Background: Adverse childhood experiences (ACEs) have been associated with deleterious effects on mental health in pregnancy. Methods: The ACE International Questionnaire (ACE-IQ) was used to measure neglect, abuse, and household dysfunction. Longitudinal mixed effect modelling was used to test the effect of ACEs on pregnancy-related anxiety, depressive symptoms, and perceived stress at two time points (12–19 and 22–29 weeks) during pregnancy. Results: A total of 215 women who were predominantly married (81%) and had attained tertiary education (96%) were enrolled. Total ACEs were significantly associated with depressive symptoms (r = 0.23, p < 0.05) and perceived stress (r = 0.18, p < 0.05). As depressive symptoms decreased, t (167) = −8.44, p < 0.001, perceived stress increased, t (167) = 4.60, p < 0.001, and pregnancy-related anxiety remained unchanged as pregnancy progressed. Contact sexual abuse (p < 0.01) and parental death or divorce (p = 0.01) were significantly associated with depression over time (p < 0.01). Total ACEs in this study were associated with depressive symptoms early but not late in pregnancy. Conclusions: Higher total ACEs were positively associated with depressive symptoms and perceived stress during pregnancy, suggesting that mental disorders may have an impact on pregnancy outcomes and ought to be addressed. Further validation of the Edinburgh Postnatal Depression Scale (EPDS) tool in local settings is required.
PURPOSE: Vulvar squamous cell carcinoma (VSCC), a rare gynecologic malignancy, has been rising in incidence. Molecular classification on the basis of human papilloma virus (HPV) and tumor protein 53 (p53) status has identified three clinically distinct subtypes, but we still treat all VSCCs the same. Here, we review molecular classification of VSCC, outline treatment landscape, and highlight potential for targeted therapies in advanced VSCC. DESIGN: We conducted a comprehensive review of the literature on treatment of advanced VSCC with particular focus on the implications of molecular stratification on the basis of HPV and p53 status on the treatment landscape of advanced VSCC. RESULTS: Incorporation of HPV and p53 status in locoregional treatment decision making has the potential to advise (de)escalation strategies. The role of immunotherapy, alone and in combination, requires further exploration particularly earlier in the course of the disease. In advanced stages, potential for targeted therapies in VSCCs include inhibitors of vascular endothelial growth factor, endothelial growth factor receptor, cell cycle, and DNA damage response, particularly in HPV-negative (HPV–) VSCCs. Targeting the phosphoinositide 3 kinase/mammalian target of rapamycin pathway is attractive in HPV-positive and HPV–/p53 wildtype VSCCs. Trials incorporating antibody-drug conjugates (eg, trophoblast cell-surface antigen 2, human epidermal growth factor receptor 2) should be considered, and basket trials in perineal squamous cell cancers are warranted. Preclinical models are limited and should be expanded to inform trial design. CONCLUSION: Like other rare cancers, vulvar cancer lags behind in the identification and optimization of precision medicine strategies. Molecular-based preclinical models and rationally designed clinical trials, incorporating high-quality translational studies, are urgently required. These trials will require international collaboration to ensure feasibility and improvement of outcomes for women diagnosed with this disease.
As simulation science continues to advance, the focus previously put on scenario creation and debriefing must now be applied to other components of the learning experience. There is a need to examine the effectiveness of pre-simulation activities and how they relate to the overall simulation experience and learning outcomes. However, few randomized controlled trials have been conducted comparing different approaches in the pre-simulation preparatory phase and the impact on learning outcomes. A randomized controlled trial was conducted with undergraduate nursing students (n=83) who were randomized to a traditional paper case study (control group) or an interactive pre-simulation activity (intervention group). The use of the two-challenge rule and Satisfaction and Self Confidence in Learning (SSL) was evaluated. The proportion of students who utilized the two-challenge rule in the intervention group was significantly higher than the control group. Results from the two independent-samples Wilcoxon-Mann-Whitney test showed a significant difference in the median of the total score of the SSL W=2.5, p <0.001, satisfaction W=6.0, p <0.001, and self-confidence W=68.0, p <0.001 in learning between third-year nursing students in the control and intervention groups. Our results showed significant differences in the use of the two-challenge rule by students who completed an interactive pre-simulation activity (intervention group) compared to those who completed the paper case study (control group). Additionally, students in the intervention group were more self-confident and satisfied with the entire simulation intervention than the control group. From a pedagogical perspective, this study also emphasizes the need to ground simulations in theory. Moreover, there is value in using progressive frameworks, i.e., revised Medical Research Council (2014) in simulation design and research to ensure high quality. More studies are required to examine the right dosage and type of pre-simulation activity and impact on learning outcomes.
We surveyed 383 men who have sex with men attending sexual health clinics regarding interest in hypothetical preexposure prophylaxis against herpes simplex virus. Overall interest was 62.5% and was associated with the number of different sexually transmitted infections previously diagnosed (adjusted odds ratio, 1.9; 95% confidence interval, 1.5–2.6) and previous HIV preexposure prophylaxis use (adjusted odds ratio, 2.9; 95% confidence interval, 1.1–8.3).
Background: Vulvar cancer is a rare gynecologic malignancy comprising 1–3% of all cases. No established standard exists for advanced disease, and treatment is often extrapolated from cervical cancer. Although HER2 overexpression is well defined in breast cancer and recognized across multiple solid tumors, its prevalence and significance in vulvar cancer remain unclear. Recent activity of HER2-directed antibody–drug conjugate Trastuzumab deruxtecan in solid tumors with an objective response rate (ORR) of around 37% highlights the need to better characterize HER2 expression in vulvar cancer. Methods: We performed a systematic search of Medline, Embase, and the Cochrane Library up to May 2025. Eligible studies included ≥10 vulvar cancer cases, predominantly vulvar squamous cell carcinoma (VSCC), excluding vulvar Paget’s disease, with available HER2 assessment by immunohistochemistry and/or in situ hybridization. Two reviewers independently screened the studies. A random-effects model was used to estimate pooled HER2 positivity. Heterogeneity was assessed using Cochrane’s Q and Higgins’s I2. Results: Of 506 records, nine retrospective studies including 769 patients with predominantly squamous cell carcinoma histology (98%, n = 752) met inclusion criteria. A total of 50 HER2-positive cases were observed. Median age at diagnosis of vulvar cancer was between 55 and 78, reported in three studies. Molecular profiling was limited. Among three studies with known TP53 status (n = 206), 59% of the tumors expressed TP53 (n = 122), and among two studies with known human papilloma virus (HPV) status (n = 128), 21% (n = 27) were HPV-positive. Six studies used American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines in breast cancer. Pooled HER2-positive expression across ASCO/CAP-based studies was 2% (95% CI: 1%, 3%) and for non-ASCO/CAP-based studies was 21% (95% CI: 2%, 52%). Exploratory pooled estimated proportion of HER2-positive expression was 5% (95% CI: 0.4%, 14%). There was substantial heterogeneity across studies, I2 value of 91.1% [95% CI: 85.4%; 94.6%], and no significant publication bias was observed (Egger’s test p = 0.364). This study could not assess prognostic value of HER2 overexpression in VSCC. Conclusions: HER2 positivity in VSCC appears uncommon but it remains to be fully explored. Standardized assessment using contemporary ASCO/CAP breast, endometrial-specific and/or gastric criteria are needed to clarify the prevalence of HER2-positive versus HER2-low/ultralow disease to inform potential use of HER2-targeted therapy.
Backgrounds: Positive attitudes toward human immunodeficiency virus (HIV) treatment, such as reduced concern about HIV transmissibility, are associated with sexual behaviors that may increase the risk of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM). We examined associations between HIV treatment attitudes and bacterial STI diagnoses among GBM in Canada's three largest cities. Methods: We fit a structural equation model between HIV treatment attitudes and bacterial STI diagnoses via sexual behaviors in the Engage study's baseline data. We estimated direct and indirect paths between scores on HIV treatment attitudes and STIs via number of male anal sex partners, condomless anal sex, and oral sex. We conducted sub-analyses with participants stratified by HIV serostatus. Results: Among 2449 GBM recruited in 2017 to 2019, there was a direct association between HIV treatment attitudes and current STI diagnoses (β = 0.13; 95% CI, 0.07–0.19; P < 0.001). The mediated model revealed a positive total indirect effect through 2 pathways: (1) engaging in condomless anal sex and (2) number of male anal sex partners and condomless anal sex. These 2 indirect pathways remained in the stratified mediation models for both HIV negative GBM and for GBM living with HIV. Conclusions: The association between HIV treatment attitudes and diagnosed STIs is mediated through a higher number of male anal sex partners and condomless anal sex. The results highlight the importance of providers educating patients when providing effective STI counseling, testing, and prevention for GBM about how accurate HIV treatment attitudes may inadvertently be associated with the bacterial STI epidemic.