Sex-differences in oral anticoagulation therapy in patients hospitalized with atrial fibrillation:a nationwide cohort study

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67–0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66–0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90–0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The provocation of Gaïa: learning to pay attention in Rotary Park

How do we learn with the environments we inhabit to promote mutual flourishing? This paper argues that environmental arts practice is a key component in the pedagogical process of getting to know where we live and, through a more-than-human intersubjective exchange, enriching our response-ability to the environment. To think through and work towards this pedagogy we explore a small patch of Gaïa – the Rotary Park Rainforest Reserve in Lismore, New South Wales – via a photography and video project that contemplates didactic and interpretive signs along a short walking circuit. Crucial to our contemplation of this environmental arts project are concepts for action that we develop by putting into conversation ideas from the environmental humanities and early childhood education: progettazione, time to learn, provocation and attention. Through aesthetic immersion in, and in dialogue with the forest, these concepts help us conceptualise a regenerative curriculum and relational pedagogy that energise, amongst other things, environmental arts in-the-making

Petitioners as a Reflection of Their Community

Petitioners of direct democracy play a fundamental role in the democratic process. These individuals are those who circulate petitions and endeavor to change laws through initiatives. Petitioners are motivated by a variety of reasons, and this can lead to differences not only in the laws they propose but also in their success. This chapter will examine the impact that community connections have on the petitioning process by exploring the effects of different typologies of petitioners on how connected they are to their community, attitudes toward fellow citizens, and happiness. To accomplish this task, this chapter will look at the different petitioner typology and the role of community networks in each.https://digitalcommons.chapman.edu/education_books/1025/thumbnail.jp

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK

Objective: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE. Methods: Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions. Results: Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed. Conclusion: Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualising care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations

Sex-differences in oral anticoagulation therapy in patients hospitalized with atrial fibrillation: a nationwide cohort study

No abstract available