Showing papers by "Emory University published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
Health Effects Institute1, University of British Columbia2, Health Canada3, St George's, University of London4, Institute for Health Metrics and Evaluation5, Sri Ramachandra University6, Utrecht University7, Public Health Foundation of India8, Auckland University of Technology9, United States Environmental Protection Agency10, University of Bath11, Fudan University12, University of Queensland13, Emory University14, Dalhousie University15, Queensland University of Technology16, Brigham Young University17, International Agency for Research on Cancer18
TL;DR: In this paper, the authors explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels, and estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using nonlinear exposure-response functions spanning the global range of exposure.
3,960 citations
Simon I. Hay, Amanuel Alemu Abajobir1, Kalkidan Hassen Abate2, Cristiana Abbafati3 +800 more•Institutions (32)
TL;DR: At a global level, DALYs and HALE continue to show improvements and the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning.
3,029 citations
Valery L. Feigin1, Amanuel Alemu Abajobir2, Kalkidan Hassen Abate3, Foad Abd-Allah4 +267 more•Institutions (138)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
2,995 citations
TL;DR: The scope and purpose of this work is to synthesize the available evidence and to translate it into recommendations, so that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient.
Abstract: The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.
2,703 citations
St George’s University Hospitals NHS Foundation Trust1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Autonomous University of Barcelona6, University of Manitoba7, Emory University8, Hebrew University of Jerusalem9, University of Toronto10, University of Pittsburgh11, St Thomas' Hospital12, University College London13, Vanderbilt University14, Keio University15, Memorial Hospital of South Bend16, Rowan University17, University of Mississippi18, Rush University Medical Center19, University of Ulsan20, Universidade Federal do Rio Grande do Sul21, Federal University of São Paulo22, Regions Hospital23, Washington University in St. Louis24, University of Ottawa25, University of Sydney26, University of New South Wales27, Fujita Health University28, University of Copenhagen29, Sapienza University of Rome30, Christiana Care Health System31, Stanford University32, King Abdullah University of Science and Technology33, University of Kansas34, Harvard University35, California Pacific Medical Center36, University of Amsterdam37, Université libre de Bruxelles38, Houston Methodist Hospital39
TL;DR: A consensus committee of 55 international experts representing 25 international organizations was assembled at key international meetings (forSurviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012 as discussed by the authors ).
Abstract: Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for
2,414 citations
TL;DR: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer as mentioned in this paper.
Abstract: BackgroundOsimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non–small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. MethodsIn this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non–small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed pro...
2,337 citations
TL;DR: Prevention and early detection of lung cancer with an emphasis on lung cancer screening is discussed, and the importance of smoking prevention and cessation is acknowledged.
2,027 citations
Centers for Disease Control and Prevention1, Emory University2, University of New South Wales3, Pan American Health Organization4, National Health Laboratory Service5, Norwegian Institute of Public Health6, University of Oslo7, Li Ka Shing Faculty of Medicine, University of Hong Kong8, Singapore Ministry of Health9, Medical University of Vienna10, Chinese Center for Disease Control and Prevention11, Statens Serum Institut12, All India Institute of Medical Sciences13, Thailand Ministry of Public Health14, Robert Koch Institute15
TL;DR: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden.
1,658 citations
Stony Brook University1, University of Minnesota2, University of Notre Dame3, University of Vermont4, University of Toronto5, Boston University6, University of Maryland, Baltimore7, Duke University8, University of Kansas9, King's College London10, Columbia University11, Broad Institute12, Purdue University13, University of Iowa14, University of Georgia15, Texas A&M University16, Oklahoma State University–Stillwater17, University of Groningen18, Florida State University19, Uniformed Services University of the Health Sciences20, Bryn Mawr College21, University of North Texas22, University of Otago23, University at Buffalo24, University of Arizona25, University of New South Wales26, Northwestern University27, Emory University28, University of Kentucky29, University of Pittsburgh30, Brown University31
TL;DR: The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies and provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response.
Abstract: The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record
1,635 citations
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.
New York University1, National and Kapodistrian University of Athens2, University of Barcelona3, Texas Oncology4, Complutense University of Madrid5, Aix-Marseille University6, University of Toronto7, University of Oxford8, University of Queensland9, University of Colorado Denver10, Emory University11, Cross Cancer Institute12, Centre Hospitalier Universitaire de Toulouse13, Georgetown University14, University of Sydney15, University of Washington16, University of Paris17, Nagoya University18, Seoul National University19, Bristol-Myers Squibb20, The Royal Marsden NHS Foundation Trust21
TL;DR: Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence‐free survival and a lower rate of grade 3 or 4 adverse events than adjuant therapy with ipilimumab.
Abstract: BackgroundNivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. MethodsIn this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic ef...
TL;DR: In this article, the authors compared two approaches to assess saturation: code saturation and meaning saturation, and examined sample sizes needed to reach saturation in each approach, what saturation meant, and how to assess it.
Abstract: Saturation is a core guiding principle to determine sample sizes in qualitative research, yet little methodological research exists on parameters that influence saturation. Our study compared two approaches to assessing saturation: code saturation and meaning saturation. We examined sample sizes needed to reach saturation in each approach, what saturation meant, and how to assess saturation. Examining 25 in-depth interviews, we found that code saturation was reached at nine interviews, whereby the range of thematic issues was identified. However, 16 to 24 interviews were needed to reach meaning saturation where we developed a richly textured understanding of issues. Thus, code saturation may indicate when researchers have "heard it all," but meaning saturation is needed to "understand it all." We used our results to develop parameters that influence saturation, which may be used to estimate sample sizes for qualitative research proposals or to document in publications the grounds on which saturation was achieved.
TL;DR: It is shown here that patients with depression can be subdivided into four neurophysiological subtypes defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks, which may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.
Abstract: Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates. Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied, co-occurring symptoms and divergent responses to treatment. By using functional magnetic resonance imaging (fMRI) in a large multisite sample (n = 1,188), we show here that patients with depression can be subdivided into four neurophysiological subtypes (‘biotypes’) defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks. Clustering patients on this basis enabled the development of diagnostic classifiers (biomarkers) with high (82–93%) sensitivity and specificity for depression subtypes in multisite validation (n = 711) and out-of-sample replication (n = 477) data sets. These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinical-symptom profiles. They also predict responsiveness to transcranial magnetic stimulation therapy (n = 154). Our results define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.
University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, Centers for Disease Control and Prevention11, International Centre for Diarrhoeal Disease Research, Bangladesh12, University of Bergen13, Tribhuvan University14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Otago30, University of Auckland31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.
University of Zurich1, Northwestern University2, University of Lausanne3, Paris-Sorbonne University4, Tel Aviv Sourasky Medical Center5, Emory University6, University of California, San Diego7, Tel Aviv University8, Geisinger Medical Center9, Cleveland Clinic10, Baylor University Medical Center11, University of Pittsburgh12, Tufts University13, University of Texas Health Science Center at Houston14, Karolinska Institutet15, Washington University in St. Louis16, University of South Florida17, University of Pennsylvania18, Seoul National University19, University of Ottawa20, University of Barcelona21, Hamilton Health Sciences22
TL;DR: In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance Temozolmide alone, resulted in statistically significant improvement in progression-free survival and overall survival.
Abstract: Importance Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. Objective To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. Design, Setting, and Participants In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Interventions Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Main Outcomes and Measures Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Results Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76;P Conclusions and Relevance In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. Trial Registration clinicaltrials.gov Identifier:NCT00916409
TL;DR: This evidence‐based guideline recommends treating gender‐dysphoric/gender‐incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin‐releasing hormone agonists and recommends adding gender‐affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence.
Abstract: Objective To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. Participants The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus process Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.
Harvard University1, Brigham and Women's Hospital2, Emory University3, Centers for Disease Control and Prevention4, University of Pittsburgh5, University of Michigan6, National Institutes of Health7, Texas A&M Health Science Center College of Medicine8, Hospital Corporation of America9, Washington University in St. Louis10
TL;DR: In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsi nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014.
Abstract: Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P P P P = .23). Conclusions and Relevance In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.
Georgia Institute of Technology1, National Institutes of Health2, Florida State University3, City College of New York4, Hacettepe University5, California Institute of Technology6, University of Tromsø7, Virginia Tech8, Rikkyo University9, Emory University10, University of Georgia11, Auburn University12, Bethel University13
TL;DR: A wide range of new theoretical methods and analyses have been added to the code base, including functional-group and open-shell symmetry adapted perturbation theory, density-fitted coupled cluster with frozen natural orbitals, orbital-optimized perturbations and coupled-cluster methods, and the "X2C" approach to relativistic corrections, among many other improvements.
Abstract: Psi4 is an ab initio electronic structure program providing methods such as Hartree–Fock, density functional theory, configuration interaction, and coupled-cluster theory. The 1.1 release represents a major update meant to automate complex tasks, such as geometry optimization using complete-basis-set extrapolation or focal-point methods. Conversion of the top-level code to a Python module means that Psi4 can now be used in complex workflows alongside other Python tools. Several new features have been added with the aid of libraries providing easy access to techniques such as density fitting, Cholesky decomposition, and Laplace denominators. The build system has been completely rewritten to simplify interoperability with independent, reusable software components for quantum chemistry. Finally, a wide range of new theoretical methods and analyses have been added to the code base, including functional-group and open-shell symmetry adapted perturbation theory, density-fitted coupled cluster with frozen natura...
University of Marburg1, University of Erlangen-Nuremberg2, Rovira i Virgili University3, University of Göttingen4, Max Planck Society5, University of California, Los Angeles6, International School for Advanced Studies7, University of Melbourne8, University of Trieste9, Ikerbasque10, University of Toronto11, Nanyang Technological University12, National Institutes of Health13, Stanford University14, Shanghai Jiao Tong University15, Tongji University16, University of Seville17, Karolinska Institutet18, Drexel University19, Sichuan University20, Rice University21, Northwestern University22, University of Basel23, Zhejiang University24, Heidelberg University25, University of Tokyo26, Harvard University27, University of Utah28, University of Michigan29, Swiss Federal Laboratories for Materials Science and Technology30, Seoul National University31, Saarland University32, Columbia University33, Chinese Academy of Sciences34, Kazan Federal University35, Emory University36, University of California, Irvine37, Autonomous University of Barcelona38, University of Massachusetts Amherst39, Pennsylvania State University40, Ghent University41, Imperial College London42, National Tsing Hua University43, South China University of Technology44, University of Ulm45, Hebrew University of Jerusalem46, Huazhong University of Science and Technology47, Peking University48
TL;DR: An overview of recent developments in nanomedicine is provided and the current challenges and upcoming opportunities for the field are highlighted and translation to the clinic is highlighted.
Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
National Autonomous University of Mexico1, University of Illinois at Urbana–Champaign2, Conservation International3, German Primate Center4, Yale University5, University of Texas at Austin6, Oxford Brookes University7, Leibniz Institute for Neurobiology8, University of Colorado Boulder9, Durham University10, Emory University11, Naturhistorisches Museum12, Universidade Federal de Sergipe13, Federal University of Bahia14, Rhodes College15, University of Notre Dame16, Saint Louis University17, Northwestern University18, Federal University of Paraná19, Liverpool John Moores University20, University of Amsterdam21, Washington University in St. Louis22, University of Western Australia23, Chinese Academy of Sciences24
TL;DR: Raising global scientific and public awareness of the plight of the world’s primates and the costs of their loss to ecosystem health and human society is imperative.
Abstract: Nonhuman primates, our closest biological relatives, play important roles in the livelihoods, cultures, and religions of many societies and offer unique insights into human evolution, biology, behavior, and the threat of emerging diseases. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. Current information shows the existence of 504 species in 79 genera distributed in the Neotropics, mainland Africa, Madagascar, and Asia. Alarmingly, ~60% of primate species are now threatened with extinction and ~75% have declining populations. This situation is the result of escalating anthropogenic pressures on primates and their habitats—mainly global and local market demands, leading to extensive habitat loss through the expansion of industrial agriculture, large-scale cattle ranching, logging, oil and gas drilling, mining, dam building, and the construction of new road networks in primate range regions. Other important drivers are increased bushmeat hunting and the illegal trade of primates as pets and primate body parts, along with emerging threats, such as climate change and anthroponotic diseases. Often, these pressures act in synergy, exacerbating primate population declines. Given that primate range regions overlap extensively with a large, and rapidly growing, human population characterized by high levels of poverty, global attention is needed immediately to reverse the looming risk of primate extinctions and to attend to local human needs in sustainable ways. Raising global scientific and public awareness of the plight of the world’s primates and the costs of their loss to ecosystem health and human society is imperative.
Christian R. Marshall, Daniel P. Howrigan1, Daniel P. Howrigan2, Daniele Merico +326 more•Institutions (98)
TL;DR: In this article, a centralized analysis pipeline was applied to a SCZ cohort of 21,094 cases and 20,227 controls, and a global enrichment of copy number variants (CNVs) was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies.
Abstract: Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
Duke University1, University of Helsinki2, University of Copenhagen3, University of Nebraska Medical Center4, University of North Carolina at Chapel Hill5, Emory University6, Queen Mary University of London7, Indiana University – Purdue University Indianapolis8, Cleveland Clinic9, University of Hong Kong10, Tufts University11, Tata Memorial Hospital12, Vanderbilt University13, University of Texas MD Anderson Cancer Center14, Columbia University15, Northwestern University16, National Institutes of Health17
TL;DR: An integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of DLBCL patients is performed to comprehensively define the landscape of 150 genetic drivers of the disease and their functional roles to identify new therapeutic opportunities in the disease.
University of Toronto1, University of Düsseldorf2, German Cancer Research Center3, University of Pittsburgh4, Ontario Institute for Cancer Research5, Seoul National University6, University of Warsaw7, University of Lyon8, Mayo Clinic9, The Chinese University of Hong Kong10, Johns Hopkins University11, University of Alabama at Birmingham12, University of Washington13, Fred Hutchinson Cancer Research Center14, University of California, San Francisco15, Hamilton Health Sciences16, McMaster University17, Vanderbilt University18, University of Colorado Denver19, Semmelweis University20, Erasmus University Rotterdam21, University of Ulsan22, Kitasato University23, Mexican Social Security Institute24, Masaryk University25, Emory University26, University of Debrecen27, University of Naples Federico II28, Washington University in St. Louis29, McGill University30, Montreal Children's Hospital31, Virginia Commonwealth University32, Chonnam National University33, University of Queensland34, University of Calgary35, University of São Paulo36, University of Cincinnati37, University of Arkansas for Medical Sciences38, The Catholic University of America39, University of California, Los Angeles40, University of Sydney41, Kumamoto University42, Saint Louis University43, Case Western Reserve University44
TL;DR: Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes.
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
TL;DR: Extracorporeal life support use in the support of adults with respiratory and cardiac failure represented the largest growth in the recent time period and underscore the need for skilled ECLS management and appropriately trained ECLs personnel and teams.
Abstract: Data on extracorporeal life support (ECLS) use and survival submitted to the Extracorporeal Life Support Organization's data registry from the inception of the registry in 1989 through July 1, 2016, are summarized in this report. The registry contained information on 78,397 ECLS patients with 58% survival to hospital discharge. Extracorporeal life support use and centers providing ECLS have increased worldwide. Extracorporeal life support use in the support of adults with respiratory and cardiac failure represented the largest growth in the recent time period. Extracorporeal life support indications are expanding, and it is increasingly being used to support cardiopulmonary resuscitation in children and adults. Adverse events during the course of ECLS are common and underscore the need for skilled ECLS management and appropriately trained ECLS personnel and teams.
Hammersmith Hospital1, University College London2, Imperial College London3, Cancer Research UK4, Royal North Shore Hospital5, Flinders University6, Monash University7, Ain Shams University8, French Institute of Health and Medical Research9, Charité10, University of Oldenburg11, Magna Græcia University12, Catholic University of the Sacred Heart13, University of Verona14, Tokyo Medical University15, Aichi Medical University16, King Abdulaziz Medical City17, Seoul National University Hospital18, Keimyung University19, University of Ulsan20, Inje University21, Universidad Francisco de Vitoria22, University of Amsterdam23, VU University Amsterdam24, Istanbul University25, University of Florence26, Conquest Hospital27, University of Exeter28, Anglia Ruskin University29, Emory University30, United States Department of Veterans Affairs31, University of Washington32, Stony Brook University33, Canterbury Christ Church University34, Duke University35, Complutense University of Madrid36, Hospital Clínico San Carlos37
TL;DR: Coronary revascularization guided by iFR was noninferior to revascularizations guided by FFR with respect to the risk of major adverse cardiac events at 1 year.
Abstract: BackgroundCoronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. MethodsWe randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. ResultsAt 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference i...
TL;DR: CD28-costimulation requirement for CD8 T cell rescue is demonstrated and an important role for the CD28/B7 pathway in PD-1 therapy of cancer patients is suggested, which suggests that CD28 may predict treatment response.
Abstract: Programmed cell death–1 (PD-1)–targeted therapies enhance T cell responses and show efficacy in multiple cancers, but the role of costimulatory molecules in this T cell rescue remains elusive. Here, we demonstrate that the CD28/B7 costimulatory pathway is essential for effective PD-1 therapy during chronic viral infection. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy in tumor-bearing mice. In addition, we found that CD8 T cells proliferating in blood after PD-1 therapy of lung cancer patients were predominantly CD28-positive. Taken together, these data demonstrate CD28-costimulation requirement for CD8 T cell rescue and suggest an important role for the CD28/B7 pathway in PD-1 therapy of cancer patients.
Northwestern University1, University of Zurich2, University Hospital of Lausanne3, French Institute of Health and Medical Research4, Tel Aviv Sourasky Medical Center5, Emory University6, University of California, San Diego7, Tel Aviv University8, Geisinger Health System9, Cleveland Clinic10, Baylor University Medical Center11, University of Pittsburgh12, University of Texas Health Science Center at Houston13, Tufts Medical Center14, Karolinska University Hospital15, Barnes-Jewish Hospital16, University of Pennsylvania17, Seoul National University Bundang Hospital18, Seoul National University19, Ottawa Hospital Research Institute20, Juravinski Cancer Centre21
Oregon Health & Science University1, Emory University2, Centers for Disease Control and Prevention3, University of Colorado Denver4, California Department of Public Health5, Foundation for Innovative New Diagnostics6, McGill University7, University of Southampton8, Vanderbilt University9, University of Arkansas for Medical Sciences10
TL;DR: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided and six of the recommendations are strong, whereas the remaining 17 are conditional.
Abstract: Background Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. Methods A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. Conclusions These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.