Now showing items 1-20 of 14151

    • Taking a Stand: One EAP’s Journey to Anti-Racism, Cultural Relevance & Bridge Building

      Board, Nancy (EAPA, 2021-04-01)
      In November 2018, I joined the Washington State EAP as its Clinical Services Manager, with responsibilities for developing and managing the quality of our contracted EAP provider network. The network was comprised of licensed mental health professionals, most of whom worked in private practice. Early on I recognized the lack of racial diversity of this network and considered that our network demographics likely did not fully represent the demographics of our workforce, as just 12% of our contracted providers identified as non-white. I wanted our services to be inclusive, representative and accessible to everyone and looked to target at least 25% representation with Black, Indigenous, People of Color (BIPOC) / multi-cultural, multi-faceted providers within a year. I believed this goal was achievable since I had successfully built an EAP provider network in the Asia Pacific (APAC) region encompassing 18 countries. I also vowed to learn more about our current providers as individuals, review their practice specialties and build a strong working relationship with them.
    • EAP and COVID-19 2021: Effective Crisis Leadership During COVID-19

      VandePol, Bob (2021)
      Both blind denial and conspiracy theories abound in every conversation, but all eyes are looking to leadership to define the course of action. Your response will reverberate through your organization as people take their cue from what they see and hear from you. Of course, you will be instantly criticized regardless of your decisions and, frankly, you cannot control those responses. You CAN control how you lead and that will stand the test of time. The Pine Rest Employee Assistance Program recommends the following crisis communication process – ACT.
    • Run, Hide, Fight The Case for ‘Common Sense’ Gun Control

      Hughes, Daniel (EAPA, 2020-04)
      I was first introduced to American gun culture in 1960 when I spent six weeks in Wyoming. I was ten years old and spent the summer with my uncle, Cleo “Doc” Davis. Uncle Cleo was a self-identified “cowboy” who was born in Scotts Bluff, Nebraska and raised in Laramie, Wyoming. He served in the Merchant Marine during World War II and trained as a chiropractor on the GI Bill. Following his marriage to my mother’s sister, they settled in Wyoming where he opened a practice. I arrived in Casper, Wyoming, after a two-and-a-half-day train journey. We attended a re-enactment of the Pony Express commemorating the 100th anniversary of the legendary trans-continental Postal rides. As I watched, two riders completed a flawless, albeit furious, exchange of a mail pouch. The crowd whooped and cheered with delight. I quickly learned that Wyoming was far from Brooklyn. It was a summer of new experiences. I visited Yellowstone, attended rodeos, wore cowboy boots, explored alpine forests, and was introduced to the thrill of hunting. Uncle Cleo was a classic outdoorsman. He had grown up hunting and fishing. Each year he would obtain a license and harvest an elk. He would dress out the animal and prepare it for freezing. Elk meat would provide his family protein throughout the year. It was a lifestyle he cherished. He taught me to shoot responsibly, emphasizing safety. Repeatedly, he would remark that “all guns are loaded and every horse kicks.” He also cautioned that one should respect the power of nature. “Out here weather can kill you,” he’d say. These were valuable common sense lessons for a 10-year-old kid from the city. Today, in the wake of multiple school shootings, we teach 10-year-olds to “run, hide, and fight.”
    • Novel Myh11 Dual Reporter Mouse Model Provides Definitive Labeling and Identification of Smooth Muscle Cells - Brief Report

      Ruan, Jian; Zhang, Lu; Hu, Donghua; Qu, Xianghu; Yang, Fan; Chen, Fuxue; He, Xiangqin; Shen, Jian; Dong, Kunzhe; Sweet, Megan; et al. (Wolters Kluwer Health, 2020-12-24)
      Objective: Myh11 encodes a myosin heavy chain protein that is specifically expressed in smooth muscle cells (SMCs) and is important for maintaining vascular wall stability. The goal of this study is to generate a Myh11 dual reporter mouse line for definitive visualization of MYH11+SMCs in vivo. Approach and Results: We generated a Myh11 knock-in mouse model by inserting LoxP-nlacZ-4XpolyA-LoxP-H2B-GFP-polyA-FRT-Neo-FRT reporter cassette into the Myh11 gene locus. The nuclear (n) lacZ-4XpolyA cassette is flanked by 2 LoxP sites followed by H2B-GFP (histone 2B fused green fluorescent protein). Upon Cre-mediated recombination, nlacZ-stop cassette is removed thereby permitting nucleus localized H2B-GFP expression. Expression of the nuclear localized lacZ or H2B-GFP is under control of the endogenous Myh11 promoter. Nuclear lacZ was expressed specifically in SMCs at embryonic and adult stages. Following germline Cre-mediated deletion of nuclear lacZ, H2B-GFP was specifically expressed in the nuclei of SMCs. Comparison of nuclear lacZ expression with Wnt1Creand Mef2cCremediated-H2B-GFP expression revealed heterogenous origins of SMCs from neural crest and second heart field in the great arteries and coronary vessels adjacent to aortic root. Conclusions: The Myh11 knock-in dual reporter mouse model offers an exceptional genetic tool to visualize and trace the origins of SMCs in mice.
    • Telestroke Across the Continuum of Care: Lessons from the COVID-19 Pandemic

      Guzik, Amy K; Martin-Schild, Sheryl; Tadi, Prasanna; Chapman, Sherita N; Al Kasab, Sami; Martini, Sharyl R; Meyer, Brett C; Demaerschalk, Bart M; Wozniak, Marcella A; Southerland, Andrew M (Elsevier Inc., 2021-04-08)
      While use of telemedicine to guide emergent treatment of ischemic stroke is well established, the COVID-19 pandemic motivated the rapid expansion of care via telemedicine to provide consistent care while reducing patient and provider exposure and preserving personal protective equipment. Temporary changes in re-imbursement, inclusion of home office and patient home environments, and increased access to telehealth technologies by patients, health care staff and health care facilities were key to provide an environment for creative and consistent high-quality stroke care. The continuum of care via telestroke has broadened to include prehospital, inter-facility and intra-facility hospital-based services, stroke telerehabilitation, and ambulatory telestroke. However, disparities in technology access remain a challenge. Preservation of reimbursement and the reduction of regulatory burden that was initiated during the public health emergency will be necessary to maintain expanded patient access to the full complement of telestroke services. Here we outline many of these initiatives and discuss potential opportunities for optimal use of technology in stroke care through and beyond the pandemic.
    • Salicylic acid: Summary Report

      Yoon, SeJeong; Gianturco, Stephanie L.; Pavlech, Laura L; Storm, Kathena D.; Yuen, Melissa V.; Mattingly, Ashlee N. (2021-01)
    • Phenoxybenzamine hydrochloride: Summary Report

      Yoon, SeJeong; Gianturco, Stephanie L.; Pavlech, Laura L; Storm, Kathena D.; Yuen, Melissa V.; Mattingly, Ashlee N. (2020-12)
    • Nicotinamide adenine dinucleotide: Summary Report

      Pavlech, Laura L; Yoon, SeJeong; Gianturco, Stephanie L.; Storm, Kathena D.; Yuen, Melissa V.; Mattingly, Ashlee N. (2021-02)
    • Epinephrine bitartrate: Summary Report

      Yoon, SeJeong; Gianturco, Stephanie L.; Pavlech, Laura L.; Storm, Kathena D.; Yuen, Melissa V.; Mattingly, Ashlee N. (2021-03)
    • Mapping expanded prostate cancer index composite to EQ5D utilities to inform economic evaluations in prostate cancer: Secondary analysis of NRG/RTOG 0415

      Khairnar, Rahul; Pugh, Stephanie L; Sandler, Howard M; Lee, W Robert; Villalonga Olives, Ester; Mullins, C Daniel; Palumbo, Francis B; Bruner, Deborah W; Shaya, Fadia T; Bentzen, Soren M; et al. (Public Library of Science, 2021-04-14)
      PURPOSE: The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities. METHODS AND MATERIALS: This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE). RESULTS: A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28-1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: "EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)- 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)"; RMSE was 0.10462. CONCLUSIONS: This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations.
    • A Deferred-Vaccination Design to Assess Durability of COVID-19 Vaccine Effect After the Placebo Group Is Vaccinated

      Follmann, Dean; Fintzi, Jonathan; Fay, Michael P; Janes, Holly E; Baden, Lindsey R; El Sahly, Hana M; Fleming, Thomas R; Mehrotra, Devan V; Carpp, Lindsay N; Juraska, Michal; et al. (American College of Physicians, 2021-04-13)
      Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur before longer-term efficacy and safety are known. The absence of a placebo group could compromise assessment of longer-term vaccine effects. However, by continuing follow-up after vaccination of the placebo group, this study shows that placebo-controlled vaccine efficacy can be mathematically derived by assuming that the benefit of vaccination over time has the same profile for the original vaccine recipients and the original placebo recipients after their vaccination. Although this derivation provides less precise estimates than would be obtained by a standard trial where the placebo group remains unvaccinated, this proposed approach allows estimation of longer-term effect, including durability of vaccine efficacy and whether the vaccine eventually becomes harmful for some. Deferred vaccination, if done open-label, may lead to riskier behavior in the unblinded original vaccine group, confounding estimates of long-term vaccine efficacy. Hence, deferred vaccination via blinded crossover, where the vaccine group receives placebo and vice versa, would be the preferred way to assess vaccine durability and potential delayed harm. Deferred vaccination allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain them on placebo, yet still allows important insights about immunologic and clinical effectiveness over time.
    • Mesenchymal Stem Cells for Neurological Disorders

      Andrzejewska, Anna; Dabrowska, Sylwia; Lukomska, Barbara; Janowski, Miroslaw (Wiley-Blackwell, 2021-02-24)
      Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell-based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Researchers have extensively studied the modulatory properties of MSCs and their engineering, labeling, and delivery methods to the brain. The first part of this review provides an overview of studies on the application of MSCs to various neurological diseases, including stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, and other less frequently studied clinical entities. In the second part, stem cell delivery to the brain is focused. This fundamental but still understudied problem needs to be overcome to apply stem cells to brain diseases successfully. Here the value of cell engineering is also emphasized to facilitate MSC diapedesis, migration, and homing to brain areas affected by the disease to implement precision medicine paradigms into stem cell-based therapies.
    • Effect of prior treatments on selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma

      Mateos, Maria V.; Gavriatopoulou, Maria; Facon, Thierry; Auner, Holger W.; Leleu, Xavier; Hájek, Roman; Dimopoulos, Meletios A.; Delimpasi, Sosana; Simonova, Maryana; Špička, Ivan; et al. (Springer Nature, 2021-04-13)
      Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m2) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT.Trial registration: (NCT03110562).
    • Risks and benefits of antioxidant dietary supplement use during cancer treatment: protocol for a scoping review

      Wieland, L. Susan; Moffet, Ilana; Shade, Sydney; Emadi, Ashkan; Knott, Cheryl; Gorman, Emily F.; D'Adamo, Christopher (BMJ Publishing Group, 2021-04-13)
      Introduction: Antioxidant dietary supplements are used by many patients with cancer to reduce the side effects of chemotherapy and improve prognosis. While some research indicates oral antioxidant supplementation reduces side effects and improves patient survival, other studies suggest the use of antioxidant dietary supplements may interfere with chemotherapy and reduce its curative effects. There is a need to clarify the evidence base on the impact of dietary antioxidant supplementation during chemotherapy on both side effect and treatment efficacy outcomes. We will use a scoping review approach to identify what systematic review evidence exists regarding beneficial and harmful effects of dietary antioxidant supplements when used during cancer treatment. Methods and analysis: We will use Arksey & O'Malley and Joanna Briggs Institute methods for scoping reviews. We will systematically search PubMed, Embase, CINAHL, Scopus, Dissertations & Theses Global and the Cochrane Library from inception to October 2020. Systematic reviews of randomised controlled trials of oral dietary antioxidant supplements used by participants receiving curative chemotherapy, radiotherapy or other biological therapy for cancer will be eligible. Two reviewers will screen citations and full texts for inclusion and chart data on research questions from included reviews. Two reviewers will assess the overall confidence in systematic review results using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR-2), and summarised evidence will focus on reviews rated at high or moderate overall confidence. Tables will be used to map existing evidence and identify evidence gaps for safety and effectiveness outcomes.
    • Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers

      Colen, Rivka R; Rolfo, Christian; Ak, Murat; Ayoub, Mira; Ahmed, Sara; Elshafeey, Nabil; Mamindla, Priyadarshini; Zinn, Pascal O; Ng, Chaan; Vikram, Raghu; et al. (BMJ Publishing Group, 2021-04-13)
      Background: We present a radiomics-based model for predicting response to pembrolizumab in patients with advanced rare cancers. Methods: The study included 57 patients with advanced rare cancers who were enrolled in our phase II clinical trial of pembrolizumab. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST). Patients were categorized as 20 "controlled disease" (stable disease, partial response, or complete response) or 37 progressive disease). We used 3D-slicer to segment target lesions on standard-of-care, pretreatment contrast enhanced CT scans. We extracted 610 features (10 histogram-based features and 600 second-order texture features) from each volume of interest. Least absolute shrinkage and selection operator logistic regression was used to detect the most discriminatory features. Selected features were used to create a classification model, using XGBoost, for the prediction of tumor response to pembrolizumab. Leave-one-out cross-validation was performed to assess model performance. Findings: The 10 most relevant radiomics features were selected; XGBoost-based classification successfully differentiated between controlled disease (complete response, partial response, stable disease) and progressive disease with high accuracy, sensitivity, and specificity in patients assessed by RECIST (94.7%, 97.3%, and 90%, respectively; p<0.001) and in patients assessed by irRECIST (94.7%, 93.9%, and 95.8%, respectively; p<0.001). Additionally, the common features of the RECIST and irRECIST groups also highly predicted pembrolizumab response with accuracy, sensitivity, specificity, and p value of 94.7%, 97%, 90%, p<0.001% and 96%, 96%, 95%, p<0.001, respectively. Conclusion: Our radiomics-based signature identified imaging differences that predicted pembrolizumab response in patients with advanced rare cancer. Interpretation: Our radiomics-based signature identified imaging differences that predicted pembrolizumab response in patients with advanced rare cancer.
    • Red Blood Cell Contribution to Hemostasis

      Gillespie, Andrea H.; Doctor, Allan (Frontiers Media S.A., 2021-04-01)
      Red Blood Cells (RBCs) have been increasingly recognized to play important roles in hemostasis and the mechanisms by which they do so continue to be elucidated. First and foremost, RBC biomechanics are the principal determinant of viscosity and flow dynamics of blood, which strongly influence all features of hemostasis. Of note, morphologic pathology, such as that found in sickle cell disease, leads to increased risk of thrombotic disease. RBC surface interactions govern signaling between platelets and RBCs and also aid in the conversion of prothrombin to thrombin. Additionally, RBCs generate microparticles which have been shown to reduce clotting time. Finally, blood clot structure and maturation are dependent on the inclusion of RBCs in forming thrombi. Here, we review the above mechanisms of RBC contribution to hemostasis.
    • Exploring the utility of a novel point-of-care whole blood thrombin generation assay following trauma: A pilot study

      Ferrara, Michael J.; MacArthur, Taleen A.; Butenas, Saulius; Mann, Kenneth G.; Immermann, Joseph M.; Spears, Grant M.; Bailey, Kent R.; Kozar, Rosemary A.; Heller, Stephanie F.; Loomis, Erica A.; et al. (Wiley-Blackwell, 2021-03-08)
      Introduction: Plasma thrombin generation kinetics as measured by the calibrated automated thrombogram (CAT) assay is a predictor of symptomatic venous thromboembolism after trauma. We hypothesized that data from a new prototype assay for measurement of thrombin generation kinetics in fresh whole blood (near patient testing of thrombin generation), will correlate with the standard CAT assay in the same patients, making it a potential tool in the future care of trauma patients. Methods: Patients were enrolled from June 2018 to February 2020. Within 12 hours of injury, blood samples were collected simultaneously for both assays. Variables compared and correlated between assays were lag time, peak height, time to peak, and endogenous thrombin potential. Data are presented as median with interquartile range (IQR). Spearman and Pearson correlations were estimated and tested between both assays; a P value of <0.05 was considered to be significant. Results: A total of 64 trauma patients had samples analyzed: injury severity score = 17 (IQR), 10-26], hospital length of stay = 7.5 (IQR), 2-18) days, age = 52 (IQR, 35-63) years, 71.9% male, and 42.2% of patients received a transfusion within 24 hours of injury. Thrombin generation parameters between plasma and whole blood were compared and found that all parameters of the two assays correlate in trauma patients. Conclusion: In this pilot study, we have found that a novel point-of-care whole blood thrombin generation assay yields results with modest but statistically significant correlations to those of a standard plasma thrombin generation assay. This finding supports studying this device in a larger, adequately powered study.