{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:03:56Z","timestamp":1784178236102,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Delayed cerebral ischemia (DCI) and cerebral infarction remain major causes of disability and death after aneurysmal subarachnoid hemorrhage (aSAH). Enteral cilostazol and intravenous (IV) 25% human albumin have each been investigated as candidate therapies targeting potentially overlapping DCI mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This article aims to estimate the plausible effects of albumin, cilostazol, and combination therapy on reducing DCI after aSAH using Bayesian prior-predictive simulation and factorial component-effect decomposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We defined four treatment classes: control, albumin-only, cilostazol-only, and combination therapy. The primary endpoint was the National Institute of Neurological Disorders and Stroke Common Data Elements-defined DCI (CDE-d-DCI) on computed tomography on days 10 to 14. A prior-predictive Monte Carlo model used a control DCI-risk prior centered on the Cilostazol Albumin Treatment in Subarachnoid Hemorrhage (CATS) protocol-planning value of 31%, a cilostazol prior anchored to randomized-trial meta-analysis estimates, and an albumin prior informed by the Albumin in Subarachnoid Hemorrhage (ALISAH) dose-escalation data with wider uncertainty because ALISAH was uncontrolled. No observed CATS outcomes were analyzed. External consistency, control-prior sensitivity, weaker albumin priors, correlated-prior structures, and factorial component effects were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Under base-case priors, median absolute risk reductions (ARRs) versus control were 9.1 percentage points for albumin (90% simulation interval, \u22123.3 to 18.1; prior-predictive probability of ARR\u202f&amp;gt;\u202f0, 89.8%), 18.1 percentage points for cilostazol (11.0 to 25.4; 99.9%), and 21.7 percentage points for combination therapy (12.4 to 29.9; 99.8%). Although combination therapy had the largest projected reduction versus control, the incremental benefit of adding albumin to cilostazol was small and uncertain (3.5 percentage points; \u22123.0 to 8.9), and the additive interaction was also uncertain (\u22125.5 percentage points; \u221211.9 to 2.8). Illustrative two-group sample sizes were 343, 76, and 49 participants per group for albumin, cilostazol, and combination therapy, respectively, versus control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These simulations provide planning-level projections and do not establish efficacy. The findings support continued randomized evaluation of cilostazol and albumin, with concurrent single-agent, combination, and control arms to estimate component effects and interaction effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1889448","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:21:12Z","timestamp":1784175672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of intravenous human albumin, enteral cilostazol, and combination therapy on the reduction of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage"],"prefix":"10.3389","volume":"17","author":[{"given":"Adnan I.","family":"Qureshi","sequence":"first","affiliation":[{"name":"Zeenat Qureshi Stroke Institute","place":["Columbia, MO, United States"]},{"name":"Department of Neurology, University of Missouri","place":["Columbia, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Raza","sequence":"additional","affiliation":[{"name":"Zeenat Qureshi Stroke Institute","place":["Columbia, MO, United States"]},{"name":"Department of Neurology, University of Missouri","place":["Columbia, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Beall","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, College of Medicine, Medical University of South Carolina","place":["Charleston, SC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Gajewski","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, University of Kansas Medical Center","place":["Kansas City, KS, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee H.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, College of Medicine, Medical University of South Carolina","place":["Charleston, SC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose I.","family":"Suarez","sequence":"additional","affiliation":[{"name":"Division of Neurosciences Critical Care, Departments of Neurology, Anesthesiology and Critical Care Medicine, and Neurosurgery, Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1001\/jama.2015.16702","article-title":"Dose-finding trials: optimizing phase 2 data in the drug development 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