Antithrombotic therapy and survival in patients with malignant disease

A broad range of studies suggest a two-way relationship between cancer and venous thromboembolism (VTE). Patients with cancer have consistently been shown to be at elevated risk for VTE; this risk is partly driven by an intrinsic hypercoagulable state elicited by the tumour itself. Conversely, thromboembolic events in patients without obvious risk factors are often the first clinical manifestation of an undiagnosed malignancy. The relationship between VTE and cancer is further supported by a number of trials and meta-analyses which, when taken together, strongly suggest that antithrombotic therapy can extend survival in patients with cancer by a mechanism that extends beyond its effect in preventing VTE. Moreover, accumulating evidence from in vitro and in vivo studies has shown that tumour growth, invasion, and metastasis are governed, in part, by elements of the coagulation system. On 22 May 2009, a group of health-care providers based in the United Kingdom met in London, England, to examine recent advances in cancer-associated thrombosis and its implications for UK clinical practice. As part of the discussion, attendees evaluated evidence for and against an effect of antithrombotic therapy on survival in cancer. This paper includes a summary of the data presented at the meeting and explores potential mechanisms by which antithrombotic agents might exert antitumour effects. The summary is followed by a consensus statement developed by the group

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Co-axial dual-core resonant leaky fibre for optical amplifiers

We present a co-axial dual-core resonant leaky optical fibre design, in which the outer core is made highly leaky. A suitable choice of parameters can enable us to resonantly couple power from the inner core to the outer core. In a large-core fibre, such a resonant coupling can considerably increase the differential leakage loss between the fundamental and the higher order modes and can result in effective single-mode operation. In a small-core single-mode fibre, such a coupling can lead to sharp increase in the wavelength dependent leakage loss near the resonant wavelength and can be utilized for the suppression of amplified spontaneous emission and thereby gain equalization of an optical amplifier. We study the propagation characteristics of the fibre using the transfer matrix method and present an example of each, the large-mode-area design for high power amplifiers and the wavelength tunable leakage loss design for inherent gain equalization of optical amplifiers.Comment: 6 page

Antimicrobial use in developing countries

We conducted a study on agriculture related antimicrobial resistance (AMR) in developing countries. AMR pathogens are commonly found in animals, animal food products and agro-food environments, but the lack of surveillance systems means there are no reliable national data on the level of AMR in animals and their products. While AMR infections in animals and their products contribute to AMR infections in people in developing countries the literature is insufficient to draw firm conclusions on the extent of this contribution, which is likely to vary in different contexts. For example, a recent study found high levels of multi-drug resistance in goats kept by pastoralists in remote, isolated areas and never given treatments by veterinarians or farmers. The key driver of agriculture-related AMR is the quantity and quality of use of antimicrobials in livestock production and aquaculture. In developing countries as much as several hundred thousand tons may be used every year, agricultural use probably exceeds medical use, and most use is probably in intensive systems. The underlying driver for antimicrobial use and development of AMR is the livestock and aquaculture revolution that is the rapid growth in intensive production systems in response to increased demand for livestock and fish products. Based on livestock intensification patterns, China, Brazil and India are current hotspots, and future hotspots with fastest growth of the intensive livestock sector in Myanmar, Indonesia, Nigeria, Peru and Vietnam. China is a hotspot for aquaculture and Indonesia, Thailand, Vietnam, Bangladesh, India and Chile are other countries where antimicrobial use in fish production may be problematic. AMR is intrinsically a global problem that can only be managed at supra-national scale and the current strong momentum to take action on AMR provides an opportunity to address the problem globally and comprehensively, addressing medical and veterinary use. This will require better evidence on the use of antimicrobials in agriculture, the impacts of this use on human and animal health, the acceptability and feasibility of stricter control of antibiotic use in agriculture, and the costs and benefits of stricter control taking into account trades offs between overuse and lack of access to antimicrobial drugs

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study.

OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding