tbuckley/cabot-search huggingface dataset:
Abstract MP81: Genes Regulating Ion Transport Implicated in a Large Multi-ethnic Pharmacogenomics Study of Thiazide Diuretics and QT Interval: The Cohorts for Heart and Aging Research Using Genomic Epidemiology Pharmacogenetics Working Group (CHARGE PWG)
Authors: Amanda A Seyerle, Colleen M Sitlani, Christy L Avery
Journal: Circulation (2016)

Background: Thiazide diuretics, a commonly used antihypertensive, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We therefore examined whether common genetic variants modified the association between thiazide diuretic use and QT or its component parts: QRS interval (QRS), JT interval (JT). Methods: For each outcome (QT, QRS, JT), 15 participating CHARGE PWG studies conducted genome-wide, ancestry-stratified analyses of European (66%), African (15%), and Hispanic (19%) descent populations (N=78,199). QT, QRS, and JT were measured using standard 12-lead electrocardiograms and diuretic use was assessed with medication inventories. Models leveraged longitudinal data when available, adjusted for heart rate and clinical covariates, and incorporated corrected standard errors to account for underestimation of variance. Ancestry-specific and trans-ethnic interaction effects for approximately 2.5 million HapMap2 SNPs were combined using inverse-variance weighted meta-analysis in METAL. We also conducted combined-phenotype meta-analysis of the t-statistic, weighted by sample size, across all three traits simultaneously using CPASSOC. Finally, we evaluated evidence for gene and pathway enrichment in pre-defined and biologically motivated ion transport, drug metabolism, heart or renal function, and transcription/translation pathways using MAGENTA. Results: The interaction effects for 31 loci were genome-wide significant ( P &lt;5x10 -8 ) following combined-phenotype meta-analysis but not single-trait analysis, including SGK1 ( P =3x10 -11 ), which encodes a kinase that regulates potassium, sodium, and calcium transport and KCNN2 ( P =2x10 -10 ), which encodes a calcium-activated potassium channel. Of note, the interaction effect for the KCNN2 index signal demonstrated opposite directions for JT (-2.56, 95% confidence interval (CI): -5.11, -0.01) and QRS (1.55, 95% CI: 0.18, 2.92), components which represent opposite segments of QT. Furthermore, we detected evidence of enrichment for genes associated with transcription/translation ( ID1 , CHRAC1 , DHX15 ) and ion homeostasis ( KCTD4, PKP2, MFN2, ALPL ) as well as enrichment for ion transport pathways, including voltage gated calcium channels, sodium ion transport, and ligand-gated ion channel activity. Conclusions: Our results suggest that loci involved in the control of ion transport modify the association between thiazide diuretic use and QT, QRS, and JT. Additional work is needed to validate these findings and identify the underlying variants. Furthermore, the potentially limited power to detect interaction effects in single-trait analyses suggests that innovative statistical methods are warranted in future efforts evaluating gene-environment interaction.
Abstract 20580: Type of Cusp Fusion in Patients With Bicuspid Aortic Valves is not associated With the Progression of Aortic Regurgitation or Aortic Stenosis, but is related to Dilation of the Ascending Aorta
Authors: Renee Dallasen, Adedotun Ogunsua, Matthew Parker, Bryon Gentile, John Dickey, Amartya Kundu, Suvasini Lakshmanan, Nikhil Shah, Linda Pape
Journal: Circulation (2016)

Introduction: Bicuspid aortic valves (BAV) are associated with aortic regurgitation (AR), aortic stenosis (AS), and aortic dilation. Hypothesis: Does the type of cusp fusion impact the development ...
Improved Survival by Adding Lomustine to Conventional Chemotherapy for Elderly Patients With AML Without Unfavorable Cytogenetics: Results of the LAM-SA 2007 FILO Trial
Authors: Arnaud Pigneux, Marie Béné, Louis-Rachid Salmi, Pierre-Yves Dumas, Jacques Delaunay, Caroline Bonmati, Romain Guiéze, Isabelle Luquet, Pascale Cornillet-Lefebvre, Eric Delabesse, Jean-Christophe Ianotto, Mario Ojeda-Uribe, Mathilde Hunault-Berger, Anne Banos, Luc Fornecker, Marc Bernard, Eric Jourdan, Norbert Vey, Hacène Zerazhi, Yosr Hishri, Ariane Mineur, Julien Asselineau, Roselyne Delépine, Jean-Yves Cahn, Norbert Ifrah, Christian Recher
Journal: Journal of Clinical Oncology (2018)

Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin.Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety.From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% (P = .01). The proportional hazards assumption was rejected for OS (P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively (P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm (P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm (P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm (P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm (P = .04), and fewer patients required a second treatment after ICL.Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.
Routine collection of EQ-5D-5L derived utility scores in a brain metastases clinic: Correlation with health-related quality of life (FACT-Br).
Authors: Judy Chen, Yizhuo Gao, Justine Baek, Maha Chaudhry, Katrina Hueniken, Mindy Liang, M. Catherine Brown, Grainne M. O'Kane, Lawson Eng, Wei Xu, Doris Howell, David Benjamin Shultz, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

200 Background: Brain metastasis is a common occurrence in many cancers. However, with new therapies (stereotactic radiotherapy) and longer survival due to improved systemic therapies, more contemporary estimates of health utility scores (HUS) are required for this specialized cancer population. Further, recent efforts have tried to incorporate routine collection of such data, especially in an era when new radiation and new systemic therapies, especially targeted therapies require such data when undergoing health technology assessments. Methods: In a cross-sectional study design, patients in the specialized brain metastases clinic at Princess Margaret Cancer Centre were approached to complete the Health-related quality of life (HRQoL) tool, FACT-Br, and the EQ-5D-5L (to derived HUS using Canadian reference values) on iPad or paper. In addition, consent was obtained to collect clinico-demographic data from the patient and chart. In addition to descriptive analysis and participation rates, HUS were correlated to FACT-Br and its subscales. Results: Of 204 eligible patients, 134 were recruited (66% participation rate) from May 2017- Feb 2018. Of 105 patients in this preliminary analysis, the median age was 60 (range: 25-94) years; 73% were female; 64% were Caucasian; 20% were Asian; 49% had lung, 15% had breast, 37% had other primary cancer; 81% received some form of radiotherapy. Median time from first treatment of brain metastasis to survey was 12 (range 0.03-100) months. There were correlations with the following FACT-Br subscales: physical well-being (WB) (rho = 0.70), emotional WB (rho = 0.42), social WB (rho = 0.25), functional WB (rho = 0.59), and brain-specific subscale (rho = 0.67); overall FACT-Br (rho = 0.73); all correlations were p &lt; 0.001. Conclusions: Patients with brain metastasis were generally willing to complete EQ-5D-5L, and patients had good HUS. HUS as measured indirectly by EQ-5D-5L were correlated to HRQoL as measured by FACT-Br or its subscales, with high correlation to the overall FACT-Br. EQ-5D-5L is a practical and useful tool to assess HUS routinely in brain metastases patients.
Minority Resident Physicians’ Views on the Role of Race/Ethnicity in Their Training Experiences in the Workplace
Authors: Aba Osseo-Asare, Lilanthi Balasuriya, Stephen J. Huot, Danya Keene, David Berg, Marcella Nunez-Smith, Inginia Genao, Darin Latimore, Dowin Boatright
Journal: JAMA Network Open (2018)

Black, Hispanic, and Native American physicians remain underrepresented in medicine despite national efforts to increase diversity in the health care workforce. Understanding the unique workplace experiences of minority physicians is essential to inform strategies to create a diverse and inclusive workforce. While prior research has explored the influence of race/ethnicity on the experiences of minority faculty and medical students, there is a paucity of literature investigating how race/ethnicity affects the training experiences of resident physicians in graduate medical education.To characterize how black, Hispanic, and Native American resident physicians experience race/ethnicity in the workplace.Semistructured, in-depth qualitative interviews of black, Hispanic, and Native American residents were performed in this qualitative study. Interviews took place at the 2017 Annual Medical Education Conference (April 12-17, 2017, in Atlanta, Georgia), sponsored by the Student National Medical Association. Interviews were conducted with 27 residents from 21 residency programs representing a diverse range of medical specialties and geographic locations.The workplace experiences of black, Hispanic, and Native American resident physicians in graduate medical education.Among 27 participants, races/ethnicities were 19 (70%) black, 3 (11%) Hispanic, 1 (4%) Native American, and 4 (15%) mixed race/ethnicity; 15 (56%) were female. Participants described the following 3 major themes in their training experiences in the workplace: a daily barrage of microaggressions and bias, minority residents tasked as race/ethnicity ambassadors, and challenges negotiating professional and personal identity while seen as "other."Graduate medical education is an emotionally and physically demanding period for all physicians. Black, Hispanic, and Native American residents experience additional burdens secondary to race/ethnicity. Addressing these unique challenges related to race/ethnicity is crucial to creating a diverse and inclusive work environment.
Explainable machine-learning predictions for the prevention of hypoxaemia during surgery
Authors: Scott M. Lundberg, Bala Nair, Monica S. Vavilala, Mayumi Horibe, Michael J. Eisses, Trevor Adams, David E. Liston, Daniel King-Wai Low, Shu-Fang Newman, Jerry Kim, Su-In Lee
Journal: Nature Biomedical Engineering (2018)
Regulatory T cells in embryo implantation and the immune response to pregnancy
Authors: Sarah A. Robertson, Alison S. Care, Lachlan M. Moldenhauer
Journal: Journal of Clinical Investigation (2018)

At implantation, the embryo expresses paternally derived alloantigens and evokes inflammation that can threaten reproductive success. To ensure a robust placenta and sustainable pregnancy, an active state of maternal immune tolerance mediated by CD4+ regulatory T cells (Tregs) is essential. Tregs operate to inhibit effector immunity, contain inflammation, and support maternal vascular adaptations, thereby facilitating trophoblast invasion and placental access to the maternal blood supply. Insufficient Treg numbers or inadequate functional competence are implicated in idiopathic infertility and recurrent miscarriage as well as later-onset pregnancy complications stemming from placental insufficiency, including preeclampsia and fetal growth restriction. In this Review, we summarize the mechanisms acting in the conception environment to drive the Treg response and discuss prospects for targeting the T cell compartment to alleviate immune-based reproductive disorders.
Abstract 15666: The Mecki Score: A More Accurate Prognostic Tool in Patients With Heart Failure. A Multicenter Comparison With Shfm and Hfss in a Large Cohort of Patients
Authors: Massimo Mapelli, Stefania Paolillo, Angela Scardovi, Ugo Corrà, Michele Emdin, Rocco Lagioia, Marco Metra, Giuseppe Limongelli, Gianfranco Sinagra, Elisabetta Salvioni, Piergiuseppe Agostoni
Journal: Circulation (2016)

Introduction: Heart failure (HF) prognostication is a challenging medical judgment. Many multiparametric risk models have been proposed but available algorithms have multiple limitations. Cardiopul...
Development of a drug-drug interaction screening tool for oncology clinical trial enrollment.
Authors: Lauren A Marcath, Taylor D Coe, Bruce G. Redman, Daniel Louis Hertz
Journal: Journal of Clinical Oncology (2018)

315 Background: Screening drug-drug interactions (DDI) for subjects enrolling in oncology clinical trials is critical to ensuring patient safety and the validity of clinical trial data. We previously reported that DDI screening is not uniformly conducted when screening patients for enrollment into SWOG clinical trials and found that at the University of Michigan Rogel Cancer Center up to 24.2% of subjects enrolled in National Clinical Trial Network (NCTN) trials had a DDI. Screening tools aid in DDI reduction in clinical practice, but none have been created for clinical trial enrollment. Our objective was to develop a clinical trial specific DDI screening tool based on features requested by the end-users of the tool at U-M. Methods: Semi-structured and informal interviews were conducted with all data managers who enroll patients into NCTN clinical trials at the U-M cancer center. Data managers were asked about their current workflow and desired features of a DDI screening tool. Responses were combined and reviewed for feasibility. Desired features were conveyed to PEPID, LLC (Phoenix, AZ) for tool development. Results: Four data managers were interviewed. Protocol-guided screening was a key workflow feature, which was completed by gathering DDI information primarily from the exclusion criteria and drug information sections of each respective protocol, Google, CredibleMeds, and the Indiana University P450 Drug Interaction Table. Consequently, a critical feature was the display of drug characteristics with wording that aligned with that in the protocol including transporter and CYP450 substrates, inhibitors, or inducers and QT prolongation potential. Additional desirable features included separate entry of study and concomitant drugs, filtering to display only DDI with study drugs, and PDF export of results. PEPID developed a prototype tool including these desired attributes for a prospective implementation pilot study. Conclusions: A first generation clinical trial specific DDI screening tool was developed based on end-user feedback. We are designing a prospective study to determine whether implementation of this tool can reduce DDI, enhance patient safety, and ensure validity of clinical trial data.
Online consulting enthusiasts must engage with criticism, says GP leader
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Advocates and providers of online GP consulting must engage with criticism and be more receptive to “rigorous evaluation” of new technologies, the vice chair of the Royal College of General Practitioner has argued.

Martin Marshall, the college’s vice chair and a GP in east London, told a Westminster Forum debate on the future of general practice that there was “enormous potential” in online consulting, and said he conducted some consultations this way.

But he said it was crucial that the potential risks and benefits were properly evaluated, and that those that raised concerns over …
Submucosal tunneling endoscopic septum division for treatment of Zenker’s diverticulum
Authors: Kaveh Hajifathalian, Qais Dawod, Monica Saumoy, Michel Kahaleh
Journal: Endoscopy (2018)

A 71-year-old man who reported 4 years of dysphagia with solid food, as well as halitosis and regurgitation of undigested food, was diagnosed with Zenker's diverticulum after a barium esophagram. After discussing all potential therapeutic options with the patient, he was offered a submucosal tunneling endoscopic septum division (STESD) technique [1]. This technique involves creating a mucosal incision to create an entry point to the submucosal space, and subsequent tunneling and dissection of the submucosal space to expose the Zenker's septum on both sides, and then performing a complete myotomy under direct vision, which leads to resolution of the diverticulum ([Video 1]). STESD was performed in the patient without immediate complications.
Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals
Authors: Yotam Bar-On, Henning Gruell, Till Schoofs, Joy A. Pai, Lilian Nogueira, Allison L. Butler, Katrina Millard, Clara Lehmann, Isabelle Suárez, Thiago Y. Oliveira, Theodora Karagounis, Yehuda Z. Cohen, Christoph Wyen, Stefan Scholten, Lisa Handl, Shiraz Belblidia, Juan P. Dizon, Jörg J. Vehreschild, Maggi Witmer-Pack, Irina Shimeliovich, Kanika Jain, Kerstin Fiddike, Kelly E. Seaton, Nicole L. Yates, Jill Horowitz, Roy M. Gulick, Nico Pfeifer, Georgia D. Tomaras, Michael S. Seaman, Gerd Fätkenheuer, Marina Caskey, Florian Klein, Michel C. Nussenzweig
Journal: Nature Medicine (2018)
Symptom management pathways to reduce ED visits and hospitalizations for patients with cancer.
Authors: Mohana Roy, Brian Halbert, Scott M Devlin, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2018)

302 Background: At our academic medical center, acute on chronic pain, gastrointestinal symptoms and fever led to most preventable ED visits and hospitalizations amongst cancer patients on chemotherapy. We developed management pathways to target these symptoms. Methods: Existing symptom management algorithms and internal expert consensus of multidisciplinary stakeholders, including palliative care and infectious disease, contributed to initial symptom management algorithms. After iterative revisions, the pathways were finalized by hematology/oncology physician and nursing leadership. We identified outpatient, non-oral, cancer directed treatment events using pharmacy billing data. These events included traditional chemotherapy, immunotherapy, and hormonal therapy. We then identified any ED visit or hospitalization at our medical center within 30 days of the event. We plan a pre-post analysis to determine change in 30-day ED visits and hospitalizations for any reason and for our target symptoms. Results: We developed pathways for acute on chronic pain, nausea/vomiting, diarrhea, constipation, and fever. Each pathway follows a standardized model including warning signs with guidance on direct referral to the ED or urgent clinic referral, the specific treatment algorithm, and helpful references. The pathways were implemented in May 2018. From January 2016 to February 2018, we identified 28,764 treatment events among 4,197 patients. Patient mean age was 63 years. The most commonly used treatments were fluorouracil, leuprolide, and paclitaxel. Within 30 days, 5.7% had an associated ED visit; 5.0% had any hospitalization. Conclusions: We developed management pathways for common symptoms among patients receiving cancer treatment. Generalizing care for such a heterogeneous population can be challenging and requires significant engagement from a multidisciplinary team. Post-intervention data is forthcoming to assess the impact of the pathways on reducing ED visits and hospitalizations.
US had record flu deaths last year, says CDC
Authors: Owen Dyer
Journal: BMJ (2018)

A record number of US patients died from flu last year, with 80 000 deaths recorded in 2017-18, says the director of the Centers for Disease Control and Prevention (CDC), Robert Redfield.

He gave the 80 000 estimate during an interview with the Associated Press in New York. It has not yet been published in official data, which is expected within weeks, but the CDC said that the published figure would not be lower.

It means that the 2017-18 period will have had the highest number of deaths from flu, by some margin, since tracking began in 1976. The previous record was 56 000 in 2012-13. The lowest figure in recent years …
The Plight of the Minority Resident Physician—Similar Challenges in a Different World
Authors: Kendall M. Campbell
Journal: JAMA Network Open (2018)

Aba Osseo-Asare, MD; Lilanthi Balasuriya, MD; Stephen J. Huot, MD, PhD; Danya Keene, PhD; David Berg, PhD; Marcella Nunez-Smith, MD, MHS; Inginia Genao, MD; Darin Latimore, MD; Dowin Boatright, MD, MBA, MHS
The Role of Angiogenesis in Hepatocellular Carcinoma
Authors: Michael A. Morse, Weijing Sun, Richard Kim, Aiwu Ruth He, Paolo B. Abada, Michelle Mynderse, Richard S. Finn
Journal: Clinical Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular nature of most HCC tumors underlines the importance of angiogenesis in the pathobiology of these tumors. Several angiogenic pathways have been identified as being dysregulated in HCC, suggesting they may be involved in the development and pathogenesis of HCC. These data provide practical targets for systemic treatments such as those targeting the vascular endothelial growth factor receptor and its ligand. However, the clinical relevance of other more recently identified angiogenic pathways in HCC pathogenesis or treatment remains unclear. Research into molecular profiles and validation of prognostic or predictive biomarkers will be required to identify the patient subsets most likely to experience meaningful benefit from this important class of agents.