Showing papers by "Veterans Health Administration published in 2021"
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Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
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Baylor College of Medicine1, Icahn School of Medicine at Mount Sinai2, Veterans Health Administration3, Primary Children's Hospital4, Royal Free Hospital5, University of Massachusetts Boston6, Rush University Medical Center7, Imperial College London8, University of Colorado Denver9, Leeds Teaching Hospitals NHS Trust10, University Health Network11, University of Miami12, Genentech13, Hoffmann-La Roche14, University of California, San Diego15
TL;DR: In this paper, a randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days.
Abstract: Background Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. Methods In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. Results Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, -7.6 to 8.2; nominal P = 0.94). Conclusions In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).
666 citations
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TL;DR: A total of 33 participants who received both doses of the Moderna mRNA-1273 vaccine against SARS-CoV-2 had blood drawn over a period of 6 months.
Abstract: Persistence of Antibody after mRNA-1273 Vaccination A total of 33 participants who received both doses of the Moderna mRNA-1273 vaccine against SARS-CoV-2 had blood drawn over a period of 6 months ...
522 citations
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United States Public Health Service1, Centers for Disease Control and Prevention2, Scientific Atlanta3, Emory University4, Veterans Health Administration5, Anschutz Medical Campus6, University of Rochester7, Ohio Department of Health8, Lake County9, New York State Department of Health10, University of California, Berkeley11, Vanderbilt University12, Oregon Health Authority13, New Mexico Department of Health14, Yale University15, Oak Ridge Institute for Science and Education16
TL;DR: Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.
Abstract: Author(s): Kim, Lindsay; Garg, Shikha; O'Halloran, Alissa; Whitaker, Michael; Pham, Huong; Anderson, Evan J; Armistead, Isaac; Bennett, Nancy M; Billing, Laurie; Como-Sabetti, Kathryn; Hill, Mary; Kim, Sue; Monroe, Maya L; Muse, Alison; Reingold, Arthur L; Schaffner, William; Sutton, Melissa; Talbot, H Keipp; Torres, Salina M; Yousey-Hindes, Kimberly; Holstein, Rachel; Cummings, Charisse; Brammer, Lynnette; Hall, Aron J; Fry, Alicia M; Langley, Gayle E | Abstract: BackgroundCurrently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19.MethodsWe analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality.ResultsThe data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84, and ≥85 years versus 18-39 years (adjusted risk ratios [aRRs], 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84, and ≥ 85 years versus 18-39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19).ConclusionsIn-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.
447 citations
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TL;DR: Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID‐19, while pneumonia and end‐organ failure were associated with mortality.
Abstract: Coronavirus disease 2019 (COVID-19) has become a pandemic, but its reported characteristics and outcomes vary greatly amongst studies. We determined pooled estimates for clinical characteristics and outcomes in COVID-19 patients including subgroups by disease severity (based on World Health Organization Interim Guidance Report or Infectious Disease Society of America/American Thoracic Society criteria) and by country/region. We searched Pubmed, Embase, Scopus, Cochrane, Chinese Medical Journal, and preprint databases from 1 January 2020 to 6 April 2020. Studies of laboratory-confirmed COVID-19 patients with relevant data were included. Two reviewers independently performed study selection and data extraction. From 6007 articles, 212 studies from 11 countries/regions involving 281 461 individuals were analyzed. Overall, mean age was 46.7 years, 51.8% were male, 22.9% had severe disease, and mortality was 5.6%. Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID-19 (coefficient = 53.9, 23.4, 23.4, respectively, all P < .0007), while older age, male gender, diabetes, and hypertension were also associated with higher mortality (coefficient = 0.05 per year, 5.1, 8.2, 6.99, respectively; P = .006-.0002). Gastrointestinal (nausea, vomiting, abdominal pain) and respiratory symptoms (shortness of breath, chest pain) were associated with severe COVID-19, while pneumonia and end-organ failure were associated with mortality. COVID-19 is associated with a severe disease course in about 23% and mortality in about 6% of infected persons. Individuals with comorbidities and clinical features associated with severity should be monitored closely, and preventive efforts should especially target those with diabetes, malignancy, and immunosuppression.
397 citations
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Niamh Mullins1, Andreas J. Forstner2, Andreas J. Forstner3, Andreas J. Forstner4 +396 more•Institutions (119)
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
378 citations
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TL;DR: In this paper, liver metastases siphon activated CD8+ T cells from systemic circulation, resulting in a systemic immune desert in preclinical models, and the combination of liver-directed radiotherapy and immunotherapy could promote systemic antitumor immunity.
Abstract: Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response. In multiple mouse models, we show that liver metastases siphon activated CD8+ T cells from systemic circulation. Within the liver, activated antigen-specific Fas+CD8+ T cells undergo apoptosis following their interaction with FasL+CD11b+F4/80+ monocyte-derived macrophages. Consequently, liver metastases create a systemic immune desert in preclinical models. Similarly, patients with liver metastases have reduced peripheral T cell numbers and diminished tumoral T cell diversity and function. In preclinical models, liver-directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T cell survival and reduces hepatic siphoning of T cells. Thus, liver metastases co-opt host peripheral tolerance mechanisms to cause acquired immunotherapy resistance through CD8+ T cell deletion, and the combination of liver-directed radiotherapy and immunotherapy could promote systemic antitumor immunity. Liver metastases reduce clinical and preclinical immune-checkpoint inhibitor efficacy through hepatic siphoning of circulating activated CD8+ T cells, but therapeutic benefit can be improved by combining immunotherapy with liver-directed radiotherapy.
316 citations
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TL;DR: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties as discussed by the authors, which has been shown to reduce mortality in hospitalised adults with COVID-19.
310 citations
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TL;DR: In this paper, a suite of recently developed techniques that localize RNA within tissue, including multiplexed in situ hybridization and in situ sequencing (here defined as high-plex RNA imaging) and spatial barcoding, can help address this issue.
Abstract: Single-cell RNA sequencing (scRNA-seq) identifies cell subpopulations within tissue but does not capture their spatial distribution nor reveal local networks of intercellular communication acting in situ. A suite of recently developed techniques that localize RNA within tissue, including multiplexed in situ hybridization and in situ sequencing (here defined as high-plex RNA imaging) and spatial barcoding, can help address this issue. However, no method currently provides as complete a scope of the transcriptome as does scRNA-seq, underscoring the need for approaches to integrate single-cell and spatial data. Here, we review efforts to integrate scRNA-seq with spatial transcriptomics, including emerging integrative computational methods, and propose ways to effectively combine current methodologies.
288 citations
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TL;DR: It is shown that intravenously injected radioiodinated S1 readily crossed the blood-brain barrier (BBB) in male mice, was taken up by brain regions and entered the parenchymal brain space, and I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation.
Abstract: It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood-brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration. APOE genotype and sex did not affect whole-brain I-S1 uptake but had variable effects on uptake by the olfactory bulb, liver, spleen and kidney. I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation. Mechanistic studies indicated that I-S1 crosses the blood-brain barrier by adsorptive transcytosis and that murine angiotensin-converting enzyme 2 is involved in brain and lung uptake, but not in kidney, liver or spleen uptake.
260 citations
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01 Nov 2021
TL;DR: In this article, the authors evaluated the association of race and ethnicity with COVID-19 outcomes and examined the association between race, ethnicity, COVID19 outcomes, and socioeconomic determinants.
Abstract: Importance COVID-19 has disproportionately affected racial and ethnic minority groups, and race and ethnicity have been associated with disease severity. However, the association of socioeconomic determinants with racial disparities in COVID-19 outcomes remains unclear. Objective To evaluate the association of race and ethnicity with COVID-19 outcomes and to examine the association between race, ethnicity, COVID-19 outcomes, and socioeconomic determinants. Data sources A systematic search of PubMed, medRxiv, bioRxiv, Embase, and the World Health Organization COVID-19 databases was performed for studies published from January 1, 2020, to January 6, 2021. Study selection Studies that reported data on associations between race and ethnicity and COVID-19 positivity, disease severity, and socioeconomic status were included and screened by 2 independent reviewers. Studies that did not have a satisfactory quality score were excluded. Overall, less than 1% (0.47%) of initially identified studies met selection criteria. Data extraction and synthesis Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Associations were assessed using adjusted and unadjusted risk ratios (RRs) and odds ratios (ORs), combined prevalence, and metaregression. Data were pooled using a random-effects model. Main outcomes and measures The main measures were RRs, ORs, and combined prevalence values. Results A total of 4 318 929 patients from 68 studies were included in this meta-analysis. Overall, 370 933 patients (8.6%) were African American, 9082 (0.2%) were American Indian or Alaska Native, 101 793 (2.4%) were Asian American, 851 392 identified as Hispanic/Latino (19.7%), 7417 (0.2%) were Pacific Islander, 1 037 996 (24.0%) were White, and 269 040 (6.2%) identified as multiracial and another race or ethnicity. In age- and sex-adjusted analyses, African American individuals (RR, 3.54; 95% CI, 1.38-9.07; P = .008) and Hispanic individuals (RR, 4.68; 95% CI, 1.28-17.20; P = .02) were the most likely to test positive for COVID-19. Asian American individuals had the highest risk of intensive care unit admission (RR, 1.93; 95% CI, 1.60-2.34, P Conclusions and relevance In this study, members of racial and ethnic minority groups had higher risks of COVID-19 positivity and disease severity. Furthermore, socioeconomic determinants were strongly associated with COVID-19 outcomes in racial and ethnic minority populations.
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TL;DR: The next frontier in RA is the development of curative interventions, for example, reprogramming T cell defects during the period of asymptomatic autoimmunity, discusses how the progressive loss of immune cell tolerance underlies the immunopathology associated with rheumatoid arthritis.
Abstract: The immunopathogenesis of rheumatoid arthritis (RA) spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). After years of asymptomatic autoimmunity and progressive immune system remodeling, tissue tolerance erodes and joint inflammation ensues as tissue-invasive effector T cells emerge and protective joint-resident macrophages fail (checkpoint 2). The transition of synovial stromal cells into autoaggressive effector cells converts synovitis from acute to chronic destructive (checkpoint 3). The loss of T cell tolerance derives from defective DNA repair, causing abnormal cell cycle dynamics, telomere fragility and instability of mitochondrial DNA. Mitochondrial and lysosomal anomalies culminate in the generation of short-lived tissue-invasive effector T cells. This differentiation defect builds on a metabolic platform that shunts glucose away from energy generation toward the cell building and motility programs. The next frontier in RA is the development of curative interventions, for example, reprogramming T cell defects during the period of asymptomatic autoimmunity. Weyand and Goronzy discuss how the progressive loss of immune cell tolerance underlies the immunopathology associated with rheumatoid arthritis.
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TL;DR: The 2009 American College of Gastroenterology (ACG) CRC screening guidelines have been updated in this paper, focusing on the removal of adenomas and sessile serrated lesions and detection of early stage CRC.
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TL;DR: In this article, a meta-analysis was conducted to summarize available RCTs on the performance of real-time computer-aided polyp detection (CADe) in colorectal neoplasia detection.
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01 Jul 2021
TL;DR: Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030 as mentioned in this paper.
Abstract: Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment. Cognitive impairment is common in patients with Parkinson disease and ranges in severity. This Primer reviews the epidemiology, pathophysiology, diagnosis and treatment of cognitive impairment in Parkinson disease and describes the effects on patient quality of life and the future outlook for the field.
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Auckland University of Technology1, Institute for Health Metrics and Evaluation2, University of Washington3, Mayo Clinic4, Johns Hopkins University5, University of the Philippines Manila6, Harvard University7, Heidelberg University8, Mario Negri Institute for Pharmacological Research9, New York University10, University at Buffalo11, University of California, San Diego12, Veterans Health Administration13, University of Peradeniya14, University of Rochester15, Tufts Medical Center16, Rowan University17, Kaiser Permanente18, Istituto Superiore di Sanità19, Tehran University of Medical Sciences20, University of Texas at Austin21, Sheffield Hallam University22, Florida State University College of Arts and Sciences23, Ball State University24, Northeastern University25, Duke University26, University of Michigan27, Ohio State University28, Nationwide Children's Hospital29, University of Bari30, University of Cape Town31, National Institutes of Health32, Curtin University33, Pacific Institute34, Mizan–Tepi University35, University of Mississippi36, Iran University of Medical Sciences37, Emory University38, Lund University39, University of Central Florida40, Charité41, University of Edinburgh42, Yonsei University43, University of Alabama at Birmingham44, United States Department of Veterans Affairs45, Imperial College London46, Norwegian University of Science and Technology47, University of Maryland, Baltimore48, George Washington University49, University of California, Berkeley50
TL;DR: A large and increasing number of people have various neurological disorders in the US, with significant variation in the burden of and trends in neurological disorders across the US states, and the reasons for these geographic variations need to be explored further.
Abstract: IMPORTANCE Accurate and up-to-date estimates on incidence, prevalence, mortality, and
disability-adjusted life-years (burden) of neurological disorders are the backbone of
evidence-based health care planning and resource allocation for these disorders. It appears
that no such estimates have been reported at the state level for the US.
OBJECTIVE To present burden estimates of major neurological disorders in the US states by
age and sex from 1990 to 2017.
DESIGN, SETTING, AND PARTICIPANTS This is a systematic analysis of the Global Burden of
Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted
life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of
the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were
analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy,
multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain
injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis,
and tetanus.
EXPOSURES Any of the 14 listed neurological diseases.
MAIN OUTCOME AND MEASURE Absolute numbers in detail by age and sex and
age-standardized rates (with 95% uncertainty intervals) were calculated.
RESULTS The 3 most burdensome neurological disorders in the US in terms of absolute
number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs),
Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and
migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological
disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as
DALYs) increased from 1990 to 2017, largely because of the aging of the population.
Exceptions for this trend included traumatic brain injury incidence (−29.1% [95% UI, −32.4%
to −25.8%]); spinal cord injury prevalence (−38.5% [95% UI, −43.1% to −34.0%]); meningitis
prevalence (−44.8% [95% UI, −47.3% to −42.3%]), deaths (−64.4% [95% UI, −67.7% to
−50.3%]), and DALYs (−66.9% [95% UI, −70.1% to −55.9%]); and encephalitis DALYs
(−25.8% [95% UI, −30.7% to −5.8%]). The different metrics of age-standardized rates varied
between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for
tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while
northern states had a relatively higher burden of multiple sclerosis and eastern states had
higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache,
and meningitis, encephalitis, and tetanus.
CONCLUSIONS AND RELEVANCE There is a large and increasing burden of noncommunicable
neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in
particular neurological disorders across the US states. The information reported in this article
can be used by health care professionals and policy makers at the national and state levels to
advance their health care planning and resource allocation to prevent and reduce the burden
of neurological disorders.
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TL;DR: There was a remarkable increase in telepsychology use during the COVID-19 pandemic, and individual and practice characteristics affected psychologists' ability to adopttelepsychology.
Abstract: The COVID-19 pandemic has altered mental health care delivery like no other event in modern history. The purpose of this study was to document the magnitude of that effect by examining (a) the amount of psychologists' telepsychology use before the COVID-19 pandemic, during the pandemic, and anticipated use after the pandemic; as well as (b) the demographic, training, policy, and clinical practice predictors of these changes. This study used a cross-sectional, national online design to recruit 2,619 licensed psychologists practicing in the United States. Prior to the COVID-19 pandemic, psychologists performed 7.07% of their clinical work with telepsychology, which increased 12-fold to 85.53% during the pandemic, with 67.32% of psychologists conducting all of their clinical work with telepsychology. Psychologists projected that they would perform 34.96% of their clinical work via telepsychology after the pandemic. Psychologists working in outpatient treatment facilities reported over a 26-fold increase in telepsychology use during the pandemic, while those in Veterans Affairs medical centers only reported a sevenfold increase. A larger increase in percentage telepsychology use occurred in women, in psychologists who reported an increase in telepsychology training and supportive organizational telepsychology policies, and in psychologists who treated relationship issues, anxiety, and women's issues. The lowest increases in percentage telepsychology use were reported by psychologists working in rural areas, treating antisocial personality disorder, performing testing and evaluation, and treating rehabilitation populations. Although there was a remarkable increase in telepsychology use during the COVID-19 pandemic, individual and practice characteristics affected psychologists' ability to adopt telepsychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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TL;DR: This paper conducted a meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.
Abstract: Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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Centers for Disease Control and Prevention1, United States Public Health Service2, Colorado Department of Public Health and Environment3, Yale University4, Emory University5, Veterans Health Administration6, New Mexico Department of Health7, New York State Department of Health8, University of Rochester9, Oregon Health Authority10, Vanderbilt University11, Lake County12
TL;DR: The findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions and help guide prevention efforts and clinical care.
Abstract: BACKGROUND: Data on risk factors for COVID-19-associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors independently associated with COVID-19-associated hospitalizations. METHODS: U.S. community-dwelling adults (≥18 years) hospitalized with laboratory-confirmed COVID-19 during March 1-June 23, 2020 were identified from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a multi-state surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI ≥30 kg/m 2], severe obesity [BMI≥40 kg/m 2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRR) for hospitalization. RESULTS: Among 5,416 adults, hospitalization rates were higher among those with ≥3 underlying conditions (versus without)(aRR: 5.0; 95%CI: 3.9, 6.3), severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65, 45-64 (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites). CONCLUSION: Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.
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TL;DR: A scoping review was conducted to identify promising interventions and outcomes in advance care planning and to understand the utility of ACP.
Abstract: BACKGROUND/OBJECTIVES Advance care planning (ACP) has shown benefit in some, but not all, studies. It is important to understand the utility of ACP. We conducted a scoping review to identify promising interventions and outcomes. DESIGN Scoping review. MEASUREMENTS We searched MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science for ACP randomized controlled trials from January 1, 2010, to March 3, 2020. We used standardized Preferred Reporting Items for Systematic Review and Meta-Analyses methods to chart study characteristics, including a standardized ACP Outcome Framework: Process (e.g., readiness), Action (e.g., communication), Quality of Care (e.g., satisfaction), Health Status (e.g., anxiety), and Healthcare Utilization. Differences between arms of P < .05 were deemed positive. RESULTS Of 1,464 articles, 69 met eligibility; 94% were rated high quality. There were variable definitions, age criteria (≥18 to ≥80 years), diseases (e.g., dementia and cancer), and settings (e.g., outpatient and inpatient). Interventions included facilitated discussions (42%), video only (20%), interactive, multimedia (17%), written only (12%), and clinician training (9%). For written only, 75% of primary outcomes were positive, as were 69% for multimedia programs; 67% for facilitated discussions, 59% for video only, and 57% for clinician training. Overall, 72% of Process and 86% of Action outcomes were positive. For Quality of Care, 88% of outcomes were positive for patient-surrogate/clinician congruence, 100% for patients/surrogate/clinician satisfaction with communication, and 75% for surrogate satisfaction with patients' care, but not for goal concordance. For Health Status outcomes, 100% were positive for reducing surrogate/clinician distress, but not for patient quality of life. Healthcare Utilization data were mixed. CONCLUSION ACP is complex, and trial characteristics were heterogeneous. Outcomes for all ACP interventions were predominantly positive, as were Process and Action outcomes. Although some Quality of Care and Health Status outcomes were mixed, increased patient/surrogate satisfaction with communication and care and decreased surrogate/clinician distress were positive. Further research is needed to appropriately tailor interventions and outcomes for local contexts, set appropriate expectations of ACP outcomes, and standardize across studies.
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Baylor University Medical Center1, Imperial College London2, Charité3, University of Mississippi4, National and Kapodistrian University of Athens5, University of Lorraine6, University of London7, Veterans Health Administration8, University of Minnesota9, University of Florida10, San Francisco VA Medical Center11, University of California, San Diego12, Boehringer Ingelheim13
TL;DR: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy.
Abstract: Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but...
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Veterans Health Administration1, University of California, San Francisco2, Duke University3, Johns Hopkins University School of Medicine4, Johns Hopkins University5, University of California, San Diego6, University of Oxford7, Manipal University8, The George Institute for Global Health9, South African Medical Research Council10, University of Cape Town11, Queen Mary University of London12, University of Manitoba13, Cliniques Universitaires Saint-Luc14, Baylor College of Medicine15, Monash University16
TL;DR: KDIGO held a controversies conference and a consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately in high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.
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04 Jan 2021
TL;DR: In this paper, the authors examined the association between coronavirus disease 2019 (COVID-19) critical care capacity and mortality, and found that although facilities augmented ICU capacity during the pandemic, strains on critical care capacities were associated with increased COVID19 ICU mortality.
Abstract: Importance Although strain on hospital capacity has been associated with increased mortality in nonpandemic settings, studies are needed to examine the association between coronavirus disease 2019 (COVID-19) critical care capacity and mortality. Objective To examine whether COVID-19 mortality was associated with COVID-19 intensive care unit (ICU) strain. Design, Setting, and Participants This cohort study was conducted among veterans with COVID-19, as confirmed by polymerase chain reaction or antigen testing in the laboratory from March through August 2020, cared for at any Department of Veterans Affairs (VA) hospital with 10 or more patients with COVID-19 in the ICU. The follow-up period was through November 2020. Data were analyzed from March to November 2020. Exposures Receiving treatment for COVID-19 in the ICU during a period of increased COVID-19 ICU load, with load defined as mean number of patients with COVID-19 in the ICU during the patient’s hospital stay divided by the number of ICU beds at that facility, or increased COVID-19 ICU demand, with demand defined as mean number of patients with COVID-19 in the ICU during the patient’s stay divided by the maximum number of patients with COVID-19 in the ICU. Main Outcomes and Measures All-cause mortality was recorded through 30 days after discharge from the hospital. Results Among 8516 patients with COVID-19 admitted to 88 VA hospitals, 8014 (94.1%) were men and mean (SD) age was 67.9 (14.2) years. Mortality varied over time, with 218 of 954 patients (22.9%) dying in March, 399 of 1594 patients (25.0%) dying in April, 143 of 920 patients (15.5%) dying in May, 179 of 1314 patients (13.6%) dying in June, 297 of 2373 patients (12.5%) dying in July, and 174 of 1361 (12.8%) patients dying in August (P Conclusions and Relevance This cohort study found that although facilities augmented ICU capacity during the pandemic, strains on critical care capacity were associated with increased COVID-19 ICU mortality. Tracking COVID-19 ICU demand may be useful to hospital administrators and health officials as they coordinate COVID-19 admissions across hospitals to optimize outcomes for patients with this illness.
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TL;DR: In this paper, the authors identify variation in COVID-19 mortality rates and how those rates have changed over the first months of the pandemic and examine whether hospital characteristics were associated with RSERs or their change over time.
Abstract: Importance It is unknown how much the mortality of patients with coronavirus disease 2019 (COVID-19) depends on the hospital that cares for them, and whether COVID-19 hospital mortality rates are improving. Objective To identify variation in COVID-19 mortality rates and how those rates have changed over the first months of the pandemic. Design, Setting, and Participants This cohort study assessed 38 517 adults who were admitted with COVID-19 to 955 US hospitals from January 1, 2020, to June 30, 2020, and a subset of 27 801 adults (72.2%) who were admitted to 398 of these hospitals that treated at least 10 patients with COVID-19 during 2 periods (January 1 to April 30, 2020, and May 1 to June 30, 2020). Exposures Hospital characteristics, including size, the number of intensive care unit beds, academic and profit status, hospital setting, and regional characteristics, including COVID-19 case burden. Main Outcomes and Measures The primary outcome was the hospital’s risk-standardized event rate (RSER) of 30-day in-hospital mortality or referral to hospice adjusted for patient-level characteristics, including demographic data, comorbidities, community or nursing facility admission source, and time since January 1, 2020. We examined whether hospital characteristics were associated with RSERs or their change over time. Results The mean (SD) age among participants (18 888 men [49.0%]) was 70.2 (15.5) years. The mean (SD) hospital-level RSER for the 955 hospitals was 11.8% (2.5%). The mean RSER in the worst-performing quintile of hospitals was 15.65% compared with 9.06% in the best-performing quintile (absolute difference, 6.59 percentage points; 95% CI, 6.38%-6.80%;P Conclusions and Relevance Over the first months of the pandemic, COVID-19 mortality rates in this cohort of US hospitals declined. Hospitals did better when the prevalence of COVID-19 in their surrounding communities was lower.
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Stanford University1, Ochsner Medical Center2, Cornell University3, Harvard University4, University of Minnesota5, Hennepin County Medical Center6, Icahn School of Medicine at Mount Sinai7, University of California, San Francisco8, Brigham and Women's Hospital9, Beth Israel Deaconess Medical Center10, Duke University11, University of Pennsylvania12, Rush University Medical Center13, University of Michigan14, Veterans Health Administration15, University of Washington16, University of Arizona17, University of Kansas18, University Hospitals of Cleveland19, University of Southern California20, Mayo Clinic21, University of Pittsburgh22
TL;DR: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC.
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TL;DR: This article reported SARS-CoV-2 vaccine effectiveness against infection (VE-I) and death (VE -D) by vaccine type (n = 780,225) in the Veterans Health Administration, covering 2.7% of the U.S. population.
Abstract: We report SARS-CoV-2 vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type (n = 780,225) in the Veterans Health Administration, covering 2.7% of the U.S. population. From ...
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University of Utah1, Stanford University2, University of Tennessee Health Science Center3, Children's Hospital of Philadelphia4, University of Pennsylvania5, Southern Medical University6, University of California, San Diego7, Veterans Health Administration8, Ottawa Hospital Research Institute9, University of Alabama at Birmingham10, Pontifícia Universidade Católica do Paraná11, Tufts Medical Center12, University of Toronto13, Northern Ontario School of Medicine14, Freeman Hospital15, McMaster University16, Cochrane Collaboration17, Flinders University18, University of Sydney19, University of Calgary20, University of Erlangen-Nuremberg21
TL;DR: A systolic blood pressure target of less than 120 mm Hg is proposed using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients.
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TL;DR: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are need for validation as discussed by the authors.
Abstract: Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are need...
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TL;DR: In this paper, the authors reviewed the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of SARS-CoV-2 lineages.
Abstract: Since the COVID-19 pandemic first began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has continuously evolved with many variants emerging across the world. These variants are categorized as the variant of interest (VOI), variant of concern (VOC), and variant under monitoring (VUM). As of September 15, 2021, there are four SARS-CoV-2 lineages designated as the VOC (alpha, beta, gamma, and delta variants). VOCs have increased transmissibility compared to the original virus, and have the potential for increasing disease severity. In addition, VOCs exhibit decreased susceptibility to vaccine-induced and infection-induced immune responses, and thus possess the ability to reinfect previously infected and recovered individuals. Given their ability to evade immune responses, VOC are less susceptible to monoclonal antibody treatments. VOCs can also impact the effectiveness of mRNA and adenovirus vector vaccines, although the currently authorized COVID-19 vaccines are still effective in preventing infection and severe disease. Current measures to reduce transmission as well as efforts to monitor and understand the impact of variants should be continued. Here, we review the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of VOCs.
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Baylor College of Medicine1, Veterans Health Administration2, College of Osteopathic Medicine of the Pacific3, University of Western Australia4, The Chinese University of Hong Kong5, Duke University6, University of Oxford7, University of California, San Diego8, Harvard University9, University of Turin10, Anschutz Medical Campus11, University of Florida12
TL;DR: The American Gastroenterological Association ( AGA) developed a Clinical Care Pathway for nonalcoholic fatty liver disease (NAFLD) with clinically significant fibrosis (stage F2-F4) as mentioned in this paper.