A systematic review of patient reported outcomes in phase II or III clinical trials of myelodysplastic syndromes and acute myeloid leukemia

The purpose of this systematic literature review was to identify clinical trials of MDS and AML that included patient-reported outcome (PRO) instruments, and to summarize the symptom and other health related quality of life (HRQOL) concepts most frequently assessed and the PRO instruments that were used. Sixteen manuscripts describing 14 distinct trials met all criteria (i.e., phase 2 or 3 clinical trial for MDS or AML which included PRO assessment) and were published between 1996-2017. In trials evaluating anemia, PRO scores showed significant improvement in relevant domains (e.g. fatigue, function) among patients identified as responders. In trials evaluating the impact of anti-cancer therapies, improvements the baseline to end of treatment were observed in physical functioning and HRQOL, however the rates of missing data in many of the trials was high or unreported. PRO instruments have the ability to capture changes over time in patients’ function and well-being, and PRO instruments and guidance documents are available to support the assessment of HRQOL in AML/MDS clinical trials

A Library of Instruments Endorsed by Published Systematic Reviews for Assessing Patients and Their Care Developed by the Palliative Care Research Cooperative

Dear Editor: Palliative care research encompasses a broad array of domains, care settings, and illnesses, and the instrument literature can be difficult and time consuming to navigate. The Palliative Care Research Cooperative (PCRC) has compiled a library of *150 instruments for assessing patients and their care in palliative and end-of-life care research. This library is a resource for investigators wanting to identify relevant and high-quality instruments

Motivational Interviewing Counseling to Increase Endocrine Therapy Adherence in Diverse Patients

Background: Oral endocrine therapy (ET) is an inexpensive and effective therapy for hormone receptor-positive (HR+) breast cancer that prevents recurrence but relies upon long-term adherence for up to ten years. More than 80% of breast cancer patients have an HR+ phenotype and are candidates for ET, but approximately half discontinue or become non-adherent by five years. ET underuse is more prevalent in Black and young (18 years old, English speaking, and with stage I–III HR+ breast cancer. Participants were recruited across a large academic medical center and four community sites. Feasibility and acceptability were assessed by measures of participant recruitment, retention, session participation, and patient-reported satisfaction. ET adherence at 12 months was assessed by self-report and medication event monitoring system (MEMS) caps using a continuous measure of the proportion of days covered (PDC) as well as a dichotomous measure of the optimal adherence, defined as >80% PDC. Results: Forty-two women initiated the intervention, of whom thirty-five participants (83%) completed outcome assessments at 12 months, including thirteen Black and twenty-two non-Black participants. The average participant age was 54.8 years (range: 25–73). Overall, 97% completed at least three MI sessions and 83% completed at least four sessions. Participant retention and satisfaction were high, particularly among Black women. Self-reported adherence at 12 months was 88% overall (100% in Black women and 81% in non-Black women). The majority of women also achieved 80% of days adherent using MEMS caps, with a greater adherence in Black women. Conclusions: This study demonstrates the feasibility, acceptability, and early promise of the effectiveness of an MI counseling-based intervention to promote ET adherence and prevent breast cancer recurrence in diverse populations

Motivational Interviewing Counseling to Increase Endocrine Therapy Adherence in Diverse Patients

Background: Oral endocrine therapy (ET) is an inexpensive and effective therapy for hormone receptor-positive (HR+) breast cancer that prevents recurrence but relies upon long-term adherence for up to ten years. More than 80% of breast cancer patients have an HR+ phenotype and are candidates for ET, but approximately half discontinue or become non-adherent by five years. ET underuse is more prevalent in Black and young (18 years old, English speaking, and with stage I–III HR+ breast cancer. Participants were recruited across a large academic medical center and four community sites. Feasibility and acceptability were assessed by measures of participant recruitment, retention, session participation, and patient-reported satisfaction. ET adherence at 12 months was assessed by self-report and medication event monitoring system (MEMS) caps using a continuous measure of the proportion of days covered (PDC) as well as a dichotomous measure of the optimal adherence, defined as >80% PDC. Results: Forty-two women initiated the intervention, of whom thirty-five participants (83%) completed outcome assessments at 12 months, including thirteen Black and twenty-two non-Black participants. The average participant age was 54.8 years (range: 25–73). Overall, 97% completed at least three MI sessions and 83% completed at least four sessions. Participant retention and satisfaction were high, particularly among Black women. Self-reported adherence at 12 months was 88% overall (100% in Black women and 81% in non-Black women). The majority of women also achieved 80% of days adherent using MEMS caps, with a greater adherence in Black women. Conclusions: This study demonstrates the feasibility, acceptability, and early promise of the effectiveness of an MI counseling-based intervention to promote ET adherence and prevent breast cancer recurrence in diverse populations

DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis

International audienceStructural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) is a noncanonical SMC protein and an epigenetic regulator. Mutations in SMCHD1 cause facioscapulohumeral muscular dystrophy (FSHD), by overexpressing DUX4 in muscle cells. Here, we demonstrate that SMCHD1 is a key regulator of alternative splicing in various cell types. We show how SMCHD1 loss causes splicing alterations of DNMT3B, which can lead to hypomethylation and DUX4 overexpression. Analyzing RNA sequencing data from muscle biopsies of patients with FSHD and Smchd1 knocked out cells, we found mis-splicing of hundreds of genes upon SMCHD1 loss. We conducted a high-throughput screen of splicing factors, revealing the involvement of the splicing factor RBM5 in the mis-splicing of DNMT3B. Subsequent RNA immunoprecipitation experiments confirmed that SMCHD1 is required for RBM5 recruitment. Last, we show that mis-splicing of DNMT3B leads to hypomethylation of the D4Z4 region and to DUX4 overexpression. These results suggest that DNMT3B mis-splicing due to SMCHD1 loss plays a major role in FSHD pathogenesis

Perspectives on ENCODE

The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.11Nsciescopu

Expanded encyclopaedias of DNA elements in the human and mouse genomes

AbstractThe human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.11Nsciescopu