Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The effects of introduced tilapias on native biodiversity

1. The common name 'tilapia' refers to a group of tropical freshwater .sh in the family Cichlidae (Oreochromis, Tilapia, and Sarotherodon spp.) that are indigenous to Africa and the southwestern Middle East. Since the 1930s, tilapias have been intentionally dispersed worldwide for the biological control of aquatic weeds and insects, as bait.sh for certain capture .sheries, for aquaria, and as a food .sh. They have most recently been promoted as an important source of protein that could provide food security for developing countries without the environmental problems associated with terrestrial agriculture. In addition, market demand for tilapia in developed countries such as the United States is growing rapidly. 2. Tilapias are well-suited to aquaculture because they are highly proli.c and tolerant to a range of environmental conditions. They have come to be known as the 'aquatic chicken' because of their potential as an a.ordable, high-yield source of protein that can be easily raised in a range of environments } from subsistence or 'backyard' units to intensive .sh hatcheries. In some countries, particularly in Asia, nearly all of the introduced tilapias produced are consumed domestically; tilapias have contributed to basic food security for such societies. 3. This review indicates that tilapia species are highly invasive and exist under feral conditions in every nation in which they have been cultured or introduced. Thus, the authors have concluded that, despite potential or observed bene.ts to human society, tilapia aquaculture and open-water introductions cannot continue unchecked without further exacerbating damage to native .sh species and biodiversity. Recommendations include restricting tilapia culture to carefully managed, contained ponds, although exclusion is preferred when it is feasible. Research into culture of indigenous species is also recommended.No Full Tex

Medical Treatment Decisions and Competency in the Eyes of the Law: A Brief Survey

The question of mental competence arises in many different areas of the law. In order to make contracts and wills, have criminal responsibility, be a witness, or stand trial, a person must be mentally competent. Obviously, however, not every degree of mental deficiency or peculiarity is legally significant. Moreover, there is no single test of competence for these various contexts; rather, competency is defined in different ways for different purposes [56]. As a result, and somewhat paradoxically, a person can be legally incompetent in some areas while remaining legally competent in others. For example, since the law requires a lower degree of capacity in the making of wills than it does for the execution of contracts, one may be competent to make a will but incompetent to transact ordinary business affairs