESULTS: One hundred patients met the inclusion criteria. Mean age was 58 ± 14 years; 67% were White and 46% non-Hispanic. Seventy-nine percent of women had diagnosis(es) of prolapse, urinary complaints, or another pelvic floor disorder. From 230 unique goals identified, five thematic categories emerged: Emotional Status, Functional Status, Concurrent Pelvic Floor Disorders, Care Seeking, and Treatment Aspirations. Thematic domains not previously represented in other qualitative work include patients' focus on treatment for global pelvic health rather than solely on fecal incontinence and treatment aspirations ranging from improvement to cure. Our model captures the close relationship between all pelvic floor disorders and emotion, which in return affects all facets of care. CONCLUSIONS: Women with fecal incontinence report a range of treatment goals from improvement to complete resolution of symptoms. Focusing treatment on patient goals by addressing global pelvic health and negotiating realistic treatment outcomes may improve care in this population.

Law Accommodating Nonmotorized Road Users and Pedestrian Fatalities in Florida, 1975 to 2013.

OBJECTIVES: To examine the effect of Florida's adoption of Statute 335.065-a law requiring the routine accommodation of nonmotorized road users (i.e., a "Complete Streets" policy)-on pedestrian fatalities and to identify factors influencing its implementation. METHODS: We used a multimethod design (interrupted time-series quasi-experiment and interviews) to calculate Florida's pedestrian fatality rates from 1975 to 2013-39 quarters before and 117 quarters after adoption of the law. Using statistical models, we compared Florida with regional and national comparison groups. Semistructured interviews were conducted with 10 current and former Florida transportation professionals in 2015. RESULTS: Florida's pedestrian fatality rates decreased significantly-by at least 0.500% more each quarter-after Statute 335.065 was adopted, resulting in more than 3500 lives saved across 29 years. Interviewees described supports and challenges associated with implementing the law. CONCLUSIONS: Florida Statute 335.065 is associated with a 3-decade decrease in pedestrian fatalities. The study also reveals factors that influenced the implementation and effectiveness of the law. Public Health Implications. Transportation policies-particularly Complete Streets policies-can have significant, quantifiable impacts on population health. Multimethod designs are valuable approaches to policy evaluations.

Caregivers' experience of the decision-making process for placing a person with dementia into a nursing home: comparing caregivers from Chinese ethnic minority with those from English-speaking backgrounds.

BACKGROUND: The experience of care transitions for people with dementia from ethnic minority groups has been poorly researched. Few studies have examined the decision to put someone on a waiting list for a nursing home and then actually accept a place. Many nursing homes have long waiting lists, but sometimes offers of a place are declined. Our aims were to investigate the decision-making process for placing a person with dementia on a waiting list for a nursing home, why offers of a place are accepted or declined, and the influence of cultural factors, comparing caregivers from Chinese and English-speaking backgrounds. METHODS: Semi-structured interviews with 27 caregivers of people with dementia on waiting lists or living in nursing homes (20 Chinese background and seven English-speaking background) were conducted, with thematic analysis of factors affecting caregivers' decision-making. RESULTS: Caregivers were at different stages of decision-making when they applied for a waiting list - some were ready for placement, others applied "just in case," and for some there was no waiting time because of an urgent need for placement. Caregivers' decisions were influenced by their emotions and expectations of nursing homes. The decision-making process was similar for both cultural groups, but Chinese caregivers spoke more about their sense of duty, the need for a Chinese specific facility, and declining a place because of family disagreement. CONCLUSIONS: Understanding cultural issues, including stereotypes and concerns about nursing homes, and providing better information about admission processes may help caregivers by allaying their anxiety about nursing home placement.

Comparison of Low Dose Recombinant Factor VIIa and 4-Factor Prothrombin Complex Concentrate for Treatment of Bleeding Related to Cardiac Surgery.

Background: Recombinant factor VIIa (rFVIIa) and prothrombin concentrate complex (PCC) are used for uncontrolled bleeding in cardiac surgery (CS), however, there are limited direct comparisons of these agents. Objective: To evaluate the efficacy and safety of rFVIIa and PCC in CS related bleeding. Methods: This retrospective study included adult CS patients who received either low dose rFVIIa (<30 mcg/kg) or 4-factor PCC. The primary outcome was transfusion requirements of packed red blood cells (pRBC) within 6 hours of factor administration. Secondary efficacy outcomes included transfusion requirements 0-18 hours, doses of additional factor product, thrombotic events, and acute kidney injury (AKI). Results: A total of 179 patients were included (n = 78 rFVIIa; n = 101 PCC). Of patients who received blood products, there was no difference in the requirement of pRBCs within 6 hours (73.8 vs 68.9%, P = .5359) or in the median amount of pRBC transfused (500 mL vs 640 mL, P = .0723) in the rFVIIa and PCC groups respectively. Patients in the PCC group were more likely to require additional factor products (24.4% vs 47.5%, P = .0015), develop AKI (12.8% vs 25.7%, P = .0325), have longer ICU lengths of stay [2 (IQR 1-5) vs 4 (IQR 2-6), P = .0487] and greater in-hospital mortality (2.6% vs 10.9%, P = .033). There was no difference in thrombotic events. Conclusion: Although, there was no difference in pRBC transfusion requirements between PCC and rFVIIa, more patients in the PCC group required additional factor products and had increased adverse effects. Further comparisons of PCC and rFVIIa are warranted.

Vesicovaginal Fistula Repair Simulation Model and Hierarchical Task Analysis.

IMPORTANCE: There is a need for surgeons skilled in vesicovaginal fistula (VVF) repair, yet training opportunities are limited. OBJECTIVES: This study aimed to create a low-fidelity simulation model for transvaginal VVF repair, identify essential steps of VVF repair, and evaluate the model's ability to replicate essential steps. STUDY DESIGN: First, a low-fidelity VVF repair simulation model was designed and built by the authors. Next, a hierarchical task analysis was performed by urogynecologic surgeons with expertise in VVF repair. Each expert submitted an outline of tasks required to perform VVF repair. To control for bias, an education specialist de-identified, reviewed, and collated the submitted outlines. The education specialist then led a focus group, and through a modified Delphi process, the experts reached consensus on the essential steps. A separate group of urogynecologic surgeons then tested the model and completed an anonymous questionnaire assessing how well the model replicated the essential steps. Descriptive analyses were performed. RESULTS: Five experts submitted an outline of steps for transvaginal VVF repair, and 4 experts participated in a focus group to reach consensus on the essential steps. Nine urogynecologic surgeons, with a median of 10 years in practice (interquartile range, 7-12 years), tested the model and completed the postsimulation questionnaire. Most testers thought that tasks involving identification and closure of the fistula were replicated by the model. Testers thought that tasks involving cystoscopy or bladder filling were not replicated by the model. CONCLUSIONS: We developed a novel, low-fidelity transvaginal VVF repair simulation model that consistently replicated tasks involving identification and closure of the fistula.

The Impact of Language Discordance on Patients' Perception of a Clinical Encounter and Trust in Provider.

IMPORTANCE: The impact of language discordance on care for Spanish-speaking patients with pelvic floor disorders is unknown. OBJECTIVE: The aim of this study was to compare the impact of language concordance with the impact of language discordance on the patient experience and trust in their provider. METHODS: This cross-sectional cohort study enrolled English- and Spanish-speaking patients during initial evaluation in a urogynecology clinic. English- and Spanish-speaking patients seen by native English- or Spanish-speaking providers were recruited to the language-concordant group. The language-discordant group included Spanish-speaking patients seen with a translator or by nonnative Spanish-speaking providers. Patients completed the Trust in Physician Scale and the Consumer Assessment of Healthcare Providers and Systems Clinician and Group Survey (CG-CAHPS). Patients and providers rated the provider's Spanish proficiency on a 10-point scale from 0 (low) to 10 (high). Symptom bother questionnaires were completed 4-6 months after enrollment. RESULTS: Eighty women were recruited, with 40 in each group. Mean age was 55.4 ± 12.9 years. The majority identified as White (75%) and Hispanic (77.5%). Trust in Physician Scale scores were similar between groups (46.2 ± 8.5 vs 44.4 ± 7.5, P > 0.05). The provider communication, provider rating, and recommendation domains of the CG-CAHPS did not differ between groups (all P > 0.05). Provider self-rating of Spanish proficiency was lower than patient ratings (7.5 ± 1.8 vs 9.8 ± 0.5, P < 0.001). There was no difference between groups in symptom bother at 4-6 months (all P > 0.05). CONCLUSIONS: Patient-provider language discordance does not affect patient trust in the provider or perception of the encounter as measured by the Trust in Physician Scale and CG-CAHPS questionnaires.

Surgeon Counseling Regarding Return to Sexual Activity After Pelvic Reconstructive Surgery.

IMPORTANCE: Patients highly value surgeon counseling regarding the first sexual encounters after pelvic reconstructive surgery. OBJECTIVES: We performed a qualitative analysis of usual surgeon counseling regarding return to sexual activity after surgery for pelvic organ prolapse and/or urinary incontinence. METHODS: Participating surgeons provided a written description of their usual patient counseling regarding return to sexual activity after pelvic organ prolapse or urinary incontinence surgery. Counseling narratives were coded for major themes by 2 independent reviewers; disagreements were arbitrated by the research team. Analysis was performed utilizing Dedoose software and continued until thematic saturation was reached. RESULTS: Twenty-two surgeons participated, and thematic saturation was reached. Six major themes were identified: "Safety of Intercourse," "Specific Suggestions," "Surgical Sequelae," "Patient Control," "Partner Related," "Changes in Experience," and "No Communication." Nearly all participating surgeons included counseling on the safety of intercourse and reassurance that intercourse would not harm the surgical repair. Specific suggestions included different positions, use of lubrication, vaginal estrogen use, specific products/vendors, alternatives to (vaginal) intercourse, and the importance of foreplay. Surgical sequelae discussion included possible interventions for complications, such as persistent sutures in the vagina, abnormal bleeding, or de novo dyspareunia. Counseling regarding changes to the patient's sexual experience ranged from suggestion of improvement to an anticipated negative experience. Surgeons more commonly advised patients that their sexual experience would be worsened or different from baseline; discussion of improvement was less frequent. CONCLUSIONS: Surgeon counseling regarding the postoperative return to sexual activity varies among pelvic reconstructive surgeons. Most reassure patients that intercourse is safe after surgery.

Myofibroblast YAP/TAZ activation is a key step in organ fibrogenesis.

Fibrotic diseases account for nearly half of all deaths in the developed world. Despite its importance, the pathogenesis of fibrosis remains poorly understood. Recently, the two mechanosensitive transcription cofactors YAP and TAZ have emerged as important profibrotic regulators in multiple murine tissues. Despite this growing recognition, a number of important questions remain unanswered, including which cell types require YAP/TAZ activation for fibrosis to occur and the time course of this activation. Here, we present a detailed analysis of the role that myofibroblast YAP and TAZ play in organ fibrosis and the kinetics of their activation. Using analyses of cells, as well as multiple murine and human tissues, we demonstrated that myofibroblast YAP and TAZ were activated early after organ injury and that this activation was sustained. We further demonstrated the critical importance of myofibroblast YAP/TAZ in driving progressive scarring in the kidney, lung, and liver, using multiple transgenic models in which YAP and TAZ were either deleted or hyperactivated. Taken together, these data establish the importance of early injury-induced myofibroblast YAP and TAZ activation as a key event driving fibrosis in multiple organs. This information should help guide the development of new antifibrotic YAP/TAZ inhibition strategies.

NUAK1 promotes organ fibrosis via YAP and TGF-ß/SMAD signaling.

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor-ß (TGF-ß)-driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear. Here, we describe NUAK family kinase 1 (NUAK1) as a TGF-ß-inducible profibrotic kinase that is up-regulated in multiple fibrotic organs in mice and humans. Mechanistically, we show that TGF-ß induces a rapid increase in NUAK1 in fibroblasts. NUAK1, in turn, can promote profibrotic YAP and TGF-ß/SMAD signaling, ultimately leading to organ scarring. Moreover, activated YAP and TAZ can induce further NUAK1 expression, creating a profibrotic positive feedback loop that enables persistent fibrosis. Using mouse models of kidney, lung, and liver fibrosis, we demonstrate that this fibrogenic signaling loop can be interrupted via fibroblast-specific loss of NUAK1 expression, leading to marked attenuation of fibrosis. Pharmacologic NUAK1 inhibition also reduced scarring, either when initiated immediately after injury or when initiated after fibrosis was already established. Together, our data suggest that NUAK1 plays a critical, previously unrecognized role in fibrogenesis and represents an attractive target for strategies that aim to slow fibrotic disease progression.

Assessment of SARS-CoV-2 Seropositivity During the First and Second Viral Waves in 2020 and 2021 Among Canadian Adults.

Importance: The incidence of infection during SARS-CoV-2 viral waves, the factors associated with infection, and the durability of antibody responses to infection among Canadian adults remain undocumented. Objective: To assess the cumulative incidence of SARS-CoV-2 infection during the first 2 viral waves in Canada by measuring seropositivity among adults. Design, Setting, and Participants: The Action to Beat Coronavirus study conducted 2 rounds of an online survey about COVID-19 experience and analyzed immunoglobulin G levels based on participant-collected dried blood spots (DBS) to assess the cumulative incidence of SARS-CoV-2 infection during the first and second viral waves in Canada. A sample of 19 994 Canadian adults (aged ≥18 years) was recruited from established members of the Angus Reid Forum, a public polling organization. The study comprised 2 phases (phase 1 from May 1 to September 30, 2020, and phase 2 from December 1, 2020, to March 31, 2021) that generally corresponded to the first (April 1 to July 31, 2020) and second (October 1, 2020, to March 1, 2021) viral waves. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G seropositivity (using a chemiluminescence assay) by major geographic and demographic variables and correlation with COVID-19 symptom reporting. Results: Among 19 994 adults who completed the online questionnaire in phase 1, the mean (SD) age was 50.9 (15.4) years, and 10 522 participants (51.9%) were female; 2948 participants (14.5%) had self-identified racial and ethnic minority group status, and 1578 participants (8.2%) were self-identified Indigenous Canadians. Among participants in phase 1, 8967 had DBS testing. In phase 2, 14 621 adults completed online questionnaires, and 7102 of those had DBS testing. Of 19 994 adults who completed the online survey in phase 1, fewer had an educational level of some college or less (4747 individuals [33.1%]) compared with the general population in Canada (45.0%). Survey respondents were otherwise representative of the general population, including in prevalence of known risk factors associated with SARS-CoV-2 infection. The cumulative incidence of SARS-CoV-2 infection among unvaccinated adults increased from 1.9% in phase 1 to 6.5% in phase 2. The seropositivity pattern was demographically and geographically heterogeneous during phase 1 but more homogeneous by phase 2 (with a cumulative incidence ranging from 6.4% to 7.0% in most regions). The exception was the Atlantic region, in which cumulative incidence reached only 3.3% (odds ratio [OR] vs Ontario, 0.46; 95% CI, 0.21-1.02). A total of 47 of 188 adults (25.3%) reporting COVID-19 symptoms during phase 2 were seropositive, and the OR of seropositivity for COVID-19 symptoms was 6.15 (95% CI, 2.02-18.69). In phase 2, 94 of 444 seropositive adults (22.2%) reported having no symptoms. Of 134 seropositive adults in phase 1 who were retested in phase 2, 111 individuals (81.8%) remained seropositive. Participants who had a history of diabetes (OR, 0.58; 95% CI, 0.38-0.90) had lower odds of having detectable antibodies in phase 2. Conclusions and Relevance: The Action to Beat Coronavirus study found that the incidence of SARS-CoV-2 infection in Canada was modest until March 2021, and this incidence was lower than the levels of population immunity required to substantially reduce transmission of the virus. Ongoing vaccination efforts remain central to reducing viral transmission and mortality. Assessment of future infection-induced and vaccine-induced immunity is practicable through the use of serial online surveys and participant-collected DBS.

Stress Urinary Incontinence: Slings, Single-Incision Slings, and Nonmesh Approaches.

Synthetic midurethral slings offer optimal cure rates for the minimally invasive treatment of stress urinary incontinence in women. Performed via a retropubic or transobturator technique, midurethral sling approaches demonstrate comparable efficacy, with unique adverse event profiles. Single incision slings were introduced to minimize the complication of groin pain with full-length transobturator slings and enhance operative recovery. The earliest therapies for stress urinary incontinence including urethral bulking, retropubic colposuspension, and autologous sling offer alternative methods of surgical management without using synthetic mesh. These methods boast satisfactory efficacy with low rates of complications, and may be ideal for appropriately selected patients.

Women's Experience of Their First Sexual Encounter After Pelvic Reconstructive Surgery.

OBJECTIVE: To describe the timing, quality and patient concerns regarding the first sexual encounter after surgery for pelvic organ prolapse (POP) or urinary incontinence (UI). METHODS: Women scheduled to undergo POP or UI surgery who self-identified as sexually active were recruited to this qualitative study. Routine counseling regarding the return to sexual activity was provided 4-6 weeks postoperatively. Participants completed interviews 2-4 months after their surgery. Interviews were tape recorded, de-identified, and transcribed. Transcriptions were coded for major themes by two independent researchers; disagreements were arbitrated by the research team. Analysis was performed using Dedoose software. RESULTS: Twenty patients with an average age of 52.4 years participated. Most identified themselves as White (85%), one quarter had a history of hysterectomy, and 15% had previously undergone pelvic reconstructive surgery. Nineteen (95%) patients resumed intercourse 2-4 months after surgery. Thematic saturation was reached with major themes of Outside Influences, Conflicting Emotions, Uncertainty, Sexual Changes and Stability, Normalization, and Self-Image. First sexual encounter timing was strongly influenced by partners' desires and fears and physician counseling. Fear of damage to repairs affected patients' comfort with return to sexual activity. Although uncertain of how anatomical changes or presence of mesh would affect function, women hoped that changes would be positive, regardless of preoperative sexual function. Some women found their experience unchanged, whereas others reported need for change in sexual position, use of lubrication, and sensation of foreign body. Positive changes included increase in desire, pleasure, and improvement in orgasm. Self-image generally improved after surgery, which increased women's sexual confidence. CONCLUSION: The return to sexual activity after surgery for POP or UI represents a great unknown for many women. Reports of initial sexual activity after surgery are often positive, and physicians strongly influence initial postoperative sexual encounter timing. Frank counseling about patient and partners' fears regarding the effect of repair on sexual activity would likely improve patients' outcomes.

Overexpression of the Severe Acute Respiratory Syndrome Coronavirus-2 Receptor, Angiotensin-Converting Enzyme 2, in Diabetic Kidney Disease: Implications for Kidney Injury in Novel Coronavirus Disease 2019.

OBJECTIVES: Diabetes is associated with adverse outcomes, including death, after coronavirus disease 19 (COVID-19) infection. Beyond the lungs, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, can infect a range of other tissues, including the kidney, potentially contributing to acute kidney injury in those with severe disease. We hypothesized that the renal abundance of angiotensin-converting enzyme (ACE) 2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS). METHODS: The expression of ACE 2 was examined in 49 archival kidney biopsies from patients with diabetic kidney disease and from 12 healthy, potential living allograft donors using next-generation sequencing technology (RNA Seq). RESULTS: Mean ACE 2 messenger RNA was increased approximately 2-fold in diabetes when compared with healthy control subjects (mean ± SD, 13.2±7.9 vs 7.7±3.6 reads per million reads, respectively; p=0.001). No difference in transcript abundance was noted between recipients and nonrecipients of agents that block the RAAS (12.2±6.7 vs 16.2±10.7 reads per million reads, respectively; p=0.25). CONCLUSIONS: Increased ACE 2 messenger RNA in the diabetic kidney may increase the risk and/or severity of kidney infection with SARS-CoV-2 in the setting of COVID-19 disease. Further studies are needed to ascertain whether this diabetes-related overexpression is generalizable to other tissues, most notably the lungs.