487 research outputs found

    Operation Warp Speed: implications for global vaccine security

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    Several global efforts are underway to develop COVID-19 vaccines, and interim analyses from phase 3 clinical testing have been announced by nine organisations: Pfizer, the Gamaleya Research Institute of Epidemiology and Microbiology, Moderna, AstraZeneca, Sinopharm Group, Sinovac Biotech, Johnson & Johnson, Novavax, and CanSino Biologics. The US programme known as Operation Warp Speed provided US$18 billion in funding for development of vaccines that were intended for US populations. Depending on safety and efficacy, vaccines can become available through mechanisms for emergency use, expanded access with informed consent, or full licensure. An important question is: how will these Operation Warp Speed vaccines be used for COVID-19 prevention in global health settings? We address some key questions that arise in the transition from US to global vaccine prevention efforts and from ethical and logistical issues to those that are relevant to global vaccine security, justice, equity, and diplomacy

    Impaired renal function affects clinical outcomes and management of patients with heart failure.

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    AIMS: Inpatients with heart failure and renal impairment have poor outcomes and variable quality of care. We investigate treatment practice and outcomes in an unselected real-world cohort using historical creatinine measurements. METHODS AND RESULTS: Admissions between 1/4/2013 and 30/4/2015 diagnosed at discharge with heart failure were retrospectively analysed. Stages of chronic kidney disease (CKD) and acute kidney injury (AKI) were calculated from creatinine at discharge and 3-12 months before admission. We identified 1056 admissions of 851 patients (mean age 76 years, 56% Caucasian, 36% with diabetes mellitus, 54% with ischaemic heart disease, and 57% with valvular heart disease). CKD was common; 36%-Stage 3a/b, 11%-Stage 4/5; patients were older, more often diabetic, with higher potassium, lower haemoglobin, and more oedema but similar prevalence of left ventricular systolic dysfunction (LVSD) compared patients with Stages 0-2. AKI was present in 17.0% (10.4%-Stage 1, 3.7%-Stage 2, and 2.9%-Stage 3); these had higher potassium and lower haemoglobin than patients with no AKI. Length of stay was longer in Stage 4/5 CKD [11 days; P = 0.008] and AKI [13 days; P = 0.006]. Mortality was higher with Stage 4/5 CKD (13.8% compared with 7.7% for Stages 0-2 CKD (P = 0.036)] and increased with AKI (5%-no AKI, 20.9%-Stage 1, 35.9%-Stage 2, and 48.4%-Stage 3; P < 0.001). Adjusted for age, diabetes, and LVSD, both AKI and Stage 4/5 CKD were independent predictors of in-hospital mortality. In survivors with LVSD, the discharge prescription of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased with progressive CKD, [84%-no-mild, 59%-moderate, and 36%-severe CKD; P < 0.001]; this was not purely explained by hyperkalaemia. CONCLUSIONS: Inpatients with heart failure and renal impairment, acute and chronic, failed to receive recommended therapy and had poor outcomes

    Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists

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    Aims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with >= 1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naive to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). D-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naive subjects with treatment, whereas in VKA pre-treated patients, D-dinner levels started tow and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by similar to 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase >= 3 x upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA

    Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinérAIR-Sclérodermie study

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    Objectives. This longitudinal study investigated survival, risk factors and causes of death in the multicentre ItinérAIR-Sclérodermie cohort of patients with SSc without severe pulmonary fibrosis or severe left heart disease at baseline
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