Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer.

The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2-ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.

One Size Does Not Fit All: A Multifaceted Approach to Educate Families about Newborn Screening.

All families deserve access to readily available, accurate, and relevant information to help them navigate the newborn screening system. Current practices, limited resources, and a siloed newborn screening system create numerous challenges for both providers and families to implement educational opportunities to engage families in ways that meet their needs with relevant and meaningful approaches. Engaging families in newborn screening, especially those from historically underserved communities, is necessary to increase knowledge and confidence which leads to overall improved outcomes for families. This article describes three strategies that the Navigate Newborn Screening Program developed, tested, and implemented in the United States, including online learning modules, a prenatal education pilot program, and social media awareness campaign, as well as the extent to which they were successful in reaching and educating families about newborn screening. Using quality improvement methods and evidence-driven approaches, each of these three strategies demonstrate promising practices for advancing awareness, knowledge, and self-efficacy for families navigating the newborn screening system-particularly families in medically underserved and underrepresented communities. A model for bidirectional engagement of families is outlined to support scaling and implementing promising educational efforts for both providers and families in the newborn screening system.

Co-evolution of AR gene copy number and structural complexity in endocrine therapy resistant prostate cancer.

Androgen receptor (AR) inhibition is standard of care for advanced prostate cancer (PC). However, efficacy is limited by progression to castration-resistant PC (CRPC), usually due to AR re-activation via mechanisms that include AR amplification and structural rearrangement. These two classes of AR alterations often co-occur in CRPC tumors, but it is unclear whether this reflects intercellular or intracellular heterogeneity of AR. Resolving this is important for developing new therapies and predictive biomarkers. Here, we analyzed 41 CRPC tumors and 6 patient-derived xenografts (PDXs) using linked-read DNA-sequencing, and identified 7 tumors that developed complex, multiply-rearranged AR gene structures in conjunction with very high AR copy number. Analysis of PDX models by optical genome mapping and fluorescence in situ hybridization showed that AR residing on extrachromosomal DNA (ecDNA) was an underlying mechanism, and was associated with elevated levels and diversity of AR expression. This study identifies co-evolution of AR gene copy number and structural complexity via ecDNA as a mechanism associated with endocrine therapy resistance.

Building Evidence for Principles to Guide the Development of Products for Adults with Intellectual and Developmental Disabilities and Extreme Low Literacy-A Product Development Tool.

This article presented a new product development tool for adults with intellectual and developmental disabilities (IDD) developed by the Centers for Disease Control and Prevention (CDC). People with IDD who also have extreme low literacy (ELL) have unique communication needs; public health communicators often face challenges developing effective communication materials for this audience. To support CDC communication specialists with the development of communication products for adults with IDD/ELL, CDC, with its partners RTI International and CommunicateHealth, created a product development tool for this audience through literature review, expert input, and interviews with adults with IDD/ELL and caregivers of adults with IDD/ELL. To build evidence around the principles described in the tool, RTI conducted interviewer-administered surveys with 100 caregivers who support people with IDD/ELL. During the interviews, we presented caregivers with stimuli (portions of a communication product) that either did or did not apply a single principle and asked which would be easier for the person they support to understand. Across all 14 principles tested, the caregiver respondents indicated that the principle-based version would be easier for the person they support to understand compared with the non-principle-based version(s). These findings provide additional evidence to support the principles included in CDC's Tool for Developing Products for People with IDD/ELL.

Complexity of Data Displays in Prescription Drug Advertisements for Healthcare Providers.

BACKGROUND: Healthcare providers (HCPs) often encounter clinical trial results in the form of data displays in prescription drug promotions. Information conveyed in data displays vary in their presentation and complexity. This study describes characteristics of data displays in prescription drug advertising targeted to HCPs. METHODS: This study characterized the content of 140 data displays in 98 unique print advertisements from 2009 to present and identified in AdPharm, an online database of pharmaceutical advertisements. Two reviewers independently coded the advertisements for characteristics (κ = 0.85) including complexity, format, and quality. RESULTS: About one-third (32%) of the advertisements contained multiple data displays (range 2 to 6) and 44% showed clinical data from oncology trials; other disease domains were mental and behavioral health (14%), rheumatology and autoimmune disorders (8%), endocrinology (7%), cardiology (6%), infectious disease (6%), pulmonology and allergy (4%), and others (< 2% each). About one-half (51%) of displays were classified as "simple" which included "pseudographs" and basic tables or charts. "Complex" displays appeared as survival curves, line graphs, or bar graphs with complex features. Most complex displays included a comparator drug (90%), plain language restatement of the key finding (93%) and disclosure statements (91%) with additional study details, although their placement varied. Complex displays were of high quality, according to our selected indicators; our analysis found no data distortion or errors. CONCLUSION: Data displays in prescription drug advertising are often highly complex. Future research assessing understanding of data displays and the potentially beneficial effect of disclosures and other features is warranted.

Tips for health care providers on talking with patients who have intellectual and developmental disabilities about COVID-19.

BACKGROUND: One in four American adults reports having at least one disability. The COVID-19 pandemic has disproportionately impacted people with disabilities and widened already-existing health disparities and inequities. For many people with intellectual and developmental disabilities (IDD), these disparities are compounded by literacy limitations that make it challenging to access, understand, and act upon critical COVID-19 prevention information. METHODS: Using a design thinking framework, we conducted interviews with 27 caregivers of adults with IDD who also have extreme low literacy (ELL) to assess COVID-19 information needs and recommendations for how health care providers could best provide COVID-19 information. Based on our findings, we developed a draft tip sheet to help health care providers communicate with adults with IDD/ELL about COVID-19. We then tested the tip sheet with six health care providers via a focus group discussion. We refined and finalized the tip sheet based on our focus group findings. RESULTS: Caregivers noted the importance of visual aids, repetition, empathy and addressing the person with IDD/ELL directly when discussing COVID-19. Many health care providers indicated that the tip sheet would be most helpful for those with limited experience with patients with IDD/ELL and specific instructions for implementing the tips would be important. CONCLUSIONS: We developed an evidence-informed tip sheet to facilitate communication between health care providers and adults with IDD/ELL and their caregivers, particularly around COVID-19.

Perceptions of Health Care, Information, and Social Support Among Women Affected by Zika Virus Infection During Pregnancy in Two U.S. States.

OBJECTIVES: To understand the information needs and experiences with health care and social support among women with confirmed or possible Zika virus infection during pregnancy. METHODS: We conducted in-depth interviews with 18 women whose pregnancies were part of surveillance efforts in two states, Pennsylvania and Virginia. Using a semi-structured guide available in English and Spanish, we asked women about their experiences. We conducted a thematic analysis using NVivo 11. RESULTS: Only one participant reported that her infant had been diagnosed with health problems related to congenital Zika virus infection. Most participants said they received the information they needed about Zika virus and their infant's medical care. Most participants primarily spoke Spanish and described satisfactory experiences communicating with providers, either using a mix of Spanish and English or using an interpreter. Coordination of care and clear communication among different providers was a key factor in participants' satisfaction with health care received. Participants noted high levels of stress around the uncertainty associated with Zika virus exposure during pregnancy. CONCLUSIONS FOR PRACTICE: Although participants reported satisfaction with care, they also reported high levels of anxiety and challenges coping with the uncertainties along their journeys. Study findings support the need for guidance for providers about how to talk with women about Zika virus infection during pregnancy and specifically how to discuss the uncertainties about diagnosis and outcomes.

Visual images of prescription drug benefits in direct-to-consumer television advertisements.

OBJECTIVE: Images demonstrating a prescription drug's efficacy are often included in direct-to-consumer television advertisements. The current research assessed whether exaggerated efficacy images can mislead individuals, and whether providing accurate quantitative information can reduce these misperceptions. METHODS: We conducted two experimental studies with internet panelists 60 years and older testing drug efficacy images in television ads for wet age-related macular degeneration (N = 901) and plaque psoriasis (N = 902). In each study, participants viewed one of six ads that varied in the efficacy images included (no image, accurate image, exaggerated image) and the presentation of quantitative information (absent, present). Measures included recall, perceptions, and numeracy. RESULTS: In both studies, participants who saw exaggerated images were more likely than those who saw no image or accurate images to overestimate efficacy. Presenting quantitative information increased participants' gist and verbatim recall of drug efficacy, and in some cases, led participants to have more accurate perceptions of the drug's efficacy even in the presence of exaggerated images. Higher numeracy was associated with better gist and verbatim recall. CONCLUSIONS: These results support visual persuasion theory. Moreover, they show that exaggerating benefits visually can mislead viewers. PRACTICE IMPLICATIONS: Stakeholders should ensure that images in direct-to-consumer promotion are accurate and non-misleading.

Gaps in Knowledge About COVID-19 Among US Residents Early in the Outbreak.

OBJECTIVES: The novel coronavirus disease 2019 (COVID-19) resulting from severe acute respiratory syndrome coronavirus 2 began to affect the United States in early 2020. This study aimed to assess the US public's initial understanding about the disease and virus to inform public health communication efforts. METHODS: We conducted a survey of US households from February 28 through March 2, 2020, using a probability-based web-panel survey of 1021 US residents. To assess knowledge about COVID-19, we asked respondents a series of 16 true/false questions. We conducted descriptive statistics and linear regression analyses to examine differences in knowledge scores based on demographic and background characteristics. RESULTS: Knowledge about COVID-19 and the virus was relatively low overall at the beginning of the outbreak, with average scores of 62% on a 16-item knowledge index (ie, answers for 6 of the 16 questions were incorrect or unknown). Knowledge was especially low among people who had low education and income levels, were unemployed, were Hispanic, were non-Hispanic Black, were aged 18-24 and 35-49, indicated having "other" health insurance, and had limited exposure to information about the pandemic. Non-Hispanic Black respondents were less knowledgeable about COVID-19 and the virus at every education level compared with non-Hispanic White respondents at higher education levels. Non-Hispanic Black respondents with

Information and Emotional Support Needs of Families Whose Infant Was Diagnosed With SCID Through Newborn Screening.

Background: Now that severe combined immune deficiency (SCID) has been added to newborn screening panels in all 50 states in the U.S., there is a need to develop and disseminate well-designed educational materials to parents who need information to make informed decisions about treatment and care for identified infants. SCID Compass was designed to address this gap. We summarize the results of two needs assessment activities for parents-a journey mapping exercise and online survey-which will inform the development of a website and new resources. Methods: We conducted in-depth interviews with seven parents of children with SCID identified through newborn screening. Participants were asked to complete a journey map to describe key timepoints related to SCID, starting at diagnosis through present day. This qualitative information informed an online survey that was completed by 76 parents who had a child with SCID. All participants were from the United States. Results: Analysis of journey maps revealed five distinct stages that parents experience: (1) Diagnosis, (2) Pre-Treatment, (3) Treatment, (4) Post-Treatment, and (5) The New Normal. At each stage, parents described unique emotions, challenges, contextual factors that can make a difference in their experience, and information and resource needs. Survey results indicated the highest-rated information needs for parents were understanding available treatment options and what to expect across the SCID lifespan. Emotional support needs included dealing with uncertainty about child's future and additional opportunities to connect with other families. Parents preferred receiving new materials from their healthcare provider or other families, and preferred materials in print, from social media, or online. Several differences were found among subgroups of parents, including those whose child had been identified through newborn screening as well as those considered medically underserved. Conclusions: Findings about unmet parent needs and informational preferences will serve as the foundation for creating a suite of resources for those who have a child with SCID. The materials will be tailored to specific stages of the journey. By using a family-centered approach, we will help to ensure that the materials designed and developed as part of SCID Compass will be understandable, comprehensive, and useful.

Assessing the newborn screening education needs of families living in medically underserved areas.

Newborn screening (NBS) is a public health service available to all babies born in the United States (US). NBS is one of the first experiences families have in the US healthcare system with a new baby. A positive experience with NBS can give families a strong start to their child's health care and build trusting relationships with providers. A lack of easily accessible NBS education for families can exacerbate health inequalities through negative interactions with the healthcare system. Expecting Health, a maternal and child health education and advocacy initiative of Genetic Alliance, partnered with RTI International to implement an online survey assessing needs and preferences around NBS-related health education, with a particular interest in those of families living within medically underserved areas (MUAs). A total of 500 participants completed the survey, including 200 participants living in MUAs. The results of the survey showed that, compared with US families living outside of MUAs, families living in MUAs are generally less aware of NBS and do not receive NBS education at the optimal time (i.e., before birth), which could indicate they experience inequities in NBS education. While families across different geographic areas seem to have similar preferences in terms of content for NBS education, the results show that some distinct communication methods are needed to reach families living in MUAs. To bridge the gap in NBS education to families living in MUAs, the Expecting Health team built an online NBS educational module, using preferred communication methods-specified through the survey-for families living in MUAs.

Information needs across the family planning continuum: A survey of women with chronic autoimmune inflammatory conditions.

OBJECTIVE: This study assessed the information needs of women with chronic autoimmune inflammatory conditions across the pregnancy continuum. METHODS: We conducted a web-based survey with women about information needs related to family planning. Eligible participants were female, aged 18-44, had a diagnosis of a chronic inflammatory condition, and were at one of three pregnancy stages (planning, currently pregnant, or postpartum). RESULTS: The survey yielded 209 responses. Respondents had high levels of information needs and were active information seekers. Many respondents reported difficulty finding the information they need. Over half (56.9%) reported receiving conflicting information from different doctors, and a majority of those respondents reported doing their own research. Respondents expressed the greatest interest in resources that facilitated connections to other women and their experiences (87.4%). Pregnancy stage was significantly associated with information needs and preferences; respondents in the planning stage of pregnancy had higher information needs, reported more dissatisfaction with communication with doctors, and were less connected to pregnancy resources. PRACTICE IMPLICATIONS: Both providers and health/advocacy organizations have a role in improving information around this topic, such as developing and disseminating resources tailored to pregnancy status and supporting patient-centered communication around family planning.

The Effect of Including Quantitative Information on Multiple Endpoints in Direct-to-Consumer Prescription Drug Television Advertisements.

Background. Previous research found that adding a single piece of quantitative information about prescription drug benefits to direct-to-consumer (DTC) ads helps consumers understand how well the drug works. However, drug information often includes quantitative information on multiple benefit outcomes and risks. Thus, we examined whether consumer understanding was similarly improved when DTC television ads include varying amounts of quantitative information. Methods. We randomly assigned participants (945 Internet panelists ≥ 60 years old) to view 1 of 9 fictitious prescription drug television ads that varied the presentation of quantitative information for benefits (none, single outcome, 2 outcomes) and risks (none, 1 risk category, 3 risk categories) and then measured gist and verbatim recall/estimation and drug perceptions. Results. Adding a single benefit outcome and a single risk category replicated past results. Compared with an ad containing no quantitative information, presenting 2 benefit outcomes and multiple risk categories increased gist and verbatim recall and affected drug perceptions. Compared with presenting a single benefit outcome, presenting 2 benefit outcomes increased verbatim recall for the second outcome but decreased verbatim recall for the first outcome. Likewise, compared with presenting a single risk category, presenting multiple risk categories increased gist and verbatim recall for the multiple risk categories but decreased gist recall for a concept more closely associated with the single risk category. Adding multiple risk categories decreased risk perceptions even more than did the single risk category. Limitations. This study may have limited generalizability because it examined an ad for only 1 medical condition. Conclusions. There are tradeoffs to adding multiple quantitative benefit outcomes in DTC ads. However, presenting multiple quantitative risk categories helps consumers better understand a drug's risks.

Impact of messages about scientific uncertainty on risk perceptions and intentions to use electronic vaping products.

BACKGROUND: The science surrounding e-cigarettes and other electronic vaping products (EVPs) is rapidly evolving, and the health effects of vaping are unclear. Little research has explored how individuals respond to information acknowledging scientific uncertainty. The aim of the present study was to understand the impact of messages about scientific uncertainty regarding the health effects of vaping on risk perceptions and behavioral intentions. METHODS: Adults in an online experiment (n = 2508) were randomly exposed to view either a control message (a short factual statement about EVPs) or an uncertainty message (the control message plus additional information describing why EVP-related research is limited or inconclusive). Participants rated the risks of vaping and their intentions to try or stop vaping. RESULTS: Individuals who viewed the uncertainty message rated vaping as less risky than those who viewed the control message. Message exposure did not impact intentions to try vaping soon or intentions to stop vaping in the next 6 months. CONCLUSIONS: Acknowledging scientific uncertainty made EVP use seem less risky. Future research should explore possible drivers of this response, such as deeper message processing or emotional reactions. Researchers and practitioners designing public health campaigns about vaping might consider a cautious approach to presenting information about scientific uncertainty.

Making Decisions About Medication Use During Pregnancy: Implications for Communication Strategies.

Objective To explore women's perceptions of the risks and benefits associated with medication use during pregnancy and to better understand how women make decisions related to medication use in pregnancy. Methods We conducted online focus groups with 48 women who used medication during pregnancy or while planning a pregnancy, and 12 in-depth follow-up interviews with a subset of these women. Results We found that women were aware of general risks associated with medication use but were often unable to articulate specific negative outcomes. Women were concerned most about medications' impact on fetal development but were also concerned about how either continuing or discontinuing medication during pregnancy could affect their own health. Women indicated that if the risk of a given medication were unknown, they would not take that medication during pregnancy. Conclusion This formative research found that women face difficult decisions about medication use during pregnancy and need specific information to help them make decisions. Enhanced communication between patients and their providers regarding medication use would help address this need. We suggest that public health practitioners develop messages to (1) encourage, remind, and prompt women to proactively talk with their healthcare providers about the risks of taking, not taking, stopping, or altering the dosage of a medication while trying to become pregnant and/or while pregnant; and (2) encourage all women of childbearing age to ask their healthcare providers about medication use.

Improving Safe Use of Medications During Pregnancy: The Roles of Patients, Physicians, and Pharmacists.

Our study sought to explore the actual and potential roles of patients, physicians, and pharmacists, as well as their shared challenges and opportunities, in improving the safety of medication use during pregnancy. We conducted virtual focus groups with 48 women and in-depth interviews with nine physicians and five pharmacists. Qualitative analysis revealed that all three groups of participants reported "playing it safe," the need for an engaged patient making informed decisions, challenges surrounding communication about pregnancy status, and a lack of patient-centric resources. Patients, physicians, and pharmacists are highly motivated to protect developing babies from potential harms of medication use during pregnancy while maintaining the patient's health. Strategic messaging could maximize the effectiveness of these interactions by helping physicians discuss the benefits and risks of medication use during pregnancy, pharmacists screen for pregnancy and counsel on medication safety, and patients using medications to share pregnancy intentions with their providers pre-pregnancy.

How Health Department Contextual Factors Affect Public Health Preparedness (PHP) and Perceptions of the 15 PHP Capabilities.

OBJECTIVES: To assess how health department contextual factors influence perceptions of the 15 Public Health Preparedness Capabilities, developed by the Centers for Disease Control and Prevention (CDC) to provide guidance on organizing preparedness activities. METHODS: We conducted an online survey and focus group between September 2015 and May 2016 with directors of preparedness programs in state, metropolitan, and territorial jurisdictions funded by CDC's Public Health Emergency Preparedness (PHEP) cooperative agreement. The survey collected demographic information and data on contextual factors including leadership, partnerships, organizational structure, resources and structural capacity, and data and evaluation. RESULTS: Seventy-seven percent (48 of 62) of PHEP directors completed the survey and 8 participated in the focus group. Respondents were experienced directors (mean = 10.6 years), and 58% led 7 or more emergency responses. Leadership, partnerships, and access to fiscal and human resources were associated with perception and use of the capabilities. CONCLUSIONS: Despite some deficiencies, PHEP awardees believe the capabilities provide useful guidance and a flexible framework for organizing their work. Contextual factors affect perceptions of the capabilities and possibly the effectiveness of their use. Public Health Implications. The capabilities can be used to address challenges in preparedness, including identifying evidence-based practices, developing performance measures, and improving responses.

Direct-to-Consumer Promotion of Prescription Drugs on Mobile Devices: Content Analysis.

BACKGROUND: US Food and Drug Administration (FDA) regulations state that any prescription drug promotion that presents drug benefits to consumers must also disclose certain information about the drug's risks in a similar manner. Nearly three-quarters of all US mobile phone subscribers use a smartphone, and over half report receiving mobile advertisements on their device. OBJECTIVE: The objective of this project was to investigate how prescription drugs are being promoted to consumers using mobile technologies. We were particularly interested in the presentation of drug benefits and risks, with regard to presence, placement, and prominence. METHODS: We analyzed a sample of 51 mobile promotional communications and their associated linked landing pages. We assessed the content and format of the mobile communications and landing pages with regard to presentation of drug benefits and risks. RESULTS: Of the 51 mobile communications we coded, 41% (21/51) were product claim communications (includes the drug name, benefits, and risks), 22% (11/51) were reminder communications (includes drug name only), and 37% (19/51) were help-seeking communications (includes information about the medical condition but not the drug name). Some of the product claim communications (5/21, 24%) required scrolling to see all the benefit information; in contrast, 95% (20/21) required scrolling to see all the risk information. Of the 19 product claim communications that presented both benefits and risks, 95% (18/19) presented benefits before risks and 47% (9/19) used a bigger font for benefits than for risks. Most mobile communications (35/51, 69%) linked to branded drug websites with both benefits and risks, 25% (13/51) linked to a landing page with benefits but no visible risks, and 6% (3/51) linked to a landing page with risks but no visible benefits. Few landing pages (4/51, 8%) required scrolling to see all the benefit information; in contrast, 51% (26/51) required scrolling to see all the risk information. Of the 35 landing pages with both benefit and risk information, 71% (25/35) presented benefits before risks and 51% (18/35) used a bigger font for benefits than for risks. CONCLUSIONS: These results indicate that, while risks and benefits are both represented in mobile communications and their associated landing pages, they are not equally prominent and accessible. This has implications for compliance with FDA fair balance regulations.