tbuckley/cabot-search huggingface dataset:
Trends in U.S. Drug Overdose Deaths
Authors: Amy Berrington de Gonzalez, Neal D. Freedman, Meredith S. Shiels
Journal: Annals of Internal Medicine (2018)

Letters4 September 2018Trends in U.S. Drug Overdose DeathsAmy Berrington de Gonzalez, DPhil, Neal D. Freedman, PhD, and Meredith S. Shiels, PhDAmy Berrington de Gonzalez, DPhilNational Cancer Institute, Rockville, Maryland (A.B.D., N.D.F., M.S.S.)Search for more papers by this author, Neal D. Freedman, PhDNational Cancer Institute, Rockville, Maryland (A.B.D., N.D.F., M.S.S.)Search for more papers by this author, and Meredith S. Shiels, PhDNational Cancer Institute, Rockville, Maryland (A.B.D., N.D.F., M.S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0313 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Ms. Cox and colleagues about the critical need to study the drug overdose epidemic in the AI population. We previously showed that premature mortality rates are increasing more rapidly in AIs and Alaska Natives (ANs) than in NHW persons in the United States (1). Many causes of death contributed to these rising rates, but drug poisoning caused the largest increases.When death rates from 2011 to 2014 and 1999 to 2002 were compared, AIs and ANs had the largest increases in deaths from drug poisoning of all racial and ethnic groups. Death rates from drug ...References1. Shiels MS, Chernyavskiy P, Anderson WF, Best AF, Haozous EA, Hartge P, et al. Trends in premature mortality in the USA by sex, race, and ethnicity from 1999 to 2014: an analysis of death certificate data. Lancet. 2017;389:1043-54. [PMID: 28131493] doi:10.1016/S0140-6736(17)30187-3 CrossrefMedlineGoogle Scholar2. Abbasi J. Why are American Indians dying young? JAMA. 2018;319:109-11. [PMID: 29318275] doi:10.1001/jama.2017.10122 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: National Cancer Institute, Rockville, Maryland (A.B.D., N.D.F., M.S.S.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1812. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTrends in U.S. Drug Overdose Deaths in Non-Hispanic Black, Hispanic, and Non-Hispanic White Persons, 2000–2015 Meredith S. Shiels , Neal D. Freedman , David Thomas , and Amy Berrington de Gonzalez Trends in U.S. Drug Overdose Deaths Mary E. Cox , Nicole Dzialowy , Lillie Armstrong , and Scott Proescholdbell Metrics 4 September 2018Volume 169, Issue 5Page: 356KeywordsAddictionConflicts of interestDeath ratesDisclosureDrugsHispanic people ePublished: 4 September 2018 Issue Published: 4 September 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 19816: Effect of Diuretics on All-Cause Mortality and Cardiovascular Event Rates in Patients With Asymptomatic Aortic Stenosis
Authors: Anders M Greve, Christoph Nienaber, Christa Gohlke-Bärwolf, Polydoros Kampaktsis, Simon Ray, Ronnie Willenheimer, Antero Kesaniemi, Peter M Okin, Richard Devereux, Kristian Wachtell, Casper N Bang
Journal: Circulation (2016)

Background: There are very limited data on the safety of cardiovascular drugs in aortic stenosis (AS). We evaluated if diuretics increased the risk of death and cardiovascular events in asymptomati...
Abstract 13246: The Role of Kca3.1 in Monocyte-macrophage Polarization and Its Relevance to Atherosclerotic Plaque Instability
Authors: Rende Xu, Chenguang Li, Juying Qian, Junbo Ge
Journal: Circulation (2015)

Background Emerging evidence indicates that pro-inflammatory monocyte-macrophage polarization imbalance play key role in the atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in transcriptional regulation of monocyte-macrophage polarization and its relation to plaque instability is still unknown. Methods THP-1 monocytes were differentiated into macrophages using phorbol myristate acetate (PMA) and polarized into M1 by IFN-γ and LPS and into M2 macrophages by IL-4. Monocytes/macrophages were treated with KCa3.1 blocker TRAM-34 during differentiation or polarization. Animal model of plaque instability was induced by combined partial ligation of the left renal artery and left common carotid artery in apolipoprotein E knockout mice. From 6 weeks after surgery, the animals were treated with subcutaneous injection of TRAM-34 (120 mg/kg/d), or vehicle (miglyol 812) for 4 weeks. Phenotypic markers of macrophages and histological plaque characteristics were analysed. Results Significant up-regulation of KCa3.1 expression was found during the differentiation of THP-1 monocytes to macrophages. TRAM-34 treatment reduced the polarization of THP-1-derived macrophages to proinflammatory M1 macrophage while increasing the polarization of THP-1-derived macrophages to anti-inflammatory M2 macrophages. Further mechanistic studies indicated that KCa3.1 blocker promoted an M2 macrophage phenotype through up-regulation the activation of PPAR-γ. In animal models, KCa3.1 blockade therapy with TRAM-34 strikingly reduced the incidence of plaque rupture and luminal thrombus in carotid arteries. Moreover, macrophages within atherosclerotic lesions of mice receiving TRAM-34 injection showed decreased expression of markers associated with M1 macrophage polarization and enhanced expression of the M2 markers. Conclusion These results suggest that blockade of KCa3.1 suppresses plaque instability at the advanced stage of atherosclerosis by promoting polarization of macrophages toward an M2 phenotype.
Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction
Authors: Jasper Tromp, B. Daan Westenbrink, Wouter Ouwerkerk, Dirk J. van Veldhuisen, Nilesh J. Samani, Piotr Ponikowski, Marco Metra, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos Filippatos, Pim van der Harst, Chim C. Lang, Leong L. Ng, Faiez Zannad, Aelko H. Zwinderman, Hans L. Hillege, Peter van der Meer, Adriaan A. Voors
Journal: Journal of the American College of Cardiology (2018)
Treatment failure: Why patients with BRCA mutations are declining risk-reducing surgery.
Authors: Olivia R Khouri, Deanna Gerber, Jessica Lee, Julia Fehniger, Leslie R. Boyd, Bhavana Pothuri
Journal: Journal of Clinical Oncology (2018)

1544 Background: The NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRBSO) for patients with BRCA mutations by age 35-40 or upon completion of childbearing. We previously reported high rates of non-compliance with these guidelines, with many women pursuing RRBSO after 40, if at all. We sought to evaluate patients’ reasons for declining RRBSO to identify areas for improvement in counseling and prevention. Methods: We conducted a retrospective chart review to identify patients with BRCA mutations (diagnosed 2006–2017). Data were abstracted from electronic medical records and analyzed using descriptive and two-tailed statistics. Results: There were 345 women with BRCA mutations identified (57% BRCA1, 43% BRCA2), with median age 32(16–49) at the time of diagnosis. Eighty-seven percent (303) were Caucasian and 50% (172) were of Ashkenazi descent. A majority (87%, 287) had a family cancer history and 25% (88) had a personal cancer history. Thirty-eight percent (132) underwent risk-reducing mastectomy (RRM) and 32% (102) underwent RRBSO. Among those noncompliant with RRBSO, 21% cited menopausal symptoms, 56% fertility preservation, 15% “other,” and 8% were lost to follow up. Undergoing RRBSO was associated with age > 40 (p < 0.0001), personal cancer history (p = 0.02), family cancer history (p < 0.0001), and previous RRM (p = 0.04). Patients > 40 more often cited menopausal symptoms in declining RRBSO (p < 0.0001), while patients < 40 were more likely to cite fertility preservation (p < 0.0001). Conclusions: Patients with a personal or family history of cancer, history of RRM, or age > 40 were more apt to undergo RRBSO. The majority of women who declined RRBSO reported fertility or menopause as primary concerns. As the age of childbearing increases, counseling of BRCA patients should address early childbearing, assisted reproductive technology, and hormonal therapy to facilitate timely RRBSO for prevention of ovarian cancer and mortality reduction.
Abstract P060: Reduction of Cardiovascular Mortality in the United States Population, 1988-2004: A Larger Contribution of Declining Exposures to Cadmium and Lead Compared to Traditional Cardiovascular Risk Factors
Authors: Adrian Ruiz-Hernandez, Ana Navas-Acien, Roberto Pastor-Barriuso, Josep Redon, Eliseo Guallar, Maria Tellez-Plaza
Journal: Circulation (2016)

Introduction: Lead and cadmium exposures have markedly declined in the US following the banning of lead in gasoline and the implementation of tobacco control, air pollution reduction, and hazardous waste remediation policies since the mid 1970s. While lead and cadmium have been proposed as cardiovascular disease risk factors, little is known about their potential contribution to the decline in cardiovascular mortality in US adults. Hypothesis: We assessed the hypothesis that lead and cadmium exposure reductions partly explain the decreasing trend in cardiovascular mortality that occurred in the US from 1988-1994 to 1999-2004, after controlling for traditional cardiovascular risk factors including smoking, obesity, physical inactivity, hypertension, diabetes, chronic kidney disease, and dyslipidemia. Methods: Cohort study of 15,421 men and women ≥40 years old participating in the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2004. We implemented a mediation approach with additive hazard models to estimate the reductions in cardiovascular disease (CVD) mortality rates over time explained through changes in urine cadmium and blood lead concentrations. Results: After adjusting for age, sex, race and smoking, urine cadmium and blood lead concentrations decreased by 20.4 and 38.2%, respectively, between 1988-1934 and 1999-2004. Age-adjusted CVD mortality rates in the US decreased from 712.0 to 356.8 /100.000 person-years comparing 1988-1994 to 1999-2004. Changes in traditional CVD risk factors explained 16% of this decline. The observed reductions in urine cadmium and blood lead levels explained an additional 27.6% of this decline. Conclusions: The net impact of declining cadmium and lead exposures on mortality changes in the US was larger compared to traditional risk factors. These findings support that reducing cadmium and lead exposures resulted in a major public health achievement. The general population, however, remains exposed to cadmium and lead at concentrations that have been associated to CVD in the US population. Preventive strategies to enable additional reductions in exposure to cadmium and lead are needed.
Chronic Fatigue Care
Authors: Bridget Kuehn
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Characterization of the immune microenvironment of diffuse intrinsic pontine glioma: implications for development of immunotherapy
Authors: Nicole A P Lieberman, Kole DeGolier, Heather M Kovar, Amira Davis, Virginia Hoglund, Jeffrey Stevens, Conrad Winter, Gail Deutsch, Scott N Furlan, Nicholas A Vitanza, Sarah E S Leary, Courtney A Crane
Journal: Neuro-Oncology (2018)

Diffuse intrinsic pontine glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically; however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor expression in pediatric low- and high-grade gliomas and DIPG. Tumor microarrays were stained for infiltrating immune cells. RNA was isolated from snap-frozen tumor tissue and Nanostring analysis performed. DIPG and glioblastoma cells were co-cultured with healthy donor macrophages, T cells, or natural killer (NK) cells, and flow cytometry and cytotoxicity assays performed to characterize the phenotype and function, respectively, of the immune cells. DIPG tumors do not have increased macrophage or T-cell infiltration relative to nontumor control, nor do they overexpress immunosuppressive factors such as programmed death ligand 1 and/or transforming growth factor β1. H3.3-K27M DIPG cells do not repolarize macrophages, but are not effectively targeted by activated allogeneic T cells. NK cells lysed all DIPG cultures. DIPG tumors have neither a highly immunosuppressive nor inflammatory microenvironment. Therefore, major considerations for the development of immunotherapy will be the recruitment, activation, and retention of tumor-specific effector immune cells.
Abstract 16712: Premedical Students are an Effective and Cost Efficient Way to Teach Large Numbers of People Hands Only CPR in a Community Based Approach
Authors: Alexandria Oliver, Kayla King, Anna Scalzo, William C Dillon
Journal: Circulation (2015)

Introduction: There are approximately 750 cases of cardiac arrest in Jefferson Co, KY each year and only an estimated 6-14% of these individuals survive. The overwhelming death rate can in part be attributed to the low amount of by-stander CPR being performed. A citywide CPR initiative was started to increase the amount of by-stander CPR and ultimately increase the cardiac arrest survival rate. Hypothesis: Premedical students can be trained as hands only CPR instructors and can teach large numbers of people hands only CPR in a community based approach cost effectively. Methods: The program officially launched in the summer of 2014. Over a 12 month period, 12 premedical students were taught to become hands only CPR instructors. These instructors went into high schools, community based organizations and churches to educate individuals on cardiac arrest, hands only CPR, and preventative health measures. Demographic data was collected as well as a pre and post test was performed by each student to gauge the efficacy of the teaching program. Results: During the study period, 7554 people in Louisville, KY participated in the hands only CPR classes. We taught classes in 30 high schools and reached over 90% of all freshmen high school students in Louisville. We taught people in each zip code in Louisville and taught greater than 75 people in 25 of the 35 (70%) zip codes in Louisville. The cost for this program was $3.40/person taught hands only CPR. Conclusions: Using premedical students as hands only CPR instructors is an effective way of teaching large numbers of people hands only CPR in a cost effective manner. This program could be reproduced in other communities.
Women in England will be allowed to take second early medical abortion pill at home
Authors: Declan Murphy
Journal: BMJ (2018)

The UK government has announced that women in England will now be legally allowed to take the second early medical abortion pill, misoprostol, at home.1

The decision brings England into line with Scotland and Wales, which have legalised misoprostol use at home for early medical abortions.

The announcement changes current practice in England, where women who chose to have an early abortion are legally obliged to attend an abortion clinic on two occasions. …
Abstract 16936: Mesenchymal Stem Cell Administration Attenuates Thoracic Aortic Aneurysm Formation
Authors: Robert B Hawkins, Morgan Salmon, Gang Su, Anna Fashandi, Michael Spinosa, Gilbert Unchurch, Ashish Sharma, Gorav Ailawadi
Journal: Circulation (2016)

Introduction: Thoracic aortic aneurysms (TAA) are characterized by inflammation, cytokine upregulation, macrophage activation and matrix degradation. Mesenchymal stem cells (MSCs) have immunomodulatory characteristics that are known to inhibit murine abdominal aortic aneurysm formation. Hypothesis: We hypothesize that MSC administration will attenuate aneurysm formation in the thoracic aorta. Methods: Wild-type mice (C57BL/6; age 8-12 weeks) underwent thoracotomy and application of topical elastase to the descending thoracic aorta (n=5-14/group) using a previously established model of TAA. All mice underwent tail vein injections on postoperative days 1 and 5 with either 1 million human umbilical cord-derived MSCs or control (phosphate buffer saline). On postoperative day 14, the aortic diameter was measured and blood and tissue were harvested. Cytokine array was performed on pooled homogenized aortas while immunohistochemistry evaluated cellular infiltration and elastin fiber disruption. Statistical compa...
Abstract 19082: Cellular Iron Regulates Mitochondrial Dynamics and Mitophagy Through the RNA-Binding Protein Tristetraprolin
Authors: Jason S Shapiro, Hsiang-Chun Chiang, Tatsuya Sato, Konrad T Sawicki, Meng Shang, Marina Bayeva, Perry Blackshear, Hossein Ardehali
Journal: Circulation (2017)

Background: Iron is a critical molecule for normal cellular and physiologic processes including mitochondrial energy production and oxygen transport in the blood. Previous work in our lab has established the RNA-binding protein TTP as an iron-responsive gene whose expression is induced by iron deprivation. TTP functions by binding to AU-rich elements in the 3’UTR of mRNAs and promotes their degradation. Iron deprivation is a form of cellular stress linked to alterations in mitochondrial dynamics. Optic atrophy 1 (OPA1) is a critical component of the mitochondrial fusion machinery and, under conditions of cellular stress, OPA1 is proteolytically cleaved to promote mitochondrial fission and recycling of damaged mitochondria. OPA1 expression and cleavage is altered in cardiomyopathy, and heterozygous mice develop spontaneous cardiomyopathy. We hypothesize that induction of TTP by low iron reduces the level of OPA1 to fragment the mitochondria and allow for mitophagic recycling of non-functional mitochondria....
Abstract 16315: Olaparib, a Clinically Used Poly(adp-ribose) Polymerase Inhibitor, Protects Against Oxidant-Induced Cardiac Myocyte Death in vitro and Improves Cardiac Contractility During Early Phase After Heart Transplantation in an in vivo Rat Model
Authors: Sevil Korkmaz-Icöz, Michela Marcatti, Shiliang Li, Mihály Ruppert, Bartosz Szczesny, Felix Lasitschka, Sivakkanan Loganathan, Csaba Szabo, Gábor Szabó
Journal: Circulation (2017)

Introduction: The concept, that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) plays a pathophysiological role in myocardial ischemia/reperfusion injury was put forward 20 ...
Myocarditis in Duchenne Muscular Dystrophy After Changing Steroids
Authors: Abdul Rahman A. Abutaleb, Elizabeth M. McNally, Sadiya S. Khan, Allen S. Anderson, James C. Carr, Jane E. Wilcox
Journal: JAMA Cardiology (2018)

Cardiac dysfunction is a leading cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). This case highlights the importance of steroids in treating cardiac complications of DMD and the dangers of discontinuing or switching between steroid classes.To recognize the presentation of acute myocardial inflammation, or dystrophinitis, in DMD, which presents as myocarditis and to treat the myocardial inflammation and dilated cardiomyopathy associated with DMD through guideline-directed medical therapy, steroids, and serial surveillance for cardiac dysfunction.A case report of an 18-year-old patient with DMD and with steroid withdrawal-induced myocarditis followed up for 3 years to observe for cardiac function recovery and the natural history of cardiomyopathy in DMD, who was hospitalized in the cardiac care unit and followed up between November 3, 2016, and March 27, 2017.Switching from deflazacort to underdosed prednisone for 7 days.Increased myocardial inflammation, edema, and fibrosis after stopping deflazacort abruptly.An 18-year-old male patient with DMD presented to the emergency department with acute-onset chest pain. Ischemic changes were present on electrocardiogram, and elevated cardiac enzymes were detected. Depressed cardiac function and potential evidence of inflammation were seen on cardiac magnetic resonance (CMR) imaging, characterized by elevated T2 values and late gadolinium enhancement. These findings were all consistent with acute myocarditis but without a viral prodrome. Several days prior to presentation, the patient's deflazacort was abruptly discontinued and converted to an equivalent dose of prednisone. After restarting deflazacort, his symptoms improved, and subsequent CMR showed resolution of myocardial edema and improved left ventricular function.This case highlights adverse effects associated with changing between corticosteroid classes in DMD cardiomyopathy and also demonstrates the utility of CMR in detecting myocardial inflammation and monitoring response to treatment.