Showing papers by "Veterans Health Administration published in 2020"
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Centers for Disease Control and Prevention1, United States Department of Health and Human Services2, Colorado Department of Public Health and Environment3, Yale University4, Veterans Health Administration5, Emory University6, Alabama Department of Public Health7, Maryland Department of Health8, New Mexico Department of Health9, New York State Department of Health10, University of Rochester11, Ohio Department of Health12, Vanderbilt University13, Lake County14
TL;DR: It is suggested that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with CO VID-19 have underlying medical conditions, which underscore the importance of preventive measures to protect older adults and persons with underlyingmedical conditions, as well as the general public.
Abstract: Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.
2,016 citations
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TL;DR: A robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening and using a combination of AI and human inputs could help to improve screening efficiency.
Abstract: Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful1. Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives2. Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening. An artificial intelligence (AI) system performs as well as or better than radiologists at detecting breast cancer from mammograms, and using a combination of AI and human inputs could help to improve screening efficiency.
1,413 citations
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Stanford University1, New York University2, Duke University3, Boston University4, Saint Louis University5, Imperial College London6, Northwick Park Hospital7, Hospital Universitario La Paz8, Durham University9, NewYork–Presbyterian Hospital10, Albany Medical College11, St. Michael's Hospital12, Montreal Heart Institute13, Auckland City Hospital14, All India Institute of Medical Sciences15, University of British Columbia16, Cedars-Sinai Medical Center17, Harvard University18, Brigham and Women's Hospital19, Columbia University Medical Center20, Saint Francis University21, University of Missouri–Kansas City22, Government Medical College, Thiruvananthapuram23, Sri Jayadeva Institute of Cardiovascular Sciences and Research24, University of São Paulo25, Veterans Health Administration26, Emory University27, Mayo Clinic28, Semmelweis University29, Flinders Medical Centre30, Université Paris-Saclay31, Uppsala University Hospital32, Uppsala University33, Keio University34, National Institutes of Health35, Vanderbilt University36, East Carolina University37, Icahn School of Medicine at Mount Sinai38
TL;DR: Evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years is not found.
Abstract: Background Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical ther...
1,324 citations
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TL;DR: The role that telehealth has played in transforming healthcare delivery during the 3 phases of the U.S. COVID-19 pandemic is described and how people, process, and technology work together to support a successful telehealth transformation is examined.
986 citations
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Tulane University1, Cedars-Sinai Medical Center2, National Institutes of Health3, University of Arizona4, Karolinska Institutet5, Brigham and Women's Hospital6, Georgia State University7, University of Colorado Denver8, Washington University in St. Louis9, Johns Hopkins University10, University of Modena and Reggio Emilia11, University of Illinois at Chicago12, University of Texas Health Science Center at Houston13, University of Zurich14, Charité15, Georgetown University16, Duke University17, Veterans Health Administration18
TL;DR: Clinicians and researchers are guided to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
781 citations
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TL;DR: This article discusses the descriptive epidemiology of gastric cancer, including its incidence, mortality, survival, and secular trends, and combines a synthesis of published studies with an analysis of data from the International Agency for Research on Cancer (IARC) GLOBOCAN project to describe the global burden.
633 citations
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Duke University1, Pontifical Catholic University of Chile2, University of Florida3, Veterans Health Administration4, Kaiser Permanente5, University of Pennsylvania6, University of Amsterdam7, Harvard University8, University of California, Davis9, McMaster University10, I.M. Sechenov First Moscow State Medical University11, Washington University in St. Louis12, Katholieke Universiteit Leuven13, University of Utah14, University of Antioquia15
TL;DR: Recommendations include the use of thrombolytic therapy for patients with PE and hemodynamic compromise, use of an international normalized ratio (INR) range, and a preference for direct oral anticoagulants over VKA for primary treatment of VTE.
497 citations
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TL;DR: Although vaccination, screening, and anti-viral treatment campaigns for hepatitis B and C have reduced CLD burden in some parts of the world, concomitant increases in injection drug use, alcohol misuse and metabolic syndrome threaten these trends.
474 citations
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Emory University1, Johns Hopkins University2, National Institutes of Health3, Stanford University4, University of Pennsylvania5, Arizona State University6, Icahn School of Medicine at Mount Sinai7, Veterans Health Administration8, Mayo Clinic9, University of Florida10, Pacific Northwest National Laboratory11, NewYork–Presbyterian Hospital12, Rush University Medical Center13, Baylor College of Medicine14
TL;DR: Large-scale, comprehensive proteomic profiling of Alzheimer’s disease brain and cerebrospinal fluid reveals disease-associated protein coexpression modules and highlights the importance of glia and energy metabolism in disease pathogenesis.
Abstract: Our understanding of Alzheimer's disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly associated with AD pathology and cognitive impairment. This module was enriched in AD genetic risk factors and in microglia and astrocyte protein markers associated with an anti-inflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were elevated in cerebrospinal fluid in early stages of the disease. In this study of >2,000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brains that may serve as therapeutic targets and fluid biomarkers for the disease.
472 citations
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TL;DR: This work presents a novel and scalable approach to regenerative medicine that combines traditional and regenerative approaches to treat central giant cell granuloma, a leading cause of cancer in women.
Abstract: 1Northwestern University Feinberg School of Medicine, Division of Nephrology and Hypertension, Chicago, Illinois 2Hospital Universitari Vall d’Hebron, Division of Nephrology Autonomous University of Barcelona, Barcelona, Spain 3Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 4Renal Section, Durham Veterans Affairs Health Care System, Durham, North Carolina 5Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada 6Department of Pediatrics, Section of Nephrology, Wake Forest School of Medicine, Winston Salem, North Carolina 7School of Medicine, Departments of Medicine and Physiology, Johns Hopkins University, Baltimore, Maryland 8Division of Nephrology, and Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, Virginia
459 citations
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TL;DR: Methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors are reported.
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TL;DR: The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) initiated the hepatitis C virus guidance project (hereafter HCV guidance) in 2013 and disseminates up-to-date, peer-reviewed, unbiased, evidence-based recommendations to aid clinicians making decisions regarding the testing, management, and treatment of HCV infection.
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TL;DR: To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin were combined.
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Karlsruhe Institute of Technology1, University of Grenoble2, Qatar Airways3, University of Trieste4, University of Florida5, La Jolla Institute for Allergy and Immunology6, Rice University7, University of Toronto8, University of Pennsylvania9, Veterans Health Administration10, Ankara University11, Imperial College London12, Spanish National Research Council13, Catalan Institution for Research and Advanced Studies14, Houston Methodist Hospital15, University of Texas MD Anderson Cancer Center16, Drexel University17, École Polytechnique Fédérale de Lausanne18, University of Padua19
TL;DR: Nanoimmunity by design can help to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively.
Abstract: The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.
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Katrina L. Grasby1, Neda Jahanshad2, Jodie N. Painter1, Lucía Colodro-Conde3 +356 more•Institutions (115)
TL;DR: Results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness and find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
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Centers for Disease Control and Prevention1, University of California, Berkeley2, Anschutz Medical Campus3, Colorado Department of Public Health and Environment4, Yale University5, Emory University6, Veterans Health Administration7, United States Department of Veterans Affairs8, Alabama Department of Public Health9, Maryland Department of Health10, New Mexico Department of Health11, New York State Department of Health12, University of Rochester13, Ohio Department of Health14, Oregon Health Authority15, Vanderbilt University16, Lake County17, United States Department of Health and Human Services18
TL;DR: The cumulative rate of pediatric COVID-19-associated hospitalization remains low compared with that among adults, but weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults.
Abstract: Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.
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Centers for Disease Control and Prevention1, University of Miami2, New York City Department of Health and Mental Hygiene3, Broad Institute4, Harvard University5, University of Southern Maine6, United States Department of Health and Human Services7, Maine Medical Center8, Louisiana State University9, Veterans Health Administration10, Emory University11, United States Department of Energy12
TL;DR: Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms, and interventions that prevent COVID-19 might prevent MIS-B, as well as the role for antibody testing in identifying similar cases among adults.
Abstract: During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.
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TL;DR: The findings suggest that obesity should not be the sole criterion for NAFLD screening and that both non-obese and lean groups had substantial long-term liver and non-liver comorbidities.
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TL;DR: How ICU professionals can use knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the COVID-19 pandemic is discussed.
Abstract: The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.
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Paul M. Thompson1, Neda Jahanshad1, Christopher R.K. Ching1, Lauren E. Salminen1 +210 more•Institutions (99)
TL;DR: This review summarizes the last decade of work by the ENIGMA Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease, and highlights the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings.
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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Tufts Medical Center1, Charité2, American Medical Association3, Erasmus University Rotterdam4, Harvard University5, University of British Columbia6, University of Washington7, University of Pittsburgh8, Yale University9, Veterans Health Administration10, Children's Hospital at Westmead11, Great Ormond Street Hospital for Children NHS Foundation Trust12, American Society of Nephrology13, University of Maryland, Baltimore14, Royal Free London NHS Foundation Trust15, University of Pennsylvania16, University Medical Center Groningen17, Mayo Clinic18, University of Calgary19, University of Michigan20, Keele University21, University of Oklahoma Health Sciences Center22, St Thomas' Hospital23, French Institute of Health and Medical Research24, University of Paris25, Heidelberg University26, National Kidney Foundation27, University College London28, Cliniques Universitaires Saint-Luc29, Baylor College of Medicine30
TL;DR: Recommendations to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function and to use the KDIGO definition and classification of chronic kidney disease rather than alternative descriptions to define and classify severity of CKD.
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01 Jun 2020
TL;DR: It is suggested that patients with SARS-CoV-2 infection can present with gastrointestinal symptoms with possible fecal-oral route of transmission due to the presence of viral RNA in stool.
Abstract: Importance Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. Objective To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. Data Sources An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included “COVID-19,” “SARS-Cov-2,” and/or “novel coronavirus.” Study Selection Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. Data Extraction and Synthesis Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I2). Main Outcomes and Measures Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. Results Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I2 = 94%), but no statistically significant publication bias noted. Conclusions and Relevance These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.
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Stanford University1, Washington University in St. Louis2, Veterans Health Administration3, Vanderbilt University4, Mayo Clinic5, University of Texas MD Anderson Cancer Center6, Harvard University7, Howard Hughes Medical Institute8, United States Department of Veterans Affairs9, Fred Hutchinson Cancer Research Center10, University of Washington11
TL;DR: It is shown that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic, and a machine-learning method termed ‘lung cancer likelihood in plasma’ (Lung-CLiP) is developed, which can robustly discriminate early-Stage lung cancer patients from risk-matched controls.
Abstract: Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.
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TL;DR: In the CANTOS trial, targeted anti-cytokine therapy with a monoclonal antibody against IL-1β resulted in improved heart failure outcomes in patients with myocardial infarction with or without established heart failure.
Abstract: The observation that heart failure with reduced ejection fraction is associated with elevated circulating levels of pro-inflammatory cytokines opened a new area of research that has revealed a potentially important role for the immune system in the pathogenesis of heart failure. However, until the publication in 2019 of the CANTOS trial findings on heart failure outcomes, all attempts to target inflammation in the heart failure setting in phase III clinical trials resulted in neutral effects or worsening of clinical outcomes. This lack of positive results in turn prompted questions on whether inflammation is a cause or consequence of heart failure. This Review summarizes the latest developments in our understanding of the role of the innate and adaptive immune systems in the pathogenesis of heart failure, and highlights the results of phase III clinical trials of therapies targeting inflammatory processes in the heart failure setting, such as anti-inflammatory and immunomodulatory strategies. The most recent of these studies, the CANTOS trial, raises the exciting possibility that, in the foreseeable future, we might be able to identify those patients with heart failure who have a cardio-inflammatory phenotype and will thus benefit from therapies targeting inflammation. Inflammation has an important role in the pathogenesis of acute and chronic heart failure. This Review summarizes the latest findings on the role of the innate and adaptive immune systems in the pathogenesis of heart failure, and highlights the results of phase III clinical trials of therapies targeting inflammatory processes in this condition, such as anti-inflammatory and immunomodulatory strategies.
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TL;DR: In a multicenter, randomized trial, it is found that including CADe in real-time colonoscopy significantly increases adenoma detection rate (ADR) and adenomas detected per Colonoscopy without increasing withdrawal time.
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TL;DR: This study uses US national survey data to characterize trends in the prevalence of metabolic syndrome among adults in the US between 2011 and 2016.
Abstract: This study uses US national survey data to characterize trends in the prevalence of metabolic syndrome among adults in the US between 2011 and 2016
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01 Sep 2020TL;DR: Most deaths from SARS-CoV-2 occurred in patients with age of 50 years or older, male sex, and greater comorbidity burden, while obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking were not associated with mortality.
Abstract: Importance Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can support prognostication, resource utilization, and treatment. Objective To identify excess risk and risk factors associated with hospitalization, mechanical ventilation, and mortality in patients with SARS-CoV-2 infection. Design, setting, and participants This longitudinal cohort study included 88 747 patients tested for SARS-CoV-2 nucleic acid by polymerase chain reaction between Feburary 28 and May 14, 2020, and followed up through June 22, 2020, in the Department of Veterans Affairs (VA) national health care system, including 10 131 patients (11.4%) who tested positive. Exposures Sociodemographic characteristics, comorbid conditions, symptoms, and laboratory test results. Main outcomes and measures Risk of hospitalization, mechanical ventilation, and death were estimated in time-to-event analyses using Cox proportional hazards models. Results The 10 131 veterans with SARS-CoV-2 were predominantly male (9221 [91.0%]), with diverse race/ethnicity (5022 [49.6%] White, 4215 [41.6%] Black, and 944 [9.3%] Hispanic) and a mean (SD) age of 63.6 (16.2) years. Compared with patients who tested negative for SARS-CoV-2, those who tested positive had higher rates of 30-day hospitalization (30.4% vs 29.3%; adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.13), mechanical ventilation (6.7% vs 1.7%; aHR, 4.15; 95% CI, 3.74-4.61), and death (10.8% vs 2.4%; aHR, 4.44; 95% CI, 4.07-4.83). Among patients who tested positive for SARS-CoV-2, characteristics significantly associated with mortality included older age (eg, ≥80 years vs 89 U/L vs ≤25 U/L: aHR, 1.86; 95% CI, 1.35-2.57), creatinine (>3.80 mg/dL vs 0.98 mg/dL: aHR, 3.79; 95% CI, 2.62-5.48), and neutrophil to lymphocyte ratio (>12.70 vs ≤2.71: aHR, 2.88; 95% CI, 2.12-3.91). With the exception of geographic region, the same covariates were independently associated with mechanical ventilation along with Black race (aHR, 1.52; 95% CI, 1.25-1.85), male sex (aHR, 2.07; 95% CI, 1.30-3.32), diabetes (aHR, 1.40; 95% CI, 1.18-1.67), and hypertension (aHR, 1.30; 95% CI, 1.03-1.64). Notable characteristics that were not significantly associated with mortality in adjusted analyses included obesity (body mass index ≥35 vs 18.5-24.9: aHR, 0.97; 95% CI, 0.77-1.21), Black race (aHR, 1.04; 95% CI, 0.88-1.21), Hispanic ethnicity (aHR, 1.03; 95% CI, 0.79-1.35), chronic obstructive pulmonary disease (aHR, 1.02; 95% CI, 0.88-1.19), hypertension (aHR, 0.95; 95% CI, 0.81-1.12), and smoking (eg, current vs never: aHR, 0.87; 95% CI, 0.67-1.13). Most deaths in this cohort occurred in patients with age of 50 years or older (63.4%), male sex (12.3%), and Charlson Comorbidity Index score of at least 1 (11.1%). Conclusions and relevance In this national cohort of VA patients, most SARS-CoV-2 deaths were associated with older age, male sex, and comorbidity burden. Many factors previously reported to be associated with mortality in smaller studies were not confirmed, such as obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking.
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TL;DR: 5xFAD shows a proteomic signature similar to symptomatic AD but exhibits activation of autophagy and interferon response and lacks human-specific deleterious events, such as downregulation of neurotrophic factors and synaptic proteins.
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National Institute for Health Research1, Harvard University2, Montreal Heart Institute3, University of North Carolina at Chapel Hill4, Wellcome Trust Sanger Institute5, VA Boston Healthcare System6, Osaka University7, Icahn School of Medicine at Mount Sinai8, University of Wisconsin–Milwaukee9, Kyushu University10, University of Washington11, University of Bristol12, University of Copenhagen13, Erasmus University Medical Center14, National Institutes of Health15, Veterans Health Administration16, Kaiser Permanente17, International Agency for Research on Cancer18, Wake Forest University19, Imperial College London20, Broad Institute21, Greifswald University Hospital22, University of Pennsylvania23, British Heart Foundation24, Fred Hutchinson Cancer Research Center25, Chinese National Human Genome Center26, Technische Universität München27, University of Tampere28, University of Tokyo29, University of Ioannina30, University of Colorado Denver31, Duke University32, University of Virginia33, University of Minnesota34, Turku University Hospital35, Los Angeles Biomedical Research Institute36, Stanford University37, Mashhad University of Medical Sciences38, NHS Blood and Transplant39, Brigham and Women's Hospital40, University of Oxford41, University of Liège42, European Bioinformatics Institute43, John Radcliffe Hospital44
TL;DR: The results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
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TL;DR: Great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources, and established and emerging screening methods are discussed.