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Precision medicine can significantly improve outcomes for cancer patients, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine (Ara-C), but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared to cells with monoallelic mutation. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for cancer patients.

Objective To address the opioid overdose epidemic, it is important to understand the broad scope of efforts under way in states, particularly states in which the rate of opioid-involved overdose deaths is declining. The primary objective of this study was to examine core elements of overdose prevention activities in 4 states with a high rate of opioid-involved overdose deaths that experienced a decrease in opioid-involved overdose deaths from 2016 to 2017. Methods We identified 5 states experiencing decreases in age-adjusted mortality rates for opioid-involved overdoses from 2016 to 2017 and examined their overdose prevention programs via program narratives developed with collaborators from each state’s overdose prevention program. These program narratives used 10 predetermined categories to organize activities: legislative policies; strategic planning; data access, capacity, and dissemination; capacity building; public-facing resources (eg, web-based dashboards); training resources; enhancements and improvements to prescription drug monitoring programs; linkage to care; treatment; and community-focused initiatives. Using qualitative thematic analysis techniques, core elements and context-specific activities emerged. Results In the predetermined categories of programmatic activities, we identified the following core elements of overdose prevention and response: comprehensive state policies; strategic planning; local engagement; data access, capacity, and dissemination; training of professional audiences (eg, prescribers); treatment infrastructure; and harm reduction. Conclusions The identification of core elements and context-specific activities underscores the importance of implementation and adaptation of evidence-based prevention strategies, interdisciplinary partnerships, and collaborations to address opioid overdose. Further evaluation of these state programs and other overdose prevention efforts in states where mortality rates for opioid-involved overdoses declined should focus on impact, optimal timing, and combinations of program activities during the life span of an overdose prevention program.

Background While overall opioid prescribing has been decreasing in the United States, the rates of prescribing at the county level have been variable. Previous studies show that social determinants of health (the social and economic conditions in which we live) may play a role in opioid prescribing; however, researchers have not examined this relationship across US counties. This cross-sectional study seeks to determine whether county-level sociodemographic characteristics (e.g., economic, housing, social environment, healthcare environment, and population characteristics) are associated with county level differences in opioid dispensing. Methods Data from 2,881 counties in the United States from 2017 to 2018 were used for this study. Opioid dispensing was measured using morphine milligram equivalents (MME) per capita. Spatial error models were used to measure the association between county-level sociodemographic characteristics and MME per capita while adjusting for spatial correlation between neighboring counties. Results In the adjusted model, counties with a higher percentage of people below the poverty line, with less than a 4-year college degree, and without health insurance were associated with higher MME dispensed per capita, as were counties with higher percentages of families headed by a single parent, persons separated or divorced, and those with disabilities. Conversely, minority race/ethnicity and rural population were associated with lower opioid dispensing. Conclusions County-level sociodemographics can differ in their association with opioid dispensing, hence examining which county-level factors help in improving opioid prescribing, and implementing overdose prevention strategies that tackle these factors is important.

Background The Centers for Disease Control and Prevention's Prevention for States (PfS) program funded 29 state health departments to prevent opioid overdose by implementing evidence-based prevention strategies. The objectives of this analysis were to describe the scope of activities implemented across the four PfS strategies and identify implementation challenges. Methods PfS recipients submitted annual progress reports (APRs) to state support staff at CDC from 2015 to 2017. APR data were used to calculate the number of required and optional activities implemented under each PfS strategy. APR data were qualitatively analyzed using a systematic content analysis approach to identify key implementation challenges. Results From 2015 to 2017, PfS recipients implemented 177 activities across four strategies from 2015 to 2017. Cross-cutting implementation challenges were (1) multi-sector collaboration, (2) lack of knowledge and misperceptions about opioid used disorder (OUD) among some partners and local communities and; (3) management and access to opioid data among PfS recipients. Conclusions PfS recipients implemented an array of prevention interventions to address the opioid overdose crisis and encountered several cross-cutting implementation challenges. Challenges and state driven solutions over the course of implementing PfS led to several lessons learned and actions that CDC enacted to continue to support and expand overdose prevention.

ImportanceClinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings.ObjectiveTo automatically extract acute brain pathological data and their features from head CT reports.Design, Setting, and ParticipantsThis diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021.Main Outcomes and MeasuresPerformance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets.ResultsA total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%.Conclusions and RelevanceThese findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

Introduction : Since 1999, overdose deaths involving opioids have substantially increased. In 2016, 42,249 opioid-related deaths occurred—a 27.7% increase from the previous year (Hedegaard et al., 2017). As the nation's public health agency, the Centers for Disease Control and Prevention (CDC) has been actively involved in efforts to prevent opioid misuse, opioid use disorder, and opioid overdose since 2014. One of CDC's three principal opioid overdose prevention programs, the Prevention for States (PfS) program, began funding 16 state partners in August 2015 and then expanded to fund a total of 29 states in March 2016. The PfS program aims to prevent opioid morbidity and mortality by implementing evidence-based strategies such as enhancing and maximizing prescription drug monitoring programs (PDMPs) and implementing community or health systems interventions. Methods: In this article, we will describe the origins of the PfS program, provide an overview of program strategies, and locate PfS strategies in the larger landscape of nation-wide opioid overdose prevention efforts advanced by other partners and stakeholders. To describe the implementation of PfS, we offer an iterative model of using information to inform strategy selection, implementation, and evaluation. This model is a product of our observations of program implementation over time and has emerged, post hoc, as a helpful framework for organizing our insights and reflections on the work. Results: For each step of the model, we provide examples of how CDC has supported funded state partners in these efforts. Lastly, we describe innovative facets of the program and implications for both ongoing and future programs. Practical applications: Opioid overdose morbidity and mortality continues to increase across the United States. Adoption of the strategies and the program implementation paradigm described in this article when implementing prevention activities could improve the ability of public health programs to reverse this trend.

Background Practitioners and policy makers need evidence to facilitate the selection of effective prevention interventions that can address the ongoing opioid overdose epidemic in the United States. Methods We conducted a systematic review of publications reporting on rigorous evaluations of systems-level interventions to address provider and patient/public behavior and prevent prescription and illicit opioid overdose. A total of 251 studies were reviewed. Interventions studied included 1) state legislation and regulation, 2) prescription drug monitoring programs (PDMPs), 3) insurance strategies, 4) clinical guideline implementation, 5) provider education, 6) health system interventions, 7) naloxone education and distribution, 8) safe storage and disposal, 9) public education, 10) community coalitions, and 11) interventions employing public safety and public health collaborations. Results The quality of evidence supporting selected interventions was low to moderate. Interventions with the strongest evidence include PDMP and pain clinic legislation, insurance strategies, motivational interviewing in clinical settings, feedback to providers on opioid prescribing behavior, intensive school and family-based programs, and patient education in the clinical setting. Conclusions Although evidence is growing, further high-quality research is needed. Investigators should aim to identify strategies that can prevent overdose, as well as influence public, patient, and provider behavior. Identifying which strategies are most effective at addressing prescription compared to illicit opioid misuse and overdose could be fruitful, as well as investigating synergistic effects and unintended consequences.

Background Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia. Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown. Patients/Methods Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care unit (ICU). The objective was to evaluate the association between platelet transfusions and adjudicated major bleeding events. Platelet transfusion episodes were reviewed for timing of administration, product type, and dose. Major bleeding with and without platelet transfusions was adjusted for severity of thrombocytopenia, use of anti‐platelet agents, surgery and other covariates. Secondary outcomes were thrombosis, death in ICU and platelet count increment. Results Among 2,256 patients, 71 (3.1%) received 190 platelet transfusions. Of those, 121 (63.7%) were administered to 54 non‐bleeding, thrombocytopenic patients. Adjusted rates of major bleeding were not statistically different with or without the administration of platelet transfusions (hazard ratio for transfused patients 0.85; 95% confidence interval, 0.42‐1.72). We did not find a significant association between platelet transfusion use and thrombosis or death in ICU in adjusted analyses. Thrombocytopenia, anemia, major or minor bleeding and use of anticoagulants were associated with platelet transfusion administration. The median post‐transfusion platelet count increment was 20×109/L at 3.5 hours post‐transfusion. Conclusions Rates of major bleeding were not different for patients who did and did not receive platelet transfusions. Inferences were limited by the small number of transfused patients. Clinical trials are needed to better investigate the potential hemostatic benefit and potential harms of platelet transfusions for this high‐risk population.

Background: Traditional evaluation of mild cognitive impairment (MCI) can be costly, time consuming, and impractical for widespread screening. DETECT is a portable device developed to rapidly perform cognitive testing in diverse settings. This study compares DETECT with formal clinical assessment.Methods: A prospective cross-sectional comparison of the DETECT device versus an expert neuropsychologist’s assessment (NPA). A total of 405 participants ≥65 years old, recruited from geriatric clinics and retirement facilities, completed both DETECT and NPA. Multivariable logistic regression methods were used to evaluate the degree of correlation between DETECT testing and the NPA diagnosis.Results: Predictive modeling demonstrated very good ability to discriminate between normal, MCI, and dementia per the NPA reference standard using DETECT subtests (c = 0.85 for any impairment; c = 0.99 for dementia). Conclusion: DETECT scores closely correlate with NPA. DETECT can identify and discriminate between normal, MCI, and dementia and could be incorporated as a screener for MCI.

Wiand's (1997) study supported the use of music therapy to decrease pain and anxiety. The results of this study could be used to support a research utilization project to educate nurses on the potential benefits of music therapy among laboring women. Nurses and physicians could collaborate together to educate clients on music therapy to decrease pain and anxiety. Feasibility issues would include education of the nurses to use music therapy and the cost of developing different types of music. Future research could be done to study a larger sample size. Other research is needed to determine what type of music works best with laboring women.