Showing papers by "Vanderbilt University published in 2020"
Centers for Disease Control and Prevention1, University of Arizona2, University of Arkansas for Medical Sciences3, Colorado Department of Public Health and Environment4, University of Colorado Denver5, Johns Hopkins University6, University of Minnesota7, Washington University in St. Louis8, Rutgers University9, University of North Carolina at Chapel Hill10, Vanderbilt University11, University of Wisconsin-Madison12
TL;DR: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014, highlighting the variability in the evaluation and detection of ASD across communities and between sociodemographic groups.
Abstract: Problem/condition Autism spectrum disorder (ASD). Period covered 2016. Description of system The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). Interpretation The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. Public health action These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.
2,613 citations
TL;DR: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified, which support further development of this vaccine.
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vacci...
2,556 citations
NewYork–Presbyterian Hospital1, University of Insubria2, University of Texas Health Science Center at Houston3, Chinese PLA General Hospital4, University of Vermont Medical Center5, Beth Israel Deaconess Medical Center6, Harvard University7, Loyola University Medical Center8, University of Chicago9, University of Milan10, Auckland City Hospital11, St Thomas' Hospital12, Hofstra University13, University of Michigan14, Population Health Research Institute15, Hamilton Health Sciences16, Ottawa Hospital Research Institute17, Brigham and Women's Hospital18, Vanderbilt University19, Universidad Católica San Antonio de Murcia20, University of Mainz21, McMaster University22, Aalborg University23, University of Liverpool24
TL;DR: The current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexistingThrombotic disease who develop CO VID-19 are reviewed.
2,222 citations
Centers for Disease Control and Prevention1, United States Department of Health and Human Services2, Colorado Department of Public Health and Environment3, Yale University4, Emory University5, Veterans Health Administration6, 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
Emory University1, United States Public Health Service2, Rutgers University3, Harvard University4, Central Michigan University5, Westchester Medical Center6, Icahn School of Medicine at Mount Sinai7, New York University8, Saint Barnabas Medical Center9, University of Pennsylvania10, SUNY Downstate Medical Center11, Yale University12, University of Colorado Denver13, Boston Children's Hospital14, Case Western Reserve University15, Louisiana State University16, University of Washington17, Johns Hopkins University18, University of Texas Health Science Center at Houston19, University of Mississippi20, Tufts University21, Vanderbilt University22
TL;DR: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.
Abstract: Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...
1,887 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
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 University32, Uppsala University Hospital33, 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
F. Kyle Satterstrom1, F. Kyle Satterstrom2, Jack A. Kosmicki, Jiebiao Wang3 +198 more•Institutions (53)
TL;DR: The largest exome sequencing study of autism spectrum disorder (ASD) to date, using an enhanced analytical framework to integrate de novo and case-control rare variation, identifies 102 risk genes at a false discovery rate of 0.1 or less, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
1,169 citations
TL;DR: The phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein in healthy adults found it induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100- μg dose in a phase 3 vaccine trial.
Abstract: Background Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased inciden...
1,136 citations
Northwestern University1, Seattle Cancer Care Alliance2, Case Western Reserve University3, Washington University in St. Louis4, Ohio State University5, Stanford University6, University of California, San Diego7, Brigham and Women's Hospital8, Memorial Sloan Kettering Cancer Center9, University of Colorado Boulder10, University of Texas MD Anderson Cancer Center11, Mayo Clinic12, Fox Chase Cancer Center13, Harvard University14, Duke University15, University of Pennsylvania16, Vanderbilt University17, Yale University18, City of Hope National Medical Center19, University of Wisconsin-Madison20, University of Michigan21, University of California, San Francisco22, Johns Hopkins University23, University of South Florida24, University of Alabama at Birmingham25, University of Utah26, Roswell Park Cancer Institute27, National Comprehensive Cancer Network28
TL;DR: The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.
1,018 citations
United States Department of Energy1, Vanderbilt University2, Harvard University3, Wake Forest University4, Hennepin County Medical Center5, Tufts University6, Yeshiva University7, Ohio State University8, University of Washington9, Stanford University10, Oregon Health & Science University11, University of California, Los Angeles12, Primary Children's Hospital13, Johns Hopkins University14, University of Colorado Denver15
TL;DR: It is indicated that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults, and effective public health messaging targeting these groups is warranted.
Abstract: Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.
TL;DR: It is recommended that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that the authors could not make a determination whether the benefits outweigh harms for most treatments.
Abstract: Background There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. Objective Develop evidence-based rapid guidelines intended to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19. Methods IDSA formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. Conclusions The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.
TL;DR: An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.
Abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-24. Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein5, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (SRBD) from interacting with human angiotensin-converting enzyme 2 (ACE2). Using competition-binding, structural and functional studies, we show that the monoclonal antibodies can be clustered into classes that recognize distinct epitopes on the SRBD, as well as distinct conformational states of the S trimer. Two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130 or a combination of both of these antibodies protected mice from weight loss and reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents. An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.
Romina Ahumada1, Carlos Allende Prieto2, Carlos Allende Prieto3, Andres Almeida4 +342 more•Institutions (94)
TL;DR: The most recent data release from the Sloan Digital Sky Surveys (SDSS-IV) is DR16 as mentioned in this paper, which is the fourth and penultimate from the fourth phase of the survey.
Abstract: This paper documents the sixteenth data release (DR16) from the Sloan Digital Sky Surveys; the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the southern hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey (TDSS) and new data from the SPectroscopic IDentification of ERosita Survey (SPIDERS) programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).
TL;DR: The coronavirus disease pandemic has had a substantial tandem impact on parents and children in the United States and policy makers should consider the unique needs of families with children.
Abstract: BACKGROUND: As the coronavirus disease pandemic spread across the United States and protective measures to mitigate its impact were enacted, parents and children experienced widespread disruptions in daily life. Our objective with this national survey was to determine how the pandemic and mitigation efforts affected the physical and emotional well-being of parents and children in the United States through early June 2020. METHODS: In June 2020, we conducted a national survey of parents with children age RESULTS: Since March 2020, 27% of parents reported worsening mental health for themselves, and 14% reported worsening behavioral health for their children. The proportion of families with moderate or severe food insecurity increased from 6% before March 2020 to 8% after, employer-sponsored insurance coverage of children decreased from 63% to 60%, and 24% of parents reported a loss of regular child care. Worsening mental health for parents occurred alongside worsening behavioral health for children in nearly 1 in 10 families, among whom 48% reported loss of regular child care, 16% reported change in insurance status, and 11% reported worsening food security. CONCLUSIONS: The coronavirus disease pandemic has had a substantial tandem impact on parents and children in the United States. As policy makers consider additional measures to mitigate the health and economic effects of the pandemic, they should consider the unique needs of families with children.
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Rutgers University5, University of Pennsylvania6, Cornell University7, Rush University Medical Center8, Anschutz Medical Campus9, Northwestern University10, Medical College of Wisconsin11, Rowan University12, Hackensack University Medical Center Mountainside13, Tufts University14, Washington University in St. Louis15, Ochsner Health System16, University of Queensland17, Johns Hopkins University18, Baylor University Medical Center19, Indiana University – Purdue University Indianapolis20, University of Vermont21, Boston University22, University of Miami23, Massachusetts Institute of Technology24, Vanderbilt University25
TL;DR: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
Abstract: Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
University of Texas MD Anderson Cancer Center1, Peter MacCallum Cancer Centre2, The Royal Marsden NHS Foundation Trust3, Emory University4, Sarah Cannon Research Institute5, University of California, Los Angeles6, Harvard University7, Anschutz Medical Campus8, Vanderbilt University9, Duke University10, Rambam Health Care Campus11, University of Hamburg12, BOTAŞ13, Université catholique de Louvain14, Edinburgh Cancer Research Centre15, University of North Carolina at Chapel Hill16, University of Nebraska Medical Center17, Stanford University18, Seattle Genetics19
TL;DR: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo.
Abstract: Background Patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents hav...
TL;DR: In this article, the authors provide guidance on how to calculate the sample size required to develop a clinical prediction model.
Abstract: Clinical prediction models aim to predict outcomes in individuals, to inform diagnosis or prognosis in healthcare. Hundreds of prediction models are published in the medical literature each year, yet many are developed using a dataset that is too small for the total number of participants or outcome events. This leads to inaccurate predictions and consequently incorrect healthcare decisions for some individuals. In this article, the authors provide guidance on how to calculate the sample size required to develop a clinical prediction model.
14 Sep 2020
TL;DR: In this article, the authors consider key factors contributing to this issue, explore how federated learning may provide a solution for the future of digital health and highlight the challenges and considerations that need to be addressed.
Abstract: Data-driven machine learning (ML) has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how federated learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.
Memorial Sloan Kettering Cancer Center1, University Hospitals of Cleveland2, Washington University in St. Louis3, University of Utah4, Duke University5, University of Wisconsin-Madison6, Harvard University7, Moffitt Cancer Center8, Vanderbilt University9, Stanford University10, Johns Hopkins University11, University of Tennessee Health Science Center12, Mayo Clinic13, Fox Chase Cancer Center14, University of Texas MD Anderson Cancer Center15, Brigham and Women's Hospital16, Roswell Park Cancer Institute17, University of Colorado Boulder18, City of Hope National Medical Center19, University of California, San Diego20, Northwestern University21, Ohio State University22, Fred Hutchinson Cancer Research Center23, University of Pennsylvania24, University of Michigan25, University of California, San Francisco26, National Comprehensive Cancer Network27
TL;DR: The NCCN Guidelines for Head and Neck Cancers as mentioned in this paper describe supportive care recommendations for patients with H&N cancers and the rationale supporting a new section on imaging recommendations for head and neck cancers.
Abstract: Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
TL;DR: This paper considers key factors contributing to this issue, explores how federated learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.
Abstract: Data-driven Machine Learning has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how Federated Learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.
University of Sharjah1, McMaster University2, Kuwait Cancer Control Center3, University of Toronto4, University of Texas MD Anderson Cancer Center5, Min Sheng General Hospital6, National University of Singapore7, University of Western Ontario8, Vanderbilt University9, University of Tennessee Health Science Center10, Wuhan University11
TL;DR: The potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches.
Abstract: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by rapid human-to-human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS-CoV-2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID-19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID-19 epidemic include clear communication and education about hand hygiene, infection control measures, high-risk exposure, and the signs and symptoms of COVID-19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case-by-case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS-CoV-2 virology and epidemiology.
TL;DR: It is found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin, and it is hoped that open access to this reagent will expedite development of medical countermeasures.
Abstract: The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures.
University of Milan1, University of Washington2, University of South Florida3, Georgetown University4, University of Minnesota5, Mayo Clinic6, University of Kansas7, University of Liège8, University of Chicago9, Vanderbilt University10, Stanford University11, Université libre de Bruxelles12, Washington University in St. Louis13, Tel Aviv University14, University of Pennsylvania15, City of Hope National Medical Center16, Duke University17, Heidelberg University18
TL;DR: Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment, and guidance regarding prevention, screening, monitoring and treatment of CV toxicity is provided.
Vanderbilt University Medical Center1, Mario Negri Institute for Pharmacological Research2, Marche Polytechnic University3, University of L'Aquila4, Hebron University5, University of Alcalá6, Vita-Salute San Raffaele University7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Georgetown University9, University of Lausanne10, Academy for Urban School Leadership11, University of Parma12, Guangdong General Hospital13, Erasmus University Medical Center14, Aix-Marseille University15, Stanford University16, Vanderbilt University17
TL;DR: With an ongoing global pandemic of COVID-19, the data suggest high mortality and low admission to intensive care in patients with thoracic cancer and whether mortality could be reduced with treatment in intensive care remains to be determined.
Abstract: Summary Background Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. Methods The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. Findings Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8–75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0–1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00–3·62), being a current or former smoker (4·24, 1·70–12·95), receiving treatment with chemotherapy alone (2·54, 1·09–6·11), and the presence of any comorbidities (2·65, 1·09–7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11–9·06) was associated with increased risk of death. Interpretation With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. Funding None.
TL;DR: It is reported that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and several previously unrecognized epithelialcell phenotypes are identified, including a KRT5−/KRT17+ pathologic, ECM-producing epithel cell population that was highly enriched in PF lungs.
Abstract: Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5−/KRT17+ pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.
Goddard Space Flight Center1, Widener University2, West Virginia University3, Montana State University4, Cornell University5, Canadian Institute for Advanced Research6, Centre national de la recherche scientifique7, University of Orléans8, Franklin & Marshall College9, University of Virginia10, Lafayette College11, United States Naval Research Laboratory12, National Radio Astronomy Observatory13, Hillsdale College14, Durham University15, McGill University16, University of British Columbia17, University of Washington18, Carnegie Mellon University19, University of Illinois at Urbana–Champaign20, University of Wisconsin–Milwaukee21, Northwestern University22, Oregon State University23, Rochester Institute of Technology24, California Institute of Technology25, University of Toronto26, First Green Bank27, University of Connecticut28, York University29, Eötvös Loránd University30, Vanderbilt University31, University of Colorado Boulder32, Swinburne University of Technology33, Oberlin College34
TL;DR: In this article, the authors search for an isotropic stochastic GWB in the 12.5-yr pulsar-timing data set collected by the North American Nanohertz Observatory for Gravitational Waves.
Abstract: We search for an isotropic stochastic gravitational-wave background (GWB) in the 12.5 yr pulsar-timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. Our analysis finds strong evidence of a stochastic process, modeled as a power law, with common amplitude and spectral slope across pulsars. Under our fiducial model, the Bayesian posterior of the amplitude for an f −2/3 power-law spectrum, expressed as the characteristic GW strain, has median 1.92 × 10−15 and 5%–95% quantiles of 1.37–2.67 × 10−15 at a reference frequency of the Bayes factor in favor of the common-spectrum process versus independent red-noise processes in each pulsar exceeds 10,000. However, we find no statistically significant evidence that this process has quadrupolar spatial correlations, which we would consider necessary to claim a GWB detection consistent with general relativity. We find that the process has neither monopolar nor dipolar correlations, which may arise from, for example, reference clock or solar system ephemeris systematics, respectively. The amplitude posterior has significant support above previously reported upper limits; we explain this in terms of the Bayesian priors assumed for intrinsic pulsar red noise. We examine potential implications for the supermassive black hole binary population under the hypothesis that the signal is indeed astrophysical in nature.
New York University1, Johns Hopkins University2, University of Washington3, University of North Carolina at Chapel Hill4, Duke University5, Scripps Research Institute6, Hebrew University of Jerusalem7, Ohio State University8, University of California, San Francisco9, École Polytechnique Fédérale de Lausanne10, Baylor College of Medicine11, Vanderbilt University12, Rutgers University13, Swiss Institute of Bioinformatics14, Fred Hutchinson Cancer Research Center15, Rensselaer Polytechnic Institute16, Northeastern University17, Stanford University18, DSM19, Fox Chase Cancer Center20, University of Maryland, College Park21, University of Warsaw22, University of Denver23, Australian National University24, University of Kansas25, University of Zurich26, University of Massachusetts Dartmouth27, University of Tokyo28, Franklin & Marshall College29, Weizmann Institute of Science30, Lund University31, University of California, Santa Cruz32, University of California, Davis33
TL;DR: This Perspective reviews tools developed over the past five years in the Rosetta software, including over 80 methods, and discusses improvements to the score function, user interfaces and usability.
Abstract: The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.
Centers for Disease Control and Prevention1, University of California, Berkeley2, Anschutz Medical Campus3, Colorado Department of Public Health and Environment4, Yale University5, Veterans Health Administration6, Emory University7, 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.
Icahn School of Medicine at Mount Sinai1, California Institute of Technology2, Kobe University3, Nagoya University4, University of Minnesota5, University of Virginia6, Beth Israel Deaconess Medical Center7, Vanderbilt University8, Brigham and Women's Hospital9, University of Texas Health Science Center at San Antonio10, Northwestern University11, Washington University in St. Louis12, Broad Institute13
TL;DR: It is suggested that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease.
Abstract: Microglia, the brain’s resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival1. Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A1R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease. Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.