Patient-reported reasons for declining or discontinuing statin therapy: Insights from the PALM registry

Background: Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation.Methods and Results: This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin.Conclusions: More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered

Holocene Earthquakes and Right-lateral Slip on the Left-lateral Darrington-Devils Mountain Fault Zone, Northern Puget Sound, Washington

Sources of seismic hazard in the Puget Sound region of northwestern Washington include deep earthquakes associated with the Cascadia subduction zone, and shallow earthquakes associated with some of the numerous crustal (upper-plate) faults that crisscross the region. Our paleoseismic investigations on one of the more prominent crustal faults, the Darrington–Devils Mountain fault zone, included trenching of fault scarps developed on latest Pleistocene glacial sediments and analysis of cores from an adjacent wetland near Lake Creek, 14 km southeast of Mount Vernon, Washington. Trench excavations revealed evidence of a single earthquake, radiocarbon dated to ca. 2 ka, but extensive burrowing and root mixing of sediments within 50–100 cm of the ground surface may have destroyed evidence of other earthquakes. Cores in a small wetland adjacent to our trench site provided stratigraphic evidence (formation of a laterally extensive, prograding wedge of hillslope colluvium) of an earthquake ca. 2 ka, which we interpret to be the same earthquake documented in the trenches. A similar colluvial wedge lower in the wetland section provides possible evidence for a second earthquake dated to ca. 8 ka. Three-dimensional trenching techniques revealed evidence for 2.2 ± 1.1 m of right-lateral offset of a glacial outwash channel margin, and 45–70 cm of north-side-up vertical separation across the fault zone. These offsets indicate a net slip vector of 2.3 ± 1.1 m, plunging 14° west on a 286°-striking, 90°-dipping fault plane. The dominant right-lateral sense of slip is supported by the presence of numerous Riedel R shears preserved in two of our trenches, and probable right-lateral offset of a distinctive bedrock fault zone in a third trench. Holocene north-side-up, right-lateral oblique slip is opposite the south-side-up, left-lateral oblique sense of slip inferred from geologic mapping of Eocene and older rocks along the fault zone. The cause of this slip reversal is unknown but may be related to clockwise rotation of the Darrington–Devils Mountain fault zone into a position more favorable to right-lateral slip in the modern N-S compressional stress field

Minimal stratigraphic evidence for coseismic coastal subsidence during 2000 yr of megathrust earthquakes at the central Cascadia subduction zone

Lithology and microfossil biostratigraphy beneath the marshes of a central Oregon estuary limit geophysical models of Cascadia megathrust rupture during successive earthquakes by ruling out >0.5 m of coseismic coastal subsidence for the past 2000 yr. Although the stratigraphy in cores and outcrops includes as many as 12 peat-mud contacts, like those commonly inferred to record subsidence during megathrust earthquakes, mapping, qualitative diatom analysis, foraminiferal transfer function analysis, and 14C dating of the contacts failed to confirm that any contacts formed through subsidence during great earthquakes. Based on the youngest peat-mud contact’s distinctness, >400 m distribution, ~0.6 m depth, and overlying probable tsunami deposit, we attribute it to the great 1700 CE Cascadia earthquake and(or) its accompanying tsunami. Minimal changes in diatom assemblages from below the contact to above its probable tsunami deposit suggest that the lower of several foraminiferal transfer function reconstructions of coseismic subsidence across the contact (0.1–0.5 m) is most accurate. The more limited stratigraphic extent and minimal changes in lithology, foraminifera, and(or) diatom assemblages across the other 11 peat-mud contacts are insufficient to distinguish them from contacts formed through small, gradual, or localized changes in tide levels during river floods, storm surges, and gradual sea-level rise. Although no data preclude any contacts from being synchronous with a megathrust earthquake, the evidence is equally consistent with all contacts recording relative sea-level changes below the ~0.5 m detection threshold for distinguishing coseismic from nonseismic changes

Active Site Mutations Change the Cleavage Specificity of Neprilysin

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid β1–40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß1–40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential

A broadly implementable research course in phage discovery and genomics for first-year undergraduate students

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students\u27 interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training

Effects of varying case definition on carpal tunnel syndrome prevalence estimates in a pooled cohort

OBJECTIVE: To analyze differences in carpal tunnel syndrome (CTS) prevalence using a combination of electrodiagnostic studies (EDSs) and symptoms using EDS criteria varied across a range of cutpoints and compared with symptoms in both ≥1 and ≥2 median nerve–served digits. DESIGN: Pooled data from 5 prospective cohorts. SETTING: Hand-intensive industrial settings, including manufacturing, assembly, production, service, construction, and health care. PARTICIPANTS: Employed, working-age participants who are able to provide consent and undergo EDS testing (N=3130). INTERVENTIONS: None. MAIN OUTCOME MEASURES: CTS prevalence was estimated while varying the thresholds for median sensory latency, median motor latency, and transcarpal delta latency difference. EDS criteria examined included the following: median sensory latency of 3.3 to 4.1 milliseconds, median motor latency of 4.1 to 4.9 milliseconds, and median-ulnar sensory difference of 0.4 to 1.2 milliseconds. EDS criteria were combined with symptoms in ≥1 or ≥2 median nerve–served digits. EDS criteria from other published studies were applied to allow for comparison. RESULTS: CTS prevalence ranged from 6.3% to 11.7%. CTS prevalence estimates changed most per millisecond of sensory latency compared with motor latency or transcarpal delta. CTS prevalence decreased by 0.9% to 2.0% if the criteria required symptoms in 2 digits instead of 1. CONCLUSIONS: There are meaningful differences in CTS prevalence when different EDS criteria are applied. The digital sensory latency criteria result in the largest variance in prevalence