A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML.

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine.

Real-world genomic testing and treatment patterns of newly diagnosed adult acute myeloid leukemia patients within a comprehensive health system.

Background: We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State.

Methods: Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011-2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations.

Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories.

Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

Background: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.

Methods: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.

From Nano-Gels to Marine Snow: A Synthesis of Gel Formation Processes and Modeling Efforts Involved with Particle Flux in the Ocean.

Marine gels (nano-, micro-, macro-) and marine snow play important roles in regulating global and basin-scale ocean biogeochemical cycling. Exopolymeric substances (EPS) including transparent exopolymer particles (TEP) that form from nano-gel precursors are abundant materials in the ocean, accounting for an estimated 700 Gt of carbon in seawater. This supports local microbial communities that play a critical role in the cycling of carbon and other macro- and micro-elements in the ocean.

A precision medicine classification for treatment of acute myeloid leukemia in older patients.

Background: Older patients (≥ 60 years) with acute myeloid leukemia (AML) often have multiple, sequentially acquired, somatic mutations that drive leukemogenesis and are associated with poor outcome. Beat AML is a Leukemia and Lymphoma Society-sponsored, multicenter umbrella study that algorithmically segregates AML patients based upon cytogenetic and dominant molecular abnormalities (variant allele frequencies (VAF) ≥ 0.2) into different cohorts to select for targeted therapies.

Streamlined Operational Approaches and Use of e-Technologies in Clinical Trials: Beat Acute Myeloid Leukemia Master Trial.

Advances in genomic technologies and an increased understanding of the molecular pathogenesis of cancer have resulted in development of new effective, mutation-targeted therapies. In turn, these informed the development of Master Trial designs to test these therapies. The Beat Acute Myeloid Leukemia (BAML) Master Trial (Sponsor: The Leukemia & Lymphoma Society) tests several targeted therapies in patients aged ≥ 60 years with AML based on genomic profiling obtained within 7 days of study enrollment.

Recruitment and enrollment of participants in an online diabetes self-management intervention in a virtual environment.

Effective recruitment of research participants is essential for successful randomized controlled trials and remains one of the most challenging and labor-intensive aspects of conducting research. The purpose of this manuscript is to describe recruitment methods for this two-group, internet-based intervention trial and enrollment status in relation to recruitment methods, accounting for accrual rates and recruitment costs and to discuss our recruitment results and limitations informed by the Clinical Trials Transformation Initiative (CTTI) team's evidence and expert-based recommendations for recruitment. The primary study was a two-group randomized controlled trial designed to evaluate the efficacy of a virtual environment, Diabetes LIVE©, compared to a traditional website format to provide diabetes self-management education and support to adults with type 2 diabetes.

Integrating marine oil snow and MOSSFA into oil spill response and damage assessment.

Marine snow formation and vertical transport are naturally occurring processes that carry organic matter from the surface to deeper waters, providing food and sequestering carbon. During the Deepwater Horizon well blowout, oil was incorporated with marine snow aggregates, triggering a Marine Oil Snow (MOS) Sedimentation and Flocculent Accumulation (MOSSFA) event, that transferred a significant percentage of the total released oil to the seafloor. An improved understanding of processes controlling MOS formation and MOSSFA events is necessary for evaluating their impacts on the fate of spilled oil.

Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial.

Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome. AML originates from a dominant mutation, then acquires collaborative transformative mutations leading to myeloid transformation and clinical/biological heterogeneity.

Active narrowband filter based on inductance and capacitance for low-frequency applications.

Most analog filter solutions operating in the kilohertz frequency range are based on RC elements. However, it is not possible to design a very narrow filter (high q-factor around 1000) by using this architecture. In this article, we would like to show a filter implemented based on a simple series LC resonance circuit (consisting of just an inductor and a capacitor) and an analog circuit.

Challenges and approaches to implementing master/basket trials in oncology.

The appetite for cutting-edge cancer research, across medical institutions, scientific researchers, and health care providers, is increasing based on the promise of true breakthroughs and cures with new therapeutics available for investigation. At the same time, the barriers for advancing clinical research are impacting how quickly drug development efforts are conducted. For example, we know now that under a microscope, patients with the same type of cancer and histology might look the same; however, the reality is that most cancers are driven by genomic, transcriptional, and epigenetic changes that make each patient unique.

Management Team Perceptions of Risks and Strategies for Preventing Falls Among Short-Stay Patients in Nursing Homes.

We sought to understand strategies reported by members of the nursing home management team used to prevent falls in short-stay nursing home patients. Using Donabedian's model of structure, process, and outcomes, we interviewed 16 managers from 4 nursing homes in central North Carolina. Nursing home managers identified specific barriers to fall prevention among short-stay patients including rapid changes in functional and cognitive status, staff unfamiliarity with short-stay patient needs and patterns, and policies impacting care.

Ocean biogeochemistry modeled with emergent trait-based genomics.

Marine ecosystem models have advanced to incorporate metabolic pathways discovered with genomic sequencing, but direct comparisons between models and "omics" data are lacking. We developed a model that directly simulates metagenomes and metatranscriptomes for comparison with observations. Model microbes were randomly assigned genes for specialized functions, and communities of 68 species were simulated in the Atlantic Ocean.

Resident Vignettes for Assessing Care Quality in Nursing Homes.

Objectives: Validated process measures that correlate with patient outcomes are needed for research and quality improvement.

Design: Cross-sectional analysis within a cluster-randomized fall prevention study.

Setting: Nursing homes in North Carolina (n = 16).

Newborn Care Curriculum: Palliative Care for the Newborn.

Introduction: Because pediatric hospitalists have increasing responsibilities in newborn hospitalization, training in perinatal palliative care is beneficial. A 2015 needs assessment revealed 68% of surveyed pediatric hospitalists were interested in more education on this topic. Thus, this learning module was designed to provide a concise, easy-to-use introduction to palliative care for the newborn.

Effect of Promoting High-Quality Staff Interactions on Fall Prevention in Nursing Homes: A Cluster-Randomized Trial.

Importance: New approaches are needed to enhance implementation of complex interventions for geriatric syndromes such as falls.

Objective: To test whether a complexity science-based staff training intervention (CONNECT) promoting high-quality staff interactions improves the impact of an evidence-based falls quality improvement program (FALLS).

Design, Setting, And Participants: Cluster-randomized trial in 24 nursing homes receiving either CONNECT followed by FALLS (intervention), or FALLS alone (control).

A novel program for ABSN students to generate interest in geriatrics and geriatric nursing research.

The current shortage of nurse researchers in geriatrics adversely affects the capacity of nurses to conduct research to advance the evidence-based care of older adults. In an effort to generate interest in geriatrics and geriatric nursing research, the Duke University School of Nursing designed a summer internship for four students enrolled in the accelerated baccalaureate nursing (ABSN) program. This paper describes the experience of these ABSN students and the staff and faculty who worked with them.

Study of Individualization and Bias in Nursing Home Fall Prevention Practices.

Objectives: Little is known about how nursing home staff use resident characteristics to individualize care delivery or whether care is affected by implicit bias.

Design: Randomized factorial clinical vignette survey.

Setting: Sixteen nursing homes in North Carolina.

Sustaining complex interventions in long-term care: a qualitative study of direct care staff and managers.

Background: Little is known about the sustainability of behavioral change interventions in long-term care (LTC). Following a cluster randomized trial of an intervention to improve staff communication (CONNECT), we conducted focus groups of direct care staff and managers to elicit their perceptions of factors that enhance or reduce sustainability in the LTC setting. The overall aim was to generate hypotheses about how to sustain complex interventions in LTC.