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1. Lifetime effects and cost-effectiveness of standard and higher-intensity statin therapy across population categories in the UK: a microsimulation modelling studyResearch in context

Author: Borislava Mihaylova, Runguo Wu, Junwen Zhou, Claire Williams, Iryna Schlackow, Jonathan Emberson, Christina Reith, Anthony Keech, John Robson, Richard Parnell, Jane Armitage, Alastair Gray, John Simes, and Colin Baigent
Subjects: Cardiovascular diseases, Statin, Cost-effectiveness, Quality-adjusted life years, Health care costs, Microsimulation model, Public aspects of medicine, RA1-1270
Abstract: Summary: Background: Cardiovascular disease incidence and mortality have declined across developed economies and granular up-to-date cost-effectiveness evidence is required for treatments targeting large populations. To assess the health benefits and cost-effectiveness of standard and higher intensity statin therapy in the contemporary UK population 40–70 years old. Methods: A cardiovascular disease microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration data (117,896 participants; 5 years follow-up), and calibrated in the UK Biobank cohort (501,854 participants; 9 years follow-up), projected risks of myocardial infarction, stroke, coronary revascularization, diabetes, cancer and vascular and nonvascular death for all UK Biobank participants without and with statin treatment. Meta-analyses of trials and cohort studies informed statins’ relative effects on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. UK healthcare perspective was taken (2020/2021 UK£) with costs per 28 tablets of £1.10 for standard (35%–45% LDL cholesterol (LDL-C) reduction) and £1.68 for higher intensity (≥45% LDL-C reduction) generic statin. Findings: Across categories by sex, age, LDL-C, and cardiovascular disease history/10-year cardiovascular risk, lifetime standard statin increased survival by 0.28–1.85 years (0.20–1.09 quality-adjusted life years (QALYs)), and higher intensity statin by further 0.06–0.40 years (0.03–0.20 QALYs) per person. Standard statin was cost-effective across all categories with incremental cost per QALY from £280 to £8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels. Stopping statin early reduced benefits and was not cost-effective. Interpretation: Lifetime low-cost statin therapy is cost-effective across all 40–70 years old in UK. Strengthening and widening statin treatment could cost-effectively improve population health. Funding: UK NIHR Health Technology Assessment Programme (17/140/02).
Published: 2024
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2. Predictive value of circulating NMR metabolic biomarkers for type 2 diabetes risk in the UK Biobank study

Author: Fiona Bragg, Eirini Trichia, Diego Aguilar-Ramirez, Jelena Bešević, Sarah Lewington, and Jonathan Emberson
Subjects: Biomarkers, Diabetes, Metabolomics, Risk prediction, Medicine
Abstract: Abstract Background Effective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors. Methods Nuclear magnetic resonance (NMR) metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Among a subset of 50,519 participants with data available on all relevant co-variates (sociodemographic characteristics, parental history of diabetes, lifestyle—including dietary—factors, anthropometric measures and fasting time), Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of the total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction among the full study population, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed. Results During median 11.9 (IQR 11.1–12.6) years’ follow-up, after accounting for multiple testing, 90 metabolic biomarkers showed independent associations with T2D risk among 50,519 participants (1211 incident T2D cases) and 76 showed associations after additional adjustment for HbA1c (false discovery rate controlled p < 0.01). Overall, 8 metabolic biomarker PCs were independently associated with T2D. Among the full study population of 65,684 participants, of whom 1719 developed T2D, addition of PCs to an established risk prediction model, including age, sex, parental history of diabetes, body mass index and HbA1c, improved T2D risk prediction as assessed by the c-statistic (increased from 0.802 [95% CI 0.791–0.812] to 0.830 [0.822–0.841]), continuous NRI (0.44 [0.38–0.49]) and relative (15.0% [10.5–20.4%]) and absolute (1.5 [1.0–1.9]) IDI. More modest improvements were observed when metabolic biomarker PCs were added to a more comprehensive established T2D risk prediction model additionally including waist circumference, blood pressure and plasma lipid concentrations (c-statistic, 0.829 [0.819–0.838] to 0.837 [0.831–0.848]; continuous NRI, 0.22 [0.17–0.28]; relative IDI, 6.3% [4.1–9.8%]; absolute IDI, 0.7 [0.4–1.1]). Conclusions When added to conventional risk factors, circulating NMR-based metabolic biomarkers modestly enhanced T2D risk prediction.
Published: 2022
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3. Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants

Author: Nurys B Armas Rojas, Ben Lacey, Monica Soni, Shaquille Charles, Jennifer Carter, Patricia Varona-Pérez, Julie Ann Burrett, Marcy Calderón Martínez, Elba Lorenzo-Vázquez, Sonia Bess Constantén, Hannah Taylor, Paul Sherliker, José Manuel Morales Rigau, Stephanie Ross, M. Sofia Massa, Osvaldo Jesús Hernández López, Nazrul Islam, Miguel Ángel Martínez Morales, Ismell Alonso Alomá, Fernando Achiong Estupiñan, Mayda Díaz González, Noel Rosquete Muñoz, Marelis Cendra Asencio, Oscar Díaz-Diaz, Ileydis Iglesias-Marichal, Jonathan Emberson, Richard Peto, and Sarah Lewington
Subjects: Cuba, Cardiovascular, Body-mass index, Blood pressure, Diabetes, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Cardiovascular disease accounts for about one-third of all premature deaths (ie, age =120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88–2.18]), as did diabetes (2.15, 1.95–2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64–2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively. Conclusions This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
Published: 2021
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4. Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials

Author: Natalie Staplin, PhD, Alistair J. Roddick, MBBS, Jonathan Emberson, PhD, Christina Reith, FFPM, Alex Riding, PhD, Alexa Wonnacott, PhD, Apexa Kuverji, MBChB, Sunil Bhandari, PhD, Colin Baigent, FMedSci, Richard Haynes, DM, and William G Herrington, FRCP
Subjects: Sodium-glucose co-transporter 2 inhibitors, Safety, Heart failure, CKD, Randomized trials, Medicine (General), R5-920
Abstract: ABSTRACT: Background: The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified. Methods: We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468). Findings: Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS). Interpretations: The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date. Funding: MRC-UK & KRUK.
Published: 2021
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5. Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults

Author: Nurys B. Armas Rojas, MD, Ben Lacey, DPhil, Daniel Martin Simadibrata, MRes, Stephanie Ross, PhD, Patricia Varona-Pérez, MD, Julie Ann Burrett, PhD, Marcy Calderón Martínez, MD, Elba Lorenzo-Vázquez, MD, Sonia Bess Constantén, MD, Blake Thomson, DPhil, Paul Sherliker, BA, José Manuel Morales Rigau, MSc, Jennifer Carter, PhD, M. Sofia Massa, PhD, Osvaldo Jesús Hernández López, MSc, Nazrul Islam, PhD, Miguel Ángel Martínez Morales, MD, Ismell Alonso Alomá, MD, Fernando Achiong Estupiñan, MD, Mayda Díaz González, MD, Noel Rosquete Muñoz, MD, Marelis Cendra Asencio, MD, Jonathan Emberson, PhD, Richard Peto, FRS, and Sarah Lewington, DPhil
Subjects: Cuba, Alcohol, Mortality, Prospective study, Medicine (General), R5-920
Abstract: Background: The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. Methods: In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35–79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. Findings: After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (
Published: 2021
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6. Childhood Smoking, Adult Cessation, and Cardiovascular Mortality: Prospective Study of 390 000 US Adults

Author: Blake Thomson, Jonathan Emberson, Ben Lacey, Richard Peto, Mark Woodward, and Sarah Lewington
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Published: 2020
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7. Association of childhood smoking and adult mortality: prospective study of 120 000 Cuban adults

Author: Blake Thomson, DPhil, Nurys Armas Rojas, MD, Ben Lacey, DPhil, Julie Ann Burrett, PhD, Patricia Varona-Pérez, MD, Marcy Calderón Martínez, MD, Elba Lorenzo-Vázquez, MD, Sonia Bess Constantén, MD, José Manuel Morales Rigau, MSc, Osvaldo Jesús Hernández López, MSc, Miguel Ángel Martínez Morales, MD, Ismell Alonso Alomá, MD, Fernando Achiong Estupiñan, MD, Mayda Díaz González, MD, Noel Rosquete Muñoz, MD, Marelis Cendra Asencio, MD, Jonathan Emberson, ProfPhD, Richard Peto, ProfFRS, Sarah Lewington, ProfDPhil, and Alfredo Dueñas Herrera, ProfMD
Subjects: Public aspects of medicine, RA1-1270
Abstract: Summary: Background: The average age at which people start smoking has been decreasing in many countries, but insufficient evidence exists on the adult hazards of having started smoking in childhood and, especially, in early childhood. We aimed to investigate the association between smoking habits (focusing on the age when smokers started) and cause-specific premature mortality in a cohort of adults in Cuba. Methods: For this prospective study, adults were recruited from five provinces in Cuba. Participants were interviewed (data collected included socioeconomic status, medical history, alcohol consumption, and smoking habits) and had their height, weight, and blood pressure measured. Participants were followed up until Jan 1, 2017 for cause-specific mortality; a subset was resurveyed in 2006–08. We used Cox regression to calculate adjusted rate ratios (RRs) for mortality at ages 30–69 years, comparing never-smokers with current smokers by age they started smoking and number of cigarettes smoked per day and with ex-smokers by the age at which they had quit. Findings: Between Jan 1, 1996, and Nov 24, 2002, 146 556 adults were recruited into the study, of whom 118 840 participants aged 30–69 years at recruitment contributed to the main analyses. 27 264 (52%) of 52 524 men and 19 313 (29%) of 66 316 women were current smokers. Most participants reported smoking cigarettes; few smoked only cigars. About a third of current cigarette smokers had started before age 15 years. Compared with never-smokers, the all-cause mortality RR was highest in participants who had started smoking at ages 5–9 years (RR 2·51, 95% CI 2·21–2·85), followed by ages 10–14 years (1·83, 1·72–1·95), 15–19 years (1·56, 1·46–1·65), and ages 20 years or older (1·50, 1·39–1·62). Smoking accounted for a quarter of all premature deaths in this population, but quitting before about age 40 years avoided almost all of the excess mortality due to smoking. Interpretation: In this cohort of adults in Cuba, starting to smoke in childhood was common and quitting was not. Starting in childhood approximately doubled the rate of premature death (ie, before age 70 years). If this 2-fold mortality RR continues into old age, about half of participants who start smoking before age 15 years and do not stop will eventually die of complications from their habit. The greatest risks were found among adults who began smoking before age 10 years. Funding: UK Medical Research Council, Cancer Research UK, British Heart Foundation, US Centers for Disease Control and Prevention (CDC) Foundation (with support from Amgen).
Published: 2020
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8. Impact of CKD on Household Income

Author: Rachael L. Morton, Iryna Schlackow, Alastair Gray, Jonathan Emberson, William Herrington, Natalie Staplin, Christina Reith, Kirsten Howard, Martin J. Landray, Alan Cass, Colin Baigent, Borislava Mihaylova, R. Collins, C. Baigent, M.J. Landray, C. Bray, Y. Chen, A. Baxter, A. Young, M. Hill, C. Knott, A. Cass, B. Feldt-Rasmussen, B. Fellström, D.E. Grobbee, C. Grönhagen-Riska, M. Haas, H. Holdaas, L.S. Hooi, L. Jiang, B. Kasiske, U. Krairittichai, A. Levin, Z.A. Massy, V. Tesar, R. Walker, C. Wanner, D.C. Wheeler, A. Wiecek, T. Dasgupta, W. Herrington, D. Lewis, M. Mafham, W. Majoni, C. Reith, J. Emberson, S. Parish, D. Simpson, J. Strony, T. Musliner, L. Agodoa, J. Armitage, Z. Chen, J. Craig, D. de Zeeuw, J.M. Gaziano, R. Grimm, V. Krane, B. Neal, V. Ophascharoensuk, T. Pedersen, P. Sleight, J. Tobert, and C. Tomson
Subjects: Diseases of the genitourinary system. Urology, RC870-923
Abstract: Introduction: The impact of chronic kidney disease (CKD) on income is unclear. We sought to determine whether CKD severity, serious adverse events, and CKD progression affected household income. Methods: Analyses were undertaken in a prospective cohort of adults with moderate-to-severe CKD in the Study of Heart and Renal Protection (SHARP), with household income information available at baseline screening and study end. Logistic regressions, adjusted for sociodemographic characteristics, smoking, and prior diseases at baseline, estimated associations during the 5-year follow-up, among (i) baseline CKD severity, (ii) incident nonfatal serious adverse events (vascular or cancer), and (iii) CKD treatment modality (predialysis, dialysis, or transplanted) at study end and the outcome “fall into relative poverty.” This was defined as household income
Published: 2018
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9. Genomic Response to Vitamin D Supplementation in the Setting of a Randomized, Placebo-Controlled Trial

Author: Antonio J. Berlanga-Taylor, Katharine Plant, Andrew Dahl, Evelyn Lau, Michael Hill, David Sims, Andreas Heger, Jonathan Emberson, Jane Armitage, Robert Clarke, and Julian C. Knight
Subjects: Medicine, Medicine (General), R5-920
Abstract: Background: Vitamin D deficiency has been associated with multiple diseases, but the causal relevance and underlying processes are not fully understood. Elucidating the mechanisms of action of drug treatments in humans is challenging, but application of functional genomic approaches in randomized trials may afford an opportunity to systematically assess molecular responses. Methods: In the Biochemical Efficacy and Safety Trial of Vitamin D (BEST-D), a double-blind, placebo-controlled, dose-finding, randomized clinical trial, 305 community-dwelling individuals aged over 65 years were randomly allocated to treatment with vitamin D3 4000 IU, 2000 IU or placebo daily for 12 months. Genome-wide genotypes at baseline, and transcriptome and plasma levels of cytokines (IFN-γ, IL-10, IL-8, IL-6 and TNF-α) at baseline and after 12 months, were measured. The trial had >90% power to detect 1.2-fold changes in gene expression. Findings: Allocation to vitamin D for 12-months was associated with 2-fold higher plasma levels of 25-hydroxy-vitamin D (25[OH]D, 4000 IU regimen), but had no significant effect on whole-blood gene expression (FDR
Published: 2018
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10. Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study

Author: Nurys Armas Rojas, ProfMBChB, Emily Dobell, MBBS, Ben Lacey, FFPH, Patricia Varona-Pérez, ProfMD, Julie Ann Burrett, PhD, Elba Lorenzo-Vázquez, MD, Marcy Calderón Martínez, MD, Paul Sherliker, BA, Sonia Bess Constantén, MD, José Manuel Morales Rigau, ProfMSc, Osvaldo Jesús Hernández López, MSc, Miguel Ángel Martínez Morales, MD, Ismell Alonso Alomá, MD, Fernando Achiong Estupiñan, ProfMD, Mayda Díaz González, MD, Noel Rosquete Muñoz, MD, Marelis Cendra Asencio, MD, Richard Peto, ProfFRS, Jonathan Emberson, PhD, Alfredo Dueñas Herrera, ProfMS, and Sarah Lewington, ProfDPhil
Subjects: Public aspects of medicine, RA1-1270
Abstract: Summary: Background: In Cuba, hypertension control in primary care has been prioritised as a cost-effective means of addressing premature death from cardiovascular disease. However, there is little evidence from large-scale studies on the prevalence and management of hypertension in Cuba, and no direct evidence of the expected benefit of such efforts on cardiovascular mortality. Methods: In a prospective cohort study, adults in the general population identified via local family medical practices were interviewed between Jan 1, 1996, and Nov 24, 2002, in five areas of Cuba, and a subset of participants were resurveyed between July 14, 2006, and Oct 19, 2008, in one area. During household visits, blood pressure was measured and information obtained on diagnosis and treatment of hypertension. We calculated the prevalence of hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or receiving treatment for hypertension) and the proportion of people with hypertension in whom it was diagnosed, treated, and controlled (systolic blood pressure
Published: 2019
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11. Effects of Vitamin D on Blood Pressure, Arterial Stiffness, and Cardiac Function in Older People After 1 Year: BEST‐D (Biochemical Efficacy and Safety Trial of Vitamin D)

Author: Joseph Tomson, Harold Hin, Jonathan Emberson, Rijo Kurien, Michael Lay, Jolyon Cox, Michael Hill, Linda Arnold, Paul Leeson, Jane Armitage, and Robert Clarke
Subjects: blood pressure, cardiac dysfunction, vitamin D, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundThe relevance of vitamin D for prevention of cardiovascular disease is uncertain. The BEST‐D (Biochemical Efficacy and Safety Trial of vitamin D) trial previously reported effects of vitamin D on plasma markers of vitamin D status, and the present report describes the effects on blood pressure, heart rate, arterial stiffness, and cardiac function. Methods and ResultsThis was a randomized, double‐blind, placebo‐controlled trial of 305 older people living in United Kingdom, who were allocated vitamin D 4000 IU (100 μg), vitamin D 2000 IU (50 μg), or placebo daily. Primary outcomes were plasma concentrations of 25‐hydroxy‐vitamin D and secondary outcomes were blood pressure, heart rate, and arterial stiffness in all participants at 6 and 12 months, plasma N‐terminal prohormone of brain natriuretic peptide levels in all participants at 12 months, and echocardiographic measures of cardiac function in a randomly selected subset (n=177) at 12 months. Mean (SE) plasma 25‐hydroxy‐vitamin D concentrations were 50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4) nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or placebo, respectively. Allocation to vitamin D had no significant effect on mean levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12 months, nor on any echocardiographic measures of cardiac function, or plasma N‐terminal prohormone of brain natriuretic peptide concentration at 12 months. ConclusionsThe absence of any significant effect of vitamin D on blood pressure, arterial stiffness, or cardiac function suggests that any beneficial effects of vitamin D on cardiovascular disease are unlikely to be mediated through these mechanisms. Clinical Trial RegistrationURL: https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier: EudraCT number: 2011–005763‐24a
Published: 2017
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12. Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials.

Author: Kazem Rahimi, Neeraj Bhala, Pieter Kamphuisen, Jonathan Emberson, Sara Biere-Rafi, Vera Krane, Michele Robertson, John Wikstrand, and John McMurray
Subjects: Medicine
Abstract: BackgroundIt has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins.Methods and findingsWe searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78-1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72-1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76-1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82-1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80-1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary.ConclusionsThe findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out.
Published: 2012
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13. Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: a meta-analysis.

Author: Marion Mafham, Jonathan Emberson, Martin J Landray, Chi-Pang Wen, and Colin Baigent
Subjects: Medicine, Science
Abstract: Lower estimated glomerular filtration rate (eGFR) has been associated with an increased risk of major vascular events (MVEs) and death, but differences in methodology make between-study comparisons difficult. We used a novel method to summarise the published results.Studies assessing the relationship between baseline eGFR and subsequent MVEs or all cause mortality were identified using Pubmed. Those which involved at least 500 individuals, planned at least 1 year of follow-up, reported age and sex adjusted relative risks, and provided the mean eGFR in each category (or sufficient information to allow its estimation) were included. To take account of differences in underlying risk between studies, proportional within-study differences in eGFR (rather than absolute eGFR values) were related to risk. Fifty studies (2 million participants) assessing MVEs and 67 studies (5 million participants) assessing all cause mortality were eligible. There was an inverse relationship between lower eGFR and the risk of MVEs and of death. In studies among people without prior vascular disease, a 30% lower eGFR level was on average associated with a 29% (SE 0.2%) increase in the risk of a MVE and a 31% (SE 0.2%) increase in the risk of death from any cause. In studies among people with prior vascular disease, these estimates were 26% (SE 1.0%) and 23% (SE 0.2%) respectively. While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design.Lower eGFR was consistently associated with a moderate increase in the risk of death and MVEs. If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment.
Published: 2011
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14. Prediction Models for Individual-Level Healthcare Costs Associated with Cardiovascular Events in the UK

Author: Junwen Zhou, Runguo Wu, Claire Williams, Jonathan Emberson, Christina Reith, Anthony Keech, John Robson, Kenneth Wilkinson, Jane Armitage, Alastair Gray, John Simes, Colin Baigent, and Borislava Mihaylova
Subjects: Pharmacology, Health Policy, Public Health, Environmental and Occupational Health
Abstract: Objectives The aim of this study was to develop prediction models for the individual-level impacts of cardiovascular events on UK healthcare costs. Methods In the UK Biobank, people 40–70 years old, recruited in 2006–2010, were followed in linked primary (N = 192,983 individuals) and hospital care (N = 501,807 individuals) datasets. Regression models of annual primary and annual hospital care costs (2020 UK£) associated with individual characteristics and experiences of myocardial infarction (MI), stroke, coronary revascularization, incident diabetes mellitus and cancer, and vascular and nonvascular death are reported. Results For both people without and with previous cardiovascular disease (CVD), primary care costs were modelled using one-part generalised linear models (GLMs) with identity link and Poisson distribution, and hospital costs with two-part models (part 1: logistic regression models the probability of incurring costs; part 2: GLM with identity link and Poisson distribution models the costs conditional on incurring any). In people without previous CVD, mean annual primary and hospital care costs were £360 and £514, respectively. The excess primary care costs were £190 and £360 following MI and stroke, respectively, whereas excess hospital costs decreased from £4340 and £5590, respectively, in the year of these events, to £190 and £410 two years later. People with previous CVD had more than twice higher annual costs, and incurred higher excess costs for cardiovascular events. Other characteristics associated with higher costs included older age, female sex, south Asian ethnicity, higher socioeconomic deprivation, smoking, lower level of physical activities, unhealthy body mass index, and comorbidities. Conclusions These individual-level healthcare cost prediction models could inform assessments of the value of health technologies and policies to reduce cardiovascular and other disease risks and healthcare costs. An accompanying Excel calculator is available to facilitate the use of the models.
Published: 2023

15. Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology

Author: Natalie Staplin, William G. Herrington, Federico Murgia, Maysson Ibrahim, Katherine R. Bull, Parminder K. Judge, Sarah Y.A. Ng, Michael Turner, Doreen Zhu, Jonathan Emberson, Martin J. Landray, Colin Baigent, Richard Haynes, and Jemma C. Hopewell
Subjects: Molecular Epidemiology, Creatinine, Albumins, Hypertension, Internal Medicine, Humans, Albuminuria, Blood Pressure, Renal Insufficiency, Chronic, Kidney, Glomerular Filtration Rate
Abstract: Background: It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration. Methods: 311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m 2 , or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m 2 ) considered evidence of glomerular hyperfiltration. Results: 21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m 2 . Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29–1.45) and 19% (1.14–1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and 2 were 49% higher (95% CI, 1.21–1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity. Conclusions: In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.
Published: 2022

16. Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes

Author: Abhishek Nag, Ryan S. Dhindsa, Jonathan Mitchell, Chirag Vasavda, Andrew R. Harper, Dimitrios Vitsios, Andrea Ahnmark, Bilada Bilican, Katja Madeyski-Bengtson, Bader Zarrouki, Anthony W. Zoghbi, Quanli Wang, Katherine R. Smith, Jesus Alegre-Díaz, Pablo Kuri-Morales, Jaime Berumen, Roberto Tapia-Conyer, Jonathan Emberson, Jason M. Torres, Rory Collins, David M. Smith, Benjamin Challis, Dirk S. Paul, Mohammad Bohlooly-Y, Mike Snowden, David Baker, Regina Fritsche-Danielson, Menelas N. Pangalos, and Slavé Petrovski
Subjects: Multidisciplinary
Abstract: We performed collapsing analyses on 454,796 UK Biobank (UKB) exomes to detect gene-level associations with diabetes. Recessive carriers of nonsynonymous variants in MAP3K15 were 30% less likely to develop diabetes ( P = 5.7 × 10 −10 ) and had lower glycosylated hemoglobin (β = −0.14 SD units, P = 1.1 × 10 −24 ). These associations were independent of body mass index, suggesting protection against insulin resistance even in the setting of obesity. We replicated these findings in 96,811 Admixed Americans in the Mexico City Prospective Study ( P < 0.05)Moreover, the protective effect of MAP3K15 variants was stronger in individuals who did not carry the Latino-enriched SLC16A11 risk haplotype ( P = 6.0 × 10 −4 ). Separately, we identified a Finnish-enriched MAP3K15 protein-truncating variant associated with decreased odds of both type 1 and type 2 diabetes ( P < 0.05) in FinnGen. No adverse phenotypes were associated with protein-truncating MAP3K15 variants in the UKB, supporting this gene as a therapeutic target for diabetes.
Published: 2023

17. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul Cader, Ruslinda Mustafar, Lydia Kamaruzaman, Rozita Mohd, Rahimah Ismail, Chong Men Leong, Chee Koon Low, Liang Wei Wong, Norlezah Adnan, Sabariah Ibrahim, Mohamad Zaimi Abdul Wahab, Sunita Bavanandan, Yik Shen Lim, Wan Hazlina Wan Mohamad, Siti Munirah Jaafar, Nur Ashykeen Mohd Fauzi, Aziee Sudin, Soo Kun Lim, Chye Chung Gan, Albert Hing, Wan Ahmad Faizal Alaidin Razali, Yew Fong Liew, Chelsia Bao Tyng Chan, Mei Chih Cheng, Yu Chen Ong, Loke Meng Ong, Farah Amalina Mohamed Affandi, Korina Rahmat, Ban Chai Peng, Masayu Amat, Nuzaimin Hadafi Ahmad, Doo Yee Mah, Yi Loon Tye, Zaid Azhari, Siti Nabilah Mohamad Zaini, Mohd Aidil Musa, Norazinizah Ahmad Miswan, Rafizanur Ramli, Nor Aziah Ahmad, Bak Leong Goh, Nurul Izah Ahmad, Fairol Huda Ibrahim, Tze Jian Ng, Malini Shanmuganathan, Li Lian Tay, Zaiha Harun, Salmi Ramli, Nurul 'Ain Yusof, Rossenizal Abd Rahman, Muhammad Iqbal Abdul Hafidz, Nur Hidayati Mohd Sharif, Irda Yasmoon Awang, Eitaro Nakashima, Rui Imamine, Makiko Minatoguchi, Yukari Miura, Miduki Nakaoka, Yoshiki Suzuki, Hitomi Yoshikawa, Koki Shin, Kanae Fujita, Misuzu Iwasa, Haruka Sasajima, Airi Sato, Yoshiyuki Hamamoto, Yuki Fujita, Takuya Haraguchi, Takanori Hyo, Kiyohiro Izumi, Toshiyuki Komiya, Sodai Kubota, Takeshi Kurose, Hitoshi Kuwata, Susumu Nakatani, Kaori Oishi, Saki Okamoto, Kaori Okamura, Jun Takeoka, Nagaaki Tanaka, Katsuya Tanigaki, Naohiro Toda, Koin Watanabe, Hiromi Komori, Rika Kumuji, Asako Takesada, Aya Tanaka, Shoichi Maruyama, Tomonori Hasegawa, Akiko Ishiguro, Takuji Ishimoto, Kazuhiro Ito, Yutaka Kamimura, Noritoshi Kato, Sawako Kato, Hiroshi Kojima, Tomoki Kosugi, Kayaho Maeda, Masasi Mizuno, Shoji Saito, Hitomi Sato, Yuka Sato, Yasuhiro Suzuki, Akihito Tanaka, Yoshinari Yasuda, Fujiko Hasegawa, Maiko Hayashi, Shizuka Higashi, Kaho Shimamura, Momoko Sumi, Kazuki Tajima, Chimaki Unekawa, Kana Wakayama, Yukiko Wakita, Takatoshi Otani, Ayako Imai, Sayaka Kawashima, Eri Kogure, Tomoe Sato, Misato Takezawa, Shinya Yoshida, Hideo Araki, Yuko Katsuda, Masahiro Konishi, Takahiro Matsunaga, Masashi Oe, Kunihiro Ogane, Masato Sakai, Tomoko Takahashi, Takahiro Yamano, Takuya Yokoyama, Hitomi Ito, Masayo Katayama, Emi Kuroda, Toru Ikeda, Takuma Kojo, Etsuo Yoshidome, Rieko Mizumachi, Akane Yamamoto, Narihisa Yamasaki, Yoshihiko Yamasaki, Jun Wada, Jun Eguchi, Chigusa Higuchi, Akihiro Katayama, Masaru Kinomura, Masashi Kitagawa, Shinji Kitamura, Satoshi Miyamoto, Hiroshi Morinaga, Atsuko Nakatsuka, Ichiro Nojima, Kenichi Shikata, Hitoshi Sugiyama, Katsuyuki Tanabe, Kenji Tsuji, Haruhito Uchida, Mayu Watanabe, Chie Hashimoto, Takahiro Kato, Sayaka Yamamoto, Takehiko Wada, Masafumi Fukagawa, Naoto Hamano, Masahiro Koizumi, Hirotaka Komaba, Yosuke Nakagawa, Michiyo Iwamoto, Kosuke Masutani, Akane Katanosaka, Mayu Kiyota, Hikari Uchi, Yuka Ueda, Sonoka Yamamoto, Hajime Nagasu, Seiji Itano, Tsukasa Iwakura, Hiroyuki Kadoya, Eiichiro Kanda, Naoki Kashihara, Kengo Kidokoro, Megumi Kondo, Tamaki Sasaki, Minoru Satoh, Atsuyuki Tokuyama, Reina Umeno, Yoshihisa Wada, Toshiya Yamamoto, Yu Yamanouchi, Masumi Abe, Yoko Inukai, Wataru Ogawa, Shunichiro Asahara, Hideki Fujii, Shunsuke Goto, Yushi Hirota, Tetsuya Hosooka, Keiji Kono, Shinichi Nishi, Yuko Okada, Kazuhiko Sakaguchi, Kenji Sugawara, Michiko Takahashi, Tomoko Takai, Yoshikazu Tamori, Kentaro Watanabe, Miyu Kitajima, Misaki Nishi, Junko Wada, Yasuhiko Ito, Hideki Kamiya, Akimasa Asai, Nao Asai, Saeko Asano, Shogo Banno, Yohei Ejima, Hanako Hase, Tomohide Hayami, Tatsuhito Himeno, Takahiro Ishikawa, Mayumi Ito, Shiho Iwagaitsu, Rina Kasagi, Yoshiro Kato, Makoto Kato, Koichi Kato, Takayuki Katsuno, Miyuka Kawai, Hiroshi Kinashi, Masaki Kondo, Masako Koshino, Naoya Matsuoka, Yoshiaki Morishita, Mikio Motegi, Jiro Nakamura, Hiromi Shimoda, Hirokazu Sugiyama, Shin Tsunekawa, Makoto Yamaguchi, Kazuyo Takahashi, Hirotaka Watada, Takashi Funayama, Yasuhiko Furukawa, Tomohito Gohda, Hiromasa Goto, Hideyoshi Kaga, Yasuhiko Kanaguchi, Akio Kanazawa, Kayo Kaneko, Toshiki Kano, Masao Kihara, Shogo Kimura, Takashi Kobayashi, Masayuki Maiguma, Yuko Makita, Satoshi Mano, Tomoya Mita, Takeshi Miyatsuka, Maki Murakoshi, Masahiro Muto, Masami Nakata, Junichiro Nakata, Yuya Nishida, Nao Nohara, Takeshi Ogihara, Daisuke Sato, Junko Sato, Hiroaki Sato, Yusuke Suzuki, Ruka Suzuki, Hitoshi Suzuki, Miyuki Takagi, Yoshifumi Tamura, Toyoyoshi Uchida, Seiji Ueda, Miki Asawa, Minako Miyaji, Eri Nagashima, Yoshie Shibata, Eri Yanagisawa, Toshimasa Yamauchi, Yosuke Hirakawa, Hiroshi Nishi, Nobuhiro Shojima, Satoko Horikawa, Yukiko Nakayama, Naoko Yamada, Yuki Omori, Shintaro Yano, Miyabi Ioka, Nahoko Kuwabara, Remi Nagano, Megumi Nozawa, Yumi Osawa, Hiroshi Maegawa, Shinji Kume, Shinichi Araki, Itsuko Miyazawa, Katsutaro Morino, Ikuko Kawai, Masumi Sobata, Motoko Takaoka, Yasushi Iwaita, Takashi Udagawa, Ami Inamori, Aya Kawase, Aya Yamanaka, Hitoshi Shimano, Akiko Fujita, Hitoshi Iwasaki, Hirayasu Kai, Yoshinori Osaki, Chie Saito, Motohiro Sekiya, Ryoya Tsunoda, 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Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

18. Higher dose corticosteroids in hospitalised COVID-19 patients with hypoxia but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Peter Horby, Mark Campbell, Natalie Staplin, Jeremy Nel, Alexander James Richards, Buddha Basnyat, and Jonathan Emberson
Abstract: SUMMARYBackgroundLow-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.MethodsThis randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturation clinicaltrials.gov(NCT04381936).FindingsBetween 25 May 2021 and 12 May 2022, 1272 COVID-19 patients with hypoxia and receiving no oxygen (1%) or simple oxygen only (99%) were randomly allocated to receive usual care plus higher dose corticosteroids versus usual care alone (of whom 87% received low dose corticosteroids during the follow-up period). Of those randomised, 745 (59%) were in Asia, 512 (40%) in the UK and 15 (1%) in Africa. 248 (19%) had diabetes mellitus. Overall, 121 (18%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio [RR] 1·56; 95% CI 1·18-2·06; p=0·0020). There was also an excess of pneumonia reported to be due to non-COVID infection (10% vs. 6%; absolute difference 3.7%; 95% CI 0.7-6.6) and an increase in hyperglycaemia requiring increased insulin dose (22% vs. 14%; absolute difference 7.4%; 95% CI 3.2-11.5).InterpretationIn patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to usual care, which included low dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health and Care Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).
Published: 2022

19. Association between smoking, smoking cessation, and mortality by race/ethnicity and sex among US adults

Author: Blake Thomson, Jonathan Emberson, Ben Lacey, Sarah Lewington, Richard Peto, Ahmedin Jemal, and Farhad Islami
Subjects: Adult, Male, Smokers, Ethnicity, Humans, Female, Smoking Cessation, Prospective Studies, General Medicine, Cigarette Smoking
Abstract: ImportancePatterns of cigarette smoking and smoking cessation vary considerably across demographic groups in the US, but there is limited evidence on whether the hazards of smoking and benefits of quitting vary across these groups. Population-specific evidence on the benefits of quitting smoking may motivate cessation among groups historically underrepresented in medical research.ObjectiveTo quantify the association between smoking, smoking cessation, and mortality by race, ethnicity, and sex.Design, Setting, and ParticipantsThis nationally representative, prospective cohort study used data from the US National Health Interview Survey collected via questionnaire between January 1997 and December 2018 among adults aged 25 to 84 years at recruitment. Participants were followed up for cause-specific mortality through December 31, 2019.ExposuresSelf-reported smoking status at recruitment, age at quitting smoking, and years since quitting smoking.Main Outcomes and MeasuresThe main outcomes were all-cause mortality and mortality from cancer, cardiovascular disease, and lower respiratory disease. Adjusted mortality rate ratios comparing never, former, and current smokers were calculated using Cox proportional hazards regression. Weighted analyses were conducted by race, ethnicity, and sex as reported by participants.ResultsAmong the 551 388 participants in the main analyses, the mean (SD) age at recruitment was 48.9 (15.3) years; 307 601 (55.8%) were women, 87 207 (15.8%) were Hispanic, 75 545 (13.7%) were non-Hispanic Black, 355 782 (64.5%) were non-Hispanic White, and 32 854 (6.0%) identified as other non-Hispanic race and ethnicity. There were 74 870 deaths among participants aged 25 to 89 years during follow-up (36 792 [49.1%] among men; 38 078 [50.9%] among women). The all-cause mortality rate ratio (RR) for current vs never smoking was 2.80 (95% CI, 2.73-2.88) overall. The RRs were similar by sex but varied by race and ethnicity: Hispanic, 2.01 (95% CI, 1.84-2.18); non-Hispanic Black, 2.19 (95% CI, 2.06-2.33); non-Hispanic White, 3.00 (95% CI, 2.91-3.10); and other non-Hispanic race and ethnicity, 2.16 (95% CI, 1.88-2.47). When comparing those who quit smoking before age 45 years with never smokers, all-cause mortality RRs were 1.15 (95% CI, 1.03-1.28) among Hispanic individuals, 1.16 (95% CI, 1.07-1.25) among non-Hispanic Black individuals, 1.11 (95% CI, 1.08-1.15) among non-Hispanic White individuals, and 1.17 (95% CI, 0.99-1.39) among other non-Hispanic individuals.Conclusions and RelevanceIn this prospective cohort study, among men and women from diverse racial and ethnic groups, current smoking was associated with at least twice the all-cause mortality rate of never smoking. Quitting smoking, particularly at younger ages, was associated with substantial reductions in the relative excess mortality associated with continued smoking.
Published: 2022

20. Human genetics uncovers

Author: Abhishek, Nag, Ryan S, Dhindsa, Jonathan, Mitchell, Chirag, Vasavda, Andrew R, Harper, Dimitrios, Vitsios, Andrea, Ahnmark, Bilada, Bilican, Katja, Madeyski-Bengtson, Bader, Zarrouki, Anthony W, Zoghbi, Quanli, Wang, Katherine R, Smith, Jesus, Alegre-Díaz, Pablo, Kuri-Morales, Jaime, Berumen, Roberto, Tapia-Conyer, Jonathan, Emberson, Jason M, Torres, Rory, Collins, David M, Smith, Benjamin, Challis, Dirk S, Paul, Mohammad, Bohlooly-Y, Mike, Snowden, David, Baker, Regina, Fritsche-Danielson, Menelas N, Pangalos, and Slavé, Petrovski
Subjects: Monocarboxylic Acid Transporters, Diabetes Mellitus, Type 2, Humans, Genetic Predisposition to Disease, Obesity, Prospective Studies, MAP Kinase Kinase Kinases
Abstract: We performed collapsing analyses on 454,796 UK Biobank (UKB) exomes to detect gene-level associations with diabetes. Recessive carriers of nonsynonymous variants in
Published: 2022

21. Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Peter Horby, Paul Collini, Mark Campbell, Natalie Staplin, Manish Patel, Alexander James Richards, and Jonathan Emberson
Abstract: SUMMARYBackgroundDimethyl fumarate (DMF) is an anti-inflammatory drug that has been proposed as a treatment for patients hospitalised with COVID-19MethodsThis randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. In this initial assessment of DMF, performed at 27 UK hospitals, eligible and consenting adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF 120mg twice daily for 2 days followed by 240mg twice daily for 8 days, or until discharge if sooner. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale, assessed using a proportional odds model. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).FindingsBetween 2 March 2021 and 18 November 2021, 713 patients were enrolled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients were receiving corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.85-1.46; p=0.42). There was no significant effect of DMF on any secondary outcome. As expected, DMF caused flushing and gastrointestinal symptoms, each in around 6% of patients, but no new adverse effects were identified.InterpretationIn adults hospitalised with COVID-19, DMF was not associated with an improvement in clinical outcomes.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
Published: 2022

22. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials

Author: Christina Reith, Colin Baigent, Lisa Blackwell, Jonathan Emberson, Enti Spata, Kelly Davies, Heather Halls, Lisa Holland, Kate Wilson, Jane Armitage, Charlie Harper, David Preiss, Alistair Roddick, Anthony Keech, John Simes, Rory Collins, Elizabeth Barnes, Jordan Fulcher, William G Herrington, Adrienne Kirby, Borislava Mihaylova, Rachel O'Connell, Pierre Amarenco, Philip Barter, D John Betteridge (deceased), Michael Blazing, Jackie Bosch, Louise Bowman, Eugene Braunwald, Christopher P Cannon, Michael Clearfield, Stuart Cobbe, Helen M Colhoun, Björn Dahlöf, Barry Davis, James de Lemos, John R Downs, Paul N Durrington, Bengt Fellström, Ian Ford, Maria Grazia Franzosi, John Fuller (deceased), Curt Furberg, Robert Glynn, David Gordon, Antonio Gotto Jr, Richard Grimm, Ajay Gupta, C Morton Hawkins, Graham A Hitman, Hallvard Holdaas (deceased), Alan Jardine, J Wouter Jukema, John JP Kastelein, Sharon Kean, John Kjekshus, Genell Knatterud (deceased), Robert H Knopp (deceased), Wolfgang Koenig, Michael Koren, Vera Krane, Martin Landray, John LaRosa, Roberto Latini, Eva Lonn, Donata Lucci, Jean MacFadyen, Peter Macfarlane, Stephen MacMahon, Aldo Maggioni, Roberto Marchioli, Ian Marschner, Lemuel Moyé, Sabina Murphy, Andrew Neil, Enrico B Nicolis, Chris Packard, Sarah Parish, Terje R Pedersen, Richard Peto, Marc Pfeffer, Neil Poulter, Sara Pressel, Jeffrey Probstfield, Mahboob Rahman, Paul M Ridker, Michele Robertson, Frank Sacks, Naveed Sattar, Roland Schmieder, Patrick W Serruys, Peter Sever, John Shaw (deceased), James Shepherd (deceased), Lara Simpson, Peter Sleight (deceased), Luigi Tavazzi, Gianni Tognoni, Andrew Tonkin, Stella Trompet, Christoph Wanner, Hans Wedel, Stephen Weis, K Michael Welch, Harvey White, John Wikstrand, Lars Wilhelmsen, Stephen Wiviott, Robin Young, Salim Yusuf, Faiez Zannad, Hiroyuki Arashi, Robert Byington, Robert Clarke, Marcus Flather, Uri Goldbourt, Shinya Goto, Jemma Hopewell, Kees Hovingh, Patricia Kearney, George Kitas, Connie Newman, Marc S Sabatine, Greg Schwartz, Liam Smeeth, Jonathan Tobert, John Varigos, Junichi Yamaguchi, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, and Collaboration, Cholesterol Treatment Trialists'
Subjects: Male, Muscles, Australia, Humans, Female, General Medicine, Myalgia, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Middle Aged, Atherosclerosis, Randomized Controlled Trials as Topic
Abstract: Background: Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy. Methods: Randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. We analysed individual participant data from 19 double-blind trials of statin versus placebo (n=123 940) and four double-blind trials of a more intensive versus a less intensive statin regimen (n=30 724). Standard inverse-variance-weighted meta-analyses of the effects on muscle outcomes were conducted according to a prespecified protocol. Findings: Among 19 placebo-controlled trials (mean age 63 years [SD 8], with 34 533 [27·9%] women, 59 610 [48·1%] participants with previous vascular disease, and 22 925 [18·5%] participants with diabetes), during a weighted average median follow-up of 4·3 years, 16 835 (27·1%) allocated statin versus 16 446 (26·6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1·03; 95% CI 1·01–1·06). During year 1, statin therapy produced a 7% relative increase in muscle pain or weakness (1·07; 1·04–1·10), corresponding to an absolute excess rate of 11 (6–16) events per 1000 person-years, which indicates that only one in 15 ([1·07–1·00]/1·07) of these muscle-related reports by participants allocated to statin therapy were actually due to the statin. After year 1, there was no significant excess in first reports of muscle pain or weakness (0·99; 0·96–1·02). For all years combined, more intensive statin regimens (ie, 40–80 mg atorvastatin or 20–40 mg rosuvastatin once per day) yielded a higher RR than less intensive or moderate-intensity regimens (1·08 [1·04–1·13] vs 1·03 [1·00–1·05]) compared with placebo, and a small excess was present (1·05 [0·99–1·12]) for more intensive regimens after year 1. There was no clear evidence that the RR differed for different statins, or in different clinical circumstances. Statin therapy yielded a small, clinically insignificant increase in median creatine kinase values of approximately 0·02 times the upper limit of normal. Interpretation: Statin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower than the known cardiovascular benefits. There is a need to review the clinical management of muscle symptoms in patients taking a statin. Funding: British Heart Foundation, Medical Research Council, Australian National Health and Medical Research Council.
Published: 2022

23. Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Author: Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A. L., M. Diez A. R., A. Fernandez A. R., F. Fruhwald A. T., Fazlibegovic, E., P. Gatzov B. G., A. Kurlianskaya B. Y., R. Hullin C. H., T. Christodoulides C. Y., J. Hradec C. Z., O. Wendelboe Nielsen D. K., R. Nedjar D. Z., T. Uuetoa E. E., M. Hassanein E. G., J. F. Delgado Jimenez E. S., P. Harjola F. I., V, D. Logeart F. R., V. Chumburidze G. E., D. Tousoulis G. R., D. Milicic H. R., B. Merkely H. U., O'Donoghue IE, E., O. Amir I. L., A. Shotan I. L., D. Shafie I. R., M. Metra I. T., A. Matsumori J. P., E. Mirrakhimov K. G., A. Kavoliuniene L. T., A. Erglis L. V., Vataman, E., M. Otljanska M. K., E. Srbinovska Kostovska M. K., D. Cassar DeMarco M. T., J. Drozdz P. L., Fonseca, C., O. Chioncel R. O., M. Dekleva R. S., E. Shkolnik R. U., U. Dahlstrom S. E., M. Lainscak S. I., E. Goncalvesova S. K., A. Temizhan T. R., V. Estrago U. Y., G. Bajraktari X. K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., J. -F., Ly, Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A., L., M. Diez A., R., A. Fernandez A., R., F. Fruhwald A., T., Fazlibegovic, E., P. Gatzov B., G., A. Kurlianskaya B., Y., R. Hullin C., H., T. Christodoulides C., Y., J. Hradec C., Z., O. Wendelboe Nielsen D., K., R. Nedjar D., Z., T. Uuetoa E., E., M. Hassanein E., G., J. F. Delgado Jimenez E., S., V-, P. Harjola F. I., D. Logeart F., R., V. Chumburidze G., E., D. Tousoulis G., R., D. Milicic H., R., B. Merkely H., U., O'Donoghue IE, E., O. Amir I., L., A. Shotan I., L., D. Shafie I., R., M. Metra I., T., A. Matsumori J., P., E. Mirrakhimov K., G., A. Kavoliuniene L., T., A. Erglis L., V., Vataman, E., M. Otljanska M., K., E. Srbinovska Kostovska M., K., D. Cassar DeMarco M., T., J. Drozdz P., L., Fonseca, C., O. Chioncel R., O., M. Dekleva R., S., E. Shkolnik R., U., U. Dahlstrom S., E., M. Lainscak S., I., E. Goncalvesova S., K., A. Temizhan T., R., V. Estrago U., Y., G. Bajraktari X., K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., University of Zurich, and Seferović, Petar M
Subjects: Male, Registry, medicine.medical_specialty, Adverse outcomes, 610 Medicine & health, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Independent predictor, 2705 Cardiology and Cardiovascular Medicine, Ventricular Function, Left, 03 medical and health sciences, Age, 0302 clinical medicine, Internal medicine, Age related, Hospitalization, Mortality, Sex, medicine, Humans, Registries, Medical prescription, Aged, Heart Failure, Ejection fraction, business.industry, Stroke Volume, medicine.disease, Ageing, Heart failure, 10209 Clinic for Cardiology, Female, Angiotensin Receptor Blockers, Cardiology and Cardiovascular Medicine, business
Abstract: [Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.
Published: 2019

24. Genotyping, sequencing and analysis of 140,000 adults from the Mexico City Prospective Study

Author: Joelle Mbatchou, Michael Turner, Jonathan Emberson, Yuxin Zou, and JESUS ALEGRE - DIAZ
Abstract: The Mexico City Prospective Study (MCPS) is a prospective cohort of over 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City. We generated genotype and exome sequencing data for all individuals, and whole genome sequencing for 10,000 selected individuals. We uncovered high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Native American, European and African ancestry, with extensive admixture from indigenous groups in Central, Southern and South Eastern Mexico. Native Mexican segments of the genome had lower levels of coding variation, but an excess of homozygous loss of function variants compared with segments of African and European origin. We estimated population specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Native Mexico at exome variants, all available via a public browser. Using whole genome sequencing, we developed an imputation reference panel which outperforms existing panels at common variants in individuals with high proportions of Central, South and South Eastern Native Mexican ancestry. Our work illustrates the value of genetic studies in populations with diverse ancestry and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States where the Hispanic/Latino population is predominantly of Mexican descent.
Published: 2022

25. 83 Determinants of post-operative atrial fibrillation in 1613 patients undergoing coronary artery bypass grafting in the statin therapy in cardiac surgery (stics) trial

Author: Rohan Wijesurendra, Rebecca Sardell, Michael Hill, Raja Jayaram, Natalie Staplin, Rory Collins, Zhengming Chen, Jonathan Emberson, Richard Haynes, and Barbara Casadei
Published: 2022

26. Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study

Author: Paula Curnow, Dominic Gair, Matthew D Rutter, Enti Spata, Jonathan Emberson, Jem Rashbass, Colin Baigent, Barbara Casadei, Michael J Richards, Brian D Nicholson, K. Spencer, P. J. Finan, Rory Collins, Raphael Goldacre, Martin J Landray, M Mafham, Sam Hollings, Jon Shelton, Chris Cunningham, Eva Morris, and David Sebag-Montefiore
Subjects: Male, Laparoscopic surgery, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Population, State Medicine, 03 medical and health sciences, 0302 clinical medicine, Correspondence, Pandemic, Epidemiology, medicine, Humans, education, Referral and Consultation, Early Detection of Cancer, Health Services Needs and Demand, education.field_of_study, Radiotherapy, Hepatology, SARS-CoV-2, business.industry, Public health, Gastroenterology, COVID-19, Cancer, Colonoscopy, Middle Aged, medicine.disease, Patient Care Management, Radiation therapy, England, 030220 oncology & carcinogenesis, Emergency medicine, Female, 030211 gastroenterology & hepatology, Colorectal Neoplasms, business, Colorectal Surgery, Delivery of Health Care
Abstract: Summary Background There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England. Methods Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated. Findings As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53–71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89–95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8–34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19–42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17–76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020. Interpretation The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England. Funding Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.
Published: 2021

27. Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme

Author: Oktay Tutarel, Karishma P. Ramlakhan, Lucia Baris, Maria T. Subirana, Judith Bouchardy, Attila Nemes, Niels G. Vejlstrup, Olga A. Osipova, Mark R. Johnson, Roger Hall, Jolien W. Roos‐Hesselink, Christopher Peter Gale, Branko Beleslin, Andrzej Budaj, Ovidiu Chioncel, Nikolaos Dagres, Nicolas Danchin, David Erlinge, Jonathan Emberson, Michael Glikson, Alastair Gray, Meral Kayikcioglu, Aldo Maggioni, Klaudia Vivien Nagy, Aleksandr Nedoshivin, Anna‐Sonia Petronio, Jolien Roos‐Hesselink, Lars Wallentin, Uwe Zeymer, Joerg Stein, William Anthony Parsonage, Werner Budts, Julie De Backer, Jasmin Grewal, Ariane Marelli, Harald Kaemmerer, Guillaume Jondeau, Mark Johnson, Aldo P. Maggioni, Luigi Tavazzi, Ulf Thilen, Uri Elkayam, Catherine Otto, Karen Sliwa, A. Aquieri, A. Saad, H. Ruda Vega, J. Hojman, J. M. Caparros, M. Vazquez Blanco, M. Arstall, C. M. Chung, G. Mahadavan, E. Aldridge, M. Wittwer, Y. Y. Chow, W. A. Parsonage, K. Lust, N. Collins, G. Warner, R. Hatton, A. Gordon, E. Nyman, J. Stein, E. Donhauser, H. Gabriel, A. Bahshaliyev, F. Guliyev, I. Hasanova, T. Jahangirov, Z. Gasimov, A. Salim, C. M. Ahmed, F. Begum, M. H. Hoque, M. Mahmood, M. N. Islam, P. P. Haque, S. K. Banerjee, T. Parveen, M. Morissens, J. De Backer, L. Demulier, M. de Hosson, W. Budts, M. Beckx, M. Kozic, M. Lovric, T. Kovacevic‐Preradovic, N. Chilingirova, P. Kratunkov, N. Wahab, S. McLean, E. Gordon, L. Walter, A. Marelli, A. R. Montesclaros, G. Monsalve, C. Rodriguez, F. Balthazar, V. Quintero, W. Palacio, L. A. Mejía Cadavid, E. Munoz Ortiz, F. Fortich Hoyos, E. Arevalo Guerrero, J. Gandara Ricardo, J. Velasquez Penagos, Z. Vavera, J. Popelova, N. Vejlstrup, L. Grønbeck, M. Johansen, A. Ersboll, Y. Elrakshy, K. Eltamawy, M. Gamal Abd‐El Aziz, A. El Nagar, H. Ebaid, H. Abo Elenin, M. Saed, S. Farag, W. Makled, K. Sorour, Z. Ashour, G. El‐Sayed, M. Abdel Meguid Mahdy, N. Taha, A. Dardeer, M. Shabaan, M. Ali, P. Moceri, G. Duthoit, M. Gouton, J. Nizard, L. Baris, S. Cohen, M. Ladouceur, D. Khimoud, B. Iung, F. Berger, A. Olsson, U. Gembruch, W. M. Merz, E. Reinert, S. Clade, Y. Kliesch, C. Wald, C. Sinning, R. Kozlik‐Feldmann, S. Blankenberg, E. Zengin‐Sahm, G. Mueller, M. Hillebrand, P. Hauck, Y. von Kodolitsch, N. Zarniko, H. Baumgartner, R. Schmidt, A. Hellige, O. Tutarel, H. Kaemmerer, B. Kuschel, N. Nagdyman, R. Motz, D. Maisuradze, A. Frogoudaki, E. Iliodromitis, M. Anastasiou‐Nana, D. Triantafyllis, G. Bekiaris, H. Karvounis, G. Giannakoulas, D. Ntiloudi, S. A. Mouratoglou, A. Temesvari, H. Balint, D. Kohalmi, B. Merkely, C. Liptai, A. Nemes, T. Forster, A. Kalapos, K. Berek, K. Havasi, N. Ambrus, A. Shelke, R. Kawade, S. Patil, E. Martanto, T. M. Aprami, A. Purnomowati, C. J. Cool, M. Hasan, R. Akbar, S. Hidayat, T. I. Dewi, W. Permadi, D. A. Soedarsono, M. M. Ansari‐Ramandi, N. Samiei, A. Tabib, F. Kashfi, S. Ansari‐Ramandi, S. Rezaei, H. Ali Farhan, A. Al‐Hussein, G. Al‐Saedi, G. Mahmood, I. F. Yaseen, L. Al‐Yousuf, M. AlBayati, S. Mahmood, S. Raheem, T. AlHaidari, Z. Dakhil, P. Thornton, J. Donnelly, M. Bowen, A. Blatt, G. Elbaz‐Greener, A. Shotan, S. Yalonetsky, S. Goland, M. Biener, G. Egidy Assenza, M. Bonvicini, A. Donti, A. Bulgarelli, D. Prandstraller, C. Romeo, R. Crepaz, E. Sciatti, M. Metra, R. Orabona, L. Ait Ali, P. Festa, V. Fesslova, C. Bonanomi, M. Calcagnino, F. Lombardi, null Colli, M. W. Ossola, C. Gobbi, E. Gherbesi, L. Tondi, M. Schiavone, M. Squillace, M. G. Carmina, A. Maina, C. Macchi, E. Gollo, F. M. Comoglio, N. Montali, P. Re, R. Bordese, T. Todros, V. Donvito, W. Grosso Marra, G. Sinagra, B. D'Agata Mottolese, M. Bobbo, V. Gesuete, S. Rakar, F. Ramani, K. Niwa, D. Mekebekova, A. Mussagaliyeva, T. Lee, E. Mirrakhimov, S. Abilova, E. Bektasheva, K. Neronova, O. Lunegova, R. Žaliūnas, R. Jonkaitienė, J. Petrauskaitė, A. Laucevicius, D. Jancauskaite, L. Lauciuviene, L. Gumbiene, L. Lankutiene, S. Glaveckaite, M. Laukyte, S. Solovjova, V Rudiene, K. H. Chee, C. C.‐W. Yim, H. L. Ang, R. Kuppusamy, T. Watson, M. Caruana, M.‐E. Estensen, M. G. A. Mahmood Kayani, R. Munir, A. Tomaszuk‐Kazberuk, B. Sobkowicz, J. Przepiesc, A. Lesniak‐Sobelga, L. Tomkiewicz‐Pajak, M. Komar, M. Olszowska, P. Podolec, S. Wisniowska‐Smialek, M. Lelonek, U. Faflik, A. Cichocka‐Radwan, K. Plaskota, O. Trojnarska, N. Guerra, L. de Sousa, C. Cruz, V. Ribeiro, S. Jovanova, V. Petrescu, R. Jurcut, C. Ginghina, I. Mircea Coman, M. Musteata, O. Osipova, T. Golivets, I. Khamnagadaev, O. Golovchenko, A. Nagibina, I. Ropatko, I. R. Gaisin, L. Valeryevna Shilina, N. Sharashkina, E. Shlyakhto, O. Irtyuga, O. Moiseeva, E. Karelkina, I. Zazerskaya, A. Kozlenok, I. Sukhova, L. Jovovic, K. Prokšelj, M. Koželj, A. O. Askar, A. A. Abdilaahi, M. H. Mohamed, A. M. Dirir, K. Sliwa, P. Manga, A. Pijuan‐Domenech, L. Galian‐Gay, P. Tornos, M. T. Subirana, N. Murga, J. M. Oliver, B. Garcia‐Aranda Dominguez, I. Hernandez Gonzalez, J. F. Delgado Jimenez, P. Escribano Subias, A. Elbushi, A. Suliman, K. Jazzar, M. Murtada, N. Ahamed, M. Dellborg, E. Furenas, M. Jinesjo, K. Skoglund, P. Eriksson, T. Gilljam, U. Thilen, D. Tobler, K. Wustmann, F. Schwitz, M. Schwerzmann, T. Rutz, J. Bouchardy, M. Greutmann, B. M. Santos Lopes, L. Meier, M. Arrigo, K. de Boer, T. Konings, E. Wajon, L. J. Wagenaar, P. Polak, E. P. G. Pieper, J. Roos‐Hesselink, I. van Hagen, H. Duvekot, J. M. J. Cornette, C. De Groot, C. van Oppen, L. Sarac, O. Batukan Esen, S. Catirli Enar, C. Mondo, P. Ingabire, B. Nalwanga, T. Semu, B. T. Salih, W. A. R. Almahmeed, S. Wani, F. S. Mohamed Farook, Al Ain, F. Gerges, A. M. Komaranchath, F. Al bakshi, A. Al Mulla, A. H. Yusufali, E. I. Al Hatou, N. Bazargani, F. Hussain, L. Hudsmith, P. Thompson, S. Thorne, S. Bowater, A. Money‐Kyrle, P. Clifford, P. Ramrakha, S. Firoozan, J. Chaplin, N. Bowers, D. Adamson, F. Schroeder, R. Wendler, S. Hammond, P. Nihoyannopoulos, R. Hall, L. Freeman, G. Veldtman, J. Kerr, L. Tellett, N. Scott, A. B. Bhatt, D. DeFaria Yeh, M. A. Youniss, M. Wood, A. A. Sarma, S. Tsiaras, A. Stefanescu, J. M. Duran, L. Stone, D. S. Majdalany, J. Chapa, K. Chintala, P. Gupta, J. Botti, J. Ting, W. R. Davidson, G. Wells, D. Sparks, V. Paruchuri, K. Marzo, D. Patel, W. Wagner, S. N. Ahanya, L. Colicchia, T. Jentink, K. Han, M. Loichinger, M. Parker, C. Longtin, A. Yetman, K. Erickson, J. Cramer, S. Tsai, B. Fletcher, S. Warta, C. Cohen, C. Lindblade, R. Puntel, K. Nagaran, N. Croft, M. Gurvitz, C. Otto, C. Talluto, D. Murphy, M. G. Perlroth, ROPAC (Registry of Pregnancy and Cardiac Disease) Investigators Group, Gale, C.P., Beleslin, B., Budaj, A., Chioncel, O., Dagres, N., Danchin, N., Erlinge, D., Emberson, J., Glikson, M., Gray, A., Kayikcioglu, M., Maggioni, A., Nagy, K.V., Nedoshivin, A., Petronio, A.S., Roos-Hesselink, J., Wallentin, L., Zeymer, U., Hall, R., Stein, J., Parsonage, W.A., Budts, W., De Backer, J., Grewal, J., Marelli, A., Kaemmerer, H., Jondeau, G., Johnson, M., Maggioni, A.P., Tavazzi, L., Thilen, U., Elkayam, U., Otto, C., Sliwa, K., Aquieri, A., Saad, A., Ruda Vega, H., Hojman, J., Caparros, J.M., Vazquez Blanco, M., Arstall, M., Chung, C.M., Mahadavan, G., Aldridge, E., Wittwer, M., Chow, Y.Y., Lust, K., Collins, N., Warner, G., Hatton, R., Gordon, A., Nyman, E., Donhauser, E., Gabriel, H., Bahshaliyev, A., Guliyev, F., Hasanova, I., Jahangirov, T., Gasimov, Z., Salim, A., Ahmed, C.M., Begum, F., Hoque, M.H., Mahmood, M., Islam, M.N., Haque, P.P., Banerjee, S.K., Parveen, T., Morissens, M., Demulier, L., de Hosson, M., Beckx, M., Kozic, M., Lovric, M., Kovacevic-Preradovic, T., Chilingirova, N., Kratunkov, P., Wahab, N., McLean, S., Gordon, E., Walter, L., Montesclaros, A.R., Monsalve, G., Rodriguez, C., Balthazar, F., Quintero, V., Palacio, W., Mejía Cadavid, L.A., Munoz Ortiz, E., Fortich Hoyos, F., Arevalo Guerrero, E., Gandara Ricardo, J., Velasquez Penagos, J., Vavera, Z., Popelova, J., Vejlstrup, N., Grønbeck, L., Johansen, M., Ersboll, A., Elrakshy, Y., Eltamawy, K., Gamal Abd-El Aziz, M., El Nagar, A., Ebaid, H., Abo Elenin, H., Saed, M., Farag, S., Makled, W., Sorour, K., Ashour, Z., El-Sayed, G., Abdel Meguid Mahdy, M., Taha, N., Dardeer, A., Shabaan, M., Ali, M., Moceri, P., Duthoit, G., Gouton, M., Nizard, J., Baris, L., Cohen, S., Ladouceur, M., Khimoud, D., Iung, B., Berger, F., Olsson, A., Gembruch, U., Merz, W.M., Reinert, E., Clade, S., Kliesch, Y., Wald, C., Sinning, C., Kozlik-Feldmann, R., Blankenberg, S., Zengin-Sahm, E., Mueller, G., Hillebrand, M., Hauck, P., von Kodolitsch, Y., Zarniko, N., Baumgartner, H., Schmidt, R., Hellige, A., Tutarel, O., Kuschel, B., Nagdyman, N., Motz, R., Maisuradze, D., Frogoudaki, A., Iliodromitis, E., Anastasiou-Nana, M., Triantafyllis, D., Bekiaris, G., Karvounis, H., Giannakoulas, G., Ntiloudi, D., Mouratoglou, S.A., Temesvari, A., Balint, H., Kohalmi, D., Merkely, B., Liptai, C., Nemes, A., Forster, T., Kalapos, A., Berek, K., Havasi, K., Ambrus, N., Shelke, A., Kawade, R., Patil, S., Martanto, E., Aprami, T.M., Purnomowati, A., Cool, C.J., Hasan, M., Akbar, R., Hidayat, S., Dewi, T.I., Permadi, W., Soedarsono, D.A., Ansari-Ramandi, M.M., Samiei, N., Tabib, A., Kashfi, F., Ansari-Ramandi, S., Rezaei, S., Ali Farhan, H., Al-Hussein, A., Al-Saedi, G., Mahmood, G., Yaseen, I.F., Al-Yousuf, L., AlBayati, M., Mahmood, S., Raheem, S., AlHaidari, T., Dakhil, Z., Thornton, P., Donnelly, J., Bowen, M., Blatt, A., Elbaz-Greener, G., Shotan, A., Yalonetsky, S., Goland, S., Biener, M., Egidy Assenza, G., Bonvicini, M., Donti, A., Bulgarelli, A., Prandstraller, D., Romeo, C., Crepaz, R., Sciatti, E., Metra, M., Orabona, R., Ait Ali, L., Festa, P., Fesslova, V., Bonanomi, C., Calcagnino, M., Lombardi, F., Colli, C., Ossola, M.W., Gobbi, C., Gherbesi, E., Tondi, L., Schiavone, M., Squillace, M., Carmina, M.G., Maina, A., Macchi, C., Gollo, E., Comoglio, F.M., Montali, N., Re, P., Bordese, R., Todros, T., Donvito, V., Grosso Marra, W., Sinagra, G., D'Agata Mottolese, B., Bobbo, M., Gesuete, V., Rakar, S., Ramani, F., Niwa, K., Mekebekova, D., Mussagaliyeva, A., Lee, T., Mirrakhimov, E., Abilova, S., Bektasheva, E., Neronova, K., Lunegova, O., Žaliūnas, R., Jonkaitienė, R., Petrauskaitė, J., Laucevicius, A., Jancauskaite, D., Lauciuviene, L., Gumbiene, L., Lankutiene, L., Glaveckaite, S., Laukyte, M., Solovjova, S., Rudiene, V., Chee, K.H., Yim, C.C., Ang, H.L., Kuppusamy, R., Watson, T., Caruana, M., Estensen, M.E., Mahmood Kayani, MGA, Munir, R., Tomaszuk-Kazberuk, A., Sobkowicz, B., Przepiesc, J., Lesniak-Sobelga, A., Tomkiewicz-Pajak, L., Komar, M., Olszowska, M., Podolec, P., Wisniowska-Smialek, S., Lelonek, M., Faflik, U., Cichocka-Radwan, A., Plaskota, K., Trojnarska, O., Guerra, N., de Sousa, L., Cruz, C., Ribeiro, V., Jovanova, S., Petrescu, V., Jurcut, R., Ginghina, C., Mircea Coman, I., Musteata, M., Osipova, O., Golivets, T., Khamnagadaev, I., Golovchenko, O., Nagibina, A., Ropatko, I., Gaisin, I.R., Valeryevna Shilina, L., Sharashkina, N., Shlyakhto, E., Irtyuga, O., Moiseeva, O., Karelkina, E., Zazerskaya, I., Kozlenok, A., Sukhova, I., Jovovic, L., Prokšelj, K., Koželj, M., Askar, A.O., Abdilaahi, A.A., Mohamed, M.H., Dirir, A.M., Manga, P., Pijuan-Domenech, A., Galian-Gay, L., Tornos, P., Subirana, M.T., Murga, N., Oliver, J.M., Garcia-Aranda Dominguez, B., Hernandez Gonzalez, I., Delgado Jimenez, J.F., Escribano Subias, P., Elbushi, A., Suliman, A., Jazzar, K., Murtada, M., Ahamed, N., Dellborg, M., Furenas, E., Jinesjo, M., Skoglund, K., Eriksson, P., Gilljam, T., Tobler, D., Wustmann, K., Schwitz, F., Schwerzmann, M., Rutz, T., Bouchardy, J., Greutmann, M., Santos Lopes, B.M., Meier, L., Arrigo, M., de Boer, K., Konings, T., Wajon, E., Wagenaar, L.J., Polak, P., Pieper, EPG, van Hagen, I., Duvekot, H., Cornette, JMJ, De Groot, C., van Oppen, C., Sarac, L., Batukan Esen, O., Catirli Enar, S., Mondo, C., Ingabire, P., Nalwanga, B., Semu, T., Salih, B.T., Almahmeed, WAR, Wani, S., Mohamed Farook, F.S., Ain, A., Gerges, F., Komaranchath, A.M., Al Bakshi, F., Al Mulla, A., Yusufali, A.H., Al Hatou, E.I., Bazargani, N., Hussain, F., Hudsmith, L., Thompson, P., Thorne, S., Bowater, S., Money-Kyrle, A., Clifford, P., Ramrakha, P., Firoozan, S., Chaplin, J., Bowers, N., Adamson, D., Schroeder, F., Wendler, R., Hammond, S., Nihoyannopoulos, P., Freeman, L., Veldtman, G., Kerr, J., Tellett, L., Scott, N., Bhatt, A.B., DeFaria Yeh, D., Youniss, M.A., Wood, M., Sarma, A.A., Tsiaras, S., Stefanescu, A., Duran, J.M., Stone, L., Majdalany, D.S., Chapa, J., Chintala, K., Gupta, P., Botti, J., Ting, J., Davidson, W.R., Wells, G., Sparks, D., Paruchuri, V., Marzo, K., Patel, D., Wagner, W., Ahanya, S.N., Colicchia, L., Jentink, T., Han, K., Loichinger, M., Parker, M., Longtin, C., Yetman, A., Erickson, K., Cramer, J., Tsai, S., Fletcher, B., Warta, S., Cohen, C., Lindblade, C., Puntel, R., Nagaran, K., Croft, N., Gurvitz, M., Talluto, C., Murphy, D., Perlroth, M.G., Neurosurgery, Pediatrics, Cardiology, ACS - Heart failure & arrhythmias, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Institut Català de la Salut, [Tutarel O] Department of Congenital Heart Disease and Paediatric Cardiology German Heart Centre MunichTechnical University of Munich School of MedicineTechnical University of Munich Germany. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance Munich Germany. [Ramlakhan KP, Baris L] Department of Cardiology Erasmus University Medical Center Rotterdam the Netherlands. [Subirana MT] Unitat de Cardiopaties congènites de l’adult, Vall d'Hebron Hospital Universitari, Barcelona Spain. Hospital Sant Pau, Barcelona Spain. [Bouchardy J] Service of Cardiology University Hospital Lausanne and University of Lausanne Switzerland. Service of Cardiology University of Geneva Switzerland. [Nemes A] 2nd Department of Medicine and Cardiology Centre Medical Faculty Albert Szent-Györgyi Clinical Center University of Szeged Hungary, Szeged, Hungary, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Transposition of Great Vessels, pregnancy outcomes, enfermedades cardiovasculares::anomalías cardiovasculares::cardiopatías congénitas::transposición de los grandes vasos [ENFERMEDADES], Disease, 030204 cardiovascular system & hematology, Sistema cardiovascular - Malalties, Ventricular tachycardia, Vasos sanguinis - Cirurgia, 0302 clinical medicine, Pregnancy, Clinical endpoint, Registries, 030212 general & internal medicine, Cardiovascular Diseases::Pregnancy Complications, Cardiovascular [DISEASES], Original Research, Aortic dissection, Pregnancy Outcome, Congenital Heart Disease, Other subheadings::Other subheadings::/surgery [Other subheadings], arterial switch operation, pregnancy and cardiac disease, transposition of the great arteries, Europe, Great arteries, Cardiology, enfermedades cardiovasculares::complicaciones cardiovasculares del embarazo [ENFERMEDADES], Female, Maternal death, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, diagnóstico::pronóstico::resultado del embarazo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Pregnancy Complications, Cardiovascular, Embaràs - Complicacions, Cardiovascular Diseases::Cardiovascular Abnormalities::Heart Defects, Congenital::Transposition of Great Vessels [DISEASES], Risk Assessment, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Heart Failure, business.industry, Infant, Newborn, Otros calificadores::Otros calificadores::/cirugía [Otros calificadores], Diagnosis::Prognosis::Pregnancy Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, Arterial Switch Operation, Heart failure, Tachycardia, Ventricular, business
Abstract: Embaràs i malaltia cardíaca; Resultats de l’embaràs; Transposició de les grans artèries Embarazo y enfermedad cardíaca; Resultados del embarazo; Transposición de las grandes arterias Pregnancy and cardiac disease; Pregnancy outcomes, Transposition of the great arteries Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate. Funding from “Zabawas Foundation” and “De Hoop Foundation” in addition to the support from EURObservational Research Programme (EORP) is greatly acknowledged. Since the start of EORP, the following companies have supported the program: Abbott Vascular Int (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc (2014–2016), Menarini Int Op (2009–2012), MSD‐Merck & Co (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2021), and Vifor (2019–2022).
Published: 2021

28. Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Peter Horby, M Mafham, Louise Linsell, Richard Haynes, Lucy C Chappell, Edmund Juszczak, Martin J Landray, Jonathan Emberson, Jason Raw, Kathryn M Rowan, Matthew N. Davies, J Kenneth Baillie, Saul N. Faust, Simon Carley, Jennifer L Bell, Thomas Jaki, Christopher A Green, Katie Jefferey, Alan A Montgomery, Natalie Staplin, Wei Shen Lim, Adrian Palfreeman, B Prudon, David Chadwick, Matt P. Wise, E Elmahi, Horby, PW, and Landray, MJ
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Lopinavir/ritonavir, 030204 cardiovascular system & hematology, Azithromycin, Rate ratio, Antiviral Agents, Lopinavir, Treatment and control groups, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Aged, 80 and over, Mechanical ventilation, Ritonavir, SARS-CoV-2, business.industry, Comment, COVID-19, Hydroxychloroquine, Articles, General Medicine, COVID-19 Drug Treatment, Hospitalization, Drug Combinations, Treatment Outcome, Relative risk, Female, Observational study, business, medicine.drug
Abstract: Background: Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir–ritonavir improves outcomes in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir–ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir–ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91–1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91–1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99–1·20; p=0·092). Interpretation: In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19. Funding: Medical Research Council and National Institute for Health Research.
Published: 2020

29. Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

Author: Jack A. Kosmicki, Charles Paulding, Nan Lin, Andrew J. Murphy, Jerome I. Rotter, Brian Zambrowicz, Niek Verweij, Luca A. Lotta, Michal L. Schwartzman, Giusy Della Gatta, Yii-Der Ida Chen, Alexander H. Li, Suganthi Balasubramanian, Jason M. Torres, Hyun Min Kang, Rory Collins, Parsa Akbari, Michael E. Dunn, Gonçalo R. Abecasis, Christian Benner, David J. Carey, Svati H. Shah, Jonathan Marchini, Giovanni Coppola, Marcus B. Jones, Olle Melander, Christopher D. Still, Yi-Ya Fang, Olukayode A. Sosina, Manuel A. R. Ferreira, Roberto Tapia-Conyer, Michael Cantor, Aris N. Economides, Dylan Sun, Adam E. Locke, Jonathan V. Pascale, Daniel J. Rader, Ankit Gilani, Joelle Mbatchou, Jesus Alegre-Díaz, Mark W. Sleeman, Trikaldarshi Persaud, Jeffrey G. Reid, Pablo Kuri-Morales, Jaime Berumen-Campos, John D. Overton, Aris Baras, Ercument Dirice, Sakib Hossain, Alicia Hawes, George D. Yancopoulos, Jonathan Emberson, Victor Garcia, Judith Altarejos, Lori Khrimian, Katia Karalis, William E. Kraus, Tooraj Mirshahi, Kevin Agostinucci, Alan R. Shuldiner, Center, Regeneron Genetics, and Collaboration, DiscovEHR
Subjects: 0301 basic medicine, Genetics, medicine.medical_specialty, Multidisciplinary, Body Weight, Genomics, Organ Size, Biology, medicine.disease, Obesity, Article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Genetic variation, medicine, Medical genetics, Humans, medicine.symptom, Body mass index, Weight gain, 030217 neurology & neurosurgery, Exome sequencing, Glycemic
Abstract: Introduction Obesity accounts for a substantial and growing burden of disease globally. Body adiposity is highly heritable, and human genetic studies can lead to biological and therapeutic insights. Rationale Whole-exome sequencing of hundreds of thousands of individuals is complementary to approaches used to date in obesity genetics and has the potential to identify rare protein-coding variants with large phenotypic impact. We sequenced the exomes of 645,626 individuals from the UK, the US, and Mexico and estimated associations of rare coding variants with body mass index (BMI), a measure of overall adiposity used to define obesity in clinical practice. We complemented exome sequencing with fine-mapping of common alleles, polygenic score analysis, and in vitro and in vivo modeling work. Results We identified 16 genes for which the burden of rare nonsynonymous variants was associated with BMI at exome-wide statistical significance (inverse-variance weighted meta-analysis P < 3.6 × 10−7), including associations at five brain-expressed G protein–coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). We observed an overrepresentation of genes highly expressed in the hypothalamus, a key center for the neuroendocrine regulation of energy balance. Protein-truncating variants in GPR75 were found in ~4/10,000 sequenced people and were associated with 1.8 kg/m2 lower BMI, 5.3 kg lower bodyweight, and 54% lower odds of obesity in heterozygous carriers. Knock out of Gpr75 in mice resulted in resistance to weight gain in a high-fat diet model, which was allele-dose dependent (25% and 44% lower weight gain, respectively, for heterozygous Gpr75−/+ mice and knockout Gpr75−/− mice compared with wild type) and accompanied by improved glycemic control and insulin sensitivity. Protein-truncating variants in CALCR were associated with higher BMI and obesity risk, whereas protein-truncating variants in GIPR and two missense alleles [Arg190→Gln (Arg190Gln), Glu288Gly], which we show result in loss of function in vitro, were associated with lower adiposity. Among monogenic obesity genes in the leptin-melanocortin pathway, heterozygous predicted loss-of-function variants in LEP, POMC, PCSK1, and MC4R (but not LEPR) were associated with higher BMI. Rare protein-truncating variants in UBR2, ANO4, and PCSK1 were associated with more than twofold higher odds of obesity in heterozygous carriers, similar to predicted-deleterious nonsynonymous variants in MC4R, which are considered the most common cause of monogenic obesity. Polygenic predisposition due to >2 million common genetic variants influenced the penetrance of obesity in rare variant carriers in an additive fashion. Conclusion These results suggest that inhibition of GPR75 may be a therapeutic strategy for obesity and illustrate the power of massive-scale exome sequencing for the identification of large-effect coding variant associations and drug targets for complex traits.
Published: 2022

30. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

Author: Tom Newman, Peter Horby, Andrew Mumford, Richard Haynes, Paul Collini, Megan Plowright, Enti Spata, Wei Shen Lim, Mark Campbell, Natalie Staplin, Saul Faust, Alexander James Richards, and Jonathan Emberson
Abstract: SUMMARYBackgroundWe evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for the treatment of patients admitted to hospital because of COVID-19.MethodsThis randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was conducted that included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).FindingsBetween 2 February 2021 and 29 December 2021, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% receiving tocilizumab (with planned use within the next 24 hours recorded for a further 9%). Overall, 513 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·98; p=0·026). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of 8 previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths) in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0.57; 95% CI 0.45-0.72). Including the results from RECOVERY into an updated meta-analysis of all 9 completed trials (involving 11,888 randomised patients and 1484 deaths) allocation to baricitinib or other JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0.80; 95% CI 0.71-0.89; pInterpretationIn patients hospitalised for COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
Published: 2022

31. Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial

Author: Richard Haynes, David Preiss, William Herrington, Aldo Pietro Maggioni, Jonathan Emberson, Kaitlin Mayne, and Group, The EMPA-KIDNEY Collaborative
Subjects: Male, Transplantation, Kidney, Diabetes Mellitus, Type 2, Double-Blind Method, Nephrology, Disease Progression, Humans, Diabetic Nephropathies, Female, Benzhydryl Compounds, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors, Glomerular Filtration Rate
Abstract: Background The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD). Methods The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) ≥20 but Results Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73 m2 (SD 14.8), including 5185 (78%) with an eGFR Conclusions EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.
Published: 2022

32. Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank

Author: Pengfei Zhu, Sarah Lewington, Natalie Staplin, Jonathan Emberson, David Z.I. Cherney, William G. Herrington, Colin Baigent, Mark Woodward, Martin J Landray, and Richard Haynes
Subjects: Male, medicine.medical_specialty, Epidemiology, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Blood Pressure, 030204 cardiovascular system & hematology, Article, Odds, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Diabetes Mellitus, Albuminuria, Humans, 030212 general & internal medicine, Prospective Studies, Adiposity, Biological Specimen Banks, Glycated Hemoglobin, Nutrition and Dietetics, business.industry, Waist-Hip Ratio, Confounding, nutritional and metabolic diseases, Middle Aged, medicine.disease, United Kingdom, Blood pressure, Cross-Sectional Studies, Risk factors, Obesity, Abdominal, Female, Ordered logit, medicine.symptom, business, Body mass index, Demography
Abstract: Background Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain. Methods Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators. Results Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53–57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30–34%). Each 5 kg/m2 higher BMI was associated with a 47% (46–49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33–37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure. Conclusions Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity–albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.
Published: 2020

33. The ESC-EORP Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry

Author: Mathieu Kerneis, Elena Efremova, Joanna Jaroch, Marc-Alexander Ohlow, LAURA MAZILU, José Miguel Rivera-Caravaca, Chris Gale, Aldo Pietro Maggioni, Leonard Simoni, Erkin Mirrakhimov, Stefano Figliozzi, Philippe Gabriel STEG, Tatiana Brodskaya, Mohammad Kermani-Alghoraishi, Tomasz Zapolski, Alicja Sołtowska, LUIGI TAVAZZI, Marco Valgimigli, George Chalikias, Salvatore De Rosa, Irina PARVU, Andrzej Przybylski, Jonathan Emberson, Francesco Cosentino, and Andrzej Budaj
Subjects: Acute coronary syndrome, medicine.medical_specialty, Population, Cardiology, Ischemia, Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Disease registry, Quality of life, Internal medicine, Atrial Fibrillation, Humans, Medicine, Registries, 030212 general & internal medicine, education, education.field_of_study, business.industry, Health Policy, ST elevation, medicine.disease, 3. Good health, Cardiovascular Diseases, Quality of Life, Cardiology and Cardiovascular Medicine, business
Abstract: Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry aims to study the clinical profile, treatment modalities, and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular (CV) risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid- and long-term outcomes and their determinants in this population. Methods and results Nine thousand one hundred and seventy-four patients over 18 years with documented CICD defined by a history acute coronary syndrome with/without ST elevation, previous coronary revascularization, or stable coronary artery disease were enrolled between 1 May 2015 and 31 July 2018. Individual patient data on clinical profile, biology, and treatment modalities were collected across 154 centres from 20 ESC countries. Two years of follow-up is scheduled in order to determine the following clinical outcomes: all-cause and CV death, all-cause and CV hospitalizations, changes in medications, and quality of life using the EuroQol5D-5L score. Conclusion The CICD LT is an international registry of care and outcomes of patients hospitalized with CICD which will provide insights into the contemporary profile and management of patients with this common disease.
Published: 2019

34. Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials

Author: Alex M. Riding, Sunil Bhandari, William G. Herrington, Colin Baigent, Alistair J. Roddick, Natalie Staplin, Richard Haynes, Jonathan Emberson, Alexa Wonnacott, Apexa Kuverji, and Christina Reith
Subjects: Sodium-glucose co-transporter 2 inhibitors, Medicine (General), medicine.medical_specialty, Research paper, business.industry, Acute kidney injury, Heart failure, General Medicine, medicine.disease, Placebo, law.invention, Ketoacidosis, Randomized trials, R5-920, Randomized controlled trial, law, Internal medicine, Relative risk, Diabetes mellitus, medicine, CKD, Safety, business, Kidney disease
Abstract: Background The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified. Methods We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468). Findings Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS). Interpretations The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date. Funding MRC-UK & KRUK.
Published: 2021

35. Predictive value of circulating NMR metabolic biomarkers for type 2 diabetes risk in the UK Biobank study

Author: Jonathan Emberson, Eirini Trichia, Sarah Lewington, Jelena Bešević, Diego Aguilar-Ramirez, and Fiona Bragg
Subjects: False discovery rate, Oncology, medicine.medical_specialty, business.industry, Proportional hazards model, Hazard ratio, Type 2 diabetes, medicine.disease, Diabetes mellitus, Internal medicine, Multiple comparisons problem, medicine, Biomarker (medicine), business, Body mass index
Abstract: SummaryBackgroundEffective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors.MethodsNMR-metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed.FindingsDuring median 11.9 (IQR 11.1-12.6) years’ follow-up, 1719 participants developed T2D. After accounting for multiple testing, 118 metabolic biomarkers showed independent associations with T2D risk (false discovery rate controlled pInterpretationWhen added to conventional risk factors, circulating NMR-based metabolic biomarkers enhanced T2D risk prediction.FundingBHF, MRC, CRUK
Published: 2021

36. A model of lifetime health outcomes in cardiovascular disease based on clinical trials and large cohorts

Author: Rory Collins, Borislava Mihaylova, J Zhou, Jane Armitage, Iryna Schlackow, Anthony C Keech, Jonathan Emberson, Christina Reith, John Robson, John Simes, K Wilkinson, Alastair Gray, Colin Baigent, R Wu, and C Williams
Subjects: Clinical trial, medicine.medical_specialty, business.industry, medicine, Disease, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Health outcomes
Abstract: Background and purpose Cardiovascular disease (CVD) risk of individuals depends on their socio-demographic characteristics, clinical risk factors, and treatments, and strongly influences their quality of life and survival. Individual-based long-term disease models, which aim to more accurately calculate the lifetime consequences, can help to target treatments, develop disease management programmes, and assess the value of new therapies. We present a new micro-simulation CVD model. Methods This micro-simulation model was developed using individual participant data from the Cholesterol Treatment Trialists' collaboration (CTT: 118,000 participants; 15 trials) and calibrated (with added socioeconomic deprivation, ethnicity, physical activity, mental illness, cancer and incident diabetes) in the UK Biobank cohort (UKB: 502,000 participants). Parametric survival models estimated risks of key endpoints (myocardial infarction (MI), stroke, coronary revascularisation (CRV), diabetes, cancer and vascular (VD) and nonvascular death (NVD) using participants' age, sex, ethnicity, physical activity, socioeconomic deprivation, smoking history, lipids, blood pressure, creatinine, previous cardiovascular diseases, diabetes, mental illness and cancer at entry and non-fatal incidents of the key endpoints during follow-up. The model integrates the risk equations and enables annual projection of endpoints and survival over individuals' lifetimes. The model was used to project remaining life expectancy across UK Biobank participants. Results Nonfatal cardiovascular events and age were the major determinants of CVD risk and, together with incident diabetes and cancer, of individuals' survival. The cumulative incidence of the key endpoints predicted by the CTT-UKB model corresponded well to their observed incidence in the UK Biobank cohort, overall (Figure 1) and in categories of participants by age, sex, prior CVD and CVD risk. Predicted remaining life expectancy across UK Biobank participants without history of CVD ranged between 22 and 43 years in men and between 24 and 46 years in women, depending on their age and CVD risk (Figure 2). Among UK Biobank participants with history of CVD, depending on their age, predicted remaining life expectancy ranged from 20 to 32 years in men and from 26 to 38 years in women. Conclusion This new lifetime CVD model accurately predicts morbidity and mortality in a large UK population cohort. It will be made available to provide individualised projections of expected lifetime health outcomes and benefits of treatments. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, UK Medical Research Council (MRC), British Heart Foundation Figure 1. Predicted (in black) versus observed (95% CI; in red) incidence of major clinical outcomes in the UK Biobank.Figure 2. Predicted remaining life expectancy of participants in UK Biobank cohort, by age and CVD risk or previous CVD at entry. QRISK, a 10-year CVD risk scoring algorithm for people without previous CVD, recommended for use in the UK National Health Service.
Published: 2021

37. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage: a randomised, open-label, assessor-blinded, pilot phase, non-inferiority trial

Author: Rustam Al-Shahi Salman, Catriona Keerie, Jacqueline Stephen, Steff Lewis, John Norrie, Martin S. Dennis, David E. Newby, Joanna M. Wardlaw, Gregory Y.H. Lip, Adrian Parry-Jones, Philip M. White, Colin Baigent, Dan Lasserson, Colin Oliver, Fiach O'Mahony, Shannon Amoils, John Bamford, Jane Armitage, Jonathan Emberson, Gabriël J.R. Rinkel, Gordon Lowe, Karen Innes, Kasia Adamczuk, Lynn Dinsmore, Jonathan Drever, Garry Milne, Allan Walker, Aidan Hutchison, Carol Williams, Ruth Fraser, Rosemary Anderson, Kate Covil, Kelly Stewart, Jessica Rees, Peter Hall, Alistair Bullen, Andrew Stoddart, Tom J. Moullaali, Jeb Palmer, Eleni Sakka, Joanne Perthen, Nicola Lyttle, Neshika Samarasekera, Allan MacRaild, Seona Burgess, Jessica Teasdale, Michelle Coakley, Pat Taylor, Gordon Blair, William Whiteley, Susan Shenkin, Una Clancy, Malcolm Macleod, Rachel Sutherland, Tom Moullaali, Amanda Barugh, Christine Lerpiniere, Fiona Moreton, Nicholas Fethers, Tal Anjum, Manju Krishnan, Peter Slade, Sharon Storton, Marie Williams, Caroline Davies, Lynda Connor, Glyn Gainard, Carl Murphy, Mark Barber, Derek Esson, James Choulerton, Louise Shaw, Suzanne Lucas, Sarah Hierons, Joanne Avis, Andrew Stone, Lukuman Gbadamoshi, Telma Costa, Lauren Pearce, Kirsty Harkness, Emma Richards, Jo Howe, Christine Kamara, Ralf Lindert, Ali Ali, Jahanzeb Rehan, Sarah Chapman, Maria Edwards, Raj Bathula, David Cohen, Joseph Devine, Mushiya Mpelembue, Priya Yesupatham, Swati Chhabra, Gbadebo Adewetan, Robert Ballantine, Daniel Brooks, Gemma Smith, Gill Rogers, Stuart Marsden, Sarah Clark, Ami Wilkinson, Ellen Brown, Lynsey Stephenson, Khin Nyo, Annie Abraham, Yogish Pai, Gek Shim, Vidya Baliga, Anand Nair, Matthew Robinson, Catherine Hawksworth, Jill Greig, Irfan Alam, Tonicha Nortcliffe, Ridha Ramiz, Ryan Shaw, Stephanie Lee, Tracy Marsden, Jane Perez, Emily Birleson, Rajendra Yadava, Mirriam Sangombe, Sam Stafford, Tom Hughes, Lucy Knibbs, Bethan Morse, Stefan Schwarz, Benjamin Jelley, Susan White, Bella Richard, Heidi Lawson, Sally Moseley, Michelle Tayler, Mandy Edwards, Claire Triscott, Rebecca Wallace, Angela Hall, Amanda Dell, Khalid Rashed, Sarah Board, Clare Buckley, Alfonso Tanate, Tressy Pitt-Kerby, Kate Beesley, Jess Perry, Christine Hellyer, Paul Guyler, Nisha Menon, Sharon Tysoe, Raji Prabakaran, Martin Cooper, Anoja Rajapakse, Inez Wynter, Susan Smith, Nic Weir, Cherish Boxall, Hannah Yates, Simon Smith, Pamela Crawford, James Marigold, Fiona Smith, Jake Harvey, Sue Evans, Laura Baldwin, Sarah Hammond, Paul Mudd, Angela Bowring, Samantha Keenan, Kevin Thorpe, Mohammad Haque, Joanne Taaffe, Natalie Temple, Tracey Peachey, Kim Wells, Fiona Haines, Nicola Butterworth-Cowin, Zoey Horne, Radim Licenik, Hayley Boughton, Timothy England, Amanda Hedstrom, Brian Menezes, Ruth Davies, Venetia Johnson, Simon Whittingham-Jones, David Werring, Sabaa Obarey, Caroline Watchurst, Amy Ashton, Shez Feerick, Nina Francia, Azra Banaras, Daniel Epstein, Marilena Marinescu, Annick Williams, Anna Robinson, Fiona Humphries, Ijaz Anwar, Arunkumar Annamalai, Susan Crawford, Vicky Collins, Lorna Shepherd, Elaine Siddle, Justin Penge, Sam Qureshi, Vinodh Krishnamurthy, Vasileios Papavasileiou, Dean Waugh, Emelda Veraque, Nathan Douglas, Numan Khan, Sankaranarayanan Ramachandran, Peter Sommerville, Anthony Rudd, Sagal Kullane, Ajay Bhalla, Jonathan Birns, Rowshanara Ahmed, Meegan Gibbons, Eva Klamerus, Benjie Cendreda, Keith Muir, Nicola Day, Angela Welch, Wilma Smith, Jennifer Elliot, Salwa Eltawil, Ammad Mahmood, Kim Hatherley, Shirley Mitchell, Harjit Bains, Lauren Quinn, Rachel Teal, Ivie Gbinigie, George Harston, Phil Mathieson, Gary Ford, Ursula Schulz, James Kennedy, Kirubananthan Nagaratnam, Kiran Bangalore, Neelima Bhupathiraju, Chris Wharton, Ken Fotherby, Ahmad Nasar, Angie Stevens, Angela Willberry, Rachel Evans, Baljinder Rai, Chloe Blake, Kamy Thavanesan, Gail Hann, Tanith Changuion, Sara Nix, Amanda Whiting, Michelle Dharmasiri, Louise Mallon, Marketa Keltos, Nigel Smyth, Charlotte Eglinton, John Duffy, Ela Tone, Lucy Sykes, Emily Porter, Carolyn Fitton, Nikolaos Kirkineziadis, Gillian Cluckie, Kate Kennedy, Sarah Trippier, Rebecca Williams, Elizabeth Hayter, James Rackie, Bhavini Patel, Ghatala Rita, Adrian Blight, Val Jones, Liqun Zhang, Lillian Choy, Anthony Pereira, Brian Clarke, Samer Al-Hussayni, Lynn Dixon, Andrew Young, Adrian Bergin, David Broughton, Senthil Raghunathan, Benjamin Jackson, Jason Appleton, Gwendoline Wilkes, Amanda Buck, Carla Richardson, Judith Clarke, Lucy Fleming, Gemma Squires, Zhe Law, Camille Hutchinson, Vera Cvoro, Mandy Couser, Amanda McGregor, Sean McAuley, Susan Pound, Patricia Cochrane, Clare Holmes, Peter Murphy, Nicola Devitt, Mairead Osborn, Amy Steele, Lucy Belle Guthrie, Elizabeth Smith, Jonathan Hewitt, Natalie Chaston, Min Myint, Andrew Smith, Louise Fairlie, Michelle Davis, Beth Atkinson, Stephen Woodward, Valerie Hogg, Michelle Fawcett, Louise Finlay, Anand Dixit, Eleanor Cameron, Breffni Keegan, Jim Kelly, Dónal Concannon, Dipankar Dutta, Deborah Ward, Jon Glass, Susan O'Connell, Joseph Ngeh, Alison O'Kelly, Emma Williams, Suzanne Ragab, Damian Jenkinson, Judith Dube, Laura Gleave, Jacqui Leggett, Nisha Kissoon, Louise Southern, Utpal Naghotra, Maria Bokhari, Beverley McClelland, Katja Adie, Abhijit Mate, Frances Harrington, Ali James, Elizabeth Swanson, Terri Chant, Miriam Naccache, Abbie Coutts, Gillian Courtauld, Sarah Whurr, Sue Webber, Emily Shead, Robert Luder, Maneesh Bhargava, Elodie Murali, Larissa Cuenoud, Kath Pasco, O Speirs, Lianne Chapman, Linda Inskip, Lisa Kavanagh, Meena Srinivasan, Nichola Motherwell, Indranil Mukherjee, Louise Tonks, Denise Donaldson, Heather Button, Rebecca Wilcox, Fran Hurford, Rachel Logan, Andy Taylor, Tracie Arden, Michael Carpenter, Prabal Datta, Tajammal Zahoor, Linda Jackson, Ann Needle, Andrew Stanners, Imran Ghouri, Donna Exley, Salman Akhtar, Hollie Brooke, Shannen Beadle, Eoin O'Brien, Jobbin Francis, Joanne McGee, Elaine Amis, Jennifer Mitchell, Sarah Finlay, Devesh Sinha, Csilla Manoczki, Sam King, James Tarka, Sumita Choudhary, Jegamalini Premaruban, Dorothy Sutton, Pradeep Kumar, Charlotte Culmsee, Caroline Winckley, Holly Davies, Hilary Thatcher, Evangelos Vasileiadis, Basaam Aweid, Melinda Holden, Cathy Mason, Thant Hlaing, Gladys Madzamba, Tanya Ingram, Michelle Linforth, Claire Cullen, Nibu Thomas, John France, Afaq Saulat, Biju Bhaskaran, Pauline Fitzell, Kathleen Horan, Catherine Manyoni, Josie Garfield-Smith, Hannah Griffin, Stacey Atkins, Joan Redome, Girish Muddegowda, Holly Maguire, Adrian Barry, Nenette Abano, Resti Varquez, Joanne Hiden, Susan Lyjko, Alda Remegoso, Kay Finney, Adrian Butler, Martin Strecker, Mary Joan MaCleod, Janice Irvine, Sandra Nelson, German Guzmangutierrez, Jacqueline Furnace, Vicky Taylor, Hawraman Ramadan, Kim Storton, Sohail Hassan, Eman Abdus Sami, Ruth Bellfield, Kelvin Stewart, Outi Quinn, Chris Patterson, Hedley Emsley, Bindu Gregary, Shakeel Ahmed, Shakeelah Patel, Sonia Raj, Sulaiman Sultan, Fiona Wright, Peter Langhorne, Ruth Graham, Terry Quinn, and Kate McArthur
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Population, Minimisation (clinical trials), Intracranial haemorrhage, subarachnoid haemorrhage, antiplatelet therapy, law.invention, Randomized controlled trial, law, Internal medicine, Atrial Fibrillation, Medicine, Humans, atrial fibrillation, Prospective Studies, education, Adverse effect, Stroke, oral anticoagulation, education.field_of_study, business.industry, Hazard ratio, intraventricular haemorrhage, Anticoagulants, Atrial fibrillation, intracerebral haemorrhage, Vitamin K antagonist, medicine.disease, United Kingdom, subdural haemorrhage, Neurology (clinical), business, Intracranial Hemorrhages, randomised controlled trial
Abstract: Summary Background Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation. Methods SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA2DS2-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete. Findings Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49–265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97–1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72–8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study. Interpretation Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials. Funding British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.
Published: 2021

38. Association of kidney function with NMR-quantified lipids, lipoproteins, and metabolic measures in Mexican adults

Author: Michael Hill, William G. Herrington, Jonathan Emberson, Jason M. Torres, Roberto Tapia-Conyer, Diego Aguilar-Ramirez, Natalie Staplin, Frederik Romer, Pablo Kuri-Morales, Rory Collins, Jesus Alegre-Díaz, Louisa Gnatiuc, Raúl Ramirez-Reyes, Eirini Trichia, and Rachel Wade
Subjects: Male, metabolic measures, 0301 basic medicine, Magnetic Resonance Spectroscopy, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, 030204 cardiovascular system & hematology, Kidney, Kidney Function Tests, Biochemistry, Lipoprotein particle, Choline, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Prospective Studies, kidney function, Aged, 80 and over, diabetes, biology, Fatty Acids, Middle Aged, Lipids, Cholesterol, Female, AcademicSubjects/MED00250, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Lipoproteins, Renal function, Context (language use), 03 medical and health sciences, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Humans, Renal Insufficiency, Chronic, Mexico, Triglycerides, Clinical Research Articles, Aged, Apolipoproteins B, nuclear magnetic resonance spectroscopy, business.industry, Biochemistry (medical), Atherosclerosis, medicine.disease, 030104 developmental biology, chemistry, Linear Models, biology.protein, business, Kidney disease, Lipoprotein
Abstract: Context Chronic kidney disease (CKD) and diabetes are associated with dyslipidemia, metabolic abnormalities, and atherosclerotic risk. Nuclear magnetic resonance (NMR) spectroscopy provides much more detail on lipoproteins than traditional assays. Methods In about 38 000 participants from the Mexico City Prospective Study, aged 35 to 84 years and not using lipid-lowering medication, NMR spectroscopy quantified plasma concentrations of lipoprotein particles, their lipidic compositions, and other metabolic measures. Linear regression related low estimated glomerular filtration rate (eGFR; Results Among the 38 081 participants (mean age 52 years, 64% women), low eGFR was present for 4.8% (306/6403) of those with diabetes and 1.2% (365/31 678) of those without diabetes. Among both those with and without diabetes, low eGFR was significantly associated with higher levels of 58 NMR measures, including apolipoprotein B (Apo-B), the particle numbers of most Apo-B containing lipoproteins, the cholesterol and triglycerides carried in these lipoproteins, several fatty acids, total cholines and phosphatidylcholine, citrate, glutamine, phenylalanine, β-OH-butyrate, and the inflammatory measure glycoprotein-A, and significantly lower levels of 13 NMR measures, including medium and small high-density lipoprotein particle measures, very low-density lipoprotein particle size, the ratio of saturated:total fatty acids, valine, tyrosine, and aceto-acetate. Conclusions In this Mexican population with high levels of adiposity and diabetes, low kidney function was associated with widespread alterations in lipidic and metabolic profiles, both in those with and without diabetes. These alterations may help explain the higher atherosclerotic risk experienced by people with CKD.
Published: 2021

39. Unravelling the interplay between hyperkalaemia, renin-angiotensin-aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry

Author: Rossignol, P., Lainscak, M., Crespo-Leiro, M. G., Laroche, C., Piepoli, M. F., Filippatos, G., Rosano, G. M. C., Savarese, G., Anker, S. D., Seferovic, P. M., Ruschitzka, F., Coats, A. J. S., Mebazaa, A., Mcdonagh, T., Sahuquillo, A., Penco, M., Maggioni, A. P., Lund, L. H., Christopher Peter Gale, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Coats, A., Ferrari, R., Goda, A., Diez, M., Fernandez, A., Fruhwald, F., Fazlibegovic, E., Gatzov, P., Kurlianskaya, A., Hullin, R., Christodoulides, T., Hradec, J., Nielsen, O. W., Nedjar, R., Uuetoa, T., Hassanein, M., Jimenez, J. F. D., Harjola, V. P., Logeart, D., Chumburidze, V., Tousoulis, D., Milicic, D., Merkely, B., O'Donoghue, E., Amir, O., Shotan, A., Shafie, D., Metra, M., Matsumori, A., Mirrakhimov, E., Kavoliuniene, A., Erglis, A., Vataman, E., Otljanska, M., Kostovska, E. S., Demarco, D. C., Drozdz, J., Fonseca, C., Chioncel, O., Dekleva, M., Shkolnik, E., Dahlstrom, U., Goncalvesova, E., Temizhan, A., Estrago, V., Bajraktari, G., Auer, J., Ablasser, K., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J. -C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Le Marcis, V., J. -F., Ly, Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Fuhrmann, A. V., Romano, S., Marcon, S., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Simic, D., Asanin, M., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Bayes-Genis, A., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Afzelius, M., Karlstrom, P., Tengvall, L., Olsson, B., Kalayci, S., Cavusoglu, Y., Gencer, E., Yilmaz, M. B., Gunes, H., Modena, Mg, University of Zurich, Rossignol, Patrick, Rossignol, P., Lainscak, M., Crespo-Leiro, M. G., Laroche, C., Piepoli, M. F., Filippatos, G., Rosano, G. M. C., Savarese, G., Anker, S. D., Seferovic, P. M., Ruschitzka, F., Coats, A. J. S., Mebazaa, A., Mcdonagh, T., Sahuquillo, A., Penco, M., Maggioni, A. P., Lund, L. H., Christopher Peter Gale, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Coats, A., Ferrari, R., Goda, A., Diez, M., Fernandez, A., Fruhwald, F., Fazlibegovic, E., Gatzov, P., Kurlianskaya, A., Hullin, R., Christodoulides, T., Hradec, J., Nielsen, O. W., Nedjar, R., Uuetoa, T., Hassanein, M., Jimenez, J. F. D., Harjola, V. P., Logeart, D., Chumburidze, V., Tousoulis, D., Milicic, D., Merkely, B., O'Donoghue, E., Amir, O., Shotan, A., Shafie, D., Metra, M., Matsumori, A., Mirrakhimov, E., Kavoliuniene, A., Erglis, A., Vataman, E., Otljanska, M., Kostovska, E. S., Demarco, D. C., Drozdz, J., Fonseca, C., Chioncel, O., Dekleva, M., Shkolnik, E., Dahlstrom, U., Goncalvesova, E., Temizhan, A., Estrago, V., Bajraktari, G., Auer, J., Ablasser, K., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J. -C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Fuhrmann, A. V., Romano, S., Marcon, S., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Simic, D., Asanin, M., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Bayes-Genis, A., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Afzelius, M., Karlstrom, P., Tengvall, L., Olsson, B., Kalayci, S., Cavusoglu, Y., Gencer, E., Yilmaz, M. B., Gunes, H., Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Ljubljana, University of A Coruña (UDC), EURObservational Research Programme, European Society of Cardiology, Cardiac Department, G. da Saliceto Hospital, AUSL Piacenza, National and Kapodistrian University of Athens (NKUA), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Karolinska Institutet [Stockholm], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), University hospital of Zurich [Zurich], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), King's College Hospital (KCH), Hospital de Manacor, Università degli Studi dell'Aquila (UNIVAQ), ANMCO Research Center, Firenze,Italy, Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011-2021), Amgen Cardiovascular (2009-2018), AstraZeneca (2014-2021), Bayer AG (2009-2018), Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), The Bristol Myers Squibb and Pfizer Alliance (2011-2019), Daiichi Sankyo Europe GmbH (2011-2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014-2017), Edwards (2016-2019), Gedeon Richter Plc. (2014-2016), Menarini Int. Op. (2009-2012), MSD-Merck & Co. (2011-2014), Novartis Pharma AG (2014-2020), ResMed (2014-2016), Sanofi (2009-2011), SERVIER (2009-2018), Vifor (2019-2022)., Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: medicine.medical_specialty, Angiotensin receptor, Angiotensins, Prognosi, Angiotensin-Converting Enzyme Inhibitors, Heart failure, 610 Medicine & health, 030204 cardiovascular system & hematology, Hyperkalaemia, Hypokalaemia, Mineralocorticoid receptor antagonists, Prognosis, Renin–angiotensin–aldosterone system inhibitors, 2705 Cardiology and Cardiovascular Medicine, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Mineralocorticoid receptor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Renin, Renin–angiotensin system, Humans, Medicine, Registries, cardiovascular diseases, Risk factor, Aldosterone, Ejection fraction, business.industry, Mineralocorticoid receptor antagonist, Renin-angiotensin-aldosterone system inhibitors, medicine.disease, 3. Good health, Discontinuation, Cardiology, 10209 Clinic for Cardiology, Hyperkalemia, Cardiology and Cardiovascular Medicine, business, Lower mortality
Abstract: [Abstract] Aims. We assessed the interplay between hyperkalaemia (HK) and renin–angiotensin–aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all‐cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK‐associated increased death may be related to RAASi withdrawal. Methods and results. The ESC‐HFA‐EORP Heart Failure Long‐Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid‐range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin‐converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow‐up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non‐prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all‐cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. Conclusions. In HF, hyper‐ and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. Funding for open access charge: Universidad de Granada / CBUA. The work was funded by the Courel Mountains UGGp
Published: 2020

40. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: P Desai, M Mafham, Lucy C Chappell, Edmund Juszczak, Tom Brown, Jeremy N. Day, Kathy Rowan, Alan A Montgomery, Jonathan Emberson, Enti Spata, Rahuldeb Sarkar, Andrew D Mumford, B Prudon, Christopher A Green, Tom Bewick, Peter Horby, Wei Shen Lim, Bryan Yates, Simon Tiberi, Guilherme Pessoa-Amorim, Thomas Jaki, G Thwaites, Leon Peto, Kenneth Baillie, Timothy Felton, Maya H Buch, Katie Jeffery, Richard Haynes, Saul N. Faust, Martin J Landray, David M. Weinreich, Natalie Staplin, Paul Hine, and Mark Campbell
Subjects: medicine.medical_specialty, education.field_of_study, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Spike Protein, Rate ratio, Internal medicine, Usual care, medicine, In patient, Open label, business, education
Abstract: SUMMARYBackgroundREGEN-COV is a combination of 2 monoclonal antibodies (casirivimab and imdevimab) that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and safety of REGEN-COV in patients admitted to hospital with COVID-19.MethodsIn this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus a single dose of REGEN-COV 8g (casirivimab 4g and imdevimab 4g) by intravenous infusion (REGEN-COV group). The primary outcome was 28-day mortality assessed first among patients without detectable antibodies to SARS-CoV-2 at randomisation (seronegative) and then in the overall population. The trial is registered with ISRCTN (50189673) andclinicaltrials.gov(NCT04381936).FindingsBetween 18 September 2020 and 22 May 2021, 9785 patients were randomly allocated to receive usual care plus REGEN-COV or usual care alone, including 3153 (32%) seronegative patients, 5272 (54%) seropositive patients and 1360 (14%) patients with unknown baseline antibody status. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to REGEN-COV and 451 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio 0·80; 95% CI 0·70-0·91; p=0·0010). In an analysis involving all randomised patients (regardless of baseline antibody status), 944 (20%) of 4839 patients allocated to REGEN-COV and 1026 (21%) of 4946 patients allocated to usual care died within 28 days (rate ratio 0·94; 95% CI 0·86-1·03; p=0·17). The proportional effect of REGEN-COV on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity = 0·001).InterpretationIn patients hospitalised with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) reduced 28-day mortality among patients who were seronegative at baseline.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
Published: 2021

41. Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants

Author: Paul Sherliker, Jennifer L Carter, Jonathan Emberson, Elba Lorenzo-Vázquez, Sarah Lewington, Marcy Calderón Martínez, Marelis Cendra Asencio, Monica Soni, Fernando Achiong Estupiñán, Shaquille Charles, M. Sofia Massa, Noel Rosquete Muñoz, Ileydis Iglesias-Marichal, Osvaldo Jesús Hernández López, Sonia Bess Constantén, Mayda Díaz González, Richard Peto, Oscar Díaz-Diaz, Julie Ann Burrett, Patricia Varona-Pérez, Ismell Alonso Alomá, Ben Lacey, Stephanie Ross, Miguel Morales, Nurys B. Armas Rojas, Nazrul Islam, José Manuel Morales Rigau, and Hannah Taylor
Subjects: Adult, Male, medicine.medical_specialty, Blood Pressure, Body-mass index, Disease, 030204 cardiovascular system & hematology, Cardiovascular, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Epidemiology, Diabetes Mellitus, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, business.industry, Public health, Diabetes, Public Health, Environmental and Occupational Health, Cuba, Middle Aged, medicine.disease, Blood pressure, Cardiovascular Diseases, Female, Public aspects of medicine, RA1-1270, Biostatistics, business, Body mass index, Research Article
Abstract: Background Cardiovascular disease accounts for about one-third of all premature deaths (ie, age Methods In 1996–2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006–08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35–79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, ‘usual’) levels of SBP and BMI. Results After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m2 (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88–2.18]), as did diabetes (2.15, 1.95–2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64–2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively. Conclusions This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
Published: 2021

42. Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease

Author: Iryna Schlackow, Seamus Kent, William Herrington, Jonathan Emberson, Richard Haynes, Christina Reith, Rory Collins, Martin J. Landray, Alastair Gray, Colin Baigent, Borislava Mihaylova, R. Collins, C. Baigent, M.J. Landray, C. Bray, Y. Chen, A. Baxter, A. Young, M. Hill, C. Knott, A. Cass, B. Feldt-Rasmussen, B. Fellström, D.E. Grobbee, C. Grönhagen-Riska, M. Haas, H. Holdaas, L.S. Hooi, L. Jiang, B. Kasiske, U. Krairittichai, A. Levin, Z.A. Massy, V. Tesar, R. Walker, C. Wanner, D.C. Wheeler, A. Wiecek, T. Dasgupta, W. Herrington, D. Lewis, M. Mafham, W. Majoni, C. Reith, J. Emberson, S. Parish, D. Simpson, J. Strony, T. Musliner, L. Agodoa, J. Armitage, Z. Chen, J. Craig, D. de Zeeuw, J.M. Gaziano, R. Grimm, V. Krane, B. Neal, V. Ophascharoensuk, T. Pedersen, P. Sleight, J. Tobert, C. Tomson, and Groningen Kidney Center (GKC)
Subjects: Male, 0301 basic medicine, Cost effectiveness, Cost-Benefit Analysis, Atorvastatin, RENAL PROTECTION, 030232 urology & nephrology, THERAPY, chemistry.chemical_compound, 0302 clinical medicine, Medicine, CARDIOVASCULAR PREVENTION, SHARP Collaborative Group, health care economics and organizations, Aged, 80 and over, Middle Aged, Urology & Nephrology, Models, Economic, Cardiovascular Diseases, Nephrology, SAFETY, HEART, Drug Therapy, Combination, Female, HEALTH, Life Sciences & Biomedicine, ezetimibe, medicine.drug, medicine.medical_specialty, Statin, medicine.drug_class, SIMVASTATIN PLUS EZETIMIBE, 03 medical and health sciences, Life Expectancy, Ezetimibe, Internal medicine, health care costs, Humans, Renal Insufficiency, Chronic, quality-adjusted life years, cost-effectiveness, Aged, Science & Technology, business.industry, Cholesterol, statin, 1103 Clinical Sciences, Cholesterol, LDL, EUROQOL, medicine.disease, United Kingdom, United States, RANDOMIZED-TRIAL, Quality-adjusted life year, Regimen, 030104 developmental biology, chemistry, Hydroxymethylglutaryl-CoA Reductase Inhibitors, LDL CHOLESTEROL, business, chronic kidney disease, Kidney disease
Abstract: Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or 20,000 pound/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.
Published: 2019

43. STAIR X

Author: Alexis Simpkins, Johannes Boltze, Mike Tymianski, Colin Derdeyn, Maarten Lansberg, Michael Hill, Gregory Albers, Gary Steinberg, Jean-claude Baron, and Jonathan Emberson
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, Medicine, Neurology (clinical), Endovascular treatment, Cardiology and Cardiovascular Medicine, business, Intensive care medicine
Published: 2019

44. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Daniel Zehnder, Thomas Jaki, Katie Jeffery, Peter Horby, Tina George, Steven Scott, Lucy C Chappell, Richard Haynes, Maya H Buch, Kathryn M Rowan, Alan A Montgomery, Nigel E Brunskill, M Mafham, Tom Brown, David L. Roberts, George Koshy, Ni Ni Aung, Simon Tiberi, Jonathan Emberson, Guy E. Thwaites, Lise J Estcourt, Martin J Landray, Andrew D Mumford, Natalie Staplin, Leon Peto, Edmund Juszczak, Alistair J. Roddick, John Widdrington, Mark Campbell, Wei Shen Lim, Saul N. Faust, J Kenneth Baillie, Alison Uriel, Jeremy N. Day, Enti Spata, and Guilherme Pessoa-Amorim
Subjects: Mechanical ventilation, medicine.medical_specialty, Convalescent plasma, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Mortality rate, medicine.medical_treatment, Rate ratio, Confidence interval, Internal medicine, medicine, In patient, business
Abstract: BackgroundTreatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19.MethodsIn this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to receive either usual care plus high titre convalescent plasma or usual care alone. The primary outcome was 28-day mortality.FindingsBetween 28 May 2020 and 15 January 2021, 5795 patients were randomly allocated to receive convalescent plasma and 5763 to usual care alone. There was no significant difference in 28-day mortality between the two groups: 1398 (24%) of 5795 patients allocated convalescent plasma and 1408 (24%) of 5763 patients allocated usual care died within 28 days (rate ratio [RR] 1·00; 95% confidence interval [CI] 0·93 to 1·07; p=0·93). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (66%vs. 67%; rate ratio 0·98; 95% CI 0·94-1·03, p=0·50). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death (28%vs. 29%; rate ratio 0·99; 95% CI 0·93-1·05, p=0·79).InterpretationAmong patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant refs: MC_PC_19056; COV19-RECPLA).
Published: 2021

45. Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults

Author: Noel Rosquete Muñoz, Nazrul Islam, Julie Ann Burrett, Marcy Calderón Martínez, Fernando Achiong Estupiñán, Stephanie Ross, Ismell Alonso Alomá, Mayda Díaz González, Marelis Cendra Asencio, Daniel Martin Simadibrata, Ben Lacey, M. Sofia Massa, Osvaldo Jesús Hernández López, Paul Sherliker, Jennifer L Carter, Richard Peto, José Manuel Morales Rigau, Blake Thomson, Jonathan Emberson, Miguel Morales, Elba Lorenzo-Vázquez, Nurys B. Armas Rojas, Sonia Bess Constantén, Patricia Varona-Pérez, and Sarah Lewington
Subjects: Research paper, Population, Alcohol, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medicine, 030212 general & internal medicine, 0101 mathematics, Mortality, Prospective study, Prospective cohort study, education, education.field_of_study, lcsh:R5-920, business.industry, Proportional hazards model, Mortality rate, 010102 general mathematics, Absolute risk reduction, Cause specific mortality, Cuba, General Medicine, chemistry, business, lcsh:Medicine (General), Alcohol consumption, Demography
Abstract: Background The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. Methods In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35–79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. Findings After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (Interpretation In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba. Funding Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).
Published: 2021

46. Dexamethasone in Hospitalized Patients with Covid-19

Author: Susara Blunden, Alexander Mentzer, Tom Dymond, Nazima Pathan, Sabrina Helena Rossi, Calum Robertson, Robert Heyderman, Stacy Todd, Richard Haynes, Ahmad Abu-Arafeh, William Ricketts, Davinder Dosanjh, Simon Drysdale, Danyal Jajbhay, Grant D. Stewart, Andrew Ustianowski, Jane Blazeby, Ashton Barnett-Vanes, Nicholas Kametas, Elizabeth Bancroft, Ankur Gupta-Wright, Hanif Esmail, Gerard McKnight, Catherine Harwood, Anthony De soyza, Tuck-Kay Loke, Mili Estee Torok, Wei Shen Lim, Vishal Dey, Brendan Payne, Charles Christoph Roehr, Dominic Crocombe, Imogen Skene, Ran Wang, Martin Landray, Anna Bibby, Jamie Brannigan, Søren Kudsk-Iversen, Kathryn Puxty, Katrina Cathie, Maheshi Nirmala Ramasamy, Alan Montgomery, Louis Grandjean, Xin Hui Chan, Ben Gibbison, Dinesh Saralaya, Omer Elneima, Natalie Blencowe, Eleanor Mishra, Henry HL Wu, Roy Soiza, Patrick Lillie, Christian Alexander Linares, Simon Tso, Benjamin Caplin, Sarah Burge, Sakib Rokadiya, Manish Patel, Jamie Cooper, Lee Hoggett, Gareth Jones, Matt Morgan, Alex Horsley, Saul Faust, Martin Llewelyn, Alex Scott, Kim Hinshaw, Arvind Nune, Effrossyni Gkrania-Klotsas, Elizabeth Whittaker, Shaman Jhanji, Chetan Parmar, Chris Imray, Kathryn Rowan, Christopher Green, Mark Peters, Eoin O'Sullivan, Pallav Shah, Paul Dark, Luke Hodgson, Ryan Malcolm Hum, Varun Sarodaya, Chris Brightling, Pilar Rivera Ortega, Jonathan Emberson, Lucy Chappell, Ben Shelley, Richard Adams, Joseph Barker, John Kenneth Baillie, Manu Vatish, Jaki, Thomas [0000-0002-1096-188X], Apollo - University of Cambridge Repository, University of St Andrews. School of Medicine, National Institute for Health Research, and UK Research and Innovation
Subjects: deksametazon, Male, medicine.medical_treatment, Anti-Infective Agents/therapeutic use, Administration, Oral, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Rate ratio, Dexamethasone, law.invention, 0302 clinical medicine, Randomized controlled trial, Anti-Infective Agents, RA0421, law, RA0421 Public health. Hygiene. Preventive Medicine, Odds Ratio, 030212 general & internal medicine, 11 Medical and Health Sciences, Aged, 80 and over, Respiratory Distress Syndrome, Covid19, 3rd-DAS, General Medicine, Covid-19 -- drug therapy, Multicenter Study, Hospitalization, Randomized Controlled Trial, Injections, Intravenous, Original Article, Steroids, Drug Therapy, Combination, Female, covid-19 -- terapija z zdravili, medicine.drug, Dexamethasone/administration & dosage, RM, medicine.medical_specialty, Randomization, dexamethasone, Lung injury, COVID-19/drug therapy, 03 medical and health sciences, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Journal Article, udc:616.9, medicine, Humans, Comparative Study, Glucocorticoids, Aged, Mechanical ventilation, SARS-CoV-2, business.industry, Oxygen Inhalation Therapy, Glucocorticoids/administration & dosage, COVID-19, Odds ratio, NIS, Length of Stay, Respiration, Artificial, United Kingdom, RM Therapeutics. Pharmacology, COVID-19 Drug Treatment, RECOVERY Collaborative Group, Respiratory failure, business, Anaesthesia Pain and Critical Care
Abstract: Supported by a grant (MC_PC_19056) to the University of Oxford from the Medical Research Council of United Kingdom Research and Innovation and the National Institute for Health Research (NIHR); and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. Dr. Lim is supported by core funding provided by NIHR Nottingham Biomedical Research Centre, Dr. Felton by the NIHR Manchester Biomedical Research Centre, and Dr. Jaki by a grant (MC_UU_0002/14) from the UK Medical Research Council and by an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. METHODS: In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment. RESULTS: A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P
Published: 2021

47. Abdominal and gluteo-femoral markers of adiposity and risk of vascular-metabolic mortality in a prospective study of 150,000 Mexican adults

Author: Michael Hill, Rory Collins, Diego Aguilar-Ramirez, Roberto Tapia-Conyer, Sarah Lewington, Eirini Trichia, Jason M. Torres, Robert Clarke, William G. Herrington, Richard Peto, Jonathan Emberson, Jesus Alegre-Díaz, Raúl Ramirez-Reyes, Louisa Gnatiuc, Rachel Wade, and Pablo Kuri-Morales
Subjects: Adult, Male, medicine.medical_specialty, Waist, Epidemiology, 030204 cardiovascular system & hematology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Obesity, Prospective Studies, Prospective cohort study, Mexico, Adiposity, Proportional hazards model, business.industry, Waist-Hip Ratio, Mortality rate, Confounding, Circumference, Confidence interval, Obesity, Abdominal, Female, Waist Circumference, Cardiology and Cardiovascular Medicine, business, Body mass index, Biomarkers
Abstract: Aims Results of previous studies of abdominal adiposity and risk of vascular-metabolic mortality in Hispanic populations have been conflicting. We report results from a large prospective study of Mexican adults with high levels of abdominal adiposity. Methods and results A total of 159 755 adults aged ≥35 years from Mexico City were enrolled in a prospective study and followed for 16 years. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) associated with three markers of abdominal adiposity (waist circumference, waist–hip ratio, and waist–height ratio) and one marker of gluteo-femoral adiposity (hip circumference) for cause-specific mortality before age 75 years. To reduce reverse causality, deaths in the first 5 years of follow-up and participants with diabetes or other prior chronic disease were excluded. Among 113 163 participants without prior disease and aged 35–74 years at recruitment, all adiposity markers were positively associated with vascular-metabolic mortality. Comparing the top versus bottom tenth of the sex-specific distributions, the vascular-metabolic mortality RRs at ages 40–74 years were 2.32 [95% confidence interval (CI) 1.84–2.94] for waist circumference, 2.22 (1.71–2.88) for the waist–hip ratio, 2.63 (2.06–3.36) for the waist–height ratio, and 1.58 (1.29–1.93) for hip circumference. The RRs corresponding to each standard deviation (SD) higher usual levels of these adiposity markers were 1.34 (95% CI 1.27–1.41), 1.31 (1.23–1.39), 1.38 (1.31–1.45), and 1.18 (1.13–1.24), respectively. For the markers of abdominal adiposity, the RRs did not change much after further adjustment for other adiposity markers, but for hip circumference the association was reversed; given body mass index and waist circumference, the RR for vascular-metabolic mortality for each one SD higher usual hip circumference was 0.80 (0.75–0.86). Conclusions In this study of Mexican adults, abdominal adiposity (and in particular the waist–height ratio) was strongly and positively associated with vascular-metabolic mortality. For a given amount of general and abdominal adiposity, however, higher hip circumference was associated with lower vascular-metabolic mortality.
Published: 2021

48. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Eugenia Abaleke, Mustafa Abbas, Sadia Abbasi, Alfie Abbott, Ashraf Abdelaziz, Sherif Abdelbadiee, Mohamed Abdelfattah, Basir Abdul, Althaf Abdul Rasheed, Rezan Abdul-Kadir, Abdulfatahi Abdulmumeen, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer UA Abeer Ul Amna, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmad Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Devikumar Acharya, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Kate Adams, Richard Adams, Tim Adams, Malgorzata Adamus, Kirsty Adcock, Aderonke Adebiyi, Ken Adegoke, Vicki Adell, Aldrin Adeni, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Elizabeth Adeyeye, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Lynn Afari, Debbie Affleck, Carmel Afnan, Deborah Afolabi, Muhammad Afridi, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Judith Agwada-Akeru, Kwame A Agyapong, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Jonathan Ah-Chuen, Mahin Ahmad, Ashar Ahmed, Bilal Ahmed, Forizuddin Ahmed, Iram Ahmed, Irshad Ahmed, Liban Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Syed H Ahmed, Roa Ahmed Ali, Sana Ahmer, Dhiraj Ail, Adam Ainsley, Mark Ainsworth, Myriam Aissa, Lucy Aitchson, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Muhammad N Akhtar, Nasim Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Umeh Akudo, Asma Al Balushi, Majd Al Dakhola, Narendra Aladangady, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Lorraine Albon, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter DG Alexander, Julyan Al-Fori, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Anyat Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Oudai Ali, Sakina Ali, Syed Ali, Abid Alina, Katrin Alizaedeh, Maithem Al-Jibury, Moutaz Alkhusheh, Alison Allanson, Robert Allcock, Eireann Allen, Jonathan Allen, Kerry Allen, Louise Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Christine Almadenboyle, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Mary Alvarez, Maysaa Alzetani, Susan Amamou, Sakarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Amjad Amjad, Victoria Amosun, Khaled Amsha, Atul Anand, Samantha Anandappa, Julie Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Prematie Andreou, Angela Andrews, Jill Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Bianca Araba, Angela Aramburo, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Dhawal Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Ganesh Arunachalam, Rita Arya, Salma Asam, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Ayesha Ashfaq, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Harshini Asogan, Julia Asplin, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Ahmed Attiq, Paula Aubrey, Suzannah August, Aye CT Aung, Hnin Aung, Kyaw Thu Aung, Nini Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Miriam Avery, Joanne Avis, Cristina Avram, Paula Avram, Gabriel Awadzi, Aszad Aya, Eman Ayaz, Amanda Ayers, Vivek Ayra, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Nasaruilla Babajan, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Adetona O Babs-Osibodu, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Kasra Bahadori, Gayathri Baijiu, Charles Bailey, Julie Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Peter Bailey, Hamish Baillie, Kenneth Baillie, Jennifer Bain, Karen Bain, Becky Bainton, David Baird, Yolanda Baird, Aiysha Bajandouh, Evelyn Baker, Johanne Baker, Kenneth Baker, Pearl Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Panos Bakoulas, Abhijit Bal, Niranjan Balachandran, Irvin Balagosa, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Cheryl Baldwick, Alexander Baldwin, Ashley Baldwin, Danielle Baldwin, Lisa Baldwin, Rebekah Baldwin-Jones, James Balfour, Ceri Ball, Craig Balmforth, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Kasun Bamunuarachchi, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Ritwik Banerjee, Sandip Banerjee, Harrison Banks, Luke Banks, Daniel Banner, Oliver Bannister, Christopher Bannon, Laura Banton, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Desislava Baramova, Russell Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Charlotte Barclay, Stephanie Bareford, Shahedal Bari, Amy Barker, Debbie Barker, Joseph B Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Amy Barnett, Debra Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Fiona Barrett, Jessica Barrett, Jazz Bartholomew, Sarah Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Ayten Basoglu, Amira Bassaly, G Bassett, Bengisu Bassoy, Anupam Basumatary, Adam Bataineh, Freddie Batalla, Tristan Bate, Harry John Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Rizvan Batha, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Miranda Baum, Carina Bautista, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Hannah Bayes, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Hannah Beadle, Wendy Beadles, Philip Beak, Andy Beale, Kathy Beardsal, Jack Bearpark, Karen Beaumont, Matthew Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Safia Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Lauren Bell, Louise Bell, Nicholas Bell, Stephanie Bell, Jennifer L Bell, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Ann Bennett, Caroline Bennett, Gillian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Vivienne Benson, Andrew Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Kimberley Best, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Helen Bexhell, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shweta Bhagat, Shiv Bhakta, Rekha Bhalla, Mahesh Bhalme, Khushpreet Bhandal, Kulbinder Bhandal, Ravina Bhanot, Prashanth Bhat, Nikhil Bhatia, Rahul Bhatnagar, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Alice Binns, Oliver Bintcliffe, Catherine Birch, Janine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Mark Birt, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Sabrina Black, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Francesca Blakemore, Helen Blamey, Sujata Blane, Simon Blankley, Parry Blaxill, Jane Blazeby, Natalie Blencowe, Ben Bloom, Angela Bloss, Hannah Bloxham, Louise Blundell, Susara Blunden, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Bobruk, Pritesh Bodalia, Neena Bodasing, Gabriele Boehmer, Marta Boffito, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed Owais Bokhari, Ambrose Boles, Matthew Bolton, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Lizzy Bonney, Joanne Borbone, Stephanie Borg, Catherine Borra, Samuel Bosompem, Liam Botfield, Fiona Bottrill, Hannah Bouattia, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Karen Bourne, Michelle Bourne, Rachel Bousefield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Angie Bowring, Geetha Boyapati, Jenny Boyd, Laura Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Rebecca Brady, Shirin Brady, Marie Branch, Emily Brandl-Salutz, Christina Branfield, Jamie Brannigan, Louise Brassington, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Morwenna Brend, Andrew Brereton, Chris Brewer, Gavin Bridgwood, Sara Brigham, John Bright, Christopher Brightling, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Lauren Broad, Sarah Broad, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Fiona Brogan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Alison Brooks, Kate Brooks, Nicole Brooks, Rachel Brooks, Sophie Brooks, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Louise Brown, Niall Brown, Pauline Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Charlotte Browne, Duncan Browne, Rachel Browne, Stephen Brownlee, David Bruce, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Nigel Brunskill, Luke Brunton, Margaret Brunton, Jade Bryant, Mark Bryce, Maya Buch, Ruaridh Buchanan, Amanda Buck, Elizabeth Buckingham, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, George Bugg, Ramadan Bujazia, Shanzay Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Rhian Bull, Thomas Bull, Sam Bullard, Naomi Bulteel, Katherine Bunclark, Roneleeh Bungue-Tuble, Caroline Burchett, Christy Burden, Thomas G Burden, Sarah Burge, Mika Burgess, Sophia Burgess, Emma Burke, Sara Burnard, Caroline Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Daniel Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Angus Butchart, Aaron Butler, Jo Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Ruth Cade, Donna Cairney, Claire Calderwood, James Calderwood, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sheena Cameron, Christian Camm, Renee FD Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Laura Camrasa, Julie Camsooksai, Shaula M Candido, Cielito Caneja, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Angelika Capp, Thomas Capstick, Simon Carley, Tammy Carlin, Samantha Carmichael, Margaret Carmody, Mandy Carnahan, Charlotte Caroline, Patrick Carr, Sharon Carr, Anna Carrasco, Zoe Carrington, Jonathan Carter, Paul Carter, Penny Carter, Douglas Cartwright, Claire Carty, Jaime Carungcong, Paula Carvelli, Aisling Cashell, Barbara Cassimon, Teresa Castiello, Gail Castle, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Kerry Causer, Luke Cave, Frianne Cawa, Kathryn Cawley, Philippa Cawley, Chloe Caws, Hankins Cendl, Jeva Cernova, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, James Chalmers, Georgina Chamberlain, Sarah Chamberlain, Carol Chambers, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Shreekant Champanerkar, Carmen Chan, Cheuk Chan, Evelyn Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin H Chan, Chris Chandler, Kim J Chandler, Zoe Chandler, Badrinathan Chandrasekaran, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy 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Dermody, Amisha Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Prakash Dey, Vishal Dey, Rogin Deylami, Gurlove K Dhaliwal, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Sukhjit Dhariwal, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Kayleigh Diaz-Pratt, Pamela Dicks, Matthew Dickson, Sean Dillane, Sarah Diment, Paul Dimitri, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Nandita Divikar, Lavanya Diwakar, Masroor Diwan, Caroline Dixon, Catherine Dixon, Petr Dlouhy, Paul Dmitri, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, Morven Dockery, Emma Docks, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Callum Donaldson, Denise Donaldson, Kate Donaldson, Sinead Donlon, Joanne Donnachie, Christopher Donnelly, Eilish Donnelly, Emma Dooks, Andrew Dooley, Kane Dorey, Sharon Dorgan, Davinder Dosanjh, Paula Dospinescu, Andrew Dougherty, Katie Douglas, Lucy Dowden, Michelle Dower, Sud Dowling, Hayley Downe, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Chelsea Drake, Victoria Drew, Olivia Drewett, Celine Driscoll, Helena Drogan, Ronald Druyeh, Simon Drysdale, Hazel Dube, Judith Dube, Stephen Duberley, Simon Dubrey, Roger Duckitt, Hayley Duckles-Leech, Nicola Duff, Helen Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Janice Duignan, Simon Dummer, Andrew Duncan, Barrie Duncan, Christopher Duncan, Fullerton Duncan, Alessia Dunn, Damian Dunn, Laura Dunn, Karen Dunne, Fiona Dunning, Aidan Dunphy, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Alison Durie, Emily Durie, Laura Durrans, Hannah Durrington, Akshay Dwarakanath, Laasya Dwarakanath, Ellen Dwyer, Claudia Dyball, Harvey Dymond, Tom Dymond, Chris Eades, Melissa Earwaker, Nicholas Easom, Clare East, Jack Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Andrea Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Steven Edwards, Jenny Eedle, Dawn Egginton, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Kate El Bouzidi, Ashley Elden, Jennifer Elder, Haifa Eldew, Diana Eleanor, Maysoon Elfadil, Eman Elfar, Mayy M Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Amin Elkhawad, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura Nicola Ellerton, Amy Elliott, Fiona Elliott, Kerry Elliott, Valmai Elliott, Annie Ellis, Hayley Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Rahma Elmahdi, Einas Elmahi, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Sarah Elyoussfi, Jonathan Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Charis Emmett, Michael Emms, Marieke Emonts, Angila Engden, Katy English, Nicola Entwistle, Hene Enyi, Ruth Erin Jones, Agota Ermenyi, Hanif Esmail, Ajmal Eusuf, Brynach Evans, Chris Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Lynn Evans, Melanie Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Teriann Evans, Terry J Evans, Caroline Everden, Lynsey Evison, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Andy Fairclough, Louise Fairlie, Anne Fajardo, Euan Falconer, John Fallon, David Faluyi, Qayyum Farah, Novin Fard, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Frances Farnworth, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Alex Feben, Federico Fedel, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Lisa Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Sonia Fernandez Lopez, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Catarina Ferreira-De Almeida, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Joanne Finch, Laurie Finch, Natalie Fineman, Adam Finn, Joanne Finn, Sofia Fiouni, Jo Fiquet, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Marie Fisk, Jan Flaherty, Michael Flanagan, Charles Flanders, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Lucy Fletcher, Sophie Fletcher, Christopher Flood, Jonathan Flor, Vincent Florence, Sharon Floyd, Adama Fofana, Georgina Fogarty, Linda Folkes, Aiwyne Foo, Andrew Foot, Jayne Foot, Jane Forbes, Kathryn Forcer, Jamie Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Simon Fox, Sarah-Jane Foxton, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Victoria Francois, Sharon Frayling, Martyn Fredlund, Michael Freeborn, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Anastasia Fries, Matthew Frise, Renate Fromson, Claire Froneman, John Frost, Victoria Frost, Rachel Frowd, Arun Fryatt, Bridget Fuller, Elizabeth Fuller, Tracy Fuller, Duncan Fullerton, Sarah Funnell, John Furness, Hassina Furreed, Waqas Gaba, Elizabeth Gabbitas, Claire Gabriel, Joshua Gahir, Katarzyna Gajewska-Knapik, Christopher Gale, Hugo Gale, 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Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Nicola Griffiths, Oliver Griffiths, Sofia Grigoriadou, Steph Grigsby, Russell Gritton, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Sambasivarao Gurram, Ishy Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Samantha Hagan, Jack W Hague, Rosemary Hague, Andrew Haigh, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Anne Haldeos, Carmel Halevy, William Halford, Alistair Hall, Anthony Hall, Chloe Hall, Claire Hall, Emily Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Toni Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Ruth Hamlin, Eleanor Hamlyn, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Rachel Hammond-Hall, Fiona Hammonds, Nidal Hammoud, Ibrahim Hamoodi, Karen Hampshire, Jude Hampson, Shi Han Lee, Ozan Hanci, James Hand, Soran Handrean, Georgina Hands, Sheharyar Hanif, Amy Hannington, Merhej Hannun, Aidan Hanrath, Jane Hanson, Kathryn Hanson, Mazhar U Haq, Ala Haqiqi, Monjurul Haque, Zoe Harding, Simon Hardman, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Helen Harizaj, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie H Harper, Heather Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Claire Harris, Jade Harris, Julie Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, David Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Tom Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Hans Hartung, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Neda Hasan, Brigitte Haselden, Mohammed Hashimm, Imranullah Hashmi, Zena Haslam, Abdulhakim Hassan, Adil Hassan, Ali Hassan, Waqar Ul Hassan, Philip Hassell, Alex Hastings, Bethany Hastings, Jonathan Hatton, Jennifer Haugh, May Havinden-Williams, Stefan Havlik, Dan Hawcutt, Liz Hawes, Nicola Hawes, Annie Hawkins, Nancy Hawkins, Daniel Hawley, Edward Haworth, Cathy Hay, Jamal Hayat, Anne Hayes, Melony Hayes, Fiona Hayes, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Patrick Haywood, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Amy Hearn, Angela Heath, Rowan Heath, Diane Heaton, Kerry Hebbron, Neil Hedger, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Rajdeep Heire, David Helm, Ulla Hemmila, Scott Hemphill, Deborah Hemsley, Alistair Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, David Henshall, Gillian Herdman, Rosaleen Herdmangrant, William Herrington, Emilia Heselden, Peta Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Andrew Hetreed, Chamila Hettiarachchi, Gihan Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Claire Hewitt, Davina Hewitt, Richard Hewitt, Robert S Heyderman, Matthis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, Naomi Hickey, Alexander Hicks, Jenny Hicks, Scott R Hicks, Daniel Higbee, Jennifer Higgins, Lucy Higgins, Andrew Higham, Martin Highcock, Judith 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Nicola Hornby, Sophie Horrocks, Latoya Horsford, Megan Horsford, Valana Horsham, Alex Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Ejaz Hossain, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Kathryn Houghton, Rebecca Houlihan, Gordon Houston, Hamish Houston, Eleanor Hoverd, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Richard Howard-Griffin, Serena Howe, Mark Howells, Lyn Howie, Alex Howlett, Sophie Howlett, Josh Hrycaiczuk, Desmond Hsu, Hein Htet, Zaw Htet, Naing Z Htoon, Su Htwe, Ying Hu, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Alison Hufton, Conor Huggins, Alistair Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rhian Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Charlotte Humphrey, Alasdair Humphries, Joanne Humphries, David Hunt, Fiona Hunt, Jane Hunt, Kristen Hunt, Luke Hunt, Karl Hunter, Neil Hunter, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Ibraar Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Rebecca Hussey, Christopher Hutchcroft, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Ahmed Ibrahim, Asil Ibrahim, Kamal Ibrahim, Mohamed Ibrahim, Wadah Ibrahim, Muhammad Idrees, Hina Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Haider Imtiaz, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana 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Sabrina Jansz, Deepa Japp, Catherine Jardine, Ellie Jarvie, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Lona Jawaheer, Dinakaran Jayachandran, Deepak Jayaram, Geeshath Jayasekera, Lalith Jayasekera, Saman Jeddi, Mohammad S Jeelani, Katie Jeffery, Rachel Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Edward Jenner, David Jennings, Jacqui Jennings, Louise Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge A Jesus Silva, Kishan Jethwa, Abi Jeyabalan, Akhilesh Jha, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Emma Johns, Margaret Johns, Antoinette Johnson, Gillian Johnson, Kathryn Johnson, Luke Johnson, Mark Johnson, Claire Johnston, Janet Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed 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Catherine Penman, Julie Penman, James Penny, Justin Pepperell, Adriana Pereira, Rita Pereira, Elena Perez, Jane Perez, Tanaraj Perinpanathan, Lakshmi Periyasamy, Alison Perry, Emily Perry, Meghan Perry, Guilherme Pessoa-Amorim, Ruth Petch, Lionel Peter, Cecilia Peters, Mark Peters, Steve Peters, Tim Peters, Alexandra Peterson, Leon Peto, Ilianna Petrou, Boyanka Petrova, Mirela Petrova, Paul Pfeffer, Mysore Phanish, Paul Phelan, Christopher Philbey, Jennifer Philbin, Alex Phillips, Dylan Phillips, Rachael Phillips, Marie Phipps, Virach Phongsathorn, Nang T Phoo, Mandeep Phull, Masroor M Phulpoto, Sara Pick, James Pickard, Charlotte Pickering, Gillian Pickering, Thomas Pickett, Joanna Pickles, Benjamin Pickwell-Smith, Natalia Pieniazek, Angelo Pieris, Samia Pilgrim, Paul Anthony Pillai, Zoe Pilsworth, Heather Pinches, Stacey Pinches, Kirsty Pine, Ed Pineles, Muni T Pinjala, Stefania Pintus, Graeme Piper, Tasneem Pirani, Sally Pitts, Aiden J Plant, Naomi Platt, Robert Pleass, Laura Plummer, Charles Plumptre, Tatiana Pogreban, Joshua Pointon, Stephen Poku, Rachel Pollard, Louisa Pollock, Oluwamayowa Poluyi, Gary J Polwarth, Fiona Pomery, Ponmurugan Ponnusamy, Aravind Ponnuswamy, Inês Ponte Bettencourt dos Reis, Alice Poole, Lynda Poole, Michele Poole, Sharon Poon, Tajinder Poonian, David Porter, Linda Porter, Kelly Postlethwaite, Narayana Pothina, Priyadarshan Potla, Dorota Potoczna, Jason Pott, Alison Potter, Jean Potter, Sarah Potter, Elspeth Potton, Julie Potts, Kathryn Potts, Maria Poulaka, Una Poultney, Katherine Poulton, Vanessa Poustie, James Powell, Jordan Powell, Deborah Power, Nick Power, Joseph Poxon, Robin Poyner, Helena Prady, Krishna Prasad, Fredy Prasanth Raj, Sangeetha Prasath, Anezka Pratley, Euan Pratt, Steven Pratt, David Preiss, Claire Prendergast, Lynn Prentice, Verity Prescott, Laura Presland, Catharine Prest, Stephen Preston, Natalie Prevatt, Sandra Prew, Ashley Price, Carly Price, Claire Price, David Price, Elizabeth Price, Nathan Price, Vivien Price, Anne Priest, Kate Priestley, Lorraine Primrose, Judith Prince, Laura Prince, Shirley Pringle, Veronika Pristopan, Kelly Pritchard, Lucy Pritchard, Simon Pritchard, Verma Priyash, Andrew Procter, Clare Proctor, Rebecca Proudfoot, Heather Prowse, Benjamin Prudon, David Pryor, Solomon Pudi, Amy Pugh, Joanne Pugh, Mark Pugh, Nichola Pugh, Richard Pugh, Veronika Puisa, Kirandip Punia, Saleel Punnilath Abdulsamad, Laura Purandare, Martha Purcell, Corrina Purdue, Bally Purewal, Molly Pursell, Gregory Purssord, Sarah Purvis, Kathryn Puxty, Michael Pynn, Tariq Qadeer, Sheena Quaid, Alice Quayle, Ian Quayle, Siobhan Quenby, Xinyi Qui, Vanessa Quick, Julie Quigley, Tom Quinn, Quratulain Quratulain, Danya Qureshi, Hasanain Qureshi, Khadija Qureshi, Nawaz Qureshi, Qurratulain Qurratulain, Saad Qutab, Muhammad S Rabbani, Madalina Raceala, Laura Rad, Jane Radford, Liz Radford, Jayachandran Radhakrishnan, Michael Raffles, Cecillia Rafique, Muhammad Rafique, Ravi Ragatha, Sarika Raghunath, Aiswarya Raghunathan, Abigail Raguro, Shankho D Raha, Sana Rahama, Karen Rahilly, Faisal Rahim, Haseena R Rahimi, Muhammad Rahman, Salim Ur Rahman, Lenka Raisova, Mehul Raithatha, Arjun Raj, Pradeep Rajagopalan, Nithy Rajaiah, Arvind Rajasekaran, Aylur Rajasri, Jyothi Rajeswary, Gayathri Rajmohan, Matsa Ram, Balaji Ramabhadran, Niranjani Ramachandran, Iyad Ramadan, Mohamed Ramali, Athimalaipet Ramanan, Shashikira Ramanna, Maheshi Ramasamy, Dhanishta Ramdin, Jozel Ramirez, Lidia Ramos, Shanthi Ramraj, Lisa Ramsawak, Alex Ramshaw, Aleem Rana, Ghulam F Rana, Rehman Rana, Abby Rand, James Rand, Georgina Randell, Poonam Ranga, Manu Rangar, Harini Rangarajan, Sameer Ranjan, Poormina Ranka, Christopher Ranns, Anita Rao, Deepak Rao, Sandhya Rao, Sanjay Rao, Khalid Rashid, Simbisai Ratcliff, Sam Ratcliffe, Sophy Ratcliffe, Sanjeev Rath, Mohmad I Rather, Selina Rathore, Aravinden Ratnakumar, Jonathan Ratoff, Deepa Rattehalli, Jason Raw, Gautam Ray, Samiran Ray, Adam Raymond-White, Dana Raynard, Nicola Rayner, Jareer Raza, Salman Razvi, Zarine Razvi, Kerry Read, Ajay Reddy, Anvesh Reddy, Harsha Reddy, Ravi Reddy, Aine Redfern-Walsh, Alex Redome, Joan Redome, Anna Reed, Andrew Rees, James Rees, Martyn Rees, Sarah Rees, Stephanie Rees, Tabitha Rees, Fiona Regan, Karen Regan, Susan Regan, Kanchan Rege, Ahmed Rehan, A Rehman, Siddiqur Rehman, Ada Reid, Jeremy Reid, Sharon Reid, Mkyla Reilly, Christina Reith, Alda Remegoso, Dinakaran Rengan, Stephen Renshaw, Remya Renu Vattekkat, Henrik Reschreiter, Glynis Rewitzky, Charles Reynard, Dominic Reynish, Jessica Reynolds, Peter Reynolds, Tom Reynolds, Kat Rhead, Jo Rhodes, Jonathan Rhodes, Naghma Riaz, Emily Rice, Matthew Rice, Mel Rich, Alison Richards, Suaznne Richards, Celia Richardson, Neil Richardson, Nicky Richardson, Joanne Riches, Katie Riches, William Ricketts, Anna Riddell, Laura Riddles, Carrie Ridley, Paul Ridley, Gudrun Rieck, Hannah Riley, Matthew Riley, Phil Riley, Dominic Rimmer, Robert Rintoul, Andrew Riordan, Naomi Rippon, Chloe Rishton, Michael Riste, Jane Ritchie, Andrew Ritchings, Pilar Rivera Ortega, Vanessa Rivers, Syed AS Rizvi, Syed HM Rizvi, Ian Roberts, Karen Roberts, Mark Roberts, Nicky Roberts, Rebecca Roberts, Calum Robertson, Nichola Robertson, Stuart Robertson, Caroline Robinson, Emily Robinson, Emma Robinson, Gisela Robinson, Hannah Robinson, Jemima Robinson, Kate Robinson, Matthew Robinson, Sandra Robinson, Steve Robson, Lisa Roche, Samantha Roche, Natalie Rodden, Alistair Roddick, Jack Roddy, Marion Roderick, Alison Rodger, Faye Rodger, Megan Rodger, Alicia Rodgers, Natasha Rodgers, Penny Rodgers, Sarah Rodrigues, Rocio Rodriguez-Belmonte, Nicholas Roe, Charles C Roehr, Gill Rogers, Jason Rogers, Joanne Rogers, John Rogers, Leigh Rogers, Lindsay Rogers, Michaela Rogers, Naomi Rogers, Paula Rogers, Thomas Rogers, Sakib Rokadiya, Lee Rollins, Jennifer Rollo, Catherine Rolls, Claire Rook, Kevin Rooney, Laura Rooney, Lynsey Rooney, Lace Rosaro, Alastair Rose, Annie Rose, Steve Rose, Zoe Rose, Josephine Rosier, Jennifer Rossdale, Sabrina Rossi, Andrew Ross-Parker, Alex Rothman, Joanne Rothwell, Lindsay Roughley, Guy Rousseau, Kathy Rowan, Neil Rowan, Stephen Rowan, Louise Rowe-Leete, Benjamin Rowlands, Aparajita Roy, Subarna Roy, Anna Roynon-Reed, Sam Rozewicz, Antonio Rubino, Anna Rudenko, Senthan Rudrakumar, Banu Rudran, Shannon Ruff, Prita Rughani, Mike Ruiz, Sharon Rundell, Hitasha Rupani, Darren Rusk, Joseph Russell, Peter Russell, Richard Russell, Cristina Russo, Marieke Rutgers, Aidan Ryan, Brendan Ryan, Lucy Ryan, Matthew Ryan, Pat Ryan, Phil Ryan, Declan Ryan-Wakeling, Chloe Saad, M Saad, Javeson Sabale, Suganya Sabaretnam, Gorka Sacher, Noman Sadiq, Ashiq Saffy, Diaeddin Sagar, Beth Sage, Harkiran Sagoo, Rajnish Saha, Nikhil Sahdev, Jagdeep Sahota, Nooria Said, Sreekanth Sakthi, Abdul Salam, Erika Salciute, Jessica Sale, Gina Saleeb, Mumtaz Saleh, Hizni Salih, Laylan Salih, Sarah Salisbury, Rustam Salman, Jenny Salmon, Dario Salutous, Mfon Sam, Sally Sam, Tinashe Samakovna, Razan Saman, Renaldo Samlal, Emily Sammons, David Sammut, Mark Sammut, Sunitha Sampath, Julia Sampson, Anda Samson, Debbie Samuel, Johnson Samuel, Reena Samuel, Thomas DL Samuel, Elsward Samuels, Theo Samuels, Joanna Samways, Manjula Samyraju, Ilves Sana, Aabid Sanaullah, Veronica Sanchez, Amada Sanchez, Tom Sanctuary, Peter Sandercock, Amy Sanderson, Paul Sanderson, Tom Sanderson, Kuljinder Sandhu, Loveleen Sandhu, Victoria Sandrey, Sarah Sands, Mirriam Sangombe, Matthew Sanju, Rojy Santosh, Jayanta Sanyal, Aureo F Sanz-Cepero, Najam Saqib, Sarbjit Sarai, Dinesh Saralaya, Arun Saraswatula, Avishay Sarfatti, Rebecca Sargent, Beatrix Sari, Rahul Sarkar, Sruthi Sarma, Varun Sarodaya, Zainab Sarwar, Thea Sass, Sonia Sathe, Sobitha Sathianandan, Abilash Sathyanarayanan, Thozhukat Sathyapalan, Prakash Satodia, Rachel Saunders, Samantha Saunders, Anne Saunderson, Heather Savill, Karishma Savlani, Matthew Saxton, Amrinder Sayan, Diane Scaletta, Lyndsay Scarratt, Sean Scattergood, Alvin Schadenberg, Alex Schoolmeesters, Natasha Schumacher, Nicola Schunke, Martin Schuster Bruce, Karin Schwarz, Tim Scorrer, Fiona Scothern, A Scott, Anne Scott, Christine Scott, Emily Scott, Kerrie Scott, Stephen Scott, Timothy Scott, Sarah Scourfield, Wendy Scrase, Angela Scullion, Emily Seager, Cathy Seagrave, Eleanor Sear, Isabella Seaton, Anna Seckington, Joanna Sedano, Gabrielle Seddon, Muhammad A Seelarbokus, Christopher Sefton, Matias Segovia, Gillian Sekadde, Georgina Selby, Katharine Sellers, Joseph Selley, Victoria Sellick, Gobika Selvadurai, Brintha Selvarajah, Haresh Selvaskandan, Gary Semple, Nandini Sen, Seema Sen, Namrita Sengreen, Aditya Sengupta, Niladri Sengupta, HoJan Senya, Jaskaran Sethi, Niranjan Setty, Abigail Seward, Teswaree Sewdin, Jack Seymour, Tariq Shafi, Aashni Shah, Ahmar Shah, Anand Shah, Anjnee Shah, Bhavni Shah, Neil Shah, Pallav Shah, Priyank Shah, Qasim Shah, Sarfaraz H Shah, Snehal Shah, Suraj Shah, Syed Shah, Sousan Shahi, Sipan Shahnazari, Ramli Shahrul, Muhammad Shahzeb, Amina Y Shaikh, Rajit Shail, Mariya Shaji, Korah Shalan, Nafe Shami, Nadia Shamim, Kazi Shams, Thomas Shanahan, Paul Shannon, Hamed Sharaf, Asir Sharif, Akhilesh Sharma, Ash Sharma, Mona Sharma, Ojasvi Sharma, Rajeev Sharma, Sanjeev Sharma, Sarkhara Sharma, Alexander Sharp, Charles Sharp, Gemma Sharp, Paula Sharratt, Phoebe Sharratt, Christopher Shaw, David Shaw, Deborah Shaw, Joanne Shaw, Jonathan Shaw, Lisa Shaw, Tomos G Shaw, Anna Shawcross, Jill Shawe, Sophy Shedwell, Jonathan Sheffield, Zak Shehata, Arshiya Sheik, Asif Sheikh, Noorann Sheikh, Benjamin Shelley, Sarah Shelton, Anil Shenoy, Julie Shenton, Amy Shepherd, Lorna Shepherd, Scott Shepherd, Rhian Sheppeard, Helen Sheridan, Ray Sheridan, Samuel Sherridan, Leanne Sherris, Susanna Sherwin, Shaad Shibly, Norma Shields, Chiaki Shioi, Lucy Shipp, Anand Shirgaonkar, Kim Shirley, Adebusola Shonubi, Rohan Shotton, Sarah Shotton, Ervin Shpuza, Nora Shrestha, Karen Shuker, Jack Shurmer, Loria Siamia, Seshnag Siddavaram, Nasir Siddique, Sohail Siddique, Nyma Sikondari, Malcolm Sim, Robert Sime, Oliver Simmons, Richard Simms, Angela Simpson, Anna Simpson, Danny Simpson, Georgina Simpson, Kathryn Simpson, Kerry Simpson, Phillip Simpson, Thomas Simpson, Janet Sinclair, Ankita Singh, Claire Singh, Jayaprakash Singh, Jyoti Singh, Manjeet Singh, Nadira Singh, Pankaj Singh, Prabhsimran Singh, Salil Singh, Parag Singhal, Surendra Singham, Bryan Singizi, Manas Sinha, Sharad Sinha, Utkarsh Sinha, Guy Sisson, Karthikadevi Sivakumar, Shanmugasundaram Sivakumar, Darshi Sivakumaran, Sivanthi Sivanadarajah, Nicole Skehan, Robert Skelly, Jill Skelton, Orlagh Skelton, Imogen Skene, Denise Skinner, Tabitha Skinner, Victoria Skinner, Agnieszka Skorko, Iwona Skorupinska, Mariola Skorupinska, Amy Slack, Katie Slack, Heather Slade, Mark Slade, Holly Slater, Lynda Slater, Nicola Slawson, Andrew Sloan, Brendan Sloan, Derek Sloan, Grace Sluga, Ellen Small, Samuel Small, Karen D Smallshaw, Andy Smallwood, Carien Smit, Aileen Smith, Amanda Smith, Amy Smith, Andrew Smith, Catherine Smith, Chris Smith, Christopher Smith, Dominic Smith, Eleanor Smith, Hazel Smith, Helen Smith, Jacky Smith, Jeannette Smith, Jessica Smith, John Smith, Kate Smith, Kerry Smith, Lara Smith, Lesley Smith, Linda Smith, Lisa Smith, Loren Smith, Lucy Smith, Matthew Smith, Mel Smith, Rachel Smith, Rebecca Smith, Richard Smith, Sally Smith, Stacey Smith, Stephanie Smith, Susan Smith, Sue Smolen, Sara Smuts, Jennifer Smyth, Naoise Smyth, Anette Snell, Alfred So, Beng So, Michelle Soan, Toluleyi Sobande, Alberto Sobrino Diaz, Basit Sohail, Bina Sohail, Roy Soiza, Olajumoke Solademi, Babak Soleimani, Amanda Solesbury, Louise Solomon, Subash Somalanka, Chandrashekaraiah Somashekar, Raj Sonia, Shiu-Ching Soo, Jennifer Soren, Vittoria Sorice, Apina Sothinathan, Pragalathan Sothirajah, Carmen Soto, Najwa Soussi, Donna Southam, David Southern, Iain Southern, Louise Southern, Sara M Southin, Thomas Southworth, Jason Sowter, Claudia Spalding, Enti Spata, Katie Spears, Mark Spears, Branwell Spencer, Gisele Spencer, Sue Spencer, Helen Spickett, Jennifer Spillane, William Spiller, Kerry Spinks, Michelle Spinks, Nick Spittle, Johanna Sporrer, Oliver Spring, Gemma Squires, Jack Squires, Rebecca Squires, Ram Sreenivasan, Ramesh Srinivasan, Asha Srirajamadhuveeti, Vino Srirathan, Sybil Stacpoole, Louise Stadon, Jennifer Stahle, Nikki Staines, Roxana Stanciu, Grazyna Stanczuk, Simon Stapley, Natalie Staplin, Michelle Starr, Rachael Stead, Conor Steele, Paula Stefanowska, Alison Stephens, David Stephensen, Courtney Stephenson, Elaine Stephenson, Monique Sterrenburg, Will Stevens, Amy Stevenson, Andrew Stevenson, Daniel Stevenson, Lesley Stevenson, Sarah Stevenson, Claire Stewart, Grant Stewart, Richard Stewart, Jo Stickley, Beverley Stidolph, Gemma Stiller, Sarah Stirrup, Sarah Stock, Alexander Stockdale, Lynne Stockham, Emma Stoddard, Chris Stokes, Ben Stone, Sarah Stone, Sophia Stone, Imogen Storey, Kim Storton, Frederick Stourton, Angela Strachan, Emma Stratton, Jane Stratton, Sam Straw, Dieter Streit, Emma Stride, Sally Stringer, Sophia Strong-Sheldrake, Siske Struik, Carmel Stuart, Anna Stubbs, Harrison Stubbs, Ann Sturdy, Sharon Sturney, Matt Stuttard, Cristina Suarez, Karuna Subba, Chris Subbe, Manjula Subramanian, Vaidyanathan Subramanian, Venkatram Subramanian, Chinari Subudhi, Rebecca Suckling, Srivatsan Sudershan, Taku Sugai, Peter Sugden, Rudresh Sukla, Ali Suliman, Fatimah Suliman, Sugrah Sultan, Alasdair Summers, Samyukta Sundar, Reka Sundhar, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Shilpa Suresh, Michael Surtees, Danielle Suter, Helen Sutherland, Rebecca Sutherland, Dovile Sutinyte, Deborah Sutton, Sam Sutton, Amy Sutton-Cole, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Thomas Swaine, Keshav Swarnkar, Tirion Swart, Ealish Swift, Pauline Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Yasir Syed, Catriona Sykes, Daisy Sykes, Dominic Symon, Lesley Symon, Jen Syson, Gemma Szabo, Tamas Szakmany, Megan Szekely, Matthew Szeto, Maria Tadros, Lucy Tague, Hasan Tahir, Abigail Takyi, James Talbot-Ponsonby, Bradley Tallon, Bee TT Tan, Hock Tan, Huey Tan, WeiTeen Tan, Anand Tana, Rebecca Tangney, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Hayley Tarft, Syed Tariq, David Tarpey, Antonia Tasiou, Elizabeth Tatam, Margaret Louise Tate, Paul Tate, Kate Tatham, Vera Tavoukjian, Alexander Taylor, Andrew Taylor, Beverley Taylor, Claire Taylor, David Taylor, Jennifer Taylor, Joanne Taylor, Julie Taylor, Karen Taylor, Leanne Taylor, Margaret Taylor, Matthew Taylor, Melanie Taylor, Natalie Taylor, Rachael Taylor, Rachel Taylor, Samantha Taylor, Suzanne Taylor, Tracey Taylor, Vicky Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Jessica Teasdale, Julie Tebbutt, Caroline Tee, Adam Telfer, Vibha Teli, Jennifer Tempany, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Lynne Terrett, Louise Terry, Dariusz Tetla, Daniel Tewkesbury, Manish Thakker, Mini Thankachen, Dushen Tharmaratnam, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Byron Theron, Phyu Thet, Kapeendran Thevarajah, Brinda Thillainathan, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Amy Thomas, Andrew Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Helen Thomas, James Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Megan Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Rhian Thomas-Turner, Catherine Thompson, Christopher Thompson, Clara Thompson, Fiona Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Orla Thompson, Roger Thompson, Jason Thomson, Nicola Thomson, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Jim Thornton, Richard Thornton, Sarah Thornton, Susan Thornton, Thomas Thornton, Christopher Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Guy Thwaites, Simon Tiberi, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Amanda Tiller, Elizabeth Timlick, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Sophie Tisi, Helen Tivenan, Suzy Tluk, Helen T-Michael, Anne Todd, Jackie Todd, Stacy Todd, Mohamed Tohfa, Melanie Tolson, Ana L Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Ivan Tonna, Kirsty Topham, Mathew Topping, Parisa Torabi, M Estee Torok, Mark Toshner, Ruhaif Tousis, Peter Tovey, Gareth Towersey, Jill Townley, Richard Tozer, Myat T Trafford, Helen Tranter, Christopher Travill, Sarah Traynor, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Alex Trimmings, Tom Trinick, Maria Tripouki, Ashifa Trivedi, Dawn Trodd, Amy Trotter, Madeleine Trowsdale Stannard, Nigel Trudgill, Daniel Trushell-Pottinger, Maria Truslove, Shaun Trussell, Tariq Trussell, Kyriaki Tsakiridou, Christine Tsang, Peter Tsang, Kyriaki K Tsilimpari, Georgios Tsinaslanidis, Simon Tso, Sally Tucker, Aisha Tufail, Redmond Tully, Killian Turbitt, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, Gail Turner, Kate Turner, Kelly Turner, Lucy Turner, Mark Turner, Patricia Turner, Sally Turner, Samantha Turner, Victoria Turner, Sharon Turney, Jon Turvey, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Mohammad S Uddin, Ruhama Uddin, Salamat Ullah, Sanda Ullah, Athavan Umaipalan, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Lizzie Undrell, Adam Unsworth, Veerpal SU Uppal, Gerry Upson, Alison Uriel, Sebastian Urruela, Hiromi Uru, Miranda Usher, Rebecca Usher, Andrew Ustianowski, Linda C Vaccari, Abhay Vaidya, Erika Vainieri, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Lynne Van Koutrik, Joseph Vance-Daniel, Rama Vancheeswaran, Samuel I Vandeyoon, Padma Vankayalapati, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Anu Varghese, Maria Varghese, Teena Varghese, William Varney, Giulia Varnier, Valeria Vasadi, Vimal Vasu, Vasanthi Vasudevan, Ramu Vathenen, Manu Vatish, Heloyes Vayalaman, Christopher Vaz, Niki Veale, Bar Velan, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Lyn Ventilacion, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Britney Vernon, Nathan Vernon, Mark Vertue, Natalie Vethanayagam, Lucy Veys, Jennifer Vidler, Denise Vigni, Vinod W Vijayaraghavan Nalini, Enric Vilar, Neringa Vilimiene, Joseph Villiers, Sylvia Vinay, Latha Vinayakarao, Rachel Vincent, Rosie Vincent, Lisa Vincent Smith, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Karunakaran Vithian, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Kirsten Wadsworth, Syed EI Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Khalilullah Wahdati, Sawan Waidyanatha, Rachel Wake, Alice Wakefield, Emma Wakefield, Harry Wakefield, William Wakeford, Fiona Wakinshaw, Andrew Walden, Lorna Walding, Claire Walker, Ian Walker, Kevin Walker, Kim Walker, Linda Walker, Marie Walker, Rachel Walker, Susan Walker, Elaine Wall, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Michael Waller, Rosemary Waller, Gabriel Wallis, Louise Wallis, Donna Walsh, Elizabeth Walsh, Lani Walshaw, Daniel Walter, Holt Walters, Jocelyn Walters, Eileen Walton, Maggie Walton, Michael Walton, Olivia Walton, Susan Walton, Mandy Wan, Thin Wan, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Deborah Warbrick, Samantha Warburton, Deborah Ward, Emma Ward, Katie Ward, Luke Ward, Rachael Ward, Thomas Ward, Scott A Warden, Steve Wardle, Hassan Wardy, Tobias Wareham, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Lisa Warren, Yolanda Warren, Hannah Warren-Miell, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Adam JR Watson, Ekaterina Watson, Eleanor Watson, Paul Watson, Robert Watson, Malcolm Watters, Donna Watterson, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Akhlaq Wazir, Nick Weatherly, Hayley Webb, Kathryn Webb, Stephen Webb, Ian Webster, Tim Webster, Ling Wee, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Freshtah Weidi, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Samantha Weller, Claire Wells, Susan Wellstead, Berni Welsh, RIchard Welsh, Ingeborg Welters, Rachael Welton, Lauren Wentworth, Kate Wesseldine, Magdelena West, Raha West, Ruth West, Sophie West, Heather Weston, Alice Westwood, Bill Wetherall, Helen Wheeler, Matthew Whelband, Amanda Whileman, Jenny Whitbread, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Sophie Whiteley, Gabriel Whitlingum, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Eunice Wiafe, Lou Wiblin, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Karen Wild, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Felicity Williams, Gail Williams, Hannah Williams, James Williams, Jennie Williams, John Williams, Joseph JR Williams, Karen Williams, Kathryn Williams, Marie Williams, Matthew Williams, Patricia Williams, Penny Williams, Samson Williams, Sarah Williams, Sophie Williams, Tamanna Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Francesca Willson, Alison Wilson, Andrea Wilson, Antoinette Wilson, Debbie Wilson, James Wilson, Kate Wilson, Lucinda Wilson, Mark Wilson, Toni Wilson, Tim Wilson, Marlar Win, Tin T Win, Lucinda Winckworth, Laura Winder, Piers Winder, Nicola Window, Simon Winn, Carmen Winpenny, Helen Winslow, Martin Winstanley, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Stephen Wisdom, Martin Wiselka, Sophie Wiseman, Steven Wishart, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Chi-Hung Wong, Edwin Wong, Jessica SY Wong, Kit Y Wong, Nick Wong, Sam Wong, Caroline Wood, Dianne Wood, Fiona Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Michelle Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Jane Woods, Katherine Woods, Sarah Woods, Elizabeth Woodward, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Stephy Worton, Jonathan Wraight, Lynn Wren, Caroline Wrey Brown, Demi Wright, Francesca Wright, Imogen Wright, Lianne Wright, Rachel Wright, Caroline Wroe, Henry Wu, Peishan Wu, Pensee Wu, Johnathan Wubetu, Retno Wulandari, Kim Wyness, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Zhongyang Xia, Masseh Yakubi, May Yan, Michael Yanney, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Mark Yates, Charlotte Yearwood Martin, Khin Yein, Robert Yellon, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche Melly, Inez Ynter, Cissy Yong, Jemma Yorke, Abdel Younes Ibrahim, Gail Young, Louise Young, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Ausra Zdanaviciene, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Xiaobei Zhao, Dongling Zheng, Jane Zhixin, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei T Zin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Carol Zullo, Ana Zuriaga-Alvaro, National Institute for Health Research, UK Research and Innovation, University of St Andrews. School of Medicine, Horby, PW, Roddick, A, Spata, E, Staplin, N, Emberson, JR, Pessoa-Amorim, G, Peto, L, Day, J, Thwaites, G, Mafham, M, Haynes, R, and Landray, MJ
Subjects: Male, medicine.medical_treatment, 030204 cardiovascular system & hematology, Azithromycin, ResearchInstitutes_Networks_Beacons/humanitarian_conflict_response_institute, Rate ratio, chemistry.chemical_compound, 0302 clinical medicine, RA0421, Oxygen therapy, RA0421 Public health. Hygiene. Preventive Medicine, 030212 general & internal medicine, Hospital Mortality, 11 Medical and Health Sciences, azithromycin, education.field_of_study, Covid19, clinical trial, General Medicine, 3rd-DAS, Middle Aged, Hospitalization, Survival Rate, Treatment Outcome, Humanitarian and Conflict Response Institute, Female, Life Sciences & Biomedicine, medicine.medical_specialty, RM, Population, COVID-19/drug therapy, Azithromycin/therapeutic use, 03 medical and health sciences, Pharmacotherapy, Tocilizumab, Medicine, General & Internal, SDG 3 - Good Health and Well-being, Internal medicine, General & Internal Medicine, medicine, Humans, education, Survival rate, Mechanical ventilation, Science & Technology, business.industry, COVID-19, NIS, Length of Stay, R1, United Kingdom, COVID-19 Drug Treatment, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, chemistry, Relative risk, business, RA, Anaesthesia Pain and Critical Care
Abstract: The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation (Medical Research Council) and NIHR (MC_PC_19056) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_0002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24). Interpretation: In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Publisher PDF
Published: 2021

49. Changes in the Diagnosis and Management of Diabetes in Mexico City Between 1998–2004 and 2015–2019

Author: Rory Collins, Michael Hill, Rachel Wade, Louisa Gnatiuc, Pablo Kuri-Morales, Raúl Ramirez-Reyes, Roberto Tapia-Conyer, Diego Aguilar-Ramirez, William G. Herrington, Jesus Alegre-Díaz, Richard Peto, and Jonathan Emberson
Subjects: Research design, Adult, Pediatrics, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Blood Pressure, 03 medical and health sciences, 0302 clinical medicine, Diabetes management, Diabetes mellitus, Mexico city, Internal Medicine, medicine, Diabetes Mellitus, Prevalence, Humans, 030212 general & internal medicine, Prospective Studies, Epidemiology/Health Services Research, Prospective cohort study, Mexico, Aged, Advanced and Specialized Nursing, Excess mortality, Proportional hazards model, business.industry, Diabetes prevalence, Middle Aged, medicine.disease, 3. Good health, Diabetes Mellitus, Type 2, business
Abstract: OBJECTIVE To investigate the trends in diabetes prevalence, diagnosis, and management among Mexican adults who were participants in a long-term prospective study. RESEARCH DESIGN AND METHODS From 1998 to 2004, 159,755 adults from Mexico City were recruited to a prospective study, and from 2015 to 2019, 10,144 survivors were resurveyed. Diabetes was defined as self-reported diagnosis, glucose-lowering medication use, or HbA1c ≥6.5%. Controlled diabetes was defined as HbA1c RESULTS During 1998–2004 and 2015–2019, 99,623 and 8,986 participants were aged 45–84 years. Diabetes prevalence had increased from 26% in 1998–2004 to 35% by 2015–2019. Of those with diabetes, the proportion previously diagnosed had increased from 76% to 89%, and glucose-lowering medication use among them had increased from 80% to 94%. Median HbA1c among those with diabetes had decreased from 8.2% to 7.3%, and the proportion of participants with controlled diabetes had increased from 16% to 37%. Use of blood pressure–lowering medication among those with previously diagnosed diabetes had increased from 35% to 51%, and their use of lipid-lowering therapy had increased from 1% to 14%. The excess mortality risk associated with diabetes accounted for 34% of deaths at ages 35–74 years, of which 5% were attributable to controlled and 29% to inadequately controlled diabetes. CONCLUSIONS Inadequately controlled diabetes is a leading cause of premature adult death in Mexico. Improvements in diabetes management have increased diagnosis and control, but substantial opportunities remain to improve treatment, particularly with lipid-lowering therapy.
Published: 2021

50. Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Edmund Juszczak, Andrew Ustianowski, Bryan Yates, Saul N. Faust, Martin J Landray, J Kenneth Baillie, Stacy Todd, Thomas Jaki, Katie Jeffery, Diego Maseda, Ben Prudon, Alan A Montgomery, Guy E. Thwaites, Kathryn M Rowan, Peter Horby, M Mafham, Natalie Staplin, Richard Haynes, Mark Campbell, Enti Spata, Guilherme Pessoa-Amorim, Maya H Buch, Wei Shen Lim, Abdul Ashish, Alistair J. Roddick, David Chadwick, Jonathan Emberson, Andrew D Mumford, Robert Buttery, Lucy C Chappell, Jeremy N. Day, Leon Peto, Stephen Scott, and Christopher E. Brightling
Subjects: Mechanical ventilation, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Rate ratio, Azithromycin, Confidence interval, Relative risk, Internal medicine, medicine, Active treatment, Open label, business, medicine.drug
Abstract: SUMMARYBackgroundAzithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19.MethodsIn this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).FindingsBetween 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54).InterpretationIn patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
Published: 2020

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