Race, ethnicity, community-level socioeconomic factors, and risk of COVID-19 in the United States and the United Kingdom

BACKGROUND: There is limited prior investigation of the combined influence of personal and community-level socioeconomic factors on racial/ethnic disparities in individual risk of coronavirus disease 2019 (COVID-19). METHODS: We performed a cross-sectional analysis nested within a prospective cohort of 2,102,364 participants from March 29, 2020 in the United States (US) and March 24, 2020 in the United Kingdom (UK) through December 02, 2020 via the COVID Symptom Study smartphone application. We examined the contribution of community-level deprivation using the Neighborhood Deprivation Index (NDI) and the Index of Multiple Deprivation (IMD) to observe racial/ethnic disparities in COVID-19 incidence. ClinicalTrials.gov registration: NCT04331509. FINDINGS: Compared with non-Hispanic White participants, the risk for a positive COVID-19 test was increased in the US for non-Hispanic Black (multivariable-adjusted odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18–1.47) and Hispanic participants (OR, 1.42; 95% CI, 1.33–1.52) and in the UK for Black (OR, 1.17; 95% CI, 1.02–1.34), South Asian (OR, 1.39; 95% CI, 1.30–1.49), and Middle Eastern participants (OR, 1.38; 95% CI, 1.18–1.61). This elevated risk was associated with living in more deprived communities according to the NDI/IMD. After accounting for downstream mediators of COVID-19 risk, community-level deprivation still mediated 16.6% and 7.7% of the excess risk in Black compared to White participants in the US and the UK, respectively. INTERPRETATION: Our results illustrate the critical role of social determinants of health in the disproportionate COVID-19 risk experienced by racial and ethnic minorities. FUNDING: Please refer to the Funding section at the end of the article

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

EU/US/CTAD Task Force: Lessons Learned from Recent and Current Alzheimer's Prevention Trials

At a meeting of the EU/US/Clinical Trials in Alzheimer’s Disease (CTAD) Task Force in December 2016, an international group of investigators from industry, academia, and regulatory agencies reviewed lessons learned from ongoing and planned prevention trials, which will help guide future clinical trials of AD treatments, particularly in the pre-clinical space. The Task Force discussed challenges that need to be addressed across all aspects of clinical trials, calling for innovation in recruitment and retention, infrastructure development, and the selection of outcome measures. While cognitive change provides a marker of disease progression across the disease continuum, there remains a need to identify the optimal assessment tools that provide clinically meaningful endpoints. Patient- and informant-reported assessments of cognition and function may be useful but present additional challenges. Imaging and other biomarkers are also essential to maximize the efficiency of and the information learned from clinical trials

Right to Know GMO: MOFGA\u27s Campaign in Support of LD718 and its Potential for Replication Beyond Maine

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Acro-ostéolyse au cours de la sclérodermie systémique (étude de son association aux complications vasculaires)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Key Indexing Terms: POLYARTERITIS NODOSA VISCERAL HEMATOMA Personal, non-commercial use only

P e r s o n a l n o n -c o m m e r c i a l u s e o n l y . T h e J o u r n a l o f R h e u m a t o l o g y . C o p y r i g h t © 2 0 0 4 . A l l r i g h t s r e s e r v e d The Paris, Cochin Hospital, Paris, France; and Department of Rheumatology, Bulgarian Medical Academy, Sofia, Bulgaria. Y. Allanore, MD; C. Rosenberg, MD, Department of Rheumatology; O. Vignaux, MD, PhD; P. Legmann, MD, PhD, Department of Radiology, Cochin Hospital; K. Kanev, MD, Rheumatology Clinic, Bulgarian Medical Academy; C.J. Menkes, MD; A. Kahan, MD, PhD, Department of Rheumatology, Cochin Hospital. Address reprint requests to Dr. Y. Allanore, Hôpital Cochin, Service de Rhumatologie A, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail: [email protected] Submitted December 29, 2003; revision accepted March 24, 2004. Polyarteritis nodosa (PAN) is a rare disease characterized by necrotizing vasculitis of small and medium size arteries 1 . The clinical symptoms that usually reveal PAN are neuritis, arthralgia, myalgia, cutaneous lesions, orchitis, and abdominal pain 2 . Prompt diagnosis is important because PAN can be life-threatening: severe organ manifestations include congestive heart failure, cerebrovascular events, gastrointestinal (GI) tract hemorrhage, and malignant hypertension. We describe a patient with an unusual presentation of PAN, revealed by successive spontaneous visceral hematomas involving the kidneys, bladder, and liver. CASE REPORT A 28-year-old Bulgarian man was admitted to our department for exploration of repeated spontaneous hematomas. Symptoms began in March 2000, with isolated, violent lumbar pain, and no decline in general health status. Ultrasound and computed tomography (CT) scans revealed a left perinephritic hematoma. Surgery was performed. Pathological analysis confirmed the diagnosis and identified no other abnormality. The pain disappeared with standard analgesic treatment, and he resumed all regular activities. One year later, he suffered the same symptoms, with right kidney involvement, and the same course. In June 2001, he suffered spontaneous bleeding of the bladder, as revealed by macroscopic hematuria, with no renal insufficiency. This bleeding stopped spontaneously within a few days. One year later, he reported spontaneous pain in the right upper abdominal quadrant, and CT scan revealed the presence of a hematoma in the liver. Investigations over this 2-year period revealed no coagulation or immunological abnormalities, but biological examinations showed repeated signs of transient inflammation with increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Histological analysis of a kidney sample removed during surgery revealed no inflammatory disease, specific infiltration, or vessel abnormalities other than hematoma. By the time of admission to our hospital in March 2003, our patient had lost 20 kg over 2 years (weight 58 kg; height 1.75 m); he had had fever and abdominal pain for 4 days. On physical examination, he was pale and sweating. His blood pressure was 130/80 mm Hg, pulse 100/min, and temperature 38.8°C. Diffuse tenderness was noted on abdominal pressure, without palpable abnormality. Neurological and cardiopulmonary examinations were normal. Laboratory investigations gave the following results: white blood cell count 14,000/mm 3 , ESR 74 mm/h, CRP 240 mg/l (normal &lt; 5 mg/l), hemoglobin concentration 12.6 g/dl, aspartate aminotransferase 402 IU/l, alanine aminotransferase 648 IU/l, creatininemia 67 µmol/l, and absence of proteinuria. Hemostasis test results: prothrombin time 104%, activated partial thromboplastin time 40 s (normal = 40 ± 5), lupus anticoagulant absent; and factor VIII, IX, and von Willebrand levels were normal. Blood cultures, urinalysis, and tests for tuberculosis (skin test and gastric culture), human immunodeficiency virus, hepatitis C virus, and hepatitis B virus (last generation ELISA tests) were negative. No autoantibodies, including antinuclear, anti-dsDNA, antiphospholipid, antiextractible nuclear antigens, antineutrophil cytoplasmic antibodies, rheumatoid factor, or cryoglobulinemia were detected. Thoracic and abdominal radiographs, electrocardiogram, and echocardiography results were normal. Thoracoabdominal CT scan showed 2 recent intrahepatic hematomas, visible as spontaneous hyperdensity lesions DISCUSSIO