Pelvic organ prolapse and anal incontinence in women: screening with a validated epidemiology survey.

PURPOSE: The primary objective of this study was to determine the prevalence of pelvic organ prolapse (POP) and anal incontinence (AI) in a Minnesota population using the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ). The secondary objective of this study was to determine the association of POP and AI with parity, age, smoking status, body mass index (BMI), and co-morbidities. METHODS: Women ≥ 18 years old attending the 2018 Minnesota State Fair were asked to fill out a web-based version of the EPIQ. Multivariable logistic regression models were used to investigate the association of POP and AI with the variables of interest. RESULTS: A total of 1426 women were included in the analysis. There was a 4.9% prevalence of POP and 14.9% prevalence of AI. POP was significantly associated with parity and higher BMI (p < 0.01 and p = 0.02, respectively). In this cohort, POP was not associated with older age, smoking, or presence of co-morbid conditions. Anal incontinence was associated with older age (p < 0.01), smoking status (p = 0.01), and presence of co-morbid conditions (p = 0.01) but was not associated with parity or higher BMI. CONCLUSION: POP and AI were associated with some, but not all, of the variables tested, which differs from prior studies. In addition, the prevalence of POP and AI were different than rates reported in similar studies. This may suggest regional differences in prevalence of POP and AI.

Abiraterone acetate in combination with androgen deprivation therapy compared to androgen deprivation therapy only for metastatic hormone-sensitive prostate cancer.

BACKGROUND: Systemic androgen deprivation therapy (ADT), also referred to as hormone therapy,àhas long been the primary treatment for metastatic prostate cancer. Additional agents have been reserved for the castrate-resistant disease stage when ADT start becoming less effective. Abiraterone is an agent with an established role in that disease stage, which has only recently been evaluated in the hormone-sensitive setting. OBJECTIVES: To assess the effects of early abiraterone acetate, in combination with systemic ADT, for newly diagnosed metastatic hormone-sensitive prostate cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, two trials registries, grey literature, and conference proceedings, up to 15 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized trials, in which men diagnosed with hormone-sensitive prostate cancer were administered abiraterone acetate and prednisolone with ADT or ADTàalone. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. MAIN RESULTS: The search identified two randomized controlled trials (RCT), with 2201 men, who were assigned to receive either abiraterone acetate 1000 mg once daily and low dose prednisone (5mg) in addition to ADT, or ADT alone. In the LATITUDE trial, the median age and range of men in the intervention group was 68 (38 to 89) years, and 67 (33 to 92) years in the control group. Nearly all of the men in thisàstudy (97.6%) had prostate cancer with a Gleason score of at least 8 (ISUP grade group 4). Primary outcomes The addition of abiraterone acetate to ADT reduces the probability of death from any cause compared to ADT alone (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56 to 0.73; 2 RCTs, 2201 men; high certainty of evidence); this corresponds to 163 fewer deaths per 1000 men with hormone-sensitive metastaticàprostate cancerà(210 fewer to 115 fewer) at five years. Abiraterone acetate in addition to ADT probably results in little to no differenceàin quality of life compared to ADT alone, measured with the Functional Assessment of Cancer Therapy-prostate total score (FACT-P; range 0 to 156; higher values indicates better quality of life),àat 12 months (mean difference [MD] 2.90 points, 95% CI 0.11 to 5.60; 1 RCT, 838 men; moderate certainty of evidence). Secondary outcomes Abiraterone plus ADT increases the risk of grades III to V adverse events compared to ADT alone (risk ratio [RR] 1.34, 95% CI 1.22 to 1.47; 1 RCT, 1199 men; high certainty of evidence); this corresponds to 162 more grade III to Vàevents per 1000 men with hormone-sensitive metastaticàprostate cancerà(105 more to 224 more) at a median follow-up of 30àmonths. Abiraterone acetate in addition to ADT probably reduces the probability of death due to prostate cancer compared to ADT alone (HR 0.58, 95% CI 0.50 to 0.68; 2 RCTs, 2201 men; moderate certainty of evidence). This corresponds to 120 fewer death from prostate cancer per 1000 men with hormone-sensitive metastaticàprostate cancerà(95% CI 145 fewer to 90 fewer) afteràa median follow-up of 30 months. The addition of abiraterone acetate to ADT probably decreases the probability of disease progression compared to ADT alone (HR 0.35, 95%CI 0.26 to 0.49; 2 RCTs, 2097 men; moderate certainty of evidence). This corresponds to 369 fewer incidences of disease progression per 1000 men with hormone-sensitive metastaticàprostate cancerà(456 fewer to 256 fewer)àafter a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably increases the risk of discontinuing treatment due to adverse events compared to ADT alone (RR 1.50, 95% CI 1.17 to 1.92; 1 RCT, 1199 men; moderate certainty of evidence). This corresponds to 51 more men (95% CI 17 more to 93 more) discontinuing treatment because of adverse events per 1000 men treated with abiraterone acetate and ADT compared to ADT alone afteràa median follow-up of 30 months. AUTHORS' CONCLUSIONS: The addition of abiraterone acetate to androgen deprivation therapy improves overall survival but probably not quality of life. Itàprobably also extends disease-specific survival, and delays disease progression compared to androgen deprivation therapy alone. However, the risk of grades III to V adverse events is increased, and probably, so is the risk of discontinuing treatment due to adverse events.

Alpha-blockers after shock wave lithotripsy for renal or ureteral stones in adults.

BACKGROUND: Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously down the ureter and into the bladder. Alpha-blockers may assist in promoting the passage of stone fragments, but their effectiveness remains uncertain.  OBJECTIVES: To assess the effects of alpha-blockers as adjuvant medical expulsive therapy plus usual care compared to placebo and usual care or usual care alone in adults undergoing shock wave lithotripsy for renal or ureteral stones. SEARCH METHODS: We performed a comprehensive literature search of the Cochrane Library, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, several clinical trial registries and grey literature for published and unpublished studies irrespective of language. The date of the most recent search was 27 February 2020. SELECTION CRITERIA: We included randomized controlled trials of adults undergoing SWL. Participants in the intervention group had to have received an alpha-blocker as adjuvant medical expulsive therapy plus usual care. For the comparator group, we considered studies in which participants received placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion/exclusion, and performed data abstraction and risk of bias assessment. We conducted meta-analysis for the identified dichotomous and continuous outcomes using RevManWeb according to Cochrane methods using a random-effects model. We judged the certainty of evidence on a per outcome basis using GRADE. MAIN RESULTS: We included 40 studies with 4793 participants randomized to usual care and an alpha-blocker versus usual care alone. Only four studies were placebo controlled. The mean age of participants was 28.6 to 56.8 years and the mean stone size prior to SWL was 7.1 mm to 13.2 mm. The most widely used alpha-blocker was tamsulosin; others were silodosin, doxazosin, terazosin and alfuzosin.  Alpha-blockers may improve clearance of stone fragments after SWL (risk ratio (RR) 1.16, 95% confidence interval (CI) 1.09 to 1.23; I² = 78%; studies = 36; participants = 4084; low certainty evidence). Based on the stone clearance rate of 69.3% observed in the control arm, an alpha-blocker may increase stone clearance to 80.4%. This corresponds to 111 more (62 more to 159 more) participants per 1000 clearing their stone fragments. Alpha-blockers may reduce the need for auxiliary treatments after SWL (RR 0.67, 95% CI 0.45 to 1.00; I² = 16%; studies = 12; participants = 1251; low certainty evidence), but also includes the possibility of no effect. Based on a rate of auxiliary treatments in the usual care arm of 9.7%, alpha-blockers may reduce the rate to 6.5%. This corresponds 32 fewer (53 fewer to 0 fewer) participants per 1000 undergoing auxiliary treatments. Alpha-blockers may reduce major adverse events (RR 0.60, 95% CI 0.46 to 0.80; I² = 0%; studies = 7; participants = 747; low certainty evidence). Major adverse events occurred in 25.8% of participants in the usual care group; alpha-blockers would reduce this to 15.5%. This corresponds to 103 fewer (139 fewer to 52 fewer) major adverse events per 1000 with alpha-blocker treatment. None of the reported major adverse events appeared drug-related; most were emergency room visits or rehospitalizations. Alpha-blockers may reduce stone clearance time in days (mean difference (MD) -3.74, 95% CI -5.25 to -2.23; I² = 86%; studies = 14; participants = 1790; low certainty evidence). We found no evidence for the outcome of quality of life. For those outcomes for which we were able to perform subgroup analyses, we found no evidence of interaction with stone location, stone size or type of alpha-blocker. We were unable to conduct an analysis by lithotripter type. The results were also largely unchanged when the analyses were limited to placebo controlled studies and those in which participants explicitly only received a single SWL session. AUTHORS' CONCLUSIONS: Based on low certainty evidence, adjuvant alpha-blocker therapy following SWL in addition to usual care may result in improved stone clearance, less need for auxiliary treatments, fewer major adverse events and a reduced stone clearance time compared to usual care alone. We did not find evidence for quality of life. The low certainty of evidence means that our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Health Care Provider Adherence to Surgical Guidelines for Risk-Reducing Salpingo-Oophorectomy.

OBJECTIVE: To evaluate health care provider adherence to the surgical protocol endorsed by the National Comprehensive Cancer Network and the American College of Obstetricians and Gynecologists at the time of risk-reducing salpingo-oophorectomy and compare adherence between gynecologic oncologists and obstetrician-gynecologists (ob-gyns). METHODS: In this multicenter retrospective cohort study, women were included if they had a pathogenic BRCA mutation and underwent risk-reducing salpingo-oophorectomy between 2011 and 2017. Adherence was defined as completing all of the following: collection of washings, complete resection of the fallopian tube, and performing the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) pathologic protocol. RESULTS: Of 290 patients who met inclusion criteria, 160 patients were treated by 18 gynecologic oncologists and 130 patients by 75 ob-gyns. Surgery was performed at 10 different hospitals throughout a single metropolitan area. Demographic and clinical characteristics were similar between groups. Overall, 199 cases (69%) were adherent to the surgical protocol. Gynecologic oncologists were more than twice as likely to fully adhere to the full surgical protocol as ob-gyns (91% vs 41%, P<.01). Specifically, gynecologic oncologists were more likely to resect the entire tube (99% vs 95%, P=.03), to have followed the SEE-FIM protocol (98% vs 82%, P<.01), and collect washings (94% vs 49%, P<.01). Complication rates did not differ between groups. Occult neoplasia was diagnosed in 11 patients (3.8%). The incidence of occult neoplasia was 6.3% in gynecologic oncology patients and 0.8% in obstetrics and gynecology patients (P=.03). CONCLUSION: Despite clear surgical guidelines, only two thirds of all health care providers were fully adherent to guidelines. Gynecologic oncologists were more likely to follow surgical guidelines compared with general ob-gyns and more likely to diagnose occult neoplasia despite similar patient populations. Rates of risk-reducing surgery will likely continue to increase as genetic testing becomes more widespread, highlighting the importance of health care provider education for this procedure. Centralized care or referral to subspecialists for risk-reducing salpingo-oophorectomy may be warranted.

A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection.

BACKGROUND: Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1-/HSV2-), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2-). Sixty participants received vaccine or placebo at 0, 1, and 6 months. The primary end point was the frequency of solicited local and systemic reactions to vaccination. RESULTS: Eighty-nine percent of vaccinees experienced mild-to-moderate solicited injection site reactions, compared with 47% of placebo recipients (95% confidence interval [CI], 12.9%-67.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, -17.9% to 40.2%; P = .44). Seventy-eight percent of HSV1-/HSV2- vaccine recipients had a ≥4-fold increase in neutralizing antibody titer after 3 doses of vaccine, whereas none of the participants in the other serogroups had such responses. HSV2-specific CD4+ T-cell responses were detected in 36%, 46%, and 27% of HSV1-/HSV2-, HSV1±/HSV2+, and HSV1+/HSV2- participants, respectively, 1 month after the third dose of vaccine, and CD8+ T-cell responses were detected in 14%, 8%, and 18% of participants, respectively. CONCLUSIONS: HSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees. CLINICAL TRIALS REGISTRATION: NCT01915212.