scholarly journals Severity of SARS-CoV-2 alpha variant (B.1.1.7) in England

2021 ◽  
Author(s):  
Daniel J Grint ◽  
Kevin Wing ◽  
Catherine Houlihan ◽  
Hamish P Gibbs ◽  
Stephen J W Evans ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Gene Target ◽  
Individual Level ◽  
Increased Risk ◽  
Alpha Variant

Abstract Background The SARS-CoV-2 alpha variant (B.1.1.7) is associated with higher transmissibility than wild type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. Methods With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and ONS all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases compared to wild type diagnosed from 16th November 2020 to 11th January 2021. Results Using data from 185,234 people who tested positive for SARS-CoV-2 in the community (alpha=93,153; wild-type=92,081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (aHR: 1.73 (95% CI 1.41 - 2.13; P<.0001)) and 62% higher hazards of hospital admission (aHR: 1.62 ((95% CI 1.48 - 1.78; P<.0001), compared to wild-type virus. Among patients already admitted to ICU, the association between alpha and increased all-cause mortality was smaller and the confidence interval included the null (aHR: 1.20 (95% CI 0.74 - 1.95; P=0.45)). Conclusions The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalisation and mortality than wild-type virus.

Abstract P120: Women With Menopause After Age 45 and Take Hormone Therapy After Age 60 Increase the Risk of Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Dongshan Zhu ◽  
Hsin-Fang Chung ◽  
Annette Dobson ◽  
Nirmala Pandeya ◽  
Gita Mishra
Keyword(s):  
Cardiovascular Disease ◽  
Hormone Therapy ◽  
Postmenopausal Women ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cvd Risk ◽  
Natural Menopause ◽  
Individual Level ◽  
Age At Menopause ◽  
Increased Risk

Introduction: Evidence from clinical trials and observational studies on the relationship between menopausal hormone therapy (MHT) and cardiovascular disease (CVD) risk has been discordant. Hypothesis: We hypothesized that the association between MHT and risk of CVD might be affected by both age at menopause and age when initiated MHT. Methods: We harmonised and pooled individual-level data from 15 studies across five countries/regions (Australia, Scandinavia, USA, Japan, and UK). Postmenopausal women who had reported their MHT status (user or non-user) and CVD status (occurred or not, including coronary heart disease (CHD) and stroke) were included. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association between MHT use and incident CVD. We stratified the analyses by age when initiated MHT and age at natural menopause to examine the interaction between MHT, age initiated MHT, and age at menopause on incident CVD. Results: Overall, 190 625 postmenopausal women were included. We identified 10 601 incident CVD events, including 7615 CHD and 3543 strokes. Around 39% (74 585) women were MHT users. Compared to non-users of MHT, women who were MHT users had 10% higher risk of incident CVD (HR 1.10, 95% CI 1.06-1.14), with HR (95% CI) of (1.15, 1.10-1.20) for CHD and (1.02, 0.96-1.09) for stroke. After stratifying by age at natural menopause, women who experienced menopause after age 45 years and took MHT had around 15% higher risk of CHD, while the significant association with incident stroke was only observed in women who had menopause after 55 years (1.16, 1.01-1.33). After a further stratification by age initiated MHT, we found the significant associations between MHT users and incident CVD were only observed in women who experienced menopause after age 45 years and took MHT at age 60 years or old (Table 1). Conclusions: Postmenopausal women who experienced natural menopause after age 45 years and took MHT after age 60 years had increased risk of incident CVD.

scholarly journals Serum Neutralizing Activity of mRNA-1273 Against SARS-CoV-2 Variants

2021 ◽  
Author(s):  
Angela Choi ◽  
Matthew Koch ◽  
Kai Wu ◽  
Groves Dixon ◽  
Judy Oestreicher ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Neutralizing Activity ◽  
Serum Neutralization ◽  
Vaccination Strategies ◽  
Fold Reduction ◽  
Alpha Variant ◽  
Multiple Variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated as D614G). Results showed minimal, statistically non-significant effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), P.1 (Gamma), and B.1.617.2 (Delta), showed significantly decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273–elicited serum neutralization. IMPORTANCE In light of multiple variants of SARS-CoV-2 that have been documented globally during the COVID-19 pandemic, it remains important to continually assess the ability of currently available vaccines to confer protection against newly emerging variants. Data presented herein indicate that immunization with the mRNA-1273 COVID-19 vaccine produces neutralizing antibodies against key emerging variants tested, including variants of concern and variants of interest. While the serum neutralization elicited by mRNA-1273 against most variants tested was reduced compared with the wild-type virus, they are still expected to be protective. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

The URNA Genes of Herpesvirus Saimiri (Strain C488) Are Dispensable for Transformation of Human T Cells In Vitro

1999 ◽  
Vol 73 (12) ◽  
pp. 10551-10555 ◽  
Author(s):  
Armin Ensser ◽  
André Pfinder ◽  
Ingrid Müller-Fleckenstein ◽  
Bernhard Fleckenstein
Keyword(s):  
Cell Culture ◽  
Herpesvirus Saimiri ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Human T Cell ◽  
Human T Cells ◽  
Small Nuclear Rnas ◽  
T Cell Lines

ABSTRACT The herpesvirus saimiri strain C488 genome contains five genes for small nuclear RNAs, termed herpesvirus saimiri URNAs (or HSURs). Using a cosmid-based approach, all HSURs were precisely deleted from the genome. The mutant virus replicated at levels that were similar to those of wild-type viruses in OMK cells. Although the HSURs are expressed in wild-type virus-transformed human T-cell lines, the deletion does not affect viral transformation in cell culture.

Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

2021 ◽  
pp. 000486742110096
Author(s):  
Oleguer Plana-Ripoll ◽  
Patsy Di Prinzio ◽  
John J McGrath ◽  
Preben B Mortensen ◽  
Vera A Morgan
Keyword(s):  
Confidence Interval ◽  
Western Australia ◽  
Urban Areas ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Indigenous Status ◽  
Increased Risk ◽  
The Relationship ◽  
Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Towards refining WCRF/AICR cancer prevention recommendations for red and processed meat intake: Insights from Alberta’s Tomorrow Project cohort

2021 ◽  
pp. 1-38
Author(s):  
Ala Al Rajabi ◽  
Geraldine Lo Siou ◽  
Alianu K. Akawung ◽  
Kathryn L McDonald ◽  
Tiffany R. Price ◽  
...  
Keyword(s):  
Cancer Prevention ◽  
Proportional Hazards ◽  
Red Meat ◽  
Cox Proportional Hazards ◽  
Processed Meat ◽  
Carcinogenic Effect ◽  
Meat Intake ◽  
Increased Risk ◽  
Red Meats ◽  
Red And Processed Meat

ABSTRACT Current cancer prevention recommendations advise limiting red meat intake to <500g/week and avoiding consumption of processed meat, but do not differentiate the source of processed meat. We examined the associations of processed meat derived from red vs. non-red meats with cancer risk in a prospective cohort of 26,218 adults who reported dietary intake using the Canadian Diet History Questionnaire. Incidence of cancer was obtained through data linkage with Alberta Cancer Registry with median (IQR) follow-up of 13.3 (5.1) years. Multivariable Cox proportional hazards regression models were adjusted for covariates and stratified by age and gender. The median (IQR) consumption (g/week) of red meat, processed meat from red meat and processed meat from non-red meat were 267.9 (269.9), 53.6 (83.3), and 11.9 (31.8), respectively. High intakes (4th Quartile) of processed meat from red meat was associated with increased risk of gastro-intestinal cancer Adjusted Hazard Ratio (AHR) (95% CI): 1.68 (1.09 – 2.57) and colorectal cancers AHR (95% CI): 1.90 (1.12 – 3.22), respectively in women. No statistically significant associations were observed for intakes of red meat or processed meat from non-red meat. Results suggests that the carcinogenic effect associated with processed meat intake may be limited to processed meat derived from red meats. The findings provide preliminary evidence toward refining cancer prevention recommendations for red and processed meat intake.

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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