Purpose: Copy-number changes and translocations have been studied extensively in many datasets with long-term follow-up. The impact of mutations remains debated given the short time to followup of most datasets.Experimental Design: We performed targeted panel sequencing covering 125 myeloma-specific genes and the loci involved in translocations in 223 newly diagnosed myeloma samples recruited into one of the total therapy trials.Results: As expected, the most commonly mutated genes were NRAS, KRAS, and BRAF, making up 44% of patients. Double-Hit and BRAF and DIS3 mutations had an impact on outcome alongside classical risk factors in the context of an intensive treatment approach. We were able to identify both V600E and non-V600E BRAF mutations, 58% of which were predicted to be hypoactive or kinase dead. Interestingly, 44% of the hypoactive/kinase dead BRAF-mutated patients showed co-occurring alterations in KRAS, NRAS, or activating BRAF mutations, suggesting that they play a role in the oncogenesis of multiple myeloma by facilitating MAPK activation and may lead to chemoresistance.Conclusion: Overall, these data highlight the importance of mutational screening to better understand newly diagnosed multiple myeloma and may lead to patient-specific mutationdriven treatment approaches.
Results From 01 October 2018 to 31 March 2019, 92% (13,515/14,690) of adult admissions were screened for smoking status, identifying 2,393 current smokers. Of these, 96% were given brief advice to quit by the admitting team. Through the automated 'opt-out' referral process, 61% patients completed inpatient behavioural interventions with a specialist cessation practitioner (69% within the fi rst 48 hours of admission). Overall, 66% of smokers were prescribed pharmacotherapy. Over one in fi ve of all smokers admitted during this pilot reported that they were abstinent from smoking 12 weeks after discharge (22%) at a cost £183 per quit. Discussion National implementation of this cost-effective programme would be likely to generate substantial benefi ts to public health.
Direct extraction and use of electronic health record (EHR) data is a long-term and multifaceted endeavor that includes design, development, implementation and evaluation of methods and tools for semi-automating tasks in the research data collection process, including, but not limited to, medical record abstraction (MRA). A systematic mapping of study data elements was used to measure the coverage of the Health Level Seven (HL7®) Fast Healthcare Interoperability Resources (FHIR®) standard for a federally sponsored, pragmatic cardiovascular randomized controlled trial (RCT) targeting adults. We evaluated site-level implementations of the HL7® FHIR® standard to investigate study- and site-level differences that could affect coverage and offer insight into the feasibility of a FHIR-based eSource solution for multicenter clinical research.
As the COVID-19 pandemic unfolds, radiology imaging is playing an increasingly vital role in determining therapeutic options, patient management, and research directions. Publicly available data are essential to drive new research into disease etiology, early detection, and response to therapy. In response to the COVID-19 crisis, the National Cancer Institute (NCI) has extended the Cancer Imaging Archive (TCIA) to include COVID-19 related images. Rural populations are one population at risk for underrepresentation in such public repositories. We have published in TCIA a collection of radiographic and CT imaging studies for patients who tested positive for COVID-19 in the state of Arkansas. A set of clinical data describes each patient including demographics, comorbidities, selected lab data and key radiology findings. These data are cross-linked to SARS-COV-2 cDNA sequence data extracted from clinical isolates from the same population, uploaded to the GenBank repository. We believe this collection will help to address population imbalance in COVID-19 data by providing samples from this normally underrepresented population.
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