The rise and fall of aspirin in the primary prevention of cardiovascular disease

Aspirin is one of the most frequently used drugs worldwide and is generally considered effective for the secondary prevention of cardiovascular disease. By contrast, the role of aspirin in primary prevention of cardiovascular disease is controversial. Early trials evaluating aspirin for primary prevention, done before the turn of the millennium, suggested reductions in myocardial infarction and stroke (although not mortality), and an increased risk of bleeding. In an effort to balance the risks and benefits of aspirin, international guidelines on primary prevention of cardiovascular disease have typically recommended aspirin only when a substantial 10-year risk of cardiovascular events exists. However, in 2018, three large randomised clinical trials of aspirin for the primary prevention of cardiovascular disease showed little or no benefit and have even suggested net harm. In this narrative Review, we reappraise the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials

Retaining the equilibrium point hypothesis as an abstract description of the neuromuscular system

The lambda version of the equilibrium point (EP) hypothesis for motor control is examined in light of recent criticisms of its various instantiations. Four important assumptions that have formed the basis for recent criticism are analyzed: First, the assumption that intact muscles possess invariant force-length characteristics (ICs). Second, that these ICs are of the same form in agonist-antagonist pairs. Third, that muscle control is monoparametric and that the control parameter, lambda, can be given a neurophysiological interpretation. Fourth, that reflex loop time delays and the known, asymmetric, nonlinear mechanical properties of muscles can be ignored. Mechanical and neurophysiological investigations of the neuromuscular system suggests that none of these assumptions is likely to be correct. This has been taken to mean that the EP hypothesis is oversimplified and a new approach is needed. It is argued that such an approach can be provided without rejecting the EP hypothesis, rather to regard it as an input-output description of muscle and associated segmental circuits. The operation of the segmental circuitry can be interpreted as having the function, at least in part, of compensating for a variety of nonlinearities and asymmetries such that the overall system implements the lambda-EP model equations