Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Predictors of Preexposure Prophylaxis Eligibility among Pregnant People with Opioid Use Disorder.

OBJECTIVE: We seek to evaluate risk factors for eligibility for preexposure prophylaxis (PrEP) among pregnant people with opioid use disorder (OUD). STUDY DESIGN: This is a single-site retrospective cohort study of pregnant people admitted for management of OUD at an urban, tertiary care center from 2013 to 2022. PrEP eligibility was defined based on (1) modified American College of Obstetricians and Gynecologists' (ACOG) 2014 criteria: diagnosis of a sexually transmitted infection (STI), engagement in transactional sex work, intravenous drug use (IVDU), or incarceration and (2) modified 2021 Centers for Disease Control (CDC) criteria: diagnosis of bacterial STI (e.g., gonorrhea or syphilis) or transactional sex work. Risk factors associated with PrEP eligibility were evaluated using chi- square or Fischer's exact tests for categorical variables and t-tests or Wilcoxon rank-sum tests for continuous variables. Multivariable regression was used to control for confounding covariates, defined as p < 0.10 on bivariate analysis. p < 0.05 was used to indicate statistical significance. RESULTS: A total of 132 individuals met inclusion criteria, of whom 101 (76.5%) were deemed eligible for PrEP by meeting one or more modified 2014 ACOG criteria: 42 (31.8%) were incarcerated or had one or more STIs, while 30 (22.7%) endorsed engaging in transactional sex work and 68 (58.6%) endorsed IVDU. Using modified 2021 CDC criteria, 37 (28%) met PrEP eligibility, with 12 (9.1%) diagnosed specifically with a bacterial STI and 30 (22.7%) engaging in transactional sex work. Only comorbid psychiatric illness was associated with an increased risk for PrEP eligibility based on 2014 criteria, which persisted after controlling for maternal race/ethnicity (aRR 1.52, 95% confidence interval [CI] 1.24-1.86), and 2021 criteria, which persisted after controlling for nulliparity (aRR 2.12, 95% CI 1.30-3.57). CONCLUSION: A significant number of pregnant people with OUD meet one or more criteria for PrEP, with comorbid psychiatric conditions increasing the risk of meeting criteria. KEY POINTS: · Comorbid psychiatric illness is significantly associated with high risk of PrEP eligibility.. · A large proportion of pregnant individuals with active OUD meet criteria for PrEP prescribing.. · Risk-based screening algorithms for PrEP eligibility have limitations..

Race and Ethnicity Reporting and Representation in Obstetrics and Gynecology Clinical Trials and Publications From 2007-2020.

Importance: Clinical trials guide evidence-based obstetrics and gynecology (OB-GYN) but often enroll nonrepresentative participants. Objective: To characterize race and ethnicity reporting and representation in US OB-GYN clinical trials and their subsequent publications and to analyze the association of subspecialty and funding with diverse representation. Design and Setting: Cross-sectional analysis of all OB-GYN studies registered on ClinicalTrials.gov (2007-2020) and publications from PubMed and Google Scholar (2007-2021). Analyses included logistic regression controlling for year, subspecialty, phase, funding, and site number. Data from 332 417 studies were downloaded. Studies with a noninterventional design, with a registration date before October 1, 2007, without relevance to OB-GYN, with no reported results, and with no US-based study site were excluded. Exposures: OB-GYN subspecialty and funder. Main Outcomes and Measures: Reporting of race and ethnicity data and racial and ethnic representation (the proportion of enrollees of American Indian or Alaskan Native, Asian, Black, Latinx, or White identity and odds of representation above US Census estimates by race and ethnicity). Results: Among trials with ClinicalTrials.gov results (1287 trials with 591 196 participants) and publications (1147 trials with 821 111 participants), 662 (50.9%) and 856 (74.6%) reported race and ethnicity data, respectively. Among publications, gynecology studies were significantly less likely to report race and ethnicity than obstetrics (adjusted odds ratio [aOR], 0.54; 95% CI, 0.38-0.75). Reproductive endocrinology and infertility trials had the lowest odds of reporting race and ethnicity (aOR, 0.14; 95% CI, 0.07-0.27; reference category, obstetrics). Obstetrics and family planning demonstrated the most diverse clinical trial cohorts. Compared with obstetric trials, gynecologic oncology had the lowest odds of Black representation (ClinicalTrials.gov: aOR, 0.04; 95% CI, 0.02-0.09; publications: aOR, 0.06; 95% CI, 0.03-0.11) and Latinx representation (ClinicalTrials.gov: aOR, 0.05; 95% CI, 0.02-0.14; publications: aOR, 0.23; 95% CI, 0.10-0.48), followed by urogynecology and reproductive endocrinology and infertility. Urogynecology (ClinicalTrials.gov: aOR, 0.15; 95% CI, 0.05-0.39; publications: aOR, 0.24; 95% CI, 0.09-0.58) had the lowest odds of Asian representation. Conclusions and Relevance: Race and ethnicity reporting and representation in OB-GYN trials are suboptimal. Obstetrics and family planning trials demonstrate improved representation is achievable. Nonetheless, all subspecialties should strive for more equitably representative research.

How many US obstetrical trials reach publication? A cross-sectional analysis of ClinicalTrials.gov and PubMed from 2007 to 2019.

BACKGROUND: Obstetrical clinical trials are the foundation of evidence-based medicine during pregnancy. As more obstetrical trials are conducted, understanding the publication characteristics of these trials is of utmost importance to advance obstetrical health. OBJECTIVE: This study aimed to characterize the frequency of publication and trial characteristics associated with publication among obstetrical clinical trials in the United States. We additionally sought to examine time from trial completion to publication. STUDY DESIGN: This was a cross-sectional analysis of completed obstetrical trials with an intervention design and at least 1 site in the United States registered to ClinicalTrials.gov from 2007 to 2019. Trial characteristics were cross-referenced with PubMed to determine publication status up to 2021 using the National Clinical Trial identification number. Bivariable analyses were conducted to determine trial characteristics associated with publication. Multivariable logistic regression models controlling for prespecified covariates were generated to estimate the relationship between funding, primary purpose, and therapeutic foci with publication. Additional exploratory analyses of other trial characteristics were conducted. Time to publication was analyzed using Kaplan-Meier curves and Cox regression models. RESULTS: Of the 1879 obstetrical trials with registered completion, a total of 575 (30.6%) had at least 1 site in the United States, were completed before October 1, 2019, and were included in this analysis. Between October 2007 and October 2019, fewer than two-thirds (N=348, 60.5%) of trials reached publication. Annual rates of publication ranged from 46.4% in 2018 to 70.0% in 2007. No difference was observed in publication by funding, primary purpose, or therapeutic foci (all P>.05). Trials with characteristics indicating high trial quality-including randomized allocation scheme, ≥50 participants enrolled, ≥2 sites, and presence of a data safety monitoring committee-had increased odds of publication compared with those without such characteristics (all P<.05). For example, studies with randomized allocation of intervention had 2-fold greater odds of publication than nonrandomized studies (adjusted odds ratio, 2.09; 95% confidence interval, 1.30-3.37). Studies with ≥150 participants had nearly 8-fold odds of publication (adjusted odds ratio, 7.90; 95% confidence interval, 3.78-17.49) relative to studies with <50 participants. Temporal analysis demonstrated variability in time to publication among obstetrical trials, with a median time of 20.1 months after trial completion, and with most trials that reached publication having been published by 40 months. No difference was observed in time to publication by funding, primary purpose, or therapeutic foci (all P>.05). CONCLUSION: Publication of obstetrical trials remains suboptimal, with significant differences observed between trials with indicators of high quality and those without. Most trials that reach publication are published within 2 years of registered completion on ClinicalTrials.gov.

Early Discontinuation, Results Reporting, and Publication of Gynecology Clinical Trials From 2007 to 2020.

OBJECTIVE: To characterize gynecology clinical trials over time, compare gynecology subspecialties, and analyze factors associated with early discontinuation, results reporting, and publication. METHODS: We conducted a cross-sectional analysis of all gynecology trials registered on ClinicalTrials.gov between 2007 and 2020 and their resulting publications. Trials were analyzed with descriptive, multivariable logistic, and Cox regression analyses. Primary exposure variables were trial funding and subspecialty. The three primary outcomes included early discontinuation, results reporting to ClinicalTrials.gov, and publication in a peer-reviewed journal indexed on PubMed. RESULTS: Of 223,690 trials registered on ClinicalTrials.gov between October 2007 and March 2020, only 3.7% focused on gynecology (n=8,174, approximately 3,759,086 participants). Subspecialties included reproductive endocrinology and infertility (n=1,428, 17.5%), gynecologic oncology (n=2,063, 25.2%), urogynecology (n=1,118, 13.7%), family planning (n=648, 7.9%), and other benign gynecology (n=2,917, 35.7%). Only 42.0% of completed trials disseminated results through results reporting and publication. Of all funding types, industry-funded trials were the most likely to be discontinued early (P<.001). Academic-funded trials were the least likely to report results (adjusted odds ratio [aOR] 0.38, 95% CI 0.30-0.50) but the most likely to publish (aOR 1.62, 95% CI 1.24-2.12). The number of reproductive endocrinology and infertility trials increased the most of any subspecialty between 2007 and 2020 (6.4% growth rate). Reproductive endocrinology and infertility and family planning trials were the most likely to be stopped early (reproductive endocrinology and infertility: adjusted hazard ratio [aHR] 2.08, 95% CI 1.59-2.71; family planning: aHR 1.55 95% CI 1.06-2.25). When completed, reproductive endocrinology and infertility trials were the least likely to report results (aOR 0.58, 95% CI 0.38-0.88). No significant differences were seen between subspecialties with respect to publication. CONCLUSION: Gynecology trials comprise only 3.7% of all clinical trials. The paucity of gynecology clinical trials aligns with decades of female underrepresentation in research. When completed, gynecology trials have poor dissemination. Our findings raise concern about bias in the performance, reporting, and publication of gynecology clinical trials.

Assessing provider performance of intrapartum care using simulated encounters and clinical vignettes: A comparison study from Tanzania.

OBJECTIVE: To compare clinical vignettes and objective structured clinical examinations (OSCE) as methods for assessing the quality of intrapartum care among skilled providers in rural primary-level health facilities in Tanzania. METHODS: Cross-sectional study conducted at six health facilities in the Simiyu region of Tanzania. Providers were assessed using OSCE and clinical vignettes in spontaneous delivery, neonatal resuscitation, and management of postpartum hemorrhage. Trained researchers used a structured clinical checklist. The frequencies of items are presented as percentages and the agreement of the methods of assessment are reported using kappa statistics (high: kappa > 0.80, moderate: kappa = 0.60-0.80, low: kappa < 0.60). RESULTS: Most healthcare providers were female (60.7%), registered nurses by training (29.0%), and worked in a dispensary (56.1%), with an average age of 33 years and an average of 7.4 years of experience in their respective professions. Five items had high agreement between OSCE and clinical vignettes: postpartum vital signs every 15 min, oxytocin within 1 min of birth, diagnosis of postpartum hemorrhage, elevating legs of the mother, and deciding on manual compression of the uterus. CONCLUSION: OSCE and clinical vignettes should be viewed as complimentary to one another in the assessment of provider knowledge and skill, with priority given to OSCE, particularly in intrapartum care.

Safety and efficacy of intermittent presumptive treatment with sulfadoxine-pyrimethamine using rapid diagnostic test screening and treatment with dihydroartemisinin-piperaquine at the first antenatal care visit (IPTp-SP+): study protocol for a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed. METHODS: This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday. DISCUSSION: A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP resistant parasites. TRIAL REGISTRATION: Pan African Clinical Trials Registry 201905721140808 . Registered retrospectively on 11 May 2019.

Association of time since pneumococcal polysaccharide vaccine receipt and CD4 count with antibody response to the 13-valent pneumococcal conjugate vaccine in HIV-infected adults.

INTRODUCTION: Pneumococcal infection is a leading cause of illness and death in HIV-infected adults. Current United States guidelines for HIV-infected adults recommend a single dose of the 13-valent pneumococcal conjugate vaccine (PCV-13) at any CD4 count and at least 1 y after receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV). PPV is known to lead to hyporesponsiveness to subsequent pneumococcal vaccines for at least 1 y Whether PCV-13 would be more immunogenic if administered later after PPV receipt or at higher CD4 counts has not been tested. METHODS: We prospectively collected serum from 96 HIV-infected adults before and after PCV-13 receipt, and measured antibody concentrations against 4 pneumococcal serotypes (3, 6A, 7F, and 19A) via indirect ELISA according to the WHO protocol. Post-booster antibody concentrations and fold-rise in antibody concentrations were compared according to time from PPV receipt and baseline CD4 count using univariate and multivariate analyses. RESULTS: PPV receipt >3 versus 1-3 y prior did not significantly change post-vaccination antibody concentrations, but was associated with slightly higher fold-rise in antibody concentration for the 3 tested serotypes included in PPV, though this only reached significance for serotype 7F. CD4 count was significantly associated with post-vaccination antibody concentrations for 3 of 4 serotypes, but not for fold-rise in antibody concentration for any serotype. CONCLUSION: Waiting longer than 1 y after PPV receipt to administer PCV-13 may slightly improve the antibody response to serotypes included in both vaccines. While higher CD4 count at PCV-13 administration results in higher post-vaccination antibody concentrations, this is likely because higher CD4 count is also associated with higher pre-vaccination antibody concentrations.

Interleukin-3-deficient mice have increased resistance to blood-stage malaria.

The contribution of interleukin-3 (IL-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting IL-3-deficient (knockout [KO]) mice with Plasmodium berghei NK65. Male IL-3 KO mice, but not female mice, were more resistant to infection than wild-type (WT) mice, as evidenced by lower peak parasitemia and prolonged survival. Both male and female IL-3 KO mice had increased splenomegaly and were more anemic than corresponding WT mice. Anemia was compensated for by an increase in bone marrow and splenic erythropoiesis in IL-3 KO mice, as evidenced by higher levels of erythroid progenitors. Plasma levels of gamma interferon (IFN-γ) and CXCL9 (monokine induced by IFN-γ [MIG]) were found to be significantly reduced in IL-3 KO mice during early stages of infection. In contrast, granulocyte colony-stimulating factor (G-CSF) levels were significantly higher, and the percentage of peripheral blood neutrophils lower, in infected IL-3 KO mice than in WT counterparts. Overall, our results indicate that IL-3 plays a critical role in suppressing protective immunity to P. berghei NK65 infection and that it is involved in inhibiting the development of splenomegaly, anemia, and erythropoiesis. IL-3 also influences IFN-γ, CXCL9, and G-CSF production in response to infection. The abnormal responses seen in infected IL-3 KO mice may be due to the lack of IL-3 during development, to the lack of IL-3 in the infected mature mice, or to both.