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.

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.

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.

Perceptions of emerging tobacco products and nicotine replacement therapy among pregnant women and women planning a pregnancy.

The increasing availability of emerging non-combusted tobacco products (snus, dissolvables, and electronic nicotine delivery systems or ENDS) may have implications for pregnant women and women of reproductive age. We conducted 15 focus groups to explore how women perceive emerging non-combusted tobacco products and nicotine replacement therapy (NRT) in general, and during pregnancy. Sessions were held in 2013 in four U.S. cities. Participants were 18-40 years old and were pregnant smokers, pregnant quitters, or smokers planning a pregnancy. Responses were coded and analyzed to identify key themes using NVivo 10.0 qualitative software (QSR). Several themes emerged from focus groups. Participants generally found snus unappealing, but viewed dissolvables as a discreet and stigma-free way to use tobacco during pregnancy. Participants perceived NRT as ineffective and having undesired side effects. ENDS were thought to offer advantages over cigarettes, including use in smoke-free areas, lower cost, appealing flavors, and fewer health effects, and were seen by some as a potential quit aid. Some participants, however, worried that the lack of natural stopping point could lead to excessive use. Many participants felt that the use of any tobacco or NRT product is harmful during pregnancy. Women seeking to reduce health risks or stigma related to smoking during pregnancy may perceive advantages of using some emerging products over cigarettes. These findings can inform future public health efforts to reduce risks associated with tobacco product use among women of reproductive age.