Cervical cancer remains the leading cause of cancer death among women in sub-Saharan Africa and is more severe in high HIV-burdened countries due to persistent high-risk human papillomavirus (hrHPV). In 2021, the World Health Organization recommended primary hrHPV testing for cervical cancer screening; however, optimal triage strategies following positive hrHPV tests remain unclear. We conducted a prospective cost analysis of triage methods for positive hrHPV results among women living with and without HIV in Gaborone, Botswana. We used a micro-costing approach from the perspective of the healthcare provider. The main outcomes were the implementation costs associated with three triage strategies following hrHPV testing: 8-type HPV genotype restriction, visual inspection with acetic acid (VIA), and colposcopy. We also compared the strategies by measuring the change in costs divided by the change in number of true cases of cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+) identified, based on the results of a prospective cohort study. Results indicated that the 8-type HPV genotype restriction strategy was the most cost-efficient, requiring no additional costs beyond hrHPV testing and identifying the highest number of true CIN2 + cases. VIA and colposcopy triage identified fewer true cases of CIN2+ and incurred additional costs, with colposcopy being the most expensive. Results were consistent in women with and without HIV. Sensitivity analysis highlighted personnel and hrHPV test kit cartridge costs as significant drivers of overall costs. Post-hoc analysis incorporating average treatment costs for precancer demonstrated that genotyping remained dominant at lower treatment costs but became less favorable as treatment costs increased. We found that 8-type genotype restriction was optimal compared to hrHPV screening combined with VIA or colposcopy. Cost estimates can inform future studies that examine the long-term costs and health outcomes of HPV-based two-stage screening algorithms.
Objective: To evaluate the impact of ART duration and CD4 count on risk for high grade cervical dysplasia in women with HIV (WWH) compared to women without HIV in the treat-all era with integrase strand inhibitors (INSTIs). Design: Prospective longitudinal cohort study in Botswana Methods: From February 2021 to August 2022, baseline HPV self-sampling was offered to women with and without HIV. Those HPV+ underwent biopsy for histopathological diagnosis. Using women without HIV as reference, risk ratios (RRs) were calculated for HPV, cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+), and CIN3+, stratified by ART duration and CD4 cell counts. Results: Of 3000 women enrolled, 2953(98.4%) underwent HPV testing, which was positive in 823(55.7%) WWH and in 654(44.3%) women without HIV. Histopathology was available for analysis in 1291(87.4%) women (709 WWH, 582 women without HIV). Over 99% of WWH had detectable HIV viral load and 94.4% were on a dolutegravir-based ART regimen. WWH had a higher risk of HPV (RR1.27,95%CI:1.18,1.37), CIN2+ (RR1.52,95%CI:1.16,1.98) and CIN3+ (RR1.75,95%CI:1.25,2.45) compared to women without HIV. There was attenuation of risk for CIN2+ with higher recent CD4 cell count, and those with higher nadir CD4 count had similar risk to those without HIV (nadir CD4≥500 CIN2+ RR1.15[95%CI:0.56,2.37], CIN3+ RR1.81[95% CI:0.86,3.79]; nadir CD4 350-499 CIN2+ RR1.23[95% CI:0.71,2.12], CIN3+ RR1.34[95%CI:0.68,2.64]). Conclusion: Although some attenuation of risk for CIN2+ was observed with higher recent and nadir CD4 cell counts, WWH continue to have a higher risk of CIN2+/CIN3+ compared to women without HIV. These findings support tailored cervical screening algorithms for WWH.
To explain observed disparities in health outcomes between men and women, sex essentialist approaches assign causal primacy to sex-related biology. In this essay, we present three case studies to illustrate how sex essentialism can distort human biomedical research and distill three maxims for countering this distortion: (1) engage in responsible citation practices; (2) generate and weigh alternative hypotheses for apparent observations of sex differences; (3) take care in constructing the appropriate denominator when making sex comparisons. We offer these maxims as broadly applicable standards of evidence to guide biomedical research that includes analysis of potential sex differences, as well as to support Institutional Review Boards (IRBs), funders, publishers, and peer reviewers in evaluating sex difference findings. If widely applied, these maxims would substantially improve the rigor, precision, and utility of the knowledge base of sex and gender science.
OBJECTIVE:The aim of this study was to evaluate the performance of HPV type restriction and cycle threshold (Ct)-limit setting to optimize detection of cervical intraepithelial neoplasia (CIN) with primary HPV testing. METHODS:Baseline cervical screening at time of entry into a prospective longitudinal cohort of women with and without HIV was conducted from February 2021 to July 2022 in Botswana. All women underwent HPV testing of 15 individual types using the AmpFire assay; all HPV-positive and a random subset of HPV negative had histopathology collected. Performance parameters of HPV type restriction groupings were calculated, and sensitivity by individual HPV type Ct-value limits were plotted. RESULTS:Among 2964 women who underwent primary HPV screening, 1293 (43.6%) tested HPV-positive. Among women with HIV (WWH), HPV types 16/18/33 were associated with the greatest burden of CIN2+/CIN3+ (53%/56%). In WWH, grouping by HPV types separately reported in commercial assays (16/18/45) had low sensitivity (44% [CI: 36%-52%]) but high specificity (86% [CI: 84%-88%]) for CIN2+; 8-type HPV restriction (16/18/31/33/35/45/52/58) improved sensitivity (79% [CI: 72%-86%]) and maintained reasonable specificity (67% [CI: 65%-70%]) for CIN2+. Similar results were seen in women without HIV. Ct-limit setting for medium oncogenic HPV types (31,33,35,52,58) maintained a sensitivity of 72% in WWH while reducing over-detection of non-pathogenic HPV. CONCLUSION:Eight-type HPV restriction and Ct-limit setting are promising strategies for improving the performance of primary HPV screening. A potential strategy to improve 8-type HPV restriction would be to treat all with HPV 16/18/45; treat HPV 31/33/35/52/58 if below the type-specific Ct limit and repeat HPV testing in 1-year for other positive HPV results.
High rates of anterior cruciate ligament (ACL) injuries in girls' and women's sports have garnered significant attention from researchers, sport organisations and the media. Gender/sex disparities in ACL injury rates are often estimated using the construct of athlete-exposures (AEs), a widely used measure of exposure time in sports science and epidemiology that is defined as one athlete participating in one practice or competition. In this narrative review, we explain the limitations of AEs as a measure of exposure time and develop a series of conceptual critiques regarding the use of AEs for the purposes of comparing injury rates by gender/sex. We show that the differing training-to-match ratio and average team size between women and men-rooted in persistent gendered inequities in sports participation and professionalisation-may jeopardise the validity of using AEs for cross-gender comparisons and skew gender/sex disparities in ACL injury rates. To avoid bias, we invite researchers interested in gender/sex disparities in injury rates to collect finer-grained data including individual-level AEs disaggregated by training and competition, as well as to appropriately control for team size and training-to-match ratio at the data analysis stage. Any quantitative comparisons of injury rates should also thoroughly contextualise the limitations of AEs, including their inability to capture the potential qualitative differences between women's and men's training and sporting environments that may influence injury rates.
Financial toxicity is an adverse outcome of cancer care and is often quantified by patient-reported validated survey tools, such as The Comprehensive Score for Financial Toxicity (COST). We aimed to examine the association of objective financial measures of hospital out-of-pocket (OOP) expenses and write-offs with the patient derived COST scores in patients with gynecologic cancer. We identified individuals who completed our cross-sectional survey in discrete periods between 2017 and 2021. Response rates for these periods ranged from 75 to 95
Women worldwide face barriers to kidney transplantation. A qualitative study of 40 women transplant recipients from 16 countries identified key concerns: health system limitations, gender-related stigma, parenthood struggles, and social vulnerability. The study illuminated key insights not previously recognized by providers, but did not include those unable to access transplantation, potentially missing the most substantial obstacles. Addressing these multilevel barriers to transplant equity requires recognizing systemic sexism and listening to the perspectives of women patients.
10.1093/ndt/gfae202 Video Abstract Watch the video abstract of this contribution https://academic.oup.com/ckj/pages/author_videos gfae202Media1 6363227785112
Introduction: Sex/gender inequities persist in access to kidney transplantation. Whether differences in preemptive referral (i.e., referral before dialysis start) explain this inequity remains unknown. Methods: All adults (aged 18-79 years; N 1 / 4 44,204) initiating kidney replacement therapy (KRT; dialysis or transplant) in Georgia (GA), North Carolina (NC), or South Carolina (SC) between 2015 and 2019 were identified from the United States Renal Data System (USRDS). Individuals were linked to the Early Steps to Kidney Transplant Access Registry (E-STAR) to obtain data on preemptive referral and followed-up with through November 13, 2020, for outcomes of waitlisting and living donor transplant. Logistic regression assessed the association between sex/gender and likelihood of preemptive referral among all KRT patients. Cox-proportional hazards assessed the association between sex/gender and waitlisting or living donor among preemptively referred patients. Results: Overall, men and women were similarly likely to be preemptively referred (odds ratio [OR]: 0.99 [0.95-1.04]). Preemptively referred women (vs. men) were, on average, younger and with fewer comorbidities. There were no sex/gender differences in waitlisting once patients were preemptively referred (hazard ratio [HR]: 0.97 [0.91-1.03]); however, women (vs. men) who were preemptively referred remained 25% (HR: 0.75 [0.66-0.86]) less likely to receive a living donor transplant. Conclusion: In the Southeast US, men and women initiating KRT are similarly likely to be preemptively referred for a kidney transplant, and this appears, at least in part, to mitigate known sex/gender inequities in access to waitlisting, but not living donor transplant. Despite this, preemptively referred women, on average, had a more favorable medical pro fi le relative to preemptively referred men.
BACKGROUND:Recently implemented research policies requiring the inclusion of females and males have created an urgent need for effective training in how to account for sex, and in some cases gender, in biomedical studies. METHODS:Here, we evaluated three sets of publicly available online training materials on this topic: (1) Integrating Sex & Gender in Health Research from the Canadian Institutes of Health Research (CIHR); (2) Sex as a Biological Variable: A Primer from the United States National Institutes of Health (NIH); and (3) The Sex and Gender Dimension in Biomedical Research, developed as part of "Leading Innovative measures to reach gender Balance in Research Activities" (LIBRA) from the European Commission. We reviewed each course with respect to their coverage of (1) What is required by the policy; (2) Rationale for the policy; (3) Handling of the concepts "sex" and "gender;" (4) Research design and analysis; and (5) Interpreting and reporting data. RESULTS:All three courses discussed the importance of including males and females to better generalize results, discover potential sex differences, and tailor treatments to men and women. The entangled nature of sex and gender, operationalization of sex, and potential downsides of focusing on sex more than other sources of variation were minimally discussed. Notably, all three courses explicitly endorsed invalid analytical approaches that produce bias toward false positive discoveries of difference. CONCLUSIONS:Our analysis suggests a need for revised or new training materials that incorporate four major topics: precise operationalization of sex, potential risks of over-emphasis on sex as a category, recognition of gender and sex as complex and entangled, and rigorous study design and data analysis.
BackgroundThe WHO strategy for cervical cancer elimination strives to achieve 70% coverage with high-performance cervical screening. While few low- and middle-income countries have achieved this, high-risk human papillomavirus (hrHPV) self-testing creates the possibility to rapidly upscale access to high-performance cervical screening across resource settings. However, effective hrHPV screening requires linkage to follow-up, which has been variable in prior studies. This study developed and tested an implementation strategy aimed at improving screening and linkage to follow-up care in South East District in Botswana.MethodsThis study performed primary hrHPV self-testing; those with positive results were referred for a triage visit. Withdrawals for any reason, loss-to follow-up between hrHPV test and triage visit, and number of call attempts to give hrHPV results were also documented. Acceptability of the program to patients was measured as the proportion of patients who completed a triage visit when indicated, meeting the a priori threshold of 80%. Feasibility was defined as the proportion of participants receiving the results and attending follow-up. To assess the associations between participant characteristics and loss-to-follow-up we used log-binomial regressions to estimate risk ratios and 95% confidence intervals (CI).ResultsEnrollment of 3,000 women occurred from February 2021 to August 2022. In total, 10 participants withdrew and an additional 33 were determined ineligible after consent, leaving a final cohort of 2,957 participants who underwent self-swab hrHPV testing. Half (50%) of participants tested positive for hrHPV and nearly all (98%) of participants received their hrHPV results, primarily via telephone. Few calls to participants were required to communicate results: 2,397 (82%) required one call, 386 (13%) required 2 calls, and only 151 (5%) required 3–5 calls. The median time from specimen collection to participant receiving results was 44 days (IQR, 27–65). Of all hrHPV positive participants, 1,328 (90%) attended a triage visit.DiscussionIn a large cohort we had low loss-to-follow-up of 10%, indicating that the strategy is acceptable. Telephonic results reporting was associated with high screening completion, required few calls to participants, and supports the feasibility of hrHPV self-testing in primary care followed by interval triage.
Determine if the SPIKES method was associated with less distress and more compassion than current modes of delivering negative pregnancy test results to patients undergoing in vitro fertilization. Twenty-seven nurses from two centers were randomized to use the modified SPIKES script or continue their standard of care; 136 patients with a negative hCG following embryo transfer were included. SPIKES nurses received 1 h of training by a study psychologist; nurses in the control group were instructed to deliver the news as done previously. Patients who underwent embryo transfer and received a call by a participating nurse with a negative test result received an email invitation on the following day. Control patients reported significantly less distress than SPIKES patients; 33