Longitudinal Monitoring of Circulating Tumor DNA to Assess the Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Genitourinary Malignancies.

PURPOSE: Circulating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker demonstrating improved assessment of treatment response in patients receiving immune checkpoint inhibitors (ICIs). Here, we performed a pilot study to support the role of ctDNA for longitudinal treatment response monitoring in patients with advanced genitourinary (GU) malignancies receiving ICIs. MATERIALS AND METHODS: Patients with histologically confirmed advanced GU malignancies were prospectively enrolled. All eligible patients received ICI treatment for at least 12 weeks, followed by serial collection of blood samples every 6-8 weeks and conventional scans approximately every 12 weeks until disease progression. ctDNA analysis was performed using Signatera, a tumor-informed multiplex-polymerase chain reaction next-generation sequencing assay. Overall, the objective response rate (ORR) was reported and its association with ctDNA status was evaluated. Concordance rate between ctDNA dynamics and conventional imaging was also assessed. RESULTS: ctDNA analysis was performed on 98 banked plasma samples from 20 patients (15 renal, four urothelial, and one prostate). The median follow-up from the time of initiation of ICI to progressive disease (PD) or data cutoff was 67.7 weeks (range, 19.6-169.6). The ORR was 70% (14/20). Eight patients ultimately developed PD. The overall concordance between ctDNA dynamics and radiographic response was observed in 83% (15/18) of patients. Among the three patients with discordant results, two developed CNS metastases and one progressed with extracranial systemic disease while ctDNA remained undetectable. CONCLUSION: In this pilot study, longitudinal ctDNA analysis for monitoring response to ICI in patients with advanced GU tumors was feasible. Larger prospective studies are warranted to validate the utility of ctDNA as an ICI response monitoring tool in patients with advanced GU malignancies.

Comparison of circulating tumor DNA between African American and Caucasian patients with metastatic castrate-resistant prostate cancer post-abiraterone and/or enzalutamide.

BACKGROUND: African American men are much more likely than Caucasian men to be diagnosed with and to die of prostate cancer. Genetic differences likely play a role. The cBioPortal database reveals that African American men with prostate cancer have higher rates of CDK12 somatic mutations compared to Caucasian men. However, this does not account for prior prostate cancer treatments, which are particularly important in the castrate-resistant setting. We aimed to compare somatic mutations based on circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC) between African American and Caucasian men after exposure to abiraterone and/or enzalutamide. METHODS: This single-institution retrospective study characterizes the somatic mutations detected on ctDNA for African American and Caucasian men with mCRPC who had progressed after abiraterone and/or enzalutamide from 2015 through 2022. We evaluated the gene mutations and types of mutations in this mCRPC cohort. RESULTS: There were 50 African American and 200 Caucasian men with CRPC with available ctDNA data. African American men were younger at the time of diagnosis (p = 0.008) and development of castration resistance (p = 0.006). African American men were more likely than Caucasian men to have pathogenic/likely pathogenic (P/LP) mutations in CDK12 (12% vs. 1.5%; p = 0.003) and copy number amplifications and P/LP mutations in KIT (8.0% vs. 1.5%; p = 0.031). African American men were also significantly more likely to have frameshift mutations (28% vs. 14%; p = 0.035). CONCLUSIONS: Compared to Caucasian men, African American men with mCRPC after exposure to abiraterone and/or enzalutamide had a higher incidence of somatic CDK12 P/LP mutations and KIT amplifications and P/LP mutations based on ctDNA. African American men also had more frameshift mutations. We hypothesize that these findings have potential implications for tumor immunogenicity.

The Adolescent Experience of Filling Prescriptions for the Treatment of Sexually Transmitted Infections.

PURPOSE: To describe adolescents' experience with treatment adherence when prescribed antibiotics for sexually transmitted infections (STIs) in emergency departments (ED). METHODS: Adolescents diagnosed with STIs in two EDs and prescribed outpatient treatment were interviewed to identify barriers and facilitators to treatment adherence. RESULTS: Of 26 participants, 46.2% filled their prescriptions, 38.5% returned to the ED for treatment, 7.7% received treatment elsewhere, and 7.7% received no treatment. All adolescents who filled their prescriptions notified caregivers of their diagnosis, compared with 50.0% who returned to the ED (P = 0.01). Adolescents identified cost, transportation, lack of insurance card, and lack of knowledge as perceived barriers to treatment adherence. Less than half of the participants were interested in school-based health clinics due to anonymity concerns. Most expressed interest in using mobile health (mHealth) to overcome adherence challenges. CONCLUSIONS: Adolescents identified multiple barriers to treatment adherence. Future work should explore the role of caregiver communication and incorporation of mHealth.

Rural-urban disparities in the distribution of dental caries among children in south-eastern Louisiana: a cross-sectional study.

INTRODUCTION: The purpose of this cross-sectional study was to assess the prevalence of dental caries among elementary school-aged children in rural compared to urban communities within south-eastern Louisiana that have participated in a school-based dental screening and sealant program. METHODS: The authors utilized de-identified Sealant Efficiency Assessment for Locals and States screening data for 2007-2014 provided by The Health Enrichment Network oral health program. The screening was conducted throughout 46 elementary schools in Louisiana. Screening forms recorded decayed, missing, and filled permanent teeth (DMFT). Descriptive statistics including demographic characteristics and oral health conditions were calculated. Univariate and multivariable logistic regression analyses were performed to assess the burden of caries in schools. RESULTS: Of 963 children screened, 32% had dental caries. There was an increased risk of having any DMFT among children who attended rural schools as compared to those who attended urban schools (prevalence odds ratio (POR)=2.17, 95% confidence interval (CI)=1.61-2.93). This study found that non-Hispanic black children had reduced odds of DMFT as compared to the children from other reported ethnicities (POR=0.695, 95%CI=0.503-0.960). CONCLUSION: A higher prevalence of dental caries was found in rural compared to urban communities. Further research is needed to assess the extent of geographic differences to improve oral health outcomes.

A Social Media Peer Group for Mothers To Prevent Obesity from Infancy: The Grow2Gether Randomized Trial.

BACKGROUND: Few studies have addressed obesity prevention among low-income families whose infants are at increased obesity risk. We tested a Facebook peer-group intervention for low-income mothers to foster behaviors promoting healthy infant growth. METHODS: In this randomized controlled trial, 87 pregnant women (Medicaid insured, BMI ≥25 kg/m2) were randomized to the Grow2Gether intervention or text message appointment reminders. Grow2Gether participants joined a private Facebook group of 9-13 women from 2 months before delivery until infant age 9 months. A psychologist facilitated groups featuring a curriculum of weekly videos addressing feeding, sleep, parenting, and maternal well-being. Feasibility was assessed using the frequency and content of participation, and acceptability using surveys. Maternal beliefs and behaviors and infant growth were assessed at birth, 2, 4, 6, and 9 months. Differences in infant growth between study arms were explored. We conducted intention-to-treat analyses using quasi-least-squares regression. RESULTS: Eighty-eight percent (75/85) of intervention participants (42% (36/85) food insecure, 88% (75/85) black) reported the group was helpful. Participants posted 30 times/group/week on average. At 9 months, the intervention group had significant improvement in feeding behaviors (Infant Feeding Style Questionnaire) compared to the control group (p = 0.01, effect size = 0.45). Intervention group mothers were significantly less likely to pressure infants to finish food and, at age 6 months, give cereal in the bottle. Differences were not observed for other outcomes, including maternal feeding beliefs or infant weight-for-length. CONCLUSIONS: A social media peer-group intervention was engaging and significantly impacted certain feeding behaviors in families with infants at high risk of obesity.

A Social Media Peer Group Intervention for Mothers to Prevent Obesity and Promote Healthy Growth from Infancy: Development and Pilot Trial.

BACKGROUND: Evidence increasingly indicates that childhood obesity prevention efforts should begin as early as infancy. However, few interventions meet the needs of families whose infants are at increased obesity risk due to factors including income and maternal body mass index (BMI). Social media peer groups may offer a promising new way to provide these families with the knowledge, strategies, and support they need to adopt obesity prevention behaviors. OBJECTIVE: The aim of this study is to develop and pilot test a Facebook-based peer group intervention for mothers, designed to prevent pediatric obesity and promote health beginning in infancy. METHODS: We conducted in-depth semi-structured interviews with 29 mothers of infants and focus groups with 30 pediatric clinicians, to inform the development of a theory-based intervention. We then conducted a single-group pilot trial with 8 mothers to assess its feasibility and acceptability. All participants were recruited offline at pediatric primary care practices. Participants in the pilot trial joined a private Facebook group, moderated by a psychologist, with a weekly video-based curriculum, and also had the option to meet at a face-to-face event. Within the Facebook group, mothers were encouraged to chat, ask questions, and share photos and videos of themselves and babies practicing healthy behaviors. Consistent with the literature on obesity prevention, the curriculum addressed infant feeding, sleep, activity, and maternal well-being. Feasibility was assessed using the frequency and content of group participation by mothers, and acceptability was measured using online surveys and phone interviews. RESULTS: Based on preferences of mothers interviewed (mean BMI 35 kg/m(2), all Medicaid-insured, mean age 27, all Black), we designed the intervention to include frequent posts with new information, videos showing parents of infants demonstrating healthy behaviors, and an optional face-to-face meeting. We developed a privacy and safety plan that met the needs of participants as well as the requirements of the local institutional review board (IRB), which included use of a "secret" group and frequent screening of participant posts. Clinicians, 97% (29/30) women and 87% (26/30) pediatricians, preferred no direct involvement in the intervention, but were supportive of their patients' participation. In our 8-week, single group pilot trial, all participants (mean BMI 35 kg/m(2), all Medicaid-insured, mean age 28, all Black) viewed every weekly video post, and interacted frequently, with a weekly average of 4.4 posts/comments from each participant. All participant posts were related to parenting topics. Participants initiated conversations about behaviors related to healthy infant growth including solid food introduction, feeding volume, and managing stress. All 8 pilot group participants reported that they found the group helpful and would recommend it to others. CONCLUSIONS: Our methodology was feasible and acceptable to low-income mothers of infants at high risk of obesity, and could be adapted to implement peer groups through social media for underserved populations in varied settings. CLINICALTRIAL: ClinicalTrials.gov NCT01977105; https://clinicaltrials.gov/ct2/show/NCT01977105 (Archived by WebCite at http://www.webcitation.org/6iMFfOBat).