Postoperative Prescribing Practices Following Gynecologic Surgery.

BACKGROUND: Opioids prescribed for postoperative pain have exceeded patient need in the United States, playing a significant role in the opioid epidemic. In the preintervention phase of this project (September 2018 - March 2019), a chart review and patient survey revealed that patients were prescribed double the number of opioids they consumed following gynecologic surgery. OBJECTIVE: To ascertain whether an educational intervention recommending opiate prescriptions based on postoperative opioid use decreases gynecologic surgeons' opiate prescriptions. METHODS: An educational intervention implemented in January 2021 communicated the discrepancy between patient need and medications prescribed and made prescribing recommendations for common gynecologic procedures. A postintervention (February 2021 - April 2021) retrospective chart review ascertained postoperative opioid prescribing practices. Residents were surveyed about their prescribing practices in June 2021. Descriptive statistics compared each phase. RESULTS: For laparoscopic hysterectomy, the median morphine milligram equivalent (MME) was 150 (IQR 112.5-166.9) for preintervention and 150 (IQR 112.5-150) postintervention. For vaginal hysterectomy, median MME declined from 150 (IQR 112.5-225) to 112.5 (IQR 112.5-150). For laparoscopic surgery without hysterectomy, the median MME was 75 for both preintervention (IQR 75-120) and postintervention (IQR 60-80). For vaginal surgery without hysterectomy median MME went from 75 (IQR 75-142.5) to 54 (IQR 22.5-112.5). Median MME for hysteroscopy and dilation and curettage was 0 for both phases. When surveyed, residents reported prescribing lower amounts than actual prescribing practices. CONCLUSIONS: Despite education informing gynecologic surgeons that their opioid prescribing exceeded patient need, prescribing practices did not change. The difference between actual and resident-reported prescribing practices warrants further investigation.

Evaluation and Management of Heavy Vaginal Bleeding (Noncancerous).

Heavy vaginal bleeding is a common, life-altering condition affecting around 30% of women at some point in their reproductive lives. Initial evaluation should focus on hemodynamic stability. A thorough history including the patient's menstrual cycle and personal and family bleeding history should be obtained. Causes are stratified using the structural and nonstructural International Federation of Gynecology and Obstetrics classification system. Further consideration of the patient's age is essential because this can help to narrow the differential diagnosis. Work-up includes laboratory and imaging studies. Treatment approach includes acute stabilization and long-term treatment with medical and surgical modalities.

Preventing erosion of X-chromosome inactivation in human embryonic stem cells.

X-chromosome inactivation is a paradigm of epigenetic transcriptional regulation. Female human embryonic stem cells (hESCs) often undergo erosion of X-inactivation upon prolonged culture. Here, we investigate the sources of X-inactivation instability by deriving new primed pluripotent hESC lines. We find that culture media composition dramatically influenced the expression of XIST lncRNA, a key regulator of X-inactivation. hESCs cultured in a defined xenofree medium stably maintained XIST RNA expression and coating, whereas hESCs cultured in the widely used mTeSR1 medium lost XIST RNA expression. We pinpointed lithium chloride in mTeSR1 as a cause of XIST RNA loss. The addition of lithium chloride or inhibitors of GSK-3 proteins that are targeted by lithium to the defined hESC culture medium impeded XIST RNA expression. GSK-3 inhibition in differentiating female mouse embryonic stem cells and epiblast stem cells also resulted in a loss of XIST RNA expression. Together, these data may reconcile observed variations in X-inactivation in hESCs and inform the faithful culture of pluripotent stem cells.

Professional Address during Obstetrics and Gynecology Grand Rounds Introductions: Setting the Stage, Setting the Standard.

OBJECTIVE: This study aimed to assess gender dynamics during Obstetrics and Gynecology (Ob/Gyn) Grand Rounds. DESIGN: This was an observational cohort study of Ob/Gyn Grand Rounds introductions at a large academic center. Ob/Gyn Grand Rounds introductions from December 2016 to February 2020 were included. Audio and video components of introductions for those with doctorate degrees were reviewed. Each named reference to the presenter and use of descriptors were collected. Statistical analyses included Fisher's exact test for categorical variables and Student's t-test for continuous variables. SETTING: This study was completed at the University of Wisconsin in the Department of Ob/Gyn PARTICIPANTS: Ob/Gyn Grand Rounds introducers who had complete audio and video components of introductions for those with doctorate degrees. RESULTS: Sixty-four Grand Rounds introductions were reviewed; 57 met inclusion criteria. The majority of introducers and presenters were women. Consistent use of "doctor" was similar by men and women introducers (50% vs. 29%, p = 0.427). Assistant professors were more likely to maintain professional address during introductions, compared to associate or full professors (86% vs. 0% vs. 10%, p < 0.001). Trainees were less likely than faculty to be addressed professionally at any time during introductions (42% vs. 81%, p = 0.017). Descriptors were used for men and women presenters, though men received more female-gendered descriptors than women (5 vs. 1, p = 0.011). Women introducers used productivity descriptors less often than men introducers (8 [15.1%] vs. 5 [55.6%] (p = 0.015)). CONCLUSIONS: Use of professional address was associated with academic rank, but not gender. Men endorsed and received more descriptors emphasizing accomplishments, highlighting qualifications as an expert. Given the professional environment, all Grand Rounds presenters should be introduced using professional titles.

Reasons Behind Preferences for Community-Based Continence Promotion.

OBJECTIVES: This study aimed to understand the potential reach of continence promotion intervention formats among incontinent women. METHODS: The Survey of the Health of Wisconsin conducts household interviews on a population-based sample. In 2016, 399 adult women were asked about incontinence and likelihood of participation in continence promotion via 3 formats: single lecture, interactive 3-session workshop, or online. Descriptive analyses compared women likely versus unlikely to participate in continence promotion. To understand format preferences, modified grounded theory was used to conduct and analyze telephone interviews. RESULTS: One hundred eighty-seven (76%) of 246 incontinent women reported being likely to attend continence promotion: 111 (45%) for a single lecture, 43 (17%) for an interactive 3-session workshop, and 156 (64%) for an online program. Obesity, older age, nonwhite race, prior health program participation, and Internet use for health information were associated with reported continence promotion participation. Cited advantages of a single lecture included convenience and ability to ask questions. A workshop offered accountability, hands-on learning, and opportunity to learn from others; online format offered privacy, convenience, and self-directed learning. CONCLUSIONS: Most incontinent women are willing to participate in continence promotion, especially online.

An Xist-activating antisense RNA required for X-chromosome inactivation.

The transcriptional imbalance due to the difference in the number of X chromosomes between male and female mammals is remedied through X-chromosome inactivation, the epigenetic transcriptional silencing of one of the two X chromosomes in females. The X-linked Xist long non-coding RNA functions as an X inactivation master regulator; Xist is selectively upregulated from the prospective inactive X chromosome and is required in cis for X inactivation. Here we discover an Xist antisense long non-coding RNA, XistAR (Xist Activating RNA), which is encoded within exon 1 of the mouse Xist gene and is transcribed only from the inactive X chromosome. Selective truncation of XistAR, while sparing the overlapping Xist RNA, leads to a deficiency in Xist RNA expression in cis during the initiation of X inactivation. Thus, the Xist gene carries within its coding sequence an antisense RNA that drives Xist expression.

A Primary Role for the Tsix lncRNA in Maintaining Random X-Chromosome Inactivation.

Differentiating pluripotent epiblast cells in eutherians undergo random X-inactivation, which equalizes X-linked gene expression between the sexes by silencing one of the two X-chromosomes in females. Tsix RNA is believed to orchestrate the initiation of X-inactivation, influencing the choice of which X remains active by preventing expression of the antisense Xist RNA, which is required to silence the inactive-X. Here we profile X-chromosome activity in Tsix-mutant (X(ΔTsix)) mouse embryonic epiblasts, epiblast stem cells, and embryonic stem cells. Unexpectedly, we find that Xist is stably repressed on the X(ΔTsix) in both sexes in undifferentiated epiblast cells in vivo and in vitro, resulting in stochastic X-inactivation in females despite Tsix-heterozygosity. Tsix is instead required to silence Xist on the active-X as epiblast cells differentiate in both males and females. Thus, Tsix is not required at the onset of random X-inactivation; instead, it protects the active-X from ectopic silencing once X-inactivation has commenced.

Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation.

Imprinted X-inactivation is a paradigm of mammalian transgenerational epigenetic regulation resulting in silencing of genes on the paternally inherited X-chromosome. The preprogrammed fate of the X-chromosomes is thought to be controlled in cis by the parent-of-origin-specific expression of two opposing long non-coding RNAs, Tsix and Xist, in mice. Exclusive expression of Tsix from the maternal-X has implicated it as the instrument through which the maternal germline prevents inactivation of the maternal-X in the offspring. Here, we show that Tsix is dispensable for inhibiting Xist and X-inactivation in the early embryo and in cultured stem cells of extra-embryonic lineages. Tsix is instead required to prevent Xist expression as trophectodermal progenitor cells differentiate. Despite induction of wild-type Xist RNA and accumulation of histone H3-K27me3, many Tsix-mutant X-chromosomes fail to undergo ectopic X-inactivation. We propose a novel model of lncRNA function in imprinted X-inactivation that may also apply to other genomically imprinted loci.