TORONTO: A trial-oriented multidimensional psychometric testing algorithm.

Bayesian adaptive methods for sensory threshold determination were conceived originally to track a single threshold. When applied to the testing of vision, they do not exploit the spatial patterns that underlie thresholds at different locations in the visual field. Exploiting these patterns has been recognized as key to further improving visual field test efficiency. We present a new approach (TORONTO) that outperforms other existing methods in terms of speed and accuracy. TORONTO generalizes the QUEST/ZEST algorithm to estimate simultaneously multiple thresholds. After each trial, without waiting for a fully determined threshold, the trial-oriented approach updates not only the location currently tested but also all other locations based on patterns in a reference data set. Since the availability of reference data can be limited, techniques are developed to overcome this limitation. TORONTO was evaluated using computer-simulated visual field tests: In the reliable condition (false positive [FP] = false negative [FN] = 3%), the median termination and root mean square error (RMSE) of TORONTO was 153 trials and 2.0 dB, twice as fast with equal accuracy as ZEST. In the FP = FN = 15% condition, TORONTO terminated in 151 trials and was 2.2 times faster than ZEST with better RMSE (2.6 vs. 3.7 dB). In the FP = FN = 30% condition, TORONTO achieved 4.2 dB RMSE in 148 trials, while all other techniques had > 6.5 dB RMSE and terminated much slower. In conclusion, TORONTO is a fast and accurate algorithm for determining multiple thresholds under a wide range of reliability and subject conditions.

Public perceptions of abortion complications.

BACKGROUND: Misinformation contributes to the perception that abortion has substantial health risks, despite the known safety of medication and aspiration abortion. We lack detailed information about which health risks the public believes are most likely. OBJECTIVE: This study aimed to describe public perception of short- and long-term risks of abortion. STUDY DESIGN: We conducted a cross-sectional survey of US residents aged ≥18 years using Amazon Mechanical Turk (MTurk). We collected information regarding participant demographics, reproductive history, political views, and position on abortion restrictions. We provided participants with a list of 9 short-term and 15 long-term possible complications and asked them to indicate whether they occurred never (0%), very rarely (<1%), rarely (1%-5%), occasionally (5%-20%), or frequently (>20%) following abortion. We used descriptive statistics to understand our population demographics and to capture the perceived incidence of all complications. We created a binary indicator of answering all risk estimates incorrectly vs at least 1 estimate correctly, separately for all long-term possible complications, and the 2 short-term risks of infection and bleeding. We determined the proportion of individuals who responded incorrectly to all questions in each category and used multivariable logistic regression to identify factors associated with incorrect perceptions about the risks of abortion. RESULTS: For all listed complications, participant (N=1057) estimates of risk were higher than the known incidence. For both short-term risks of bleeding and infection, over 40% of participants reported that these outcomes occur occasionally or frequently. Similarly, for both long-term risks of depression and anxiety, over 60% of respondents reported that these outcomes occur occasionally or frequently after abortion. Participants reported that possible complications known to not be associated with abortion, including hair loss, future pregnancy complications, breast cancer, and cosmetic disfigurement, occurred at least rarely. Nearly one-quarter of participants responded that death occurs occasionally or frequently (in over 5% of abortions), and 79% of participants responded that breast cancer can result from abortion. One-quarter (24.9%) of participants incorrectly overestimated both short-term outcomes of infection and bleeding, whereas 19.5% answered all long-term complication questions incorrectly, including outcomes that never occur. On multivariable analyses, we identified that the participants most likely to incorrectly identify risks of abortion identified as Asian or Black race/ethnicity, were from rural communities, or believed that abortion should have more legal restrictions. CONCLUSION: The public perceives abortion to be much riskier than it actually is. This information can be used to develop targeted clinical and public health efforts to disseminate the true risks of abortion.

Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

Impact of coronavirus disease 2019 (COVID-19) vaccination on menstrual bleeding quantity: An observational cohort study.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) vaccination impacts menstrual bleeding quantity. DESIGN: Retrospective cohort. SETTING: Five global regions. POPULATION: Vaccinated and unvaccinated individuals with regular menstrual cycles using the digital fertility-awareness application Natural Cycles°. METHODS: We used prospectively collected menstrual cycle data, multivariable longitudinal Poisson generalised estimating equation (GEE) models and multivariable multinomial logistic regression models to calculate the adjusted difference between vaccination groups. All regression models were adjusted for confounding factors. MAIN OUTCOME MEASURES: The mean number of heavy bleeding days (fewer, no change or more) and changes in bleeding quantity (less, no change or more) at three time points (first dose, second dose and post-exposure menses). RESULTS: We included 9555 individuals (7401 vaccinated and 2154 unvaccinated). About two-thirds of individuals reported no change in the number of heavy bleeding days, regardless of vaccination status. After adjusting for confounding factors, there were no significant differences in the number of heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced an increase in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; adjusted difference 4.0%, 99.2% CI 0.7%-7.2%). This translates to an estimated 40 additional people per 1000 individuals with normal menstrual cycles who experience a greater total bleeding quantity following the first vaccine dose' suffice. Differences resolved in the cycle post-exposure. CONCLUSIONS: A small increase in the probability of greater total bleeding quantity occurred following the first COVID-19 vaccine dose, which resolved in the cycle after the post-vaccination cycle. The total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transient.

Functional evaluation of the cystic fibrosis transmembrane conductance regulator in the endocervix†.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an apical membrane chloride/bicarbonate ion channel in epithelial cells. Mutations in CFTR cause cystic fibrosis, a disease characterized by thickened mucus secretions and is associated with subfertility and infertility. CFTR function has been well characterized in vitro and in vivo in airway and other epithelia studies. However, little is known about CFTR function in the cervix in health and its contribution to cyclic regulation of fertility from endocervical mucus changes. Contributing to this research gap is the lack of information on the effect of sex steroid hormones on CFTR expression in cervical epithelial cells across the menstrual cycle. Herein, we demonstrate the hormonal regulation of CFTR expression in endocervical cells both in vitro and in vivo, and that conditionally reprogrammed endocervical epithelial cells can be used to interrogate CFTR ion channel function. CFTR activity was demonstrated in vitro using electrophysiological methods and functionally inhibited by the CFTR-specific inhibitors inh-172 and GlyH-101. We also report that CFTR expression is increased by estradiol in the macaque cervix both in vitro and in vivo in Rhesus macaques treated with artificial menstrual cycles. Estrogen upregulation of CFTR is blocked in vivo by cotreatment with progesterone. Our findings provide the most comprehensive evidence to date that steroid hormones drive changes in CFTR expression. These data are integral to understanding the role of CFTR as a fertility regulator in the endocervix.

Factors Associated With Perceived Trust of False Abortion Websites: Cross-sectional Online Survey.

BACKGROUND: Most patients use the internet to search for health information. While there is a vast repository of searchable information online, much of the content is unregulated and therefore potentially incorrect, conflicting, or confusing. Abortion information online is particularly prone to being inaccurate as antichoice websites publish purposefully misleading information in formats that appear as neutral resources. To understand how antichoice websites appear neutral, we need to understand the specific website features of antichoice websites that impart an impression of trustworthiness. OBJECTIVE: We sought to identify the characteristics of false or misleading abortion websites that make these websites appear trustworthy to the public. METHODS: We conducted a cross-sectional study using Amazon's Mechanical Turk platform. We used validated questionnaires to ask participants to rate 11 antichoice websites and one neutral website identified by experts, focusing on website content, creators, and design. We collected sociodemographic data and participant views on abortion. We used a composite measure of "mean overall trust" as our primary outcome. Using correlation matrices, we determined which website characteristics were most associated with mean overall trust. Finally, we used linear regression to identify participant characteristics associated with overall trust. RESULTS: Our analytic sample included 498 participants aged from 22 to 70 years, and 50.1% (247/493) identified as female. Across 11 antichoice websites, creator confidence ("I believe that the creators of this website are honest and trustworthy") had the highest correlation coefficient (strongest relationship) with mean overall trust (coefficient=0.70). Professional appearance (coefficient=0.59), look and feel (coefficient=0.59), perception that the information is created by experts (coefficient=0.59), association with a trustworthy organization (coefficient=0.58), valued features and functionalities (coefficient=0.54), and interactive capabilities (coefficient=0.52) all demonstrated strong relationships with mean overall trust. At the individual level, prochoice leaning was associated with higher overall trust of the neutral website (B=-0.43, 95% CI -0.87 to 0.01) and lower mean overall trust of the antichoice websites (B=0.52, 95% CI 0.05 to 0.99). CONCLUSIONS: The mean overall trust of antichoice websites is most associated with design characteristics and perceived trustworthiness of website creators. Those who believe that access to abortion should be limited are more likely to have higher mean overall trust for antichoice websites.

Conditionally reprogrammed macaque endocervical cells retain steroid receptor expression and produce mucus.

Cervical mucus produced by the endocervix plays an essential role as a hormonally induced regulator of female fertility. Cervical mucus fluctuates in both physical characteristics and in sperm penetrability in response to estrogens and progestogens. However, the mechanisms by which steroid hormones change mucus remains poorly understood. Current in vitro models have limited capability to study these questions as primary endocervical cells possess limited expansion potential, and immortalized cells lose in vivo characteristics such as steroid sensitivity. Here we overcome these limitations by establishing an in vitro primary endocervical cell culture model using conditionally reprogrammed cells (CRCs). CRC culture utilizes a Rho-kinase inhibitor and a fibroblast feeder layer to expand proliferative potential of epithelial cell types that have normally short in vitro life spans. In our studies, we produce CRC cultures using primary endocervical cells from adult female rhesus macaques (Macaca mulatta). We demonstrate that primary endocervical cells from the nonhuman primate can be robustly expanded using a CRC method, while retaining steroid receptor expression. Moreover, when removed from CRC conditions and switched to differentiation conditions, these cells are able to differentiate and produce mucus including MUC5B, the most prevalent mucin of the endocervix. We conclude that this method provides a promising in vitro platform for conducting mechanistic studies of cervical mucus regulation as well as for screening new therapeutic targets for fertility regulation and diseases of the endocervix.

The Abortion Web Ecosystem: Cross-Sectional Analysis of Trustworthiness and Bias.

BACKGROUND: People use the internet as a primary source for learning about medical procedures and their associated safety profiles and risks. Although abortion is one of the most common procedures worldwide among women in their reproductive years, it is controversial and highly politicized. Substantial scientific evidence demonstrates that abortion is safe and does not increase a woman's future risk for depressive disorders or infertility. The extent to which information found on the internet reflects these medical facts in a trustworthy and unbiased manner is not known. OBJECTIVE: The purpose of this study was to collate and describe the trustworthiness and political slant or bias of web-based information about abortion safety and risks of depression and infertility following abortion. METHODS: We performed a cross-sectional study of internet websites using 3 search topics: (1) is abortion safe?, (2) does abortion cause depression?, and (3) does abortion cause infertility? We used the Google Adwords tool to identify the search terms most associated with those topics and Google's search engine to generate databases of websites related to each topic. We then classified and rated each website in terms of content slant (pro-choice, neutral, anti-choice), clarity of slant (obvious, in-between, or difficult/can't tell), trustworthiness (rating scale of 1-5, 5=most trustworthy), type (forum, feature, scholarly article, resource page, news article, blog, or video), and top-level domain (.com, .net, .org, .edu, .gov, or international domain). We compared website characteristics by search topic (safety, depression, or infertility) using bivariate tests. We summarized trustworthiness using the median and IQR, and we used box-and-whisker plots to visually compare trustworthiness by slant and domain type. RESULTS: Our search methods yielded a total of 111, 120, and 85 unique sites for safety, depression, and infertility, respectively. Of all the sites (n=316), 57.3% (181/316) were neutral, 35.4% (112/316) were anti-choice, and 7.3% (23/316) were pro-choice. The median trustworthiness score was 2.7 (IQR 1.7-3.7), which did not differ significantly across topics (P=.409). Anti-choice sites were less trustworthy (median score 1.3, IQR 1.0-1.7) than neutral (median score 3.3, IQR 2.7-4.0) and pro-choice (median score 3.7, IQR 3.3-4.3) sites. Anti-choice sites were also more likely to have slant clarity that was "difficult to tell" (41/112, 36.6%) compared with neutral (25/181, 13.8%) or pro-choice (4/23, 17.4%; P<.001) sites. A negative search term used for the topic of safety (eg, "risks") produced sites with lower trustworthiness scores than search terms with the word "safety" (median score 1.7 versus 3.7, respectively; P<.001). CONCLUSIONS: People seeking information about the safety and potential risks of abortion are likely to encounter a substantial amount of untrustworthy and slanted/biased abortion information. Anti-choice sites are prevalent, often difficult to identify as anti-choice, and less trustworthy than neutral or pro-choice sites. Web searches may lead the public to believe abortion is riskier than it is.

Do menstrual cups increase risk of IUD expulsion? A survey of self-reported IUD and menstrual hygiene product use in the United States.

Purpose: To gather preliminary data about menstrual hygiene product use and associated risk of intrauterine device (IUD) expulsion. Materials and methods: We conducted an Internet-based survey using the Amazon Mechanical Turk (MTurk) platform and Researchmatch.org. Eligible participants were women at least 18 years old and self-identified as current or previous IUD users. Results: Of 902 survey responses, 71% reported current or previous IUD use and 19.7% reported menstrual cup use. IUD users were significantly more likely than non-IUD users to use a menstrual cup or tampons. Among all IUD users, 56 individuals reported experiencing at least one expulsion (8.8%). We found a positive association between concurrent menstrual cup use and IUD expulsion (OR: 2.75, 95% CI: 1.40-5.42, p = .002), but no association with concurrent tampon or pad use. Of concurrent IUD and cup users who experienced an expulsion, one reported it occurring 'while using a menstrual cup', with others reporting the expulsion during other events. Conclusions: Menstrual cup use may be higher than previously reported, particularly in IUD users. Concurrent menstrual cup use may increase the risk of IUD expulsion. Prospective research is necessary to fully explore the relationship between menstrual hygiene product use and IUD expulsions.

Comparing cervical mucus changes in response to an oral progestin or oestrogen withdrawal in ovarian-suppressed women: a clinical pilot.

Purpose: Prior studies evaluating the effect of administered progestogens on peak cervical mucus have not controlled for the influence of endogenous hormones. To address this, we treated women with a gonadotropin-releasing hormone (GnRH) agonist to suppress the hypothalamus-pituitary-ovarian (HPO) axis and used transdermal oestradiol replacement to stimulate peak cervical mucus and then evaluated the effects of an oral progestin or oestradiol withdrawal. Materials and methods: We used a crossover design to examine cervical mucus changes in women receiving transdermal oestradiol replacement following intramuscular administration of leuprolide acetate. After increasing oestradiol patches to mid-cycle levels, subjects were assigned to either 0.35 mg oral norethindrone with continuation of the patches (NET) or oestradiol withdrawal by patch removal (E2WD). We collected serum and cervical mucus samples at 0, 2, 4, 6, 22 and 24 h following the intervention. Results: We analysed 12 cycles (6 NET, 6 E2WD) from three subjects. Baseline cervical mucus scores were favourable to sperm penetration [NET median 11, interquartile range (9-12), E2WD 13 (12-13)]. Two hours after removal of oestradiol patch or administration of norethindrone, cervical mucus scores declined [NET 8.5 (4-9), E2WD 10.5 (10-12)]. Low cervical mucus scores persisted at 24 h with NET [8.0 (7-8)] but not E2WD [10.5 (8-11)]. Conclusions: We observed a rapid decline in cervical mucus Insler scores following administration of a single dose of oral norethindrone, and scores remained lower and unfavourable through 24 h. Oestradiol withdrawal did not result in similar unfavourable changes.

Appraising cervical mucus: a new approach to evaluating contraceptives.

PURPOSE: Timing of sample collection represents a major source of variability in studies evaluating the effects of administered agents on cervical mucus in naturally-cycling women. We sought to create and validate an artificial model of the cervical mucus cycle using exogenous E2 and P4 replacement in ovarian suppressed women. MATERIALS AND METHODS: We conducted a prospective experiment (clinicaltrials.gov, NCT02969590) examining cervical mucus changes in six women during natural and artificial menstrual cycles [leuprolide acetate, estradiol transdermal patch (0.05-0.3 mg/day) and progesterone 200 mg/day]. We collected serum and mucus samples at each visit corresponding to early, mid and late follicular, ovulation and mid-luteal time points in the natural and artificial cycles. We evaluated mucus according to the modified Insler score described in the WHO laboratory Manual for the Examination and Processing of Human Semen. RESULTS: We enrolled healthy women between 27 and 40 years of age. All of the subjects achieved a mucus score of ≥10 both in the natural cycle and during peak estradiol replacement levels (0.3 mg/day) in the artificial cycle. During the simulated luteal phase, all mucus scores were ≤5 (median 3.5; range 1-5), similar to scores seen in the luteal phase of natural cycles (median 1; range 1-3). CONCLUSIONS: Our artificial cycle model (leuprolide acetate suppression) and dose escalation with estradiol patches produced favourable cervical mucus with mucus scores similar to those in the periovulatory phase of natural menstrual cycles. Additional studies are needed to validate the model for evaluation of mucus effects of contraceptive agents.

Emergency Contraception in Mexico: Trends in Knowledge and Ever-Use 2006-2014.

Objectives A package of interventions to introduce emergency contraception (EC) to Mexico was implemented, resulting in the addition of EC to the national family planning guidelines in 2004. We describe EC knowledge and use among women in Mexico over time. Methods We used the 2006, 2009, and 2014 of waves of a nationally representative demographic survey (ENADID). We assessed EC knowledge and usage in women ages 15-29 who are not using permanent methods and tested whether EC knowledge and use is changing over time after controlling for socio-demographic characteristics using logistic regression. Results Our sample included n = 99,223 (population N = 40,234,355) women ages 15-29. Overall, knowledge of EC increased over time: 62% in 2006 to 79% in 2009 to 83% in 2014 (p < 0.001). Among young women who have used contraception (n = 42,883; N = 16,816,701), the proportion that reported EC use increased from 3 to 11% to 29% (p < 0.001). Compared to non-users, women who had ever used EC were more likely to be using no method of contraception (44 vs. 35%) or barrier method (22 vs. 17%). Demographic factors including lower wealth, lower education, indigenous status and rural living are significantly associated with less EC knowledge and use. Stratified multivariate analysis found that demographic disadvantages magnify lower EC use among rural residents compared to non-rural residents. Conclusions for Practice Knowledge and use of EC are growing rapidly in Mexico, but disparities persist in demographically disadvantaged women, particularly those living in rural areas. Women who use EC appear to be at higher risk of unintended pregnancy based on current contraceptive use.

Preventing repeat pregnancy in adolescents: is immediate postpartum insertion of the contraceptive implant cost effective?

OBJECTIVE: The objective of the study was to determine the cost-effectiveness of a hypothetical state-funded program offering immediate postpartum implant (IPI) insertion for adolescent mothers. STUDY DESIGN: Participants in an adolescent prenatal-postnatal program were enrolled in a prospective observational study of IPI insertion (IPI group, n = 171) vs standard contraceptive initiation (comparison group, n = 225). Implant discontinuation, repeat pregnancies and pregnancy outcomes were determined. We compared the anticipated public expenditures for IPI recipients and comparisons at 6, 12, 24, and 36 months postpartum using the actual outcomes of this cohort and Colorado Medicaid reimbursement estimates. Costs were normalized to 1000 adolescents in each arm and included 1 year of well-baby care for delivered pregnancies. RESULTS: At 6 months, the expenditures of the IPI group exceed the comparison group by $73,000. However, at 12, 24, and 36 months, publicly funded IPIs would result in a savings of more than $550,000, $2.5 million, and $4.5 million, respectively. For every dollar spent on the IPI program, $0.79, $3.54, and $6.50 would be saved at 12, 24, and 36 months. Expenditures between the IPI and comparison groups would be equal if the comparison group pregnancy rate was 13.8%, 18.6%, and 30.5% at 12, 24, and 36 months. Actual rates were 20.1%, 46.5%, and 83.7%. CONCLUSION: Offering IPIs to adolescent mothers is cost effective. Payors that do not currently cover IPI should integrate these data into policy considerations.

Common misperceptions and public knowledge about intrauterine devices among US-based online respondents.

OBJECTIVES: Misperceptions about intrauterine devices (IUDs) may dissuade potential users and public beliefs are not well understood. We sought to describe public knowledge of mechanism of action, failure rate, and IUD health risks. Secondary objectives included identifying inaccurate information and information sources about IUDs. STUDY DESIGN: We conducted a convenience-based survey of participants living in the United States 18 years and older using Amazon Mechanical Turk and ResearchMatch. We collected information on demographics, reproductive history, and IUD knowledge. We asked about IUD mechanism of action, failure rate, potential health risks, and information sources. We used multivariable logistic regression to test the association between gender and perceived lower (vs. higher) risks of IUDs. RESULTS: We included 1597 individuals with 726 (45.5%) self-reported men and 871 (54.5%) self-reported women. For both hormonal and non-hormonal IUDs, participants most often selected implantation prevention as the primary mechanism of action. In our sample, 55.5% of individuals believed the failure rate was greater than five percent. Weight gain, uterine perforation, and expulsion were cited as health risks likely to occur ≥5% of the time by 42.1%, 34.3%, and 38.4% of participants, respectively. Participants identified healthcare providers as their primary source of contraceptive information. Our multivariable logistic regression analysis revealed women had higher odds of perceiving IUDs as higher risk (aOR=1.35, 95% CI 1.09-1.68) compared to men. CONCLUSIONS: Individuals underestimated IUD effectiveness while overestimating perceived health risks. Our results highlight areas to target education about IUDs to support informed contraceptive decision-making. IMPLICATIONS: Participants misunderstood IUD mechanism of action, underestimated efficacy, and overestimated failure rates and health risks. Providers should begin clinical counseling by assessing baseline knowledge, since mechanism of action, side effect profiles, and concepts like female anatomy should not be assumed to be known.

Effects of Virtual Reality Therapy Combined With Conventional Rehabilitation on Pain, Kinematic Function, and Disability in Patients With Chronic Neck Pain: Randomized Controlled Trial.

BACKGROUND: Neck pain is a common condition that leads to neck motor dysfunction and subsequent disability, with a significant global health care burden. As a newly emerging tool, virtual reality (VR) technology has been employed to address pain and reduce disability among patients with neck pain. However, there is still a lack of high-quality studies evaluating the efficacy of VR therapy combined with conventional rehabilitation for patients with chronic neck pain, particularly in terms of kinematic function. OBJECTIVE: This study aims to investigate the effect of VR therapy combined with conventional rehabilitation on pain, kinematic function, and disability in patients with chronic neck pain. METHODS: We conducted an assessor-blinded, allocation-concealed randomized controlled trial. Sixty-four participants experiencing chronic neck pain were randomly allocated into the experimental group that underwent VR rehabilitation plus conventional rehabilitation or the control group receiving the same amount of conventional rehabilitation alone for 10 sessions over 4 weeks. Pain intensity, disability, kinematic function (cervical range of motion, proprioception, and mean and peak velocity), degree of satisfaction, and relief of symptoms were evaluated at 3 timepoints (baseline, postintervention, and at 3 months follow-up). A 2*3 mixed repeated measures analysis of variance was utilized for analyzing the difference across indicators, with a significant difference level of .05. RESULTS: Both groups demonstrated significant improvements in pain, disability, and kinematic functions (P<.05) at postintervention and at 3-month follow-up. The experimental group showed superior therapeutic outcomes compared to the control group in pain reduction (mean difference from the baseline: 5.50 vs 1.81 at posttreatment; 5.21 vs 1.91 at the 3-month follow-up, respectively; P<.001), disability improvement (mean difference from baseline: 3.04 vs 0.50 at posttreatment; 3.20 vs 0.85 at the 3-month follow-up, respectively; P<.001), and enhanced kinematic functions (P<.05). Moreover, participants in the experimental group reported better satisfaction and relief of symptoms than the control group (P<.05), with better initiative for exercising during the follow-up period. However, there was no between-group difference of improvement in proprioception. No adverse events were reported or observed in our research. CONCLUSIONS: The findings of our study support the efficacy of combining VR therapy with conventional rehabilitation in alleviating pain, enhancing kinematic function, and reducing disability of patients with chronic neck pain. Future research should focus on refining the therapeutic protocols and dosages for VR therapy as well as on optimizing its application in clinical settings for improved convenience and effectiveness. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040132; http://www.chictr.org.cn/showproj.aspx?proj=64346.

Timing of Coronavirus Disease 2019 (COVID-19) Vaccination and Effects on Menstrual Cycle Changes.

OBJECTIVE: To assess whether menstrual cycle timing (follicular or luteal phase) of coronavirus disease 2019 (COVID-19) vaccine administration is associated with cycle length changes. METHODS: We used prospectively collected (2021-2022) menstrual cycle tracking data from 19,497 reproductive-aged users of the application "Natural Cycles." We identified whether vaccine was delivered in the follicular or luteal phase and also included an unvaccinated control group. Our primary outcome was the adjusted within-individual change in cycle length (in days) from the average of the three menstrual cycles before the first vaccination cycle (individuals in the unvaccinated control group were assigned a notional vaccine date). We also assessed cycle length changes in the second vaccination cycle and whether a clinically significant change in cycle length (8 days or more) occurred in either cycle. RESULTS: Most individuals were younger than age 35 years (80.1%) and from North America (28.6%), continental Europe (33.5%), or the United Kingdom (31.7%). In the vaccinated group, the majority received an mRNA vaccine (63.8% of the full sample). Individuals vaccinated in the follicular phase experienced an average 1-day longer adjusted cycle length with a first or second dose of COVID-19 vaccine compared with their prevaccination average (first dose: 1.00 day [98.75% CI, 0.88-1.13], second dose: 1.11 days [98.75% CI, 0.93-1.29]); those vaccinated in the luteal phase and those in the unvaccinated control group experienced no change in cycle length (respectively, first dose: -0.09 days [98.75% CI, -0.26 to 0.07], second dose: 0.06 days [98.75% CI, -0.16 to 0.29], unvaccinated notional first dose: 0.08 days [98.75% CI, -0.10 to 0.27], second dose: 0.17 days [98.75% CI, -0.04 to 0.38]). Those vaccinated during the follicular phase were also more likely to experience a clinically significant change in cycle length (8 days or more; first dose: 6.8%) than those vaccinated in the luteal phase or unvaccinated (3.3% and 5.0%, respectively; P <.001). CONCLUSION: COVID-19 vaccine-related cycle length increases are associated with receipt of vaccination in the first half of the menstrual cycle (follicular phase).

Using Fused Data from Perimetry and Optical Coherence Tomography to Improve the Detection of Visual Field Progression in Glaucoma.

Perimetry and optical coherence tomography (OCT) are both used to monitor glaucoma progression. However, combining these modalities can be a challenge due to differences in data types. To overcome this, we have developed an autoencoder data fusion (AEDF) model to learn compact encoding (AE-fused data) from both perimetry and OCT. The AEDF model, optimized specifically for visual field (VF) progression detection, incorporates an encoding loss to ensure the interpretation of the AE-fused data is similar to VF data while capturing key features from OCT measurements. For model training and evaluation, our study included 2504 longitudinal VF and OCT tests from 140 glaucoma patients. VF progression was determined from linear regression slopes of longitudinal mean deviations. Progression detection with AE-fused data was compared to VF-only data (standard clinical method) as well as data from a Bayesian linear regression (BLR) model. In the initial 2-year follow-up period, AE-fused data achieved a detection F1 score of 0.60 (95% CI: 0.57 to 0.62), significantly outperforming (p < 0.001) the clinical method (0.45, 95% CI: 0.43 to 0.47) and the BLR model (0.48, 95% CI: 0.45 to 0.51). The capacity of the AEDF model to generate clinically interpretable fused data that improves VF progression detection makes it a promising data integration tool in glaucoma management.

Hormonal regulation of non-cystic fibrosis transmembrane conductance regulator ion channels in the endocervix.

OBJECTIVE: To characterize ion channel expression and localization in the endocervix under different hormonal conditions using a nonhuman primate primary endocervical epithelial cell model. DESIGN: Experimental. SETTING: University-based, translational science laboratory. INTERVENTIONS: We cultured and treated conditionally reprogrammed primary rhesus macaque endocervix cells with estradiol and progesterone and measured gene expression changes for several known ion channel and ion channel regulators of mucus secreting epithelia. Using both rhesus macaque endocervical samples and human samples, we localized channels in the endocervix using immunohistochemistry. MAIN OUTCOME MEASURES: The relative abundance of transcripts was evaluated using real-time polymerase chain reaction. Immunostaining results were evaluated qualitatively. RESULTS: Compared with controls, we found that estradiol increased gene expression for ANO6, NKCC1, CLCA1, and PDE4D. Progesterone down-regulated gene expression for ANO6, SCNN1A, SCNN1B, NKCC1, and PDE4D (P≤.05). Immunohistochemistry confirmed endocervical cell membrane localization of ANO1, ANO6, KCNN4, LRR8CA, and NKCC1. CONCLUSIONS: We found several ion channels and ion channel regulators that are hormonally sensitive in the endocervix. These channels, therefore, may play a role in the cyclic fertility changes in the endocervix and could be further investigated as targets for future fertility and contraceptive studies.

The effect of deliberate non-adherence to a norgestrel progestin-only pill: A randomized, crossover study.

OBJECTIVES: To estimate the effects on cervical mucus, ovarian activity and theoretical contraceptive protection of a 6-hour delay and of missing one norgestrel 0.075 mg progestogen-only pill. STUDY DESIGN: In a prospective, two-site, randomized, crossover study, healthy women aged 18 to 35 with BMI <32.0 kg/m² and regular ovulatory cycles completed a baseline 28-day cycle with correct daily pill use followed by two intervention cycles in which, around mid-cycle, one pill was taken 6 hours late or missed completely. We undertook ovarian ultrasonography, estradiol and progesterone measurement, and cervical mucus assessments every 3 to 4 days (daily around the time of the incorrect use) and based the theoretical contraceptive protection score on ovarian activity status, cervical mucus and their temporal relationship. RESULTS: Of 91 potential participants screened, 52 started the study and 46 provided complete data for each intervention cycle. Fourteen participants (30%) ovulated in each of the two intervention cycles, with four during the delayed pill cycle and two during the missed pill cycle having an abnormal luteal phase. Seven participants in the delayed pill cycle, and six with a missed pill had elevated cervical mucus scores temporally associated with the intervention. However only two women, one in the delayed pill cycle and one in the missed pill cycle, had cervical mucus scores in the range considered favorable for fertility. CONCLUSIONS: Delayed or missed intake of a single norgestrel 0.075 mg progestogen-only pill appears to have little effect on theoretical contraceptive efficacy. IMPLICATIONS: This biomedical study suggests that taking a norgestrel 0.075mg progestogen-only pill 6 hours late or missing one pill have little effect on ovarian activity or cervical mucus and may not jeopardize contraceptive efficacy. Correlation with typical use outcomes is necessary to confirm pregnancy risk with delayed or missed norgestrel intake.

Transcriptional profiling of mucus production and modification in rhesus macaque endocervical cells under hormonal regulation.

Objective: Endocervical mucus production is a key regulator of fertility throughout the menstrual cycle. With cycle-dependent variability in mucus quality and quantity, cervical mucus can either facilitate or block sperm ascension into the upper female reproductive tract. This study seeks to identify genes involved in the hormonal regulation of mucus production, modification, and regulation through profiling the transcriptome of endocervical cells from the non-human primate, the Rhesus Macaque (Macaca mulatta). Design: Experimental. Setting: Translational science laboratory. Intervention: We treated differentiated primary endocervical cultures with estradiol (E2) and progesterone (P4) to mimic peri-ovulatory and luteal-phase hormonal changes. Using RNA-sequencing, we identified differential expression of gene pathways and mucus producing and modifying genes in cells treated with E2 compared to hormone-free conditions and E2 compared to E2-primed cells treated with P4. Main Outcome Measures: We pursued differential gene expression analysis on RNA-sequenced cells. Sequence validation was done using qPCR. Results: Our study identified 158 genes that show significant differential expression in E2-only conditions compared to hormone-free control, and 250 genes that show significant differential expression in P4-treated conditions compared to E2-only conditions. From this list, we found hormone-induced changes in transcriptional profiles for genes across several classes of mucus production, including ion channels and enzymes involved in post-translational mucin modification that have not previously been described as hormonally regulated. Conclusion: Our study is the first to use an in vitro culture system to create an epithelial-cell specific transcriptome of the endocervix. As a result, our study identifies new genes and pathways that are altered by sex-steroids in cervical mucus production.