The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation.
A ...comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.
The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial ...fibrillation.
A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.
The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs
and revealed how quickly viral escape can curtail effective options
. When the SARS-CoV-2 ...Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab
. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination
and is challenging to replace with existing approaches. Rapidly modifying such high-value antibodies to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign and renew the efficacy of COV2-2130 against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and subsequent variants of concern, and provides protection in vivo against the strains tested: WA1/2020, BA.1.1 and BA.5. Deep mutational scanning of tens of thousands of pseudovirus variants reveals that 2130-1-0114-112 improves broad potency without increasing escape liabilities. Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities.
A review essay covering books by 1) Frances McCall Rosenbluth and Ian Shapiro, Responsible parties: Saving democracy from itself (2018), 2) Sam Rosenfeld, The polarizers: Postwar architects of our ...partisan era (2018) and 3) Mark Wickham-Jones, Whatever happened to party government? (2018).
This article reviews the history of the Anglo-American ‘special relationship’ to assess the relative importance of shared cultures and values, common enemies and political self-interest in ...maintaining the connection over the long term and, most important, in making it closer and more salient in the short term. The paper briefly reviews the literature and argues that culture and values are seldom decisive but serve as a precondition, a facilitating factor in the alliance. It then argues that what seems most important in explaining those moments when the relationship was closest is self-interest—for the two countries, as during the Second World War, or for particular political leaders whose visions and projects are furthered by having allies who largely share such views and plans. Examples of this more particular and limited kind of self-interest are Thatcher and Reagan and Blair and Clinton—and, to a lesser extent, Blair and Bush.
Abstract
In the summer of 2019–2020, southern Australia experienced the largest fires on record, detrimentally impacting the habitat of native species, many of which were already threatened by past ...and current anthropogenic land use. A large-scale restoration effort to improve degraded species habitat would provide fire-affected species with the chance to recover and persist in burnt and unburnt habitat. To facilitate this, decision-makers require information on priority species needs for restoration intervention, the suite of potential restoration interventions, and the priority locations for applying these interventions. We prioritize actions in areas where restoration would most likely provide cost-effective benefits to priority species (defined by each species proportion of habitat burned, threat status, and vulnerability to fires), by integrating current and future species habitat suitability maps with spatially modelled costs of restoration interventions such as replanting, removing invasive species, and implementing ecologically appropriate fire management. We show that restoring the top ∼69% (112 million hectares) of the study region (current and future distributions of priority species) accounts for, on average, 95% of current and future habitat for every priority species and costs ∼AUD$73 billion yr
−1
(AUD$650 hectare
−1
yr
−1
) annualized over 30 years. This effort would include restoration actions over 6 million hectares of fire-impacted habitat, costing ∼AUD$8.8 billion/year. Large scale restoration efforts are often costly but can have significant societal co-benefits beyond biodiversity conservation. We also show that up to 291 MtCO2 (∼150 Mt DM) of carbon could be sequestered by restoration efforts, resulting in approximately AUD$253 million yr
−1
in carbon market revenue if all carbon was remunerated. Our approach highlights the scale, costs, and benefits of targeted restoration activities both inside and outside of the immediate bushfire footprint over vast areas of different land tenures.
Gastrointestinal (GI) and liver diseases inflict a heavy economic burden. Although the burden is considerable, current and accessible information on the prevalence, morbidity, and cost is sparse. ...This study was undertaken to estimate the economic burden of GI and liver disease in the United States for use by policy makers, health care providers, and the public.
Data were extracted from a number of publicly available and proprietary national databases to determine the prevalence, direct costs, and indirect costs for 17 selected GI and liver diseases. Indirect cost calculations were purposefully very conservative. These costs were compared with National Institutes of Health (NIH) research expenditures for selected GI and liver diseases.
The most prevalent diseases were non-food-borne gastroenteritis (135 million cases/year), food-borne illness (76 million), gastroesophageal reflux disease (GERD; 19 million), and irritable bowel syndrome (IBS; 15 million). The disease with the highest annual direct costs in the United States was GERD ($9.3 billion), followed by gallbladder disease ($5.8 billion), colorectal cancer ($4.8 billion), and peptic ulcer disease ($3.1 billion). The estimated direct costs for these 17 diseases in 1998 dollars were $36.0 billion, with estimated indirect costs of $22.8 billion. The estimated direct costs for ail digestive diseases were $85.5 billion. Total NIH research expenditures were $676 million in 2000.
GI and liver diseases exact heavy economic and social costs in the United States. Understanding the prevalence and costs of these diseases is important to help set priorities to reduce the burden of illness.
The Second World War created and the Cold War sustained a "special relationship" between America and Britain, and the terms on which that decades-long conflict ended would become the foundation of a ...new world order. In this penetrating analysis, a new history of recent global politics, author James Cronin explores the dramatic reconfiguring of western foreign policy that was necessitated by the interlinked crises of the 1970s and the resulting global shift toward open markets, a movement that was eagerly embraced and encouraged by the U.S./U.K. partnership.Cronin's bold revisionist argument questions long-perceived views of post-World War II America and its position in the world, especially after Vietnam. The author details the challenges the economic transition of the 1970s and 1980s engendered as the United States and Great Britain together actively pursued their shared ideal of an international assemblage of market-based democratic states. Cronin also addresses the crises that would sorely test the system in subsequent decades, from human rights violations and genocide in the Balkans and Africa to 9/11 and militant Islamism in the Middle East to the "Great Recession" of 2008.
Older patients with secondary AML or AML-MRC have poor prognosis.
Hypomethylating agents offer survival outcomes comparable to intensive chemotherapy.
Transplant eligibility and potential effects on ...QoL should drive therapy selection.
Acute myeloid leukemia (AML) in older patients is often associated with biologic and clinical characteristics that predict poor outcomes to cytarabine and anthracycline based induction chemotherapy (IC). The impact of hypomethylating agents (HMA) in the treatment of these high-risk patients is unknown. Here we retrospectively examined the remission rates and survival outcomes of 201 newly diagnosed patients ≥60 years old with therapy-related (t-AML), secondary (s-AML), or AML with myelodysplasia-related changes (AML-MRC). Ninety-eight patients received IC, and 103 received HMA. Patients in the IC cohort were younger than those who received HMA (68 vs. 74 years; p < 0.01) with lower comorbidity burden. Composite complete remission rates (CR) were 39% in IC and 27% in the HMA cohorts (p = 0.10). Overall survival (OS) was not significantly different between the two cohorts (7.59 mos vs. 5.49 mos; HR 0.75 95% CI 0.55–1.02) despite the fact that more patients in the IC cohort (33% versus 5%, p < 0.01) underwent allogeneic stem cell transplant. Patients with t-AML (HR 0.56; 95% CI 0.33–0.97) and complex karyotype without monosomal karyotype (CK + MK-; HR 0.37; 95% CI 0.19–0.75) had better OS following IC. Patients with CK + MK+ (HR 2.00; 95% CI 1.08–3.70) had improved OS following HMA. Our results support the use of HMA as an alternative upfront regimen in older individuals with newly diagnosed high-risk AML based on similar clinical outcomes to IC.
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