Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing.

Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered.

Exploring the Relationship between Food Insecurity, Chronic Health Conditions, and Serious Mental Illness in the United States: Implications for Social Work.

Food insecurity (FI) is a modifiable social determinant of health that impacts approximately 10 percent of the U.S. population. FI has been linked to poorer health outcomes and higher healthcare costs. Given the prevalence of chronic health conditions in the United States, including serious mental illness (SMI), the current study aims to better understand the relationship between FI and chronic conditions, including SMI, in a nationally representative sample. Authors analyzed data from the 2016 Medical Expenditure Panel Survey household component and food security supplement. Findings indicate the prevalence of FI among those with diabetes, lung disease, stroke, and SMI is higher than among the general population, with the prevalence for those with SMI being particularly high (43 percent of the sample). Logistic regression models indicate strong, statistically significant relationships between FI and chronic conditions, including SMI, as well as FI and two or more chronic illnesses, even when controlling for sociodemographic and health factors. There are likely bidirectional relationships between FI and chronic conditions. Findings have implications for social workers, in relation to prevention and treatment of SMI and FI through direct care, advocacy, and integrated services in health, mental health, and social services.

Results of Leveraging Pharmaceutical Patient Assistance Programs to Expand Access to High Cost Medications in a Student-Run Free Clinic.

High costs make many medications inaccessible to patients in the United States. Uninsured and underinsured patients are disproportionately affected. Pharmaceutical companies offer patient assistance programs (PAPs) to lower the cost-sharing burden of expensive prescription medications for uninsured patients. PAPs are used by various clinics, particularly oncology clinics and those caring for underserved communities, to expand patients' access to medications. Prior studies describing the implementation of PAPs in student-run free clinics have demonstrated cost-savings during the first few years of using PAPs. However, there is a lack of data regarding the efficacy and cost savings of longitudinal use of PAPs across several years. This study describes the growth of PAP use at a student-run free clinic in Nashville, Tennessee over ten years, demonstrating that PAPs can be used reliably and sustainably to expand patients' access to expensive medications. From 2012 to 2021, we increased the number of medications available through PAPs from 8 to 59 and the number of patient enrollments from 20 to 232. In 2021, our PAP enrollments demonstrated potential cost savings of over $1.2 million. Strategies, limitations, and future directions of PAP use are also discussed, highlighting that PAPs can be a powerful tool for free clinics in serving underserved communities.

A Letter to Your Care Providers: Implementation and Analysis of a Letter-based Advance Care Planning Initiative for Gynecologic Oncology Patients.

To determine the impact of a letter-based advance care planning (ACP) healthcare improvement (HI) initiative on rates of ACP conversations and documentation among gynecologic oncology (GO) inpatients. An HI initiative was implemented from January to December 2020 to improve ACP documentation among GO inpatients. Patients admitted to the GO service were given ACP packets with a letter-based ACP worksheet. GO inpatients who were interested in learning more about ACP were visited by medical students trained to lead ACP conversations. ACP documentation rates in the EMR (electronic medical record) pre- and post-intervention were evaluated. Descriptive statistics were calculated. Associations between sociodemographic characteristics and ACP documentation were analyzed using logistic regression. There were 172 patients admitted in 2019 (pre-implementation cohort). Of these, 45/172 patients (26%) had an advance directive (AD) documented in their electronic medical record (EMR). Following the implementation of the ACP HI in 2020, 55/168 patients (33%) had an AD documented in their EMR. This was a 7% absolute increase and 27% relative increase from pre-intervention AD documentation rates. Increasing age was associated with an increased likelihood of having an AD in the chart (p = 0.004). Married women were less likely to have an AD in their chart (p = 0.05). An HI utilizing a letter-based ACP packet given to GO inpatients improved AD documentation in the EMR. This HI offers a unique method for introducing ACP to patients. More work is needed to improve the occurrence and documentation of ACP conversations.

Fear of cancer recurrence and associations with mental health status and individual characteristics among cancer survivors: Findings from a nationally representative sample.

Purpose: To describe the prevalence of fear of cancer recurrence (FCR) and test its associations with validated mental health status measures.Design: Cross-sectional survey using the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement.Sample: Post-treatment cancer survivors (n = 1032).Methods: Survey-weighted U.S. population-based estimates describe the prevalence of sociodemographic, health and mental health characteristics of cancer survivors by their level of FCR. Multinomial logistic regression was used to test associations of validated measures of mental health status and individual characteristics on levels of FCR in unadjusted models and those controlling for sociodemographic and health characteristics.Findings: Overall, 34.3% of cancer survivors reported no FCR, 54.4% reported low FCR, and 11.3% reported high FCR. Cancer survivors were at increased risk of reporting high FCR relative to no FCR if they had a low 12-item Short Form Health Survey Mental Component Summary score (≤48) compared to high scores (odds ratio = 2.88; 95% confidence interval = 1.57, 5.29). Reporting depressive symptoms or psychological distress did not significantly increase the risk of reporting high or low FCR relative to no FCR.Conclusions: To our knowledge, this study is the first to provide U.S. population-based estimates of associations between FCR and individual and health characteristics.Implications for Psychosocial Providers or Policy: Our results provide valuable information about which survivors are most at-risk for FCR. Future research is needed to more clearly differentiate FCR from other constructs.

Relationships Between Fear of Cancer Recurrence and Lifestyle Factors Among Cancer Survivors.

We examine the relationships between fear of cancer recurrence (FCR), physical activity, smoking status, and engagement in healthier habits in a US population-based sample of post-treatment cancer survivors. We used data from the 2011 Medical Expenditure Panel Survey (MEPS) Experience with Cancer Survivorship Supplement. Multivariable logistic regression was used to test the relationship of FCR to physical activity, smoking status, and engagement in healthier habits. In all analyses, MEPS survey weights were applied to account for the survey design. Compared with those reporting no FCR, survivors reporting high FCR had significantly lower odds of reporting that they were not currently smokers (odds ratio [OR] = 0.46; 95% CI 0.24, 0.91) and those with any level of FCR had significantly higher odds of reporting healthier habits since diagnosis relative to those with no FCR (low FCR OR = 1.97; 95% CI 1.36, 2.85; high FCR OR = 2.40; 95% CI 1.33, 4.32). FCR was not associated with the odds of reporting physical activity. Findings from this large population-based survey suggest that some of survivors' lifestyle factors may be related to their level of FCR. Understanding the effects of FCR on lifestyle factors may help survivors, survivorship care providers, and policy makers better understand important differences among cancer survivors and personalize interventions in clinical care.

Psychosocial outcomes in active treatment through survivorship.

OBJECTIVE: The objective of the study is to understand potential differences in psychosocial outcomes from active treatment to survivorship. METHODS: Using the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement (n = 1360), we examined and compared psychosocial outcomes among respondents in active treatment with survivors by year(s) since treatment ended. Survey-weighted regression models were used to test associations between year(s) since treatment and depressive symptoms (Patient Health Questionnaire-2), psychological distress (K6), and cancer-specific worry related to recurrence. RESULTS: Unadjusted estimates showed no significant differences in depressive symptoms or psychological distress between those in active treatment and cancer survivors at any time posttreatment. In contrast, the prevalence of cancer-specific worry was lowest among survivors more than 5 years since treatment (10%), slightly higher among those with less than 1 year since treatment (15%), and highest among those in active treatment (32%). In models controlled for sociodemographic and health-related covariates, the year(s) since treatment ended was inversely associated with the odds of cancer-specific worry but was not associated with depressive symptoms or psychological distress. CONCLUSIONS: In this population-based sample, worry about cancer recurrence may diminish with years since treatment ended, while depressive symptoms and distress are persistent across the trajectory. These findings highlight unmet psychosocial needs among cancer survivors and demonstrate the importance of targeted interventions across the survivorship continuum.

Cancer Survivors' Reported Discussions with Health Care Providers About Follow-Up Care and Receipt of Written Care Plans.

Prior studies reveal gaps in cancer survivors' discussions with health care providers about follow-up care and receipt of care plans; however, whether survivorship care planning may vary by cancer type is not known. We surveyed 615 survivors of breast, colorectal, prostate, lung cancer, and melanoma enrolled in three health plans to examine cancer survivors' self-reported discussions of follow-up care, including the need for surveillance, late and long-term effects, emotional needs, and health behaviors. We assessed whether cancer survivors received a written treatment summary and post-treatment care instructions. Most (92%) survivors reported having a discussion about the need for surveillance; 75%, late and long-term effects; 69%, lifestyle and health behaviors; and 53%, emotional and social needs. Most (88%) reported receiving post-treatment care instructions and 47%, a treatment summary. While there was little difference among survivors' receipt of surveillance or health behavior recommendations by cancer type (p = 0.85 and p = 0.66, respectively), discussions of late and long-term effects occurred among 82% of prostate, 78% of breast, 73% of melanoma, 72% of colorectal, and 67% of lung survivors (p = 0.06). Approximately half of survivors reported discussions of emotional needs, with modest differences by cancer type (p = 0.08). Our findings indicate that most patient-provider discussions cover information on surveillance, with less emphasis on late and long-term effects, lifestyle and health behaviors, and substantially less focusing on emotional and social needs. No or modest differences in discussions occurred by cancer type. Whether tailoring information to individual cancer survivor needs is beneficial should be examined.

Weapon carrying, physical fighting and gang membership among youth in Washington state military families.

To examine associations between parental military service and school-based weapon carrying, school-based physical fighting and gang membership among youth. We used cross-sectional data from the 2008 Washington State Healthy Youth Survey collected in 8th, 10th, and 12th grades of public schools (n = 9,987). Parental military service was categorized as none (reference group), without combat zone deployment, or deployed to a combat zone. Multivariable logistic regression was used to test associations between parental military service and three outcomes: school-based weapon carrying, school-based physical fighting and gang membership. Standard errors were adjusted for the complex survey design. In 8th grade, parental deployment was associated with higher odds of reporting gang membership (OR = 1.8) among girls, and higher odds of physical fighting (OR = 1.6), and gang membership (OR = 1.9) among boys. In 10th/12th grade, parental deployment was associated with higher odds of reporting physical fighting (OR = 2.0) and gang membership (OR = 2.2) among girls, and physical fighting (OR = 2.0), carrying a weapon (OR = 2.3) among boys. Parental military deployment is associated with increased odds of reporting engagement in school-based physical fighting, school-based weapon carrying, and gang membership, particularly among older youth. Military, school, and public health professionals have a unique, collaborative opportunity to develop school- and community-based interventions to prevent violence-related behaviors among youth and, ultimately, improve the health and safety of youth in military families. Ideally, such programs would target families and youth before they enter eighth grade.

An in vitro CRISPR screen of cell-free DNA identifies apoptosis as the primary mediator of cell-free DNA release.

ABTRACT: Clinical circulating cell-free DNA (cfDNA) testing is now routine, however test accuracy remains limited. By understanding the life-cycle of cfDNA, we might identify opportunities to increase test performance. Here, we profile cfDNA release across a 24-cell line panel and utilize a cell-free CRISPR screen (cfCRISPR) to identify mediators of cfDNA release. Our panel outlines two distinct groups of cell lines: one which releases cfDNA fragmented similarly to clinical samples and purported as characteristic of apoptosis, and another which releases larger fragments associated with vesicular or necrotic DNA. Our cfCRISPR screens reveal that genes mediating cfDNA release are primarily involved with apoptosis, but also identify other subsets of genes such as RNA binding proteins as potential regulators of cfDNA release. We observe that both groups of cells lines identified primarily produce cfDNA through apoptosis. These results establish the utility of cfCRISPR, genetically validate apoptosis as a major mediator of DNA release in vitro, and implicate ways to improve cfDNA assays.

FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.

Analysis of DNA methylation in cell-free DNA (cfDNA) reveals clinically relevant biomarkers but requires specialized protocols and sufficient input material that limits its applicability. Millions of cfDNA samples have been profiled by genomic sequencing. To maximize the gene regulation information from the existing dataset, we developed FinaleMe, a non-homogeneous Hidden Markov Model (HMM), to predict DNA methylation of cfDNA and, therefore, tissues-of-origin directly from plasma whole-genome sequencing (WGS). We validated the performance with 80 pairs of deep and shallow-coverage WGS and whole-genome bisulfite sequencing (WGBS) data.

FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.

Receipt of preventive oral health care by U.S. children: a population-based study of the 2005-2008 medical expenditure panel surveys.

This study provides estimates of the annual use of preventive oral health care by U.S. children ages 6 months-17 years. We estimated the annual use of preventive oral health care with data from the Medical Expenditure Panel Survey for the years 2005 through 2008 (n = 18,218). Additionally, we tested associations between use of preventive oral health care and predisposing factors, enabling factors and health need within three age groups: young children, school-age children and youth. Overall, 21 % of the sample was reported to have received preventive oral health care in the prior year. More school-age children received preventive care than did young children or youth regardless of gender, race/ethnicity, health status, residence, or family size. Among the youngest children, low parental education and lack of health insurance were associated with lower odds of receiving preventive care. School-age children of racial and ethnic minority groups had a higher odds of receiving preventive care than did non-Hispanic Whites. Youth with special health care needs were less likely to receive care than their peers. Within each age group, use of preventive care increased significantly from 2005 to 2008. In the U.S. there has been an increase in use of pediatric preventive dental care. Continued effort is needed to achieve primary prevention. Outreach and education should include all parents and especially parents with low levels of education, parents of children with special health care needs and those without health insurance.

Counternarratives: An Antiracist Approach in Social Work Education, Practice, and Research.

Given renewed attention to racial equity in the social work profession, the authors suggest the use of counternarratives, an established tool of critical race theory, as an accessible method to challenge racism and examine privilege in social work education, practice, and research. Counternarratives use the technique of storytelling to elevate the lived experiences of marginalized individuals and communities and invite the listener into critical reflection about dominant, privileged discourses. The ultimate goal of counternarratives is the achievement of racial equity. The authors provide context about how counternarratives can align with social work education, practice, and research, and then use specific, illustrative examples from their own work to bring this method and its application to life. The authors also share their own processes of reflection and dialogue across disciplines and social locations in the use of counternarratives. The reflections of an experienced social justice educator provide additional insights on the use of counternarratives in the field of social work.

CHIP Happens: Clonal Hematopoiesis of Indeterminate Potential and Its Relationship to Solid Tumors.

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the expansion of hematopoietic cells harboring leukemia-associated somatic mutations in otherwise healthy people and occurs in at least 10% of adults over 70. It is well established that people with CHIP have increased rates of hematologic malignancy, increased risk of cardiovascular disease, and worse all-cause mortality compared with those without CHIP. Despite recent advancements in understanding CHIP as it relates to these known outcomes, much remains to be learned about the development and role of CHIP in other disease states. Emerging research has identified high rates of CHIP in patients with solid tumors, driven in part by oncologic therapy, and revealed associations between CHIP and differential outcomes in both solid tumors and other diseases. Recent studies have demonstrated that CHIP can contribute to dysregulated inflammatory signaling in multiple contexts, underscoring the importance of interrogating how CHIP might alter tumor immunology. Here, we review the role of CHIP mutations in clonal expansion of hematopoietic cells, explore the relationship between CHIP and solid tumors, and discuss the potential roles of CHIP in inflammation and solid tumor biology.

Oral health need and access to dental services: evidence from the National Survey of Children's Health, 2007.

This study examines associations between parents' report of their children's oral health and receipt of a dental visit for preventive care. We conducted a cross-sectional analysis of oral health status and receipt of a preventive dental visit among US children and youth, ages 1-17 years, using data from the 2007 National Survey of Children's Health (n = 86,764). Survey-weighted logistic regression was used to estimate associations between perceived oral health status and receipt of a preventive dental health visit in the prior 12 months. Overall, 78 % of children and youth received at least one preventive dental health visit in the prior year. Among the youngest children, lower oral health status was associated with higher odds of receiving a preventive dental visit; among older children, lower oral health status was associated with lower odds of receiving a dental visit for preventive care. Use of preventive dental health care is below national target goals. Younger children in worse oral health are more likely, and older youth less likely, to receive preventive dental care. Public health efforts to educate parents to seek early and ongoing preventive oral health care, rather than services in response to problems, may yield oral health benefits later in childhood and over the life course.

Recognizing the emergency department's role in oncologic care: a review of the literature on unplanned acute care.

Background: The global prevalence of cancer is rapidly increasing and will increase the acute care needs of patients with cancer, including emergency department (ED) care. Patients with cancer present to the ED across the cancer care continuum from diagnosis through treatment, survivorship, and end-of-life. This article describes the characteristics and determinants of ED visits, as well as challenges in the effort to define preventable ED visits in this population. Findings: The most recent population-based estimates suggest 4% of all ED visits are cancer-related and roughly two thirds of these ED visits result in hospitalization-a 4-fold higher ED hospitalization rate than the general population. Approximately 44% of cancer patients visit the ED within 1 year of diagnosis, and more often have repeat ED visits within a short time frame, though there is substantial variability across cancer types. Similar patterns of cancer-related ED use are observed internationally across a range of different national payment and health system settings. ED use for patients with cancer likely reflects a complex interaction of individual and contextual factors-including provider behavior, health system characteristics, and health policies-that warrants greater attention in the literature. Conclusions: Given the amount and complexity of cancer care delivered in the emergency setting, future research is recommended to examine specific symptoms associated with cancer-related ED visits, the contextual determinants of ED use, and definitions of preventable ED use specific to patients with cancer.

Zooming into the COVID Era Together.

The pre-clinical medical school curriculum provides students with extraordinary experiences in preparation to become physicians. However, it was not originally designed to be delivered remotely. The COVID-19 pandemic promptly threw the medical education process into unforeseen circumstances. A model of student-faculty collaboration created to address new challenges and implement practical solutions rapidly is presented. This model was used effectively to respond to pre-clinical educational interruptions that were imposed by the COVID-19 pandemic and maintain high-quality training. Our experience provides valuable insights and lessons learned that can be applied to the ongoing pandemic response and to future educational challenges.

Massively parallel enrichment of low-frequency alleles enables duplex sequencing at low depth.

Assaying for large numbers of low-frequency mutations requires sequencing at extremely high depth and accuracy. Increasing sequencing depth aids the detection of low-frequency mutations yet limits the number of loci that can be simultaneously probed. Here we report a method for the accurate tracking of thousands of distinct mutations that requires substantially fewer reads per locus than conventional hybrid-capture duplex sequencing. The method, which we named MAESTRO (for minor-allele-enriched sequencing through recognition oligonucleotides), combines massively parallel mutation enrichment with duplex sequencing to track up to 10,000 low-frequency mutations, with up to 100-fold fewer reads per locus. We show that MAESTRO can be used to test for chimaerism by tracking donor-exclusive single-nucleotide polymorphisms in sheared genomic DNA from human cell lines, to validate whole-exome sequencing and whole-genome sequencing for the detection of mutations in breast-tumour samples from 16 patients, and to monitor the patients for minimal residual disease via the analysis of cell-free DNA from liquid biopsies. MAESTRO improves the breadth, depth, accuracy and efficiency of mutation testing by sequencing.