bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation and Impact of Pharmacist-Initiated Home Medication Ordering in an Emergency Department Observation Unit
Authors: Koehl Jennifer , Steffenhagen Aaron , Halfpap Joe 
Published: October 2019

Purpose: To design and evaluate the accuracy and efficiency of a medication reconciliation workflow incorporating pharmacist home medication ordering. Methods: Designed and implemented an admission medication reconciliation workflow that expanded the pharmacists’ role to include an initial ordering of home medications. Performed a prospective, pre–post cohort analysis comparing preimplementation accuracy and efficiency data from inpatient medicine and cardiology patients to postimplementation accuracy and efficiency data from our emergency department observation unit. Accuracy for the preimplementation group was defined by the number of unintentional discrepancies identified by pharmacists between the prescriber admission orders and the reconciled home medication lists. Accuracy for the postimplementation group was defined by the prescriber acceptance of pharmacist-ordered home medications. Efficiency was measured by pharmacist time to complete the admission medication reconciliation process. Results: Prescribers accepted 98% of home medication orders placed by pharmacists, which correlated with a significant decrease in the occurrence of home medication orders containing a medication-related problem or discrepancy (46.4% vs 1.3%, P < .0001). The mean pharmacist time spent completing medication reconciliation per admission decreased from 64 to 23 minutes ( P < .0001). Conclusion: Implementation of an admission process that incorporates pharmacist ordering of home medications increased prescribing accuracy and efficiency.
Descriptive comparison of hospital formulary decisions with published oncology valuation methods
Authors: Lam Simon W , Siebenaller Caitlin , Earl Marc , Hill Brian T , Kalaycio Matt , Rini Brian , Carraway Hetty E , Leonard Mandy , Sekeres Mikkael A 
Published: October 2019

Introduction As cost of cancer therapy continues to increase, several organizations have developed rubrics to ascertain treatment. No studies have evaluated these methods for hospital formulary decision-making. We applied different value measurement tools to formulary decisions from one hospital system to assess their operational utility. Methods We evaluated four value systems: National Comprehensive Cancer Network Evidence Blocks, DrugAbacus drug pricing, European Society for Medical Oncology clinical benefit scale, and the American Society of Clinical Oncology net health benefit. Each value score or cost was assessed against our hospital formulary requests between 2012 and 2016. Formulary requests accepted and rejected were compared with respect to their relative numbers of National Comprehensive Cancer Network blocks, difference between DrugAbacus and actual cost, and European Society for Medical Oncology and American Society of Clinical Oncology scores. Results Twenty-two chemotherapy requests were included, with 20 approvals and 2 rejections. No correlation was observed between number of evidence blocks and formulary acceptance (p = 0.13). Most drugs had a higher actual price than the DrugAbacus suggested cost (p = 0.036). No significant differences were observed in European Society for Medical Oncology (p = 0.90) or American Society of Clinical Oncology (p = 0.70) scores between drugs that were accepted or rejected. When evaluating monthly cost per point of American Society of Clinical Oncology score, a numerical difference between groups was observed (median = $369.7 versus $1256.8 per point, p = 0.61). Conclusions Existing oncology value assessment systems only variably inform hospital formulary decisions. The American Society of Clinical Oncology net health benefit score deserves further study as a method to systematically quantify the clinical safety and efficacy of formulary medication addition relative to cost.
Financial Hardship, Motivation to Quit and Post-Quit Spending Plans among Low-Income Smokers Enrolled in a Smoking Cessation Trial
Authors: Rogers Erin , Palacios Jose , Vargas Elizabeth , Wysota Christina , Rosen Marc , Kyanko Kelly , Elbel Brian D. , Sherman Scott 
Published: October 2019

Background: Tobacco spending may exacerbate financial hardship in low-income populations by using funds that could go toward essentials. This study examined post-quit spending plans among low-income smokers and whether financial hardship was positively associated with motivation to quit in the sample. Methods: We analyzed data from the baseline survey of a randomized controlled trial testing novel a smoking cessation intervention for low-income smokers in New York City ( N = 410). Linear regression was used to examine the relationship between financial distress, food insecurity, smoking-induced deprivation (SID) and motivation to quit (measured on a 0-10 scale). We performed summative content analyses of open-ended survey questions to identify the most common plans among participants with and without SID for how to use their tobacco money after quitting. Results: Participants had an average level of motivation to quit of 7.7 ( SD = 2.5). Motivation to quit was not significantly related to having high financial distress or food insecurity ( P > .05), but participants reporting SID had significantly lower levels of motivation to quit than those without SID ( M = 7.4 versus 7.9, P = .04). Overall, participants expressed an interest in three main types of spending for after they quit: Purchases, Activities, and Savings/Investing, which could be further conceptualized as spending on Oneself or Family, and on Needs or Rewards. The top three spending plans among participants with and without SID were travel, clothing and savings. There were three needs-based spending plans unique to a small number of participants with SID: housing, health care and education. Conclusions: Financial distress and food insecurity did not enhance overall motivation to quit, while smokers with SID were less motivated to quit. Most low-income smokers, including those with SID, did not plan to use their tobacco money on household essentials after quitting.
Relationship between adherence to secondary prevention and health literacy, self-efficacy and disease knowledge among patients with coronary artery disease in China
Authors: Lu Minmin , Xia Haiou , Ma Jianying , Lin Ying , Zhang Xian , Shen Yunzhi , Hravnak Marilyn 
Published: October 2019

Background: Adherence to secondary prevention is an indispensable part of the management of patients with coronary artery disease. Finding patient factors affecting their adherence behaviours is important for improving the treatment effect and limiting further disease progression. Aims: To examine the association between health literacy, self-efficacy, disease knowledge and adherence to secondary coronary artery disease prevention in patients in China. Methods: In this cross-sectional study, 598 patients with coronary artery disease were enrolled in two tertiary hospitals in China during a hospitalisation for receiving percutaneous coronary intervention. Patient-reported data were collected on demographics, health literacy, self-efficacy, disease knowledge and adherence to secondary coronary artery disease prevention (medication-taking and heart-healthy lifestyle (exercise, reducing/eliminating alcohol intake and smoking, low salt and fat diet, stress reduction)). Chi-squared tests and regression analyses were performed. Results: The proportions of recalled self-report of adherence to medication-taking and a heart-healthy lifestyle immediately prior to the coronary artery disease hospitalisation were 84.7% and 53.2%, respectively. In logistic regression, health literacy, self-efficacy and disease knowledge was significantly associated with non-adherence to secondary coronary artery disease prevention. Limited health literacy demonstrated a 1.61-fold odds for non-adherence to a heart-healthy lifestyle. Each score increase of self-efficacy and disease knowledge had 0.98-fold odds and 1.05-fold odds of non-adherence to a heart-healthy lifestyle. Conclusions: Adherence to medication-taking was relatively good in Chinese patients prior to coronary artery disease hospitalisation, but adherence to heart-healthy lifestyle behaviours should be improved. Health literacy, self-efficacy and disease knowledge should be taken into account when intervening to improve secondary coronary artery disease prevention.
Comparison of volar locking plates with external fixation and K-wires in arthroscopically assisted intra-articular distal radial fracture fixation
Authors: Krustins Uldis , Krustins Janis , Bringina Diana , Laurane Kristine , Jumtins Andris 
Published: October 2019

This article presents the results of a prospective cohort study that included 63 patients with intra-articular (AO Type C) distal radial fractures who were treated using an arthroscopically assisted approach with either volar locking plates or external fixator and K-wires. Postoperative analysis was carried out using X-ray assessment, clinical data, Patient-Rated Wrist Evaluation score, Gartland and Werley score, Modern Activity Subjective Survey of 2007 score, range of motion, grip, pinch and tripod pinch assessment at 1, 3, 6 and 12 months postoperatively. Despite the statistically significant differences found in a number of parameters during the period of observation, there were no clinically relevant differences determined between the two methods. There was a greater number of complications in the external fixator and K-wire treated patients. Level of evidence: II
High immunoglobulin E level is associated with increased readmission in children with bronchopneumonia
Authors: You Cun , Ran Guo , Wu Xiao , Wang Yu , Tian Hua , Fan Jiabao , Yao Zezhong , Wang Fei 
Published: October 2019

Background: Increased immunoglobulin E (IgE) is associated with lower respiratory tract infections. The study aimed to evaluate the association between IgE and the rate of bronchopneumonia-related readmission within 12 months in children. Methods: A total of 1099 children aged over 1 year with bronchopneumonia, from 1 January 2015 to 31 December 2016, were enrolled. Unplanned readmissions within 12 months after discharge were observed. Multivariate regression analysis was used to identify independent risk factors for rehospitalization. Results: The rate of rehospitalization was 11.4% (125/1099). Compared to the nonreadmission children, IgE levels, the proportion of children with asthma and hospitalization duration were significantly higher in the readmission children ( p < 0.05). Compared to the children with normal IgE (≤ 165 IU/ml) levels, the risk of rehospitalization was significantly higher in children with abnormal IgE [odds ratio (OR) 1.781, 95% confidence interval (CI) 1.209–2.624, p = 0.004]. Children with IgE level more than three times the upper limit had even higher risks of readmission (OR 2.037, 95%CI 1.172–3.540, p = 0.012). Meanwhile, the risk of readmission in children with abnormal IgE combined with or without bronchial asthma was significantly higher (OR 2.548 and 1.918, 95% CI 1.490–4.358 and 1.218–3.020, p = 0.001 and 0.005, respectively). Conclusions: Children aged over 1 year with bronchopneumonia who had higher IgE levels are at increased risk for rehospitalization within the first 12 months of the index hospitalization and IgE level may be used as a predictor of rehospitalization in children with bronchopneumonia.
Overexpression of the TGF-Beta Modulator .Bambi Promotes Hematopoetic Stem Cell Proliferation.
Authors: Mao Rui , Sirin Olga , Goodell Margaret 
Published: October 2019

Abstract
Abstract 1446
Poster Board I-469
Hematopoietic stem cells (HSC) normally reside in a quiescent state in the bone marrow. During times of stress, HSCs are activated to begin differentiation and self-renewal, replenishing the supply of myeloid and lymphoid cells present in the blood. The mechanisms regulating this rapid activation have not been fully elucidated. We previously identified the TGF-beta modulator Bambi (BMP and activin membrane-bound inhibitor) to be upregulated four-fold in HSCs compared to differentiated cells. Bambi codes for a transmembrane pseudoreceptor that inhibits TGF-beta receptor activation. Since TGF-beta signaling has been established to be important for induction of HSC quiescence as well as cell-cycle inhibition in long-term progenitors, we hypothesize that Bambi may play an important role in the regulation of HSCs. Using a retroviral vector, we overexpressed Bambi in bone marrow cells. Overexpression of Bambi resulted in increased colony-formation in vitro when compared to control cells. Furthermore, transduced cells expressed higher levels of the cell-cycle marker Ki-67, indicating a greater proportion of cells in active stages of the cell cycle. To verify the results of these assays in vivo, bone marrow overexpressing Bambi was transplanted into lethally irradiated recipient mice. Bambi-overexpressing cells demonstrated a higher level of engraftment in all lineages than control cells at several time points, which confirms the previous in vitro data suggesting greater cell cycle activity. Moreover, we identified the pathway through which Bambi acts by monitoring the levels of phosphorylated Smad2 (pSmad2), a downstream target of TGF-beta. Overexpression of Bambi resulted in a distinctly lower level of pSmad2, which explains the cell-cycle effects seen in vivo and in vitro. These studies show that Bambi functions to promote HSC proliferation and a probable mode of action in HSCs is through decreased pSmad2 levels from inhibition of the TGF-beta pathway. Bambi has been shown to be upregulated in certain leukemias, and a more complete understanding of the mechanism through which Bambi acts will provide better opportunities for therapeutic innovation.
This research was graciously funded by an NIH grant and the ASH Trainee Research Award.

Disclosures
No relevant conflicts of interest to declare.
Simultaneous Targeting of SHH/ p53 Pathways in Large B Cell Lymphomas.
Authors: Chari Nikhil S , Teo Albert E.K. , Medeiros L. Jeffrey , McDonnell Timothy J. 
Published: October 2019

Abstract
Abstract 1730
Poster Board I-756
The sonic hedgehog (SHH) pathway, associated with proliferative stem cell niches of many organs, is frequently deregulated in diverse cancers. We have previously shown that the SHH pathway augments the survival of tumor cells by inducing antiapoptotic molecules including bcl-2 and provides resistance to a number of conventional cancer therapies. Aberrant activation of the SHH pathway has been associated with activation and maintenance of lymphoid malignancies. Additionally, our recent data indicates that p63, a p53 family member and an important marker of stem cells has multiple interacting nodes with the SHH pathway. Based on these observations, we hypothesized i) that there is crosstalk between the SHH and p53/p63 networks in cells and, ii) inhibition of the SHH pathway with simultaneous activation of the p53 pathway would result in increased cell death in cancer cell lines of lymphoid origin. Using SDS-PAGE followed by immunoblotting and RT-PCR we surveyed a panel of 18 leukemia/lymphoma cell lines for components of the SHH pathway and the p53/p63/p73 network. Robust SHH pathway expression was observed in 15 of the 18 cell lines examined. Interestingly, in p53 deficient cell lines there was an increase in p63/p73 expression as compared to cell lines with wild type (WT) p53. A set of the previously analyzed diffuse large B- cell lymphoma (DLBCL) cell lines were selected and were representative of both p53 deficient and WT cell lines and also the activated B-like DLBCL (ABC) and germinal center B-like DLBCL (GCB) subgroups. These cells were treated with cyclopamine, an inhibitor of the SHH pathway and/or nutlin, an HDM2 antagonist. Cell viability (MTS assay) was measured using both compounds at various drug concentrations and time points. In addition we also investigated the effects of the drugs individually and in combination on components of the p53/p63 and SHH axes and their targets. Our findings suggest that treatment of p53 (WT) cell lines with a combination of nutlin and cyclopamine results in reduced cell survival than treatment with either drug alone and at lower drug concentrations and that the p53 status of the cell line may be more important in determining therapeutic response to the selected compounds. In addition the p53/p63 pathway may have a novel role in regulation of specific components of the SHH pathway in cells of lymphoid origin. In conclusion, these observations provide proof of concept that a combinatorial therapeutic approach, targeting both the p53 and SHH axes would provide a more robust and favorable response in large B cell lymphomas.

Acknowledgments
This work was supported in part by the The Mehta Family Foundation

Disclosures
No relevant conflicts of interest to declare.
CHOP-R + Bortezomib as Initial Therapy for Mantle Cell Lymphoma (MCL).
Authors: Ruan Jia , Martin Peter , Furman Richard R , Vose Julie M. , LaCasce Ann , Cheung Ying-Kuen K. , O'Loughlin Jennifer , Elstrom Rebecca , Niesvizky Ruben , Chadburn Amy , Ely Scott , Cesarman Ethel , Coleman Morton , Leonard John P. 
Published: October 2019

Abstract
Abstract 2682
Poster Board II-658

BACKGROUND:
Bortezomib is a proteasome inhibitor with single agent activity in mantle cell lymphoma. Preclinical studies have demonstrated that addition of bortezomib to chemoimmunotherapy can enhance antitumor effects. We report findings from a phase I/II trial of dose-escalated bortezomib + standard CHOP-rituximab (R) in previously untreated MCL patients.

METHODS:
From 6/2004 to 10/2007, 36 patients with previously untreated MCL received standard CHOP-21 with rituximab (375 mg/m2 per cycle) plus bortezomib at 1.0 mg/m2 (n=4) or 1.3 mg/m2 (n=32) on days 1 and 4 of each cycle for a total of 6 cycles. Study endpoints included safety and efficacy assessment.

RESULTS:
At study entry, median age (n=36) was 66 years (range 45–80), and M:F ratio was 5:1. Thirty-four subjects (94%) had stage III/IV disease, and 18 (50%) had elevated serum lactate dehydrogenase (LDH). Patients generally had unfavorable baseline international prognostic index (IPI) scores (42% with IPI of 2, and 47% with IPI of 3–5), as well as MIPI scores (28% with intermediate risk and 39% with high risk). Treatment was generally well tolerated. Peripheral neuropathy (sometimes reversible) occurred in 20 subjects (56%) with 16 grade 1, 3 grade 2, and 1 grade 3. Grade 3/4 cytopenias included anemia (11%), neutropenia (23%) and thrombocytopenia (14%). At a median followup of 30 months (range 8–61 months), 32 patients are evaluable for efficacy. For all patients (n=36), the intent-to-treat (ITT) overall response rate (ORR) is 81% with 64% CR/CRu. For evaluable patients (n=32), the ORR is 91%, and CR/CRu 72%. The median progression free survival for all patients (n=36) is 21 months (95% CI 17-29) by Kaplan-Meier estimate, and 2 year overall survival is 86% (95% CI 69–94%). Currently eight patients remain in ongoing response (range 15–39 months). In a univariate Cox regression analysis, IPI correlated with PFS (HR 1.85, p=0.023), while MIPI correlated with both PFS (HR 1.81, p=0.027) and OS (HR 2.6, p=0.033).

CONCLUSIONS:
Bortezomib in conjunction with R-CHOP-21 can be safely administered in an outpatient regimen to previously untreated MCL patients, including the elderly. Further evaluation of combinations of bortezomib with R-CHOP is warranted.

Disclosures:
Vose: Genentech, Inc.: Consultancy, Research Funding. Coleman:Millenium: Speakers Bureau. Leonard:Millenium: Consultancy, Honoraria; Johnson & Johnson: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Biogen Idec: Consultancy, Honoraria.
FOG-1 Requires NuRD to Promote Hematopoiesis and Maintain Lineage Fidelity within the Megakaryocytic–Erythroid Compartment.
Authors: Gregory Gregory D , Miccio Annarita , Bersenev Alexey , Wang Yuhuan , Hong Wei , Zhang Zhe , Poncz Mortimer , Tong Wei , Blobel Gerd A 
Published: October 2019

Abstract
Abstract 702
Nuclear factors regulate the development of complex tissues by promoting the formation of one cell lineage over another. Transcription factors GATA-1 and GATA-2 co-operate with the cofactor FOG-1 to promote erythroid and megakaryocyte differentiation. In contrast, FOG-1 is inhibitory to the function of GATA factors in the context of mast cells. The mechanisms by which FOG-1 functions distinctly as co-activator and co-repressor are incompletely defined.
Purification of FOG-1-associated proteins led to the identification of the nucleosome remodeling and histone deacetylase NuRD complex (Hong, et al., EMBO J. 2005). To investigate the in vivo function of this interaction, we generated mice bearing point mutations in FOG-1 that disrupt NuRD binding. The phenotype of homozygous (Fog1ki/ki) mice revealed an essential role of NuRD for normal FOG-1 function in a broad range of cell types, including erythroid cells and megakaryocytes. Here we report that defects in hematopoietic development arise as early as the bipotent megakaryocyte-erythroid progenitor in adult mice. Strikingly, Fog1ki/ki megakaryocyte-erythroid progenitors (MEP) retained multi-lineage capacity, capable of generating mast cells and other myeloid lineages. We did not observe an increase in mast cell potential in E10.5 yolk sacs, as has been previously reported in Fog1null embryos, indicating a stage-specific role for FOG-1's interaction with NuRD.
Genome wide transcriptome analysis of purified Fog1ki/ki MEP revealed inappropriate expression of several mast cell-specific genes including Fcer1a, Fcer1b, Mcpt2, and Cpa3. Notably, aberrant mast cell gene expression persisted in committed Fog1ki/ki megakaryocyte and erythroid cells. Thus FOG-1 and NuRD are essential to constrain mast cell gene expression throughout erythroid and megakaryocyte ontogeny. A direct mechanism of repression is suggested as select mast cell genes are occupied by GATA-1 and FOG-1 in erythroid precursor cells. Furthermore, a mutant form of GATA-1 that is impaired for FOG-1 binding (GATA-1-V205M) failed to repress mast cell gene expression. Together, these observations suggest that a simple heritable epigenetic silencing mechanism is insufficient to permanently repress mast cell genes. Instead, the continuous presence of GATA-1, FOG-1 and NuRD is required to maintain lineage fidelity throughout megakaryocyte-erythroid ontogeny.

Disclosures:
No relevant conflicts of interest to declare.