{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:10:35Z","timestamp":1789996235251,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pairwise drug\u2013drug interaction databases flag co\u2010prescribed pairs, but they under\u2010weight multi\u2010drug combinations that drive adverse drug events in older adults. We studied that gap in Virginia All\u2010Payer Claims Database records (2016\u20132019) for adults aged 65\u2013114\u2009years with non\u2010opioid emergency department visits (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091182 cases; 16,105 matched controls across three geriatric age bands). Features came from pharmacy and medical claims in a short pre\u2010index window optimized for acute ADE timing (21\u201330\u2009days by age band; 21\u2009days for ages 65\u201384). We trained gradient\u2010boosting models separately among patients with similar pre\u2010index healthcare contact volume (2016\u20132018 training; 2019 holdout), then used Formal Feature Attribution to score drug pairs and triplets and Intervention Rate ranks to order deprescribing review. On the 2019 holdout, geriatric AUPRC was 0.101\u20130.335 (PR lift 1.6\u00d7\u20134.2\u00d7). FFA flagged 115 synergistic pairs and 312 high\u2010confidence triplets (e.g., furosemide\u2009+\u2009hydrochlorothiazide\u2009+\u2009lisinopril; digoxin\u2009+\u2009furosemide\u2009+\u2009amiodarone, IE\u2009=\u20098.7). Top Intervention Rate drugs included simvastatin, furosemide, and alprazolam. Moderate preventive Z\u2010code monitoring (Q2) was protective (OR\u2009=\u20090.25; 95% CI 0.18\u20130.34) versus no monitoring, while fragmented high\u2010intensity monitoring (Q4) was not. The framework prioritizes medication combinations for pharmacist review in claims data; it does not replace pharmacokinetic confirmation or prove that changing a drug caused fewer ED visits.\n                  <\/jats:p>","DOI":"10.1111\/cts.70718","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:57:08Z","timestamp":1788411428000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A\n                    <scp>SHAP<\/scp>\n                    \u2010Informed Formal Feature Attribution Framework for Drug\u2013Drug Interaction Risk in Large\u2010Scale Claims Data"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8622-0597","authenticated-orcid":false,"given":"R. Jerome","family":"Dixon","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Outcomes Science, School of Pharmacy Virginia Commonwealth University  Richmond Virginia USA"},{"name":"Ph.D. Program in Integrative Life Sciences, School of Life Sciences and Sustainability Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6046-7540","authenticated-orcid":false,"given":"Elvin T.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Outcomes Science, School of Pharmacy Virginia Commonwealth University  Richmond Virginia USA"},{"name":"ConvergenceLabs@VCU\u2014Health Outcomes Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877\u2010017\u20100621\u20102"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.8581"},{"key":"e_1_2_13_4_1","unstructured":"M.Duerden T.Avery andR.Payne \u201cPolypharmacy and Medicines Optimisation: Making It Safe and Sound \u201d (2013) The King's Fund The King's Fund Report https:\/\/www.kingsfund.org.uk\/insight\u2010and\u2010analysis\/reports\/polypharmacy\u2010and\u2010medicines\u2010optimisation."},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102021\u2010055551"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvac005"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)01841\u20104"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15882"},{"key":"e_1_2_13_9_1","volume-title":"Causal Inference: What If","author":"Hern\u00e1n M. A.","year":"2020"},{"key":"e_1_2_13_10_1","unstructured":"A.Ignatiev Y.Izza P. J.Stuckey andJ.Marques\u2010Silva \u201cOn Formal Feature Attribution and Its Approximation \u201d (2023) Advances in Neural Information Processing Systems (NeurIPS) https:\/\/openreview.net\/forum?id=3b5e2AFs7f."},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256\u2010019\u20100138\u20109"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.19.00149"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013203451"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1145\/2939672.2939785"},{"key":"e_1_2_13_15_1","first-page":"6638","article-title":"CatBoost: Unbiased Boosting With Categorical Features","volume":"31","author":"Prokhorenkova L.","year":"2018","journal-title":"Advances in Neural Information Processing Systems"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.7326\/M14\u20100697"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001381"},{"key":"e_1_2_13_18_1","unstructured":"R. J.Dixon \u201cPGx Analysis: Virginia APCD Pharmacogenomic Risk Modeling Pipeline \u201d (2026) https:\/\/github.com\/Jerome3590\/pgx\u2010analysis."},{"key":"e_1_2_13_19_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Adverse Event Reporting System (FAERS) Database \u201d (2026) https:\/\/www.fda.gov\/drugs\/drug\u2010approvals\u2010and\u2010databases\/fda\u2010adverse\u2010event\u2010reporting\u2010system\u2010faers\u2010database."},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068938"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2149"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2023.100804"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169\u20107439(00)00122\u20102"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511803161"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256\u2010020\u20100197\u2010y"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2813"},{"key":"e_1_2_13_27_1","first-page":"4765","article-title":"A Unified Approach to Interpreting Model Predictions","volume":"30","author":"Lundberg S. M.","year":"2017","journal-title":"Advances in Neural Information Processing Systems"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.18372"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70718","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70718","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70718","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:44:02Z","timestamp":1789994642000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/cts.70718"],"URL":"https:\/\/doi.org\/10.1111\/cts.70718","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70718"}}