{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:10:06Z","timestamp":1791429006439,"version":"4.3.3"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin\u2010related prescribing cascades has been performed to our knowledge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes (\u201cmarker\u201d classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005\u20132019). Order of initiation and secular trend\u2010adjusted sequence ratios were calculated for each statin\u2010marker class dyad, among marker class initiators \u00b190\u2009days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1\u2009year as the inverse of the excess risk among exposed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 2\u2009265\u2009519 statin initiators (mean\u2009\u00b1\u2009<jats:italic>SD<\/jats:italic> age, 56.4\u2009\u00b1\u200912.0\u2009years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin\u2010marker class dyad signals, of which 35.6% (<jats:italic>n<\/jats:italic>\u00a0=\u00a057) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43\u201346), opioids\u2009+\u2009non\u2010opioid combination analgesics (81, 95% CI 74\u201391), and first\u2010generation cephalosporins (204, 95% CI 175\u2013246).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Using high\u2010throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin\u2010related adverse events.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5607","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T08:25:51Z","timestamp":1678177551000},"page":"773-782","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["High\u2010throughput screening for prescribing cascades among real world statin initiators"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-2160","authenticated-orcid":false,"given":"Scott M.","family":"Vouri","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; Policy, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8906","authenticated-orcid":false,"given":"Earl J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; Policy, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-3612","authenticated-orcid":false,"given":"Marta","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; Policy, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Agalliu","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Dempsey","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Hochleitner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; Policy, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Muschett","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; Policy, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy University of Florida  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6011-681X","authenticated-orcid":false,"given":"Carl J.","family":"Pepine","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Center for Integrative Cardiovascular and Metabolic Disease University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-839X","authenticated-orcid":false,"given":"Steven M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; Policy, College of Pharmacy 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