Cervical cancer screening among English- and Spanish-speaking Hispanic women in an urban safety net health system, 2015-2020.

BACKGROUND: The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system. METHODS: Electronic health records were used to identify 46,094 women aged 30-65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test. RESULTS: Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: 0.93 - 0.96). Further, those with indigent healthcare plans had a higher prevalence of being UTD when compared to those with private insurance (aPR: 1.10, 95% CI: 1.09 - 1.12), while all other health insurance plans were associated with lower UTD screening when compared to private insurance. CONCLUSIONS: These findings suggest screening differences within the Hispanic population, highlighting the need for disaggregated research assessing heterogeneity within racial/ethnic groups, specifically among Hispanic populations.

Breast cancer clinical trial participation among diverse patients at a comprehensive cancer center.

This study was designed to determine the enrollment patterns in breast cancer clinical trials (CCTs) of patients with diverse backgrounds in an equal access setting and to evaluate the factors contributing to low rates of clinical trial accrual in patients of low socioeconomic status (SES). We performed a retrospective review of a prospectively maintained database of new patients seen at the Dan L. Duncan Comprehensive Cancer Center dating from 5/2015 to 9/2021, which included 3043 patients screened for breast CCTs. We compared the rate of CCT availability, eligibility, and enrollment between two patient populations: Smith Clinic, where most patients are of low SES and uninsured, and Baylor St. Luke's Medical Center (BSLMC) with mostly predominantly insured, higher income patients. We performed logistic regression to evaluate whether differences in age, clinic, race, trial type, and primary language may be underlying the differences in CCT enrollment. More patients were eligible for CCTs at Smith Clinic (53.7% vs 44.7%, p < 0.001). However, Smith Clinic patients were more likely to decline CCT enrollment compared to BSLMC (61.3% declined vs 39.4%, p < 0.001). On multivariate analysis, Black patients had a significantly higher rate of CCT refusal overall (OR = 0.26, 95% CI 0.12-0.56, p < 0.001) and BSLMC only (OR = 0.20, 95% CI 0.060-0.60, p = 0.006). Our data shows that it is likely an oversimplification to assume that equal access will lead to the elimination of CCT disparities. Efforts to diversify CCTs must include consideration of structural and institutional inequities as well as social needs.

Self-Sampling for Human Papillomavirus Testing: Acceptability in a U.S. Safety Net Health System.

INTRODUCTION: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system. METHODS: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences. RESULTS: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%). CONCLUSIONS: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.

Using Culturally Adapted Theater Outreach to Promote Cancer Screening Among Medically Underserved Minority Communities.

Black, Hispanic, and Asian individuals, the three largest US racial/ethnic minorities, continue to suffer disproportionately from breast, cervical, and colon cancers largely because cancer screening continues to be underutilized even after decades of availability. This study examined the utility of theoretically grounded and culturally adapted in-person theater monologues aimed at promoting early detection screening among the three highest population racial/ethnic groups in Harris County, Houston, TX. Nine monologues were created to promote cancer screening and early detection for breast, cervical, and colorectal cancers in three different languages (English, Spanish, Vietnamese) and targeting underserved Black, Hispanic, and Vietnamese adult Harris County residents. From January 2014 to March 2020, 265 live monologue outreach events were held with 110 focused on prevention and screening for breast cancer, 75 for colorectal cancer, and 80 for cervical cancer. A total of 5989 individuals attended these outreach events and 86.3% completed the post-performance evaluation survey. Overall for all monologues, 6.6% of participants reported a positive change in their intent to screen from 75.7 to 82.3% after intervention (p < 0.001) and audience member scores on knowledge questions for all three cancers were mostly positive. Importantly, early detection questions for all three cancers were over 90% correct for all respondents, and well over 70% for the various groups. The findings revealed opportunities for improving monologue content to cultivate cancer early detection and screening knowledge. Results suggest that a theater-based approach may be an effective strategy to disseminate cancer screening education, improve knowledge, and increase intent to obtain screening among medically underserved communities.

Risk factors and prognostic significance of platelet count abnormalities in children with HIV infection on antiretroviral therapy.

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH). DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014. METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with selected clinical variables. We constructed Kaplan-Meier curves and a Cox proportional hazards model to evaluate the impact of T/T on survival. RESULTS: Two thousand, one hundred and nine children were sampled. The incidence density of thrombocytopenia was 1 per 57.9 (95% confidence interval [CI] 50.3-66.8) CWH-years. Thrombocytopenia was higher in children with WHO Stage III/IV, lower in children on zidovudine, and had no association with use of lamivudine or nevirapine, CD4 + suppression, age, and nutrition status. Thrombocytopenia was independently associated with 2.2-fold higher mortality (95% CI 1.62-3.08). The incidence density of thrombocytosis was 1 per 11.4 (95% CI 10.7-12.1) CWH-years. Thrombocytosis was associated with higher CD4 + cell count, younger age, and use of lamivudine or nevirapine, and did not impact survival. CONCLUSIONS: Platelet count is a clinically valuable biomarker of HIV clinical progression and mortality. Laboratory studies are necessary to elucidate the mechanisms of T/T.

Phase I CAR-T Clinical Trials Review.

BACKGROUND/AIM: Chimeric antigen receptor (CAR) T cells with tumor specificity are being increasingly investigated. Phase I trials are the first step of testing for safety of novel CAR-T therapy to determine the maximum tolerated dose (MTD). Several dose escalation methods have been developed over time including rule-based, model-based, and model-assisted designs. The goal of this project is to overview the phase I designs used in current CAR-T trials. MATERIALS AND METHODS: We searched PubMed for peer-reviewed literature published between January 1, 2015 and December 31, 2021. The search was limited to human studies in the English language using the keywords "CAR-T phase I", "clinical trials", and "full text". RESULTS: One hundred nine papers with at least partial phase I components were included for analysis. 31.2% of the trials used the traditional 3+3 or a variation of said design, and 60.6% did not mention the dose escalation design. The majority of the manuscripts (59.6%) did not report cohort size while 19.3% did not specify the timing of evaluation. Although most of the studies were registered with CT.gov, only 33.9% had any results submitted or posted to CT.gov These trends persisted even in manuscripts published in journals with high impact factors. CONCLUSION: Standardizing the publication criteria and providing basic elements of phase I clinical trials are critical to ensure high quality of manuscripts. With the quick development and high costs of CAR-T cell therapy, adoption of advanced designs such as model-based and model-assisted should increase to improve efficiency of clinical trials.

Risk factors and prognostic significance of anemia in children with HIV infection on antiretroviral therapy.

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH). DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014. METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival. RESULTS: Two thousand, one hundred and thirty-seven children were sampled. The incidence density of anemia was 1 per 6.6 CLWH-years. Anemia was moderate in 31.8% and severe in 17.3% of anemia cases, which had 10-year mortality hazards of 3.4 and 4.5, respectively. Microcytic anemia (36% cases) was associated with 2.3-fold hazard of 10-year mortality, and with malnutrition and CD4 + suppression. Normocytic anemia (50.5% cases) was associated with 2.6-fold hazards of 10-year mortality, and with more severe malnutrition, CD4 + suppression, and WHO stage, but inversely associated with lamivudine and nevirapine therapy. Macrocytic anemia (13.5% cases) was neither associated with higher 10-year mortality nor with severe malnutrition or CD4 + suppression but was associated with WHO stage II/III and negatively associated with lamivudine therapy. CONCLUSION: This large multicountry study of CLWH found a high incidence density of anemia. Higher severity, normocytic and microcytic types of anemia were independently associated with long-term mortality. Laboratory studies are needed to decipher the mechanisms of anemia and how it impacts mortality in CLWH.

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer.

Purpose: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC. Materials and methods: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy. Results: All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion. Conclusion: MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC.

Adolescent electronic cigarette counselling: knowledge, attitudes and perceived barriers among clinical staff in a primary care setting.

OBJECTIVE: To assess knowledge, attitudes, and perceived barriers (KAP) regarding e-cigarette use counselling among adolescent healthcare clinical staff in an urban system, and to compare results between providers and rooming staff. METHODS: Primary care clinical staff (n = 169) completed an anonymous survey. Descriptive statistics and Chi-square tests were used to summarize data and compare KAP between medical providers and rooming staff. RESULTS: Staff wanted to learn more about e-cigarettes (87.6%). The most common knowledge deficits were how to use the 5As + 5Rs model for tobacco cessation counselling (66.7%) and the chemical content of e-liquids (55.4%), with no differences across groups. Overall, 58% of providers expressed confidence in their ability to talk with adolescent patients about e-cigarette use. The most common barriers to counselling were low knowledge about e-cigarettes (74.0%) and how to refer adolescent patients for cessation support (43.8%). CONCLUSIONS: Provider and rooming staff expressed similar educational needs surrounding e-cigarettes, counselling, and treatment for adolescent patients. Clinical staff expressed confidence in their ability to affect change. There were no differences in the identified knowledge gaps or barriers to care between rooming staff and providers, suggesting that the same educational format can be used to target both groups.

Incomplete Records as a Leading Cause of Missed Opportunity for Human Papillomavirus Vaccine Initiation in a Safety Net Health System.

OBJECTIVE: The goal of this study was to categorize reasons behind missed opportunities for human papillomavirus (HPV) vaccine initiation in an under-resourced population and to identify associated patient and clinic characteristics. METHODS: Manual chart review was performed for patients aged 11 to 18 years who visited a primary care clinic in a health system in Texas, USA between 06/01/18 and 08/31/18 and were due for an initial HPV vaccine dose but did not receive it. Reasons for HPV vaccine noninitiation were categorized as follows: incomplete immunization record, no documentation of discussion (no documentation that the HPV vaccine was offered or ordered), refusal, staff/provider error, and medical. Multinomial logistic regression was used to examine factors associated with each category. RESULTS: Of 4467 adolescents seen in the study period, 575 (12.9%) were due for the first dose of HPV vaccine but did not receive it. The most common reason for noninitiation was incomplete immunization record (37%), followed by no documentation of discussion (24%), refusal (20%), staff/provider error (15%), and medical (4%). The highest odds of incomplete immunization were among older adolescents. The highest odds of no documentation of discussion were during sick visits. The highest odds of staff/provider error were among patients with commercial insurance. The lowest odds of refusal were in patients with county/indigent insurance. CONCLUSIONS: The most common reason for missed opportunity visits for HPV vaccine initiation was lack of adequate immunization records. Our study highlights the importance of immunization record access and bidirectional reporting as important targets for future interventions.

Association between Antiretroviral Therapy and Cancers among Children Living with HIV in Sub-Saharan Africa.

Approximately 91% of the world's children living with HIV (CLWH) are in sub-Saharan Africa (SSA). Living with HIV confers a risk of developing HIV-associated cancers. To determine the incidence and risk factors for cancer among CLWH, we conducted a nested case-control study of children 0-18 years from 2004-2014 at five centers in four SSA countries. Incident cases of cancer and HIV were frequency-matched to controls with HIV and no cancer. We calculated the incidence density by cancer type, logistic regression, and relative risk to evaluate risk factors of cancer. The adjusted incidence density of all cancers, Kaposi sarcoma, and lymphoma were 47.6, 36.6, and 8.94 per 100,000 person-years, respectively. Delayed ART until after 2 years of age was associated with cancer (OR = 2.71, 95% CI 1.51, 4.89) even after adjusting for World Health Organization clinical stage at the time of enrolment for HIV care (OR = 2.85, 95% CI 1.57, 5.13). The relative risk of cancer associated with severe CD4 suppression was 6.19 (p = 0.0002), 2.33 (p = 0.0042), and 1.77 (p = 0.0305) at 1, 5, and 10 years of ART, respectively. The study demonstrates the high risk of cancers in CLWH and the potential benefit of reducing this risk by the early initiation of ART.

Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in the world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)-expressing T cells induce robust antitumor responses in patients with hematologic malignancies but have limited efficacy in patients with solid tumors, including HCC. IL15 and IL21 promote T-cell expansion, survival, and function and can improve the antitumor properties of T cells. We explored whether transgenic expression of IL15 and/or IL21 enhanced glypican-3-CAR (GPC3-CAR) T cells' antitumor properties against HCC. We previously optimized the costimulation in GPC3-CARs and selected a second-generation GPC3-CAR incorporating a 4-1BB costimulatory endodomain (GBBz) for development. Here, we generated constructs encoding IL15, IL21, or both with GBBz (15.GBBz, 21.GBBz, and 21.15.GBBz, respectively) and examined the ability of transduced T cells to kill, produce effector cytokines, and expand in an antigen-dependent manner. We performed gene-expression and phenotypic analyses of GPC3-CAR T cells and CRISPR-Cas9 knockout of the TCF7 gene. Finally, we measured GPC3-CAR T-cell antitumor activity in murine xenograft models of GPC3+ tumors. The increased proliferation of 21.15.GBBz T cells was at least in part dependent on the upregulation and maintenance of TCF-1 (encoded by TCF7) and associated with a higher percentage of stem cell memory and central memory populations after manufacturing. T cells expressing 21.15.GBBz had superior in vitro and in vivo expansion and persistence, and the most robust antitumor activity in vivo These results provided preclinical evidence to support the clinical evaluation of 21.15.GPC3-CAR T cells in patients with HCC.

Mailed self-sample HPV testing kits to improve cervical cancer screening in a safety net health system: protocol for a hybrid effectiveness-implementation randomized controlled trial.

BACKGROUND: Almost 20% of U.S. women remain at risk for cervical cancer due to their inability or unwillingness to participate in periodic clinic-based screening. Self-sampling has been shown to be an effective strategy for screening women for high-risk human papillomavirus (HR-HPV) infection in specific contexts. However, its effectiveness among medically underserved women in safety net health systems has not been evaluated. Furthermore, it is also unclear whether implementation strategies such as patient navigation can be used to improve the success of self-sample screening programs by addressing patient-level barriers to participation. METHODS/DESIGN: The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) trial is a hybrid type 2 effectiveness-implementation pragmatic randomized controlled trial of mailed self-sample HPV testing. The aim is to assess the effectiveness of mailed self-sample HPV testing kits to improve cervical cancer screening participation among patients in a safety net health system who are overdue for clinic-based screening, while simultaneously assessing patient navigation as an implementation strategy. Its setting is a large, urban safety net health system that serves a predominantly racial/ethnic minority patient population. The trial targets recruitment of 2268 participants randomized to telephone recall (enhanced usual care, n = 756), telephone recall with mailed self-sample HPV testing kit (intervention, n = 756), or telephone recall with mailed self-sample HPV testing kit and patient navigation (intervention + implementation strategy, n = 756). The primary effectiveness outcome is completion of primary screening, defined as completion and return of mailed self-sample kit or completion of a clinic-based Pap test. Secondary effectiveness outcomes are predictors of screening and attendance for clinical follow-up among women with a positive screening test. Implementation outcomes are reach, acceptability, fidelity, adaptations, and cost-effectiveness. DISCUSSION: Hybrid designs are needed to evaluate the clinical effectiveness of self-sample HPV testing in specific populations and settings, while incorporating and evaluating methods to optimize its real-world implementation. The current manuscript describes the rationale and design of a hybrid type 2 trial of self-sample HPV testing in a safety net health system. Trial findings are expected to provide meaningful data to inform screening strategies to ultimately realize the global goal of eliminating cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03898167 . Registered on 01 April 2019. TRIAL STATUS: Study start data: February 13, 2020. Recruitment status: Enrolling by invitation. Estimated primary completion date: February 15, 2023. Estimated study completion date: May 31, 2024. Protocol version 1.6 (February 25, 2020).