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This article reports on trends in organized violence, building on new data by the Uppsala Conflict Data Program (UCDP). The falling trend in fatalities stemming from organized violence in the world, observed between 2014 and 2019, was decisively reversed in 2021 as fatalities increased significantly. UCDP registered more than 119,100 deaths in organized violence in 2021, a 46% increase from the previous year. The increase was largely driven by escalating conflicts in Afghanistan, Ethiopia, and Yemen. Fatalities increased in all three categories of organized violence, despite a decrease in the number of active state-based conflicts, as well as the number of actors carrying out one-sided violence against civilians. UCDP recorded 54 state-based conflicts in 2021, a decrease by two compared to the previous year. Five of the conflicts were active at the intensity of war, the lowest number of wars since 2010. Violence in 2021 was thus concentrated to fewer but bloodier conflicts. Unmanned aerial vehicles (UAVs), commonly known as drones, have become increasingly important features of modern conflicts, and the trend in their usage is discussed in the special feature section. UAV usage has since 2019 dispersed among a significant larger number of actors, even as the downscaling in the involvement of the United States in the war on terror has led to a decrease in drone-related fatalities.

In September 2020, the UK National Institute of HealthCare Excellence (NICE) published a draft report for consultation on anticoagulation therapy for stroke prevention in people with atrial fibrillation (AF) [1]. This intervention evidence review is part of the process of updating the NICE clinical guideline on management of AF [2] and addressed the question of which nonvitamin K oral anticoagulation (NOAC) therapy is most clinically and cost-effective for stroke prevention in people with AF. Four NOACs were included in the evidence review, each with a low and high dose formulation: apixaban, dabigatran, rivaroxaban and edoxaban, and all of which had been previously evaluated and recommended in NICE single technology appraisals [3–6]. On the basis of a systematic literature review to identify relevant evidence, network meta-analysis (NMA) to address comparative effectiveness, and subsequent cost–effectiveness analysis (CEA), the committee concluded that apixaban and dabigatran had the most favorable cost–effectiveness (CE) results of the four NOACs, at the NHS list prices and this led to a draft recommendation in the report that apixaban and dabigatran should be used as first-line options [1]. A further recommendation was made that patients who are stable on one of the other anticoagulants (rivaroxaban, edoxaban or warfarin) should discuss switching with their physician [1]. This draft decision by the committee, to recommend two NOACs within a class of four, represents an unusually strong recommendation to differentiate drugs within a particular class. This is especially so, given that the committee themselves state that the acquisition costs based on NHS list prices of the four NOACs are similar (page 74, line 28) [1]. This suggests that the opinion reached by the committee was grounded in the results of the NMA produced comparative effectiveness estimates that then formed the basis of the CEA. This manuscript reports on the process of examining the committee’s draft decision to differentiate drugs within the NOAC class on the basis of clinical and CE in light of the evidence considered by the committee. This manuscript was sponsored by the manufacturer of one of the NOACs that was not recommended as a first-line option by the committee (edoxaban, Daiichi Sankyo) in order to help them respond to the consultation process NICE initiated and which closed in November 2020. The aim of this manuscript is to elucidate the methodological challenges involved in any decision made by a reimbursement authority, such as NICE in the UK, and ask an open question regarding the strength of evidence of comparative effectiveness be required in order to differentiate similarly-priced drugs within a single drug class. The manuscript is structured around three further sections. The next section looks at the evidence on comparative effectiveness of seven key clinical outcomes, the need for NMA to generate those estimates of comparative effectiveness and the representation of uncertainty in the results of NMAs. The third section looks specifically at how the results of the NMA are then turned into a CEA that uses quality-adjusted life-years (QALYs) as the metric to synthesize the seven clinical outcomes into a QALY comparison, before considering the inclusion of costs and the representation of uncertainty in the CE results. A final section then discusses the challenges of making recommendations in the context of the uncertainty in clinical and CE both between the NOAC and vitamin-K antagonist (VKA) drug classes and within the NOAC class.

Background and Aims Chronic kidney disease (CKD) is a costly public health issue, which affects 13.4% of the population globally. Anaemia is a common complication in patients with CKD resulting in reduced health-related quality of life and high healthcare costs. The objective of this analysis was to estimate the direct medical care cost offsets of the investigational agent roxadustat for the treatment of anaemia in patients with dialysis-dependent (DD) CKD from a Canadian healthcare perspective. Method Data from the roxadustat global phase 3 program were used to estimate the incidence of rescue therapy or iron supplementation use (i.e. intravenous iron, erythropoiesis-stimulating agents [ESAs] or red blood cell transfusions) and major adverse cardiovascular events (MACE+) for roxadustat compared with ESAs in DD patients with anaemia of CKD. MACE+ included myocardial infarction, stroke, unstable angina requiring hospitalization, congestive heart failure (CHF) requiring hospitalization, cardiovascular death and other death. Published Canadian cost data were used to estimate event costs. Drug acquisition costs for roxadustat and ESAs were not considered. A hypothetical cohort of 10,000 Canadian adult DD patients (90% undergoing haemodialysis, 10% undergoing peritoneal dialysis) with treatable anaemia was modelled to determine net medical care cost offsets annually and cumulatively compared with ESAs over a 4-year time horizon. Results Preliminary results for patients with DD CKD show that, compared with ESAs, roxadustat could produce sizeable net medical care cost offsets resulting from reductions in rescue therapy or iron supplementation use, specifically red blood cell transfusions, and from reductions in MACE+, specifically CHF hospitalizations. For the entire cohort of patients with DD CKD, cumulative medical care cost offsets for roxadustat were an estimated $162,609 for rescue therapy or iron supplementation use and $1,027,070 for MACE+ compared with ESAs. Conclusion This analysis provides evidence that treatment with roxadustat in DD patients with anaemia of CKD could result in considerable medical care cost offsets for roxadustat compared with ESAs.

Background The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT. Methods A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP. Results At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group. Conclusions BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.

Formetanate hydrochloride is a bifunctional pesticide with remarkable solubility, high toxicity, and potential mobility in aqueous environments. The relative stability of the formamidine and carbamate groups in this compound can be used to predict the identity of its degradation products in water. The reported NMR and UV-vis spectroscopic studies revealed that the formamidine group is more labile than the carbamate group under strongly basic conditions, as well as under predetermined field conditions. The half-life of the formamidine group was determined to be 3.9 h under strongly basic conditions (pH 12.6) and 14.4 h under mildly basic conditions (pH 7.6). The longevity of the carbamate group may exceed 6 months due its resistance to base-promoted degradation. These results may be used in the design of more specific remediation technology for formetanate-contaminated surface water.