Choosing Wisely was launched by the American Board of Internal Medicine in April 2012 as a patient- and clinician-targeted campaign to reduce potentially unnecessary "low-value" medical services. The campaign's impact on low- and high-value care beyond its first year is unknown; furthermore, it is unknown whether some patients such as members of consumer-directed health plans and people residing in different US regions have responded more than others. To evaluate the impact of Choosing Wisely, we used commercial insurance claims to track changes in the use of low-value imaging (x-ray, computed tomography, and magnetic resonance imaging) for back pain before and after the campaign began, a period running from 2010 to 2014. We selected back pain imaging because it is a prominent target of Choosing Wisely, which considers it low value except in a minority of cases, because of its relatively high out-of-pocket expense, and the large volume of low back pain visits nationally. We found only a 4 percent relative reduction in low-value back imaging 2.5 years after the start of the campaign and some differences in regional trends, but no differences associated with enrollment in consumer-directed health plans. Our findings highlight the ongoing challenge of reducing unnecessary medical care, even when patients have "skin in the game" under consumer-directed health plans.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV locus, which encodes the protein pyrin. While it is known that pyrin is expressed in myeloid cells and several fibroblastic cell types, the exact function of pyrin in these cells and the mechanism underlying the pathological effect of pyrin mutations have yet to be revealed. Here, we document that in migrating human monocytes, pyrin protein is dramatically polarized at the leading edge, where it co-localizes with polymerizing actin. ASC (Apoptosis-associated Speck protein with CARD domain), a known pyrin-interacting protein and a critical component of the inflamma-some, is also located at the leading edge in migrating monocytes. Similarly, both pyrin and ASC concentrate in dynamically polymerizing actin-rich tails generated by Listeria monocytogenes. Pyrin's B-box and coiled-coil region is required for its association with Listeria tails. Pyrin also binds, with low affinity and via the same domains, to actin, VASP, and Arp3. Though disease-causing mutations in pyrin do not appear to alter its localization to the leading edge or to Listeria rocket tails, they could potentially have important functional consequences in the context of processes such as migration and cell synapse formation. The co-localization of pyrin and ASC together at such sites may provide an important link between cytoskeletal signaling and inflammasome function.